bluuebunny/crossref_metadata_2025 huggingface dataset:
Has recombination changed during the recent evolution of the guppy Y chromosome?
Authors: Charlesworth Deborah , Qiu Suo , Bergero Roberta , Gardner Jim , Keegan Karen , Yong Lengxob , Hastings Abigail , Konczal Mateusz
Published: November 2023

Genome sequencing and genetic mapping of molecular markers have demonstrated nearly complete Y-linkage across much of the guppy (Poecilia reticulata) XY chromosome pair. Predominant Y-linkage of factors controlling visible male-specific coloration traits also suggested that these polymorphisms are sexually antagonistic (SA). However, occasional exchanges with the X are detected, and recombination patterns also appear to differ between natural guppy populations, suggesting ongoing evolution of recombination suppression under selection created by partially sex-linked SA polymorphisms. We used molecular markers to directly estimate genetic maps in sires from 4 guppy populations. The maps are very similar, suggesting that their crossover patterns have not recently changed. Our maps are consistent with population genomic results showing that variants within the terminal 5 Mb of the 26.5 Mb sex chromosome, chromosome 12, are most clearly associated with the maleness factor, albeit incompletely. We also confirmed occasional crossovers proximal to the male-determining region, defining a second, rarely recombining, pseudo-autosomal region, PAR2. This fish species may therefore have no completely male-specific region (MSY) more extensive than the male-determining factor. The positions of the few crossover events suggest a location for the male-determining factor within a physically small repetitive region. A sex-reversed XX male had few crossovers in PAR2, suggesting that this region's low crossover rate depends on the phenotypic, not the genetic, sex. Thus, rare individuals whose phenotypic and genetic sexes differ, and/or occasional PAR2 crossovers in males can explain the failure to detect fully Y-linked variants.
Glycosyltransferases as versatile tools to study the biology of glycans
Authors: Kofsky Joshua M , Babulic Jonathan L , Boddington Marie E , De León González Fabiola V , Capicciotti Chantelle J
Published: November 2023

All cells are decorated with complex carbohydrate structures called glycans that serve as ligands for glycan-binding proteins (GBPs) to mediate a wide range of biological processes. Understanding the specific functions of glycans is key to advancing an understanding of human health and disease. However, the lack of convenient and accessible tools to study glycan-based interactions has been a defining challenge in glycobiology. Thus, the development of chemical and biochemical strategies to address these limitations has been a rapidly growing area of research. In this review, we describe the use of glycosyltransferases (GTs) as versatile tools to facilitate a greater understanding of the biological roles of glycans. We highlight key examples of how GTs have streamlined the preparation of well-defined complex glycan structures through chemoenzymatic synthesis, with an emphasis on synthetic strategies allowing for site- and branch-specific display of glyco-epitopes. We also describe how GTs have facilitated expansion of glyco-engineering strategies, on both glycoproteins and cell surfaces. Coupled with advancements in bioorthogonal chemistry, GTs have enabled selective glyco-epitope editing of glycoproteins and cells, selective glycan subclass labeling, and the introduction of novel biomolecule functionalities onto cells, including defined oligosaccharides, antibodies, and other proteins. Collectively, these approaches have contributed great insight into the fundamental biological roles of glycans and are enabling their application in drug development and cellular therapies, leaving the field poised for rapid expansion.
Functional assay for assessment of pathogenicity of BAP1 variants
Authors: Repo Pauliina E , Backlund Michael P , Kivelä Tero T , Turunen Joni A
Published: November 2023

Background

Pathogