bluuebunny/crossref_metadata_2025 huggingface dataset:
Overcoming developing-world challenges in cochlear implantation: A Nigerian perspective
Authors: Jesuyajolu Damilola , Obuh Otomi , Edeh Emmanuel
Published: September 2023

The emergence of cochlear implantation (CI) in the mid-20th century was a transformation to the field of restorative otology. The advance in this field has not been felt in lower-income countries where a huge burden of profound hearing loss lies. The authors sought to review the literature on the practice of cochlea implantation in Nigeria. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews, we conducted a scoping review of the literature on CI in Nigeria. All observational studies with information on cochlear implants and/or implantation in Nigeria were included with no limitations on outcomes. The authors extracted the following data; age, sample size, sex, aetiology, outcome, type of devices, complications, challenges and the location of the surgery. The results were pooled and reported as frequencies and percentages. Three studies were utilised in this review. The study included 25 patients. The age of the identified patients ranged from 1.2 months to 63 years. There were slightly more males than females (52% males). The most common aetiology of deafness in the participants was following a febrile illness (40%), followed by deafness post-meningitis (24%). The challenges identified included high cost, lack of full rehabilitative facilities and staff, scepticism, and lack of funding. CI remains the most effective for those that are profoundly deaf. Although successful CI programmes exist in Nigeria, the number of implant programmes and the affordability are not yet commensurate to the needs of the entire Nigerian population.
Evaluation of Physicians' Knowledge About Honey/Sucralfate Treatments in Children With Button Battery Ingestion
Authors: Akca Caglar Ayla , Derinoz Guleryuz Oksan , Tomar Güneysu Songül , Çolak Özlem
Published: September 2023

Objectives

Ingestion of button batteries (BBs) causes serious mortality and morbidity. We aimed to evaluate the knowledge level of physicians working in pediatric emergency departments about the updated guidelines for BB ingestion and whether they used honey and sucralfate, which have proven positive effects in preventing mucosal damage, in their daily practice.

Methods

A “Google Form” questionnaire was prepared and used to evaluate the approach of physicians who worked in pediatric emergency department with questions about pediatric patients who were admitted with the suspicion of BB swallowing.

Results

A total of 263 physicians, 169 women (64.3%), with a mean age of 34.5 ± 7.3 years, participated in the study. Seventy-five percent of the participants were from tertiary care hospitals, and 60.8% had less than 5 years of pediatric emergency experience. Some 71.9% of the physicians who participated in the survey (n = 189) had no algorithm at their hospitals. Fifty-eight percent (n = 152) of the participants completely and correctly answered all our survey questions about battery swallowing. Fifty-eight (22.1%) of the participants administered sucralfate, and 12.2% (n = 32) used honey treatments in patients who swallowed BBs; 68.1% (n = 179) had never heard of the use of sucralfate, and 77.6% (n = 204) had never heard of honey applications before in the management of swallowed batteries.

Conclusion

It was determined that the physicians who managed pediatric battery swallowing cases had deficiencies in their treatment approaches, they had no protocol in their institutions, and the use of mucosal damage mitigation and neutralization treatments, such as honey and sucralfate, was insufficient.
Actions to Avoid in Pain Management and Sedoanalgesia Procedures in Pediatric Emergencies
Authors: Khodayar-Pardo Parisá , Miguez-Navarro María Concepción , Martín Espín Irene ,   the Analgesia and Sedation Working Group of the Spanish Society of Pediatric Emergency Medicine
Published: September 2023

Objectives

The aim of this study was to show the process of elaboration and the results obtained of the list of “do not do” recommendations for pain management and sedoanalgesia procedures in pediatric patients within the Working Group on Analgesia and Sedation of the Spanish Society of Pediatric Emergencies (Grupo de Trabajo de Analgesia y Sedación de la Sociedad Española de Urgencias de Pediatría [GTAS-SEUP]).

Methods

The process of drawing up the list was carried out in 3 phases: (1) “brainstorming,” open to all members of the GTAS-SEUP; (2) selection of recommendations, after a modified Delphi methodology; and (3) drafting and consensus of the final document.

Results

Initially, 57 proposed recommendations were obtained, which were reduced to 39 by unifying those that were similar. Of the 14 “do not do” in pain management, 6 were accepted: 3 in the first round and 3 in the second round. Of the 25 “do not do” recommendations for sedoanalgesia procedures, 6 were accepted: 4 in the first round and 2 in the second round. The final text consisted of 12 actions to avoid, 6 referring to pain management and 6 to sedoanalgesia procedures.

Conclusions

The list of “do not do” recommendations for pain management and sedoanalgesia procedures in the pediatric patient is a consensual tool, within the GTAS-SEUP. These recommendations promote an improvement in the quality of care offered to these patients, based on avoiding unnecessary measures, which can sometimes be harmful.
Unintentional Monotherapy in Rheumatoid Arthritis Patients Receiving Tofacitinib and Drug Survival Rate of Tofacitinib
Authors: Inanc Nevsun , Abacar Kerem Y. , Ozturk Mehmet A. , Tufan Abdurrahman , Karadeniz Hazan , Sari Ismail , Can Gercek , Erez Yesim , Pehlivan Yavuz , Dalkilic Huseyin E. , Ocak Tugba , Cefle Ayse , Yazici Ayten , Senel Abdurrahman S. , Akar Servet , Durak-Ediboğlu Elif , Koca Suleyman S. , Piskin-Sagir Rabia , Yilmaz Sema , Gulcemal Semral , Soysal-Gunduz Ozgul , Basibuyuk Canberk S. , Alkan Serdar , Cesur Teoman Y. , Onen Fatos
Published: September 2023

Objective

To determine the rate of unintentional monotherapy (UM; switching to monotherapy from combination therapy of patients' own volition) in rheumatoid arthritis patients receiving tofacitinib and to evaluate tofacitinib survival rate.

Methods

This national, multicenter study included patients' data from the TURKBIO Registry. Demographics, clinical characteristics, disease duration and activity, comorbidities, and treatments were analyzed.

Results

Data of 231 rheumatoid arthritis patients (84.8% female, median age, 56 years) were included; 153 were initially prescribed combination therapy and continued to their therapies; 31 were initially prescribed combination therapy but switched to monotherapy on their own volition (UM); 21 were initially prescribed monotherapy and switched to combination therapy; 26 were initially prescribed monotherapy and continued to their therapies. The rate of comorbidities at the time of data retrieval was higher in the UM group than in the combination group (83.3% vs. 60.3%, p = 0.031). Presence of comorbidities was a significant factor affecting switching to monotherapy (p = 0.039; odds ratio, 3.29; 95% confidence interval, 1.06–10.18). The combination and UM groups did not differ regarding remission rate assessed by Disease Activity Score 28-joint count C-reactive protein (60.5% and 70%, respectively; p = 0.328). Drug survival rates of the UM and combination groups did not differ. The median drug survival duration of tofacitinib was 27+ months with 1- and 4-year drug survival rates of 89.6% and 60.2%, respectively, in the UM group.

Conclusions

Although 13.4% of the study population started monotherapy unintentionally, drug survival and remission rates of the UM and combination groups were not different. Comorbidity was a factor affecting transition from combination therapy to monotherapy.
Implementing Remote Patient Monitoring of Physical Activity in Clinical Practice
Authors: McCarthy Margaret , Jevotovsky David , Mann Devin , Veerubhotla Akhila , Muise Eleanor , Whiteson Jonathan , Rizzo John Ross
Published: September 2023

Purpose

Remote patient monitoring (RPM) is a tool for patients to share data collected outside of office visits. RPM uses technology and the digital transmission of data to inform clinician decision-making in patient care. Using RPM to track routine physical activity is feasible to operationalize, given contemporary consumer-grade devices that can sync to the electronic health record. Objective monitoring through RPM can be more reliable than patient self-reporting for physical activity.

Design and Methods

This article reports on four pilot studies that highlight the utility and practicality of RPM for physical activity monitoring in outpatient clinical care. Settings include endocrinology, cardiology, neurology, and pulmonology settings.

Results

The four pilot use cases discussed demonstrate how RPM is utilized to monitor physical activity, a shift that has broad implications for prediction, prevention, diagnosis, and management of chronic disease and rehabilitation progress.

Clinical Relevance

If RPM for physical activity is to be expanded, it will be important to consider that certain populations may face challenges when accessing digital health services.

Conclusion

RPM technology provides an opportunity for clinicians to obtain objective feedback for monitoring progress of patients in rehabilitation settings. Nurses working in rehabilitation settings may need to provide additional patient education and support to improve uptake.
Laparoscopic Abdominal Surgery Under Thoracic Epidural Anesthesia in Patients with Interstitial Lung Disease: Retrospective Observational Cohort Study
Authors: Elhadidi Amro , Fawzy Anas
Published: September 2023

Background:

Patients with interstitial lung disease who present with abdominal disease carry a perioperative risk of morbidity and mortality, including the risks of general anesthesia and postoperative pulmonary complications. We investigated the efficacy of laparoscopic surgery in such patients under epidural anesthesia.

Materials and Methods:

All patients with interstitial lung disease who underwent laparoscopic abdominal surgery were retrospectively studied. At 30 days, our primary end point was acute exacerbation of pulmonary complications. The second end point was nonpulmonary complications and 30-day hospital mortality.

Results:

Eighteen patients were enrolled in this study after reviewing their medical and surgical records. Our study revealed that none of the patients suffered from acute pulmonary exacerbations, and only 1 patient experienced a nonpulmonary event. There was no reported mortality. The conversion rate was low, with 1 patient necessitating conversion from laparoscopic to open surgery, which was conducted under epidural anesthesia. No conversions from epidural to general anesthesia were performed.

Conclusion:

Epidural anesthesia is safe in a patient with interstitial lung disease, and laparoscopic surgery can be completed with low rate of conversion and, with minor complications.
Toward a Unified Classification System for Brain–Mind Disorders: Putting Calls for Integrated Clinical Neuroscience Into Action
Authors: Stanley Michael P.H. , Silbersweig David A. , Perez David L.
Published: September 2023

Dividing the brain–mind into the specialized fields of neurology and psychiatry has produced many granular advantages, but these silos have imposed barriers to comprehensively understanding and contextualizing the fundamentals governing mental life and its maladies. Scientific inquiry into these fundamentals cannot reach its full potential without interdigitating the boundaries of two specialties of the same organ for both scholarship and clinical practice. We propose that to truly integrate disorders of the brain and the mind for research and clinical care, we must carefully reexamine the classification of its disorders (nosology) as an instrument to develop a coherent pathological and psychological framework. We call on professional organizations from neurology, psychiatry, behavioral neurology, neuropsychiatry, neuropsychology, and other relevant subspecialties (eg, geriatric psychiatry) to convene a multidisciplinary task force to define the current classification principles of their subspecialties and work toward developing an integrated nosology. The effect of a shared classification system, which we acknowledge is a difficult proposition philosophically and politically, would have transformative potential across educational, clinical, scientific, programmatic, and sociocultural realms. If accomplished, this initiative would provide a definitive step toward reducing stigma (and promoting reimbursement parity) for the full spectrum of complex brain disorders (regardless of traditional neurologic vs psychiatric conceptualizations).
Poststroke Executive Function in Relation to White Matter Damage on Clinically Acquired CT Brain Imaging
Authors: Hobden Georgina , Moore Margaret Jane , Mair Grant , Pendlebury Sarah T. , Demeyere Nele
Published: September 2023

Background:

Executive function (EF) impairments are prevalent post stroke and are associated with white matter (WM) damage on MRI. However, less is known about the relationship between poststroke EF and WM damage on CT imaging.

Objective:

To investigate the relationship between poststroke EF and WM damage associated with stroke lesions and WM hypointensities (WMHs) on clinically acquired CT imaging.

Method:

This study analyzed data from the Oxford Cognitive Screening Program, which recruited individuals aged ≥18 years with a confirmed stroke from an acute stroke unit. The individuals completed a follow-up assessment 6 months post stroke. We included individuals with a CT scan showing a visible stroke who completed follow-up EF assessment using the Oxford Cognitive Screen–Plus rule-finding task. We manually delineated stroke lesions and quantified then dichotomized WM damage caused by the stroke using the HCP-842 atlas. We visually rated then dichotomized WMHs using the Age-Related White Matter Changes Scale.

Results:

Among 87 stroke survivors (Mage = 73.60 ± 11.75; 41 female; 61 ischemic stroke), multivariable linear regression showed that stroke damage to the medial lemniscus (B = –8.86, P < 0.001) and the presence of WMHs (B = –5.42, P = 0.005) were associated with poorer EF 6 months post stroke after adjusting for covariates including age and education.

Conclusion:

Poorer EF was associated with WM damage caused by stroke lesions and WMHs on CT. These results confirm the importance of WM integrity for EF post stroke and demonstrate the prognostic utility of CT-derived imaging markers for poststroke cognitive outcomes.
Barriers to the use of Methylphenidate in Pediatric Neuro-oncology Services
Authors: Hagan Alexander J. , Bailey Simon , Verity Sarah J.
Published: September 2023

Background:

Survivors of childhood CNS tumors are at a significant risk of chronic and multifaceted neurocognitive late effects. Recent findings indicate the potential utility of methylphenidate in addressing neurocognitive and academic plateauing and improving quality-of-life outcomes in this clinical population. However, the prescription of methylphenidate in neuro-oncology services remains inconsistent.

Objective:

To explore the neurocognitive assessment and rehabilitative interventions (including the use of methylphenidate) offered to survivors of childhood CNS tumors within mainland UK.

Method:

We used a semi-structured questionnaire to gather qualitative data from clinical psychologists and neuropsychologists within National Health Service pediatric neuro-oncology principal treatment centers (PTCs) during May 2018. Thematic analytical methods were used to explore themes within the collected data.

Results:

Eleven (58%) of the 19 PTCs returned the completed questionnaire. Respondents reported inadequate resource of psychology in many pediatric neuro-oncology PTCs, which limited the provision of methylphenidate to a restricted proportion of the patient group (i.e., those with the most profound neurocognitive difficulties). Respondents reported an interest in exploring the utility of methylphenidate in their patient group yet described a lack of appropriate evidence of its efficacy. In addition, respondents highlighted the need for the provision of accessible research summaries and treatment protocols addressing the use of methylphenidate.

Conclusion:

We anticipate that national collaboration between clinicians and researchers working in the cancer survivorship field will support the advancement of interventions such as methylphenidate for the growing clinical population of survivors of childhood CNS tumors.
Case report: isolation of Hydrogenophaga from septic blood culture following near-death drowning in lakewater
Authors: Feichtinger Stuart , Lazar Angela A. , Luebbe Megan A. , Accola Molly A. , Jung-Hynes Brittney D. , Anderson Patti J. , Koglin Kelly M. , Schliesman Karen S. , Ehlenbach William , Smith Jeannina , Chen Derrick J. , Rehrauer William M. , Bailey Adam L.
Published: September 2023

A patient suffered a non-fatal wet drowning in a freshwater lake and developed bacteraemia several days later. Blood culture grew a Gram-negative rod that could not be identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 16S ribosomal RNA sequencing of the isolate identified the microbe as

Hydrogenophaga laconesensis

– an environmental microbe commonly found in freshwater. The recovery of multiple pathogenic micro-organisms (although not

H. laconesensis

) from culture of respiratory specimens prompted the initiation of antibiotic therapy with cefepime and, later, vancomycin. The patient’s clinical course gradually improved over the course of 2 weeks and she was ultimately discharged home with minimal sequelae. To our knowledge, this is the first evidence of human infection with bacteria in the genus

Hydrogenophaga

.

Hydrogenophaga

may be considered in cases of freshwater near-drowning, and MALDI-TOF MS databases should be updated to include

H. laconesensis

.
Teunomyces gombertii f.a., sp. nov., Teunomyces landelliae f.a., sp. nov., Teunomyces ledahaglerae f.a., sp. nov. and Teunomyces paulamoraisiae f.a., sp. nov., four yeast species isolated from mushrooms and drosophilids in a Brazilian Amazonian rainforest biome
Authors: Santa-Brígida Rosângela , Santos Ana Raquel O. , Martins Marlúcia B. , Rosa Luiz Henrique , Lachance Marc-André , Rosa Carlos A.
Published: September 2023

Ten yeast isolates representing four candidate novel species of the genus Teunomyces were obtained from different species of mushrooms and drosophilids collected in an Amazonian Forest biome in Brazil. Sequence analyses of the ITS 5.8S region and the D1/D2 domains of the large subunit rRNA gene showed that four isolates were phylogenetically related to Teunomyces stri, two isolates related to Teunomyces atbi, two isolates related to Teunomyces aglyptinius, and another two isolates related to Teunomyces aglyptinius, Teunomyces barrocoloradensis, Teunomyces gatunensis and Teunomyces stri. The four novel species differ by 3 % or more of sequence divergence in D1/D2 domains from their closest relatives. These species were isolated from basidiocarps of the mushrooms Marasmiellus volvatus, Tricholomopsis aurea, Hydropus sp. and Favolus tenuiculus, or drosophilids feeding on these substrates. The names Teunomyces gombertii f.a., sp. nov. (holotype CBS 16168T; Mycobank MB849065), Teunomyces landelliae f.a., sp. nov. (holotype =CBS 16169T; Mycobank MB 849066), Teunomyces ledahaglerae f.a., sp. nov. (holotype CBS 16170T; Mycobank MB 849067) and Teunomyces paulamoraisiae f.a., sp. nov. (holotype CBS 16120T; Mycobank MB 849068) are proposed for these species.
Removal of Free Liquid Layer from Liquid-Infused Catheters Reduces Silicone Loss into the Environment while Maintaining Adhesion Resistance
Authors: Fong Chun Ki , Andersen Marissa Jeme , Kunesh Emma , Leonard Evan , Durand Donovan , Coombs Rachel , Flores-Mireles Ana Lidia , Howell Caitlin
Published: September 2023

Silicone urinary catheters infused with silicone liquid offer an effective alternative to antibiotic coatings, reducing microbial adhesion while decreasing bladder colonization and systemic dissemination. However, loss of free silicone liquid from the surface into the host system is undesirable. To reduce the potential for liquid loss, free silicone liquid was removed from the surface of liquid-infused catheters by either removing excess liquid from fully infused samples or by partial infusion. The effect on bacterial and host protein adhesion was then assessed. Removing the free liquid from fully infused samples resulted in a ∼64% decrease in liquid loss into the environment compared to controls, with no significant increase in deposition of the host protein fibrinogen or the adhesion of the common uropathogenEnterococcus faecalis. Partially infusing samples decreased liquid loss as total liquid content decreased, with samples infused to 70-80% of their maximum capacity showing a ∼85% reduction in liquid loss compared to fully infused controls. Furthermore, samples above 70% infusion showed no significant increase in fibrinogen orE. faecalisadhesion. Together, the results suggest that eliminating free liquid layer, mechanically or through partial infusion, can reduce liquid loss from liquid-infused catheters while preserving functionality.
Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor
Authors: Blum Steven M. , Zlotoff Daniel A. , Smith Neal P. , Kernin Isabela J. , Ramesh Swetha , Zubiri Leyre , Caplin Joshua , Samanta Nandini , Martin Sidney C. , Tirard Alice , Sen Pritha , Song Yuhui , Barth Jaimie , Slowikowski Kamil , Nasrallah Mazen , Tantivit Jessica , Manakongtreecheep Kasidet , Arnold Benjamin Y. , McGuire John , Pinto Christopher J. , McLoughlin Daniel , Jackson Monica , Chan PuiYee , Lawless Aleigha , Sharova Tatyana , Nieman Linda T. , Gainor Justin F. , Juric Dejan , Mino-Kenudsen Mari , Sullivan Ryan J. , Boland Genevieve M. , Stone James R. , Thomas Molly F. , Neilan Tomas G. , Reynolds Kerry L. , Villani Alexandra-Chloé
Published: September 2023

Immune checkpoint inhibitors (ICIs) are widely used anti-cancer therapies that can cause morbid and potentially fatal immune-related adverse events (irAEs). ICI-related myocarditis (irMyocarditis) is uncommon but has the highest mortality of any irAE. The pathogenesis of irMyocarditis and its relationship to anti-tumor immunity remain poorly understood. We sought to define immune responses in heart, tumor, and blood during irMyocarditis and identify biomarkers of clinical severity by leveraging single-cell (sc)RNA-seq coupled with T cell receptor (TCR) sequencing, microscopy, and proteomics analysis of 28 irMyocarditis patients and 23 controls. Our analysis of 284,360 cells from heart and blood specimens identified cytotoxic T cells, inflammatory macrophages, conventional dendritic cells (cDCs), and fibroblasts enriched in irMyocarditis heart tissue. Additionally, potentially targetable, pro-inflammatory transcriptional programs were upregulated across multiple cell types. TCR clones enriched in heart and paired tumor tissue were largely non-overlapping, suggesting distinct T cell responses within these tissues. We also identify the presence of cardiac-expanded TCRs in a circulating, cycling CD8 T cell population as a novel peripheral biomarker of fatality. Collectively, these findings highlight critical biology driving irMyocarditis and putative biomarkers for therapeutic intervention.
Effects of speculum lubrication on cervical smears for cervical cancer screening: a double blind randomized clinical trial
Authors: Ilika Chito P. , Eleje George U. , Chiemeka Michael E. , Ilika Frances N. , Ikechebelu Joseph I. , Ilika Valentine C. , Ugwu Emmanuel O. , Ofor Ifeanyichukwu J. , Ogelle Onyecherelam M. , Umeononihu Osita S. , Mamah Johnbosco E. , Olisa Chinedu L. , Ezeigwe Chijioke O. , Nwankwo Malarchy E. , Ofojebe Chukwuemeka J. , Okafor Chidinma C. , Ekwebene Onyeka C. , Nnabuchi Obinna K. , Okafor Chigozie G.
Published: September 2023

Background

Speculum lubrication may help to reduce the pain experienced during Pap-smears collection and hence increase uptake of cervical cancer screening and repeat testing but there are fears of its interference with cytological results.

Aim

To determine and compare adequacy of cervical cytology smears and mean pain scores of women undergoing cervical cancer screening with or without speculum lubrication.

Methods

This was a randomized controlled study of 132 women having cervical cancer screening at a tertiary hospital in Nigeria. Sixty-six participants each were randomly assigned to the ‘Gel’ and ‘No Gel’ groups respectively. Pap-smears were collected from each participant with lubricated speculum (‘Gel group’) or non-lubricated speculum (‘No Gel group’). The primary outcome measures were; the proportion of women with unsatisfactory cervical cytology smears and the mean numeric rating scale pain scores while the secondary outcome measures were the proportion of women that are willing to come for repeat testing and the cytological diagnosis of Pap-smear results.

Results

The baseline socio-demographic variables were similar in both groups. There was no significant difference in the proportion of unsatisfactory cervical smear results between the two groups (13.6% vs. 21.2% p = 0.359). However, the mean pain scores were significantly lower in the gel group than in the no gel group (45.04 vs 87.96; p<0.001). An equal proportion of the participants in each group (90.9% vs. 90.9%; p>0.999) were willing to come for repeat cervical smears in the future.

Conclusion

Speculum lubrication did not affect the adequacy of cervical-smears but significantly reduced the pain experienced during Pap-smear collection. Also, it did not significantly affect willingness to come for repeat cervical smears in the future.

The Trial was registered withPan-African Clinical Trial Registrywith unique identification/registration no:PACTR2020077533364675.
Alpha-toxin elicited CX3CL1-release via ADAM10 inStaphylococcus aureuspneumonia impairs bactericidal function of human monocytes
Authors: Shambat Srikanth Mairpady , Chen Puran , Barilla Rocky M. , Huemer Markus , Snäll Johanna , Welin Amanda , Cohen Taylor S. , Takahashi Virginia , Berry Samuel B. , Gómez-Mejia Alejandro , Schweizer Tiziano A. , Cunoosamy Danen M , Cajander Sara , Lourda Magda , Özenci Volkan , Maggio Ewerton Marques , Schüpbach Reto A. , Strålin Kristoffer , Zinkernagel Annelies S. , Norrby-Teglund Anna , Svensson Mattias
Published: September 2023

Staphylococcus aureusis an important human pathogen causing severe invasive infections. Pathogenesis is attributed to a wide array of virulence factors, including several potent exotoxins such as the pore-forming alpha-toxin. In this study, we found that patients withS. aureusrespiratory tract infections had elevated CX3CL1 levels in airway fluid and plasma. Using humanized organotypic lung models, we observed that stimulation of lung epithelium with alpha-toxin induce an intensified CX3CL1 expression apically in the epithelium as well as the release of CX3CL1. Blocking alpha-toxin or ADAM10 activity in organotypic lung using an alpha-toxin-blocking antibody or a specific ADAM-10 inhibitor confirmed their role in modulating CX3CL1 cleavage and release. Analyses of CD14+human monocytes in combination with a CX3CR1 inhibitor revealed that alpha-toxin-mediated CX3CL1 release induce CX3CL1-dependent chemotaxis. In line with these data, lung tissue from patients withS. aureusrespiratory tract infection showed elevated CX3CL1 and CD14 staining as compared to tissue from patients with non-infectious lung diseases. Functional studies of monocytes showed that CX3CL1 released by lung models resulted in upregulated CD83 and downregulated CD86, as well as impaired killing of phagocytosedS. aureus. Furthermore, stimulation of monocytes with soluble CX3CL1 hampered their reactive-oxygen and nitric-oxide production. Taken together, our data show thatS. aureustriggers the release of lung epithelial CX3CL1; a process found to be dependent on the alpha-toxin’s effect on ADAM10 mediating cytotoxicity and resulting in impaired monocyte phagocytic killing. Hence, we identify an immunomodulatory effect of alpha-toxin involving the CX3CL1-ADAM10 axis extending beyond the cytolysis function.
Massive-scale single-cell chromatin accessibility sequencing using combinatorial fluidic indexing
Authors: Zhang Xuan , Marand Alexandre P , Yan Haidong , Schmitz Robert J.
Published: September 2023

Single-cell ATAC-seq has emerged as a powerful approach for revealing candidate cis-regulatory elements genome-wide at cell-type resolution. However, current single-cell methods suffer from limited throughput and high costs. Here, we present a novel technique called single-cell combinatorial fluidic indexing ATAC-sequencing ("scifi-ATAC-seq"), which combines a barcoded Tn5 pre-indexing step with droplet-based single-cell ATAC-seq using a widely commercialized microfluidics platform (10X Genomics). With scifi-ATAC-seq, up to 200,000 nuclei across multiple samples in a single emulsion reaction can be indexed, representing a ~20-fold increase in throughput compared to the standard 10X Genomics workflow.
Development of peptides for targeting cell ablation agents concurrently to the Sertoli and Leydig cell populations of the testes: an approach to non-surgical sterilization
Authors: Fraser Barbara , Wilkins Alex , Whiting Sara , Liang Mingtao , Rebourcet Diane , Nixon Brett , Aitken R. John
Published: September 2023

The surgical sterilization of cats and dogs has been used to prevent their unwanted breeding for decades, but this is an expensive and invasive procedure, and often impractical in wider contexts, for example the control of feral populations. A sterilization agent that could be administered in a single injection would not only eliminate the risks imposed by surgery but also be a much more cost-effective solution to this worldwide problem. In this study, we sought to develop a targeting peptide that would selectively bind to Leydig cells of the testes. Subsequently, after covalently attaching a cell ablation agent, Auristatin, to this peptide we aimed to apply this conjugated product (LH2Auristatin) to adult male micein vivo, both alone and together with a previously developed Sertoli cell targeting peptide (FSH2Menadione). The application of LH2Auristatin alone resulted in an increase in DNA damage, reduced mean testes weights and mean seminiferous tubule size, along with extensive germ cell apoptosis and a reduction in litter sizes. Together with FSH2Menadione there was also an increase in embryo resorptions. These promising results were observed in around a third of all treated animals. Given this variability we discuss how these reagents might be adjusted in order to increase target cell ablation and improve their efficacy as sterilization agents.
casmini-tool: a comprehensive database for efficient and specific guide RNA design using dCasMINI
Authors: Lopp Spencer , Borrman Tyler , Jha Nishant , Silvis Melanie , Swan Ryan , Yang Xiao , Alvarez Gabriella , Klappenbach Courtney , Liu Yanxia , Hart Daniel O. , Qi Lei S. , Daley Timothy P. , Yeo Robin W.
Published: September 2023

The dCasMINI protein is a hypercompact, nuclease-inactivated CRISPR-Cas system engineered for transcriptional modulation and epigenetic editing [Xu et al., 2021]. The small size of dCas-MINI (529 amino acids), less than half the size of comparable Cas9 molecules, makes it ideal for AAV-based therapies which are frequently limited by AAV’s small cargo capacity. Unlike Cas9 or Cas12a, there are no available computational tools for designing dCasMINI guides. To facilitate and accelerate the development of dCasMINI-based applications, we synthesized knowledge regarding dCasMINI guide design and built a website to assist researchers in designing optimal guides for dCasMINI-based experiments for transcriptional inhibition (CRISPRi) and activation (CRISPRa); to ensure that our tool would be useful for therapeutic guide design, in which a guide’s off-target safety profile is of paramount importance, we specifically optimized alignment parameters for high-sensitivity to comprehensively report genome-wide off-targets. To investigate dCasMINI’s full protospacer adjacent motif (PAM) profile, we engineered libraries of PAMs and exhaustively characterized dCasMINI’s ability to activate a locus with different PAMs. We also experimentally investigated the importance of each nucleotide position on the guide RNA’s ability to activate its target, and characterized a 6bp high-fidelity seed region at the 5’ end of the protospacer sequence which we identified to be intolerant to mismatches and deletions, and thus critical for true binding events. Taken together, our tool offers CRISPRi/a guide design for every protein-coding gene in the human genome along with comprehensive off-target prediction, incorporating the most up-to-date information about dCasMINI’s full PAM and protospacer design rules. The tool is freely available to use atwww.casmini-tool.com.
Evidence associating neutrophilia, lung damage, hyperlactatemia, blood acidosis, impaired oxygen transport, and mortality in critically ill COVID-19 patients
Authors: Yasseen Basma A. , Elkhodiry Aya A. , El-sayed Hajar , Zidan Mona , Kamel Azza G. , Hamdy Rehab , El-Shqnqery Hend E. , Samir Omar , Sayed Ahmed A. , Badawy Mohamed A. , Saber Aya , Hamza Marwa , El-Messiery Riem M. , Ansary Mohamed El , Abdel-Rahman Engy A. , Ali Sameh S.
Published: September 2023

Background

COVID-19 severity and high in-hospital mortality are often associated with severe hypoxemia, hyperlactatemia, and acidosis. Since neutrophil numbers in severe COVID-19 can exceed 80% of the total circulating leukocytes and that they are massively recruited to infected lungs, we investigated whether metabolic acidosis mediated by the glycolytic neutrophils is associated with lung damage and impaired oxygen delivery in critically ill patients.

Methods

Based on prospective mortality outcome, 102 critically ill-hospitalized COVID-19 patients were divided into two groups: ICU-Survivors (ICU-S, n=36) and ICU-Non-survivors (ICU-NS, n=66). Blood samples were collected from patients and control subjects to explore correlations between neutrophil counts, lung damage, glycolysis, blood lactate, blood pH, hemoglobin oxygen saturation, and mortality outcome. We also interrogated isolated neutrophils for glycolytic activities and for apoptosis using high-throughput fluorescence imaging complemented with transcriptomic analyses. Stratified survival analyses were conducted to estimate mortality risk associated with higher lactate among predefined subgroups.

Results

Neutrophil counts were consistently higher in critically ill patients while exhibiting remarkably lower apoptosis. Transcriptomic analysis revealed miRNAs associated with downregulation of genes involved in neutrophils apoptosis. Both CT lung damage scores and neutrophil counts predicted mortality. Severinghaus fitting of hemoglobin oxygen saturation curve revealed a right-shift indicating lower oxygen capacity in non-survivors, which is consistent with lower blood-pH observed in the same group. Levels of blood lactate were increased in patients but significantly more in the ICU-NS relative to the control group. ROC analysis followed by Kaplan-Meyer survival analysis stratified to the obtained cut-off values showed that CT damage scores, neutrophil counts, and lactate levels are predictors of mortality within 15 days following blood collection.

Conclusion

The current results implicate neutrophilia as a potential player in metabolic acidosis and deranged oxygen delivery associating SARS-CoV-2 infection thus contributing to mortality outcome.
Effectiveness of a Pain Neuroscience Education program on the physical activity of patients with Chronic Low Back Pain compared to a standard back school program, a randomized controlled study - END-LC
Authors: Thébault Guillaume , Duflos Claire , Le Perf Gaël
Published: September 2023

Introduction

Education is recognized as an effective and necessary method in chronic low back pain. Nevertheless, the data on the effectiveness of education in physical activity in the medium or long term are not yet well known, nor the factors that could lead to practice such or such education. Our study aims to measure the effectiveness of a pain neuroscience education compared to a back school on physical activity three months and one year after educational sessions coupled with a multidisciplinary rehabilitation program. The study also seeks to measure the effects of these two types of education on several other factors including the intensity of pain and psycho-behavioral factors. Finally, it aims to identify the determinants of the success of the educational sessions coupled with the rehabilitation program.

Methods and analysis

The study will involve eighty-two adults with chronic low back pain. The study will be monocentric, prospective, open, controlled, and randomized, of superiority, with two parallel arms with an experimental group “pain neuroscience education” and a control group “back school”. The primary outcome will be the average number of steps taken at home over a week measured by an actigraph. Secondary outcomes include behavioral assessments. Descriptive and inferential analysis will be carried out on the primary and secondary judgment criteria. Multivariate modeling will be carried out using actimetric data and data from the main and secondary outcomes.

Ethics and dissemination

a favorable opinion was given by the Committee for Personal Protection of Ile de France VII on June 22, 2023 (National number: 2023-A00346-39). The study was previously registered with the National Agency or the Safety of Medicines and Health Products (IDRCB : 2023-A00346-39). This protocol is the version submitted to the Committee for Personal Protection of Ile de France VII entitled “Protocol Version N°1 of 03/29/2023”.

Trial Registration

NCT05840302.

Article Summary

Strengths and limitations of this study

The use of an actigraph as a measuring tool of physical activity in ecological context to evaluate effectiveness of an education in low back pain.

The follow-up at three months and one year after the rehabilitation program.

The study includes an analysis of actimetric data, behavioral, occupational and psychological variables to determine the predictive factors for the success of educational sessions.

The monocentric design of this study is a limitation.
Longitudinal Changes in the Carotid Arteries of Head and Neck Cancer Patients Following Radiation Therapy: Results from a Prospective Serial Imaging Biomarker Characterization Study
Authors:   MD Anderson Head and Neck Radiation Oncology and Cardiovascular Working Group, Koutroumpakis Efstratios , Mohamed Abdallah Sherif Radwan , Chaftari Peter , Rosenthal David I. , Gujral Dorothy , Nutting Christopher , Kim Peter , Bassett Roland , Fuller Clifton D. , Mouhayar Elie
Published: September 2023

INTRODUCTION

We prospectively evaluated morphologic and functional changes in the carotid arteries of patients treated with unilateral neck radiation therapy (RT) for head and neck cancer.

METHODS

Bilateral carotid artery duplex studies were performed at 0, 3, 6, 12, 18 months and 2, 3, 4, and 5 years following RT. Intima media thickness (IMT); global and regional circumferential, as well as radial strain, arterial elasticity, stiffness, and distensibility were calculated.

RESULTS

Thirty-eight patients were included. A significant difference in the IMT from baseline between irradiated and unirradiated carotid arteries was detected at 18 months (median, 0.073mm vs -0.003mm;P=0.014), which increased at 3 and 4 years (0.128mm vs 0.013mm,P=0.016, and 0.177mm vs 0.023mm,P=0.0002, respectively). A > 0.073mm increase at 18 months was significantly more common in patients who received concurrent chemotherapy (67% vs 25%;P=0.03). A significant transient change was noted in global circumferential strain between the irradiated and unirradiated arteries at 6 months (median difference, -0.89,P=0.023), which did not persist. No significant differences were detected in the other measures of elasticity, stiffness, and distensibility.

CONCLUSIONS

Functional and morphologic changes of the carotid arteries detected by carotid ultrasound, such as changes in global circumferential strain at 6 months and carotid IMT at 18 months, may be useful for the early detection of radiation-induced carotid artery injury, can guide future research aiming to mitigate carotid artery stenosis, and should be considered for clinical surveillance survivorship recommendations after head and neck RT.
Can we start to ignore the SARS-CoV-2 disease?
Authors: Nesteruk Igor
Published: September 2023

Current WHO reports claim a decline in COVID-19 testing. Many countries are reporting no new infections. In particular, USA, China and Japan have registered no cases and COVID-19 related deaths since May 15, 2023. To discuss consequences of ignoring SARS-CoV-2 infection, we compare endemic characteristics of the disease in 2023 with ones estimated before using 2022 datasets. The accumulated numbers of cases and deaths reported to WHO by 10 most infected countries and global figures were used to calculate the average daily numbers of cases and deaths per capita (DCCandDDC) and case fatality rates (CFR) for two periods in 2023. The average values of daily deaths per million still vary between 0.12 and 0.41. It means that annual global number of COVID-19 related deaths is still approximately twice higher than the seasonal influenza mortality. Increase ofCFRvalues in 2023 show that SARS-CoV-2 infection is still dangerous despite of increasing the vaccination level. Very lowCFRfigures in South Korea and very high ones in the UK 4 need further investigations.
Genetic architecture of telomere length in 462,675 UK Biobank whole-genome sequences
Authors: Burren Oliver S. , Dhindsa Ryan S. , Deevi Sri V. V. , Wen Sean , Nag Abhishek , Mitchell Jonathan , Hu Fengyuan , Smith Katherine R. , Razdan Neetu , Olsson Henric , Platt Adam , Vitsios Dimitrios , Wu Qiang ,   AstraZeneca Genomics Initiative, Codd Veryan , Nelson Christopher P , Samani Nilesh J , March Ruth E. , Wasilewski Sebastian , Carss Keren , Fabre Margarete , Wang Quanli , Pangalos Menelas N. , Petrovski Slavé
Published: September 2023

Telomeres protect the ends of chromosomes from damage, and genetic regulation of their length is associated with human disease and ageing. We developed a joint telomere length (TL) metric, combining both qPCR and whole genome sequencing (WGS) measurements across 462,675 UK Biobank participants that increased our ability to capture TL heritability by 36% (h2mean=0.058 to h2combined=0.079) and improved predictions of age. Exome-wide rare variant (minor allele frequency<0.001) and gene-level collapsing association studies identified 53 variants and 22 genes significantly associated with TL that included allelic series inACDandRTEL1. Five of the 31 rare-variant TL associated genes (16%) were also known drivers of clonal haematopoiesis (CH), prompting somatic variant analyses. Stratifying by CH clone size, we uncovered novel gene-specific associations with TL, including lengthened telomeres in individuals with largeSRSF2-mutant clones, in contrast to the progressive telomere shortening observed with increasing clonal expansions driven by other CH genes. Our findings demonstrate the impact of rare variants on TL with larger effects in genes associated with CH, a precursor of myeloid cancers and several other non-malignant human diseases. Telomere biology is likely to be an important focus for the prevention and treatment of these conditions.
Exposure to Heavy Metals, Obesity, and Stroke Mortality in the United States
Authors: Cao Ziqin , Bakulski Kelly M. , Paulson Henry L. , Wang Xin
Published: September 2023

We investigated the associations between blood concentrations of lead and cadmium with stroke mortality, and potential effect modification by obesity. Our study analyzed data from 23,437 individuals aged 40 and above, using the National Health and Nutrition Examination Survey (NHANES 1999-2016) linked to the National Death Index. During a median follow-up period of 8.3 years, 336 stroke-related deaths were reported. After adjusting for potential confounders, we found that higher baseline concentrations of lead and cadmium were significantly associated with increased stroke mortality. Specifically, the hazard ratios (HRs) per doubling of metal concentrations were 1.16 (95% CI: 1.11, 1.20) for lead and 1.31 (95% CI: 1.26, 1.36) for cadmium. Stratified analysis showed that stronger associations were observed among participants who were normal weight or overweight, relative to those who were obese. In conclusion, our study demonstrates that elevated blood concentrations of lead and cadmium are significantly associated with an increased risk of stroke mortality, especially among individuals who are normal weight or overweight.
Failure ofR0near the epidemic threshold in the classical SIS model
Authors: Mohammed Mozzamil
Published: September 2023

The primary predictor of a disease outbreak and severity is the basic reproduction numberR0, which represents the average number of secondary cases produced by introducing an infected individual into an entirely susceptible population. According to the classical SIS model, a disease withR0less than one will eventually die out and persist ifR0is greater than one. Using the pair-approximation method, we reconstruct the classical SIS model by explicitly accounting for neighbourhood interactions between susceptible and infected individuals. Specifically, the disease can only be transmitted, with some transmission probability, if a susceptible individual is surrounded by at least one infected individual within its direct neighborhoods. Despite the simplicity of the SIS model present here, results produced by the pair-approximation model deviates significantly from predictions by the mean-field approximation model, particularly near the epidemic threshold. Contrasting the standard SIS model based on the mean-field approach, we find scenarios where the disease dies out even ifR0is greater than one. We suggest a crucial need for redefining the basic reproduction number on a smaller spatial scale and taking the averageR0over a global scale, rather than applying it globally to an entire population. However, in the realm of more intricate models of infectious diseases, it remains an open question to what extent mean-field approximation predictions diverge from predictions produced by models that consider neighborhood interactions.
OrganL: Dynamic Triangulation of Biomembranes using Curved Elements
Authors: Allolio Christoph , Fábián Balázs , Dostalík Mark
Published: September 2023

We describe a method for simulating biomembranes of arbitrary shape. In contrast to other dynamically triangulated surface (DTS) algorithms, our method provides a rich, quasi tangent-continuous, yet local description of the surface. We use curved Nagata triangles, which we generalize to cubic order to achieve the requisite flexibility. The resulting interpolation can be constructed locally without iterations. This allows us to provide a parallelized and fine-tuned Monte Carlo implementation. As a first example of the potential benefits of the enhanced description, our method supports inhomogeneous lipid properties as well as lipid mixing. It also supports restraints and constraints of various types and is constructed to be as easily extensible as possible. We validate the approach by testing its numerical accuracy, followed by reproducing the known Helfrich solutions for shapes with rotational symmetry. Finally, we present some example applications, including curvature-driven demixing and stylized effects of proteins. Input files for these examples, as well as the implementation itself, are freely available for researchers under the name OrganL.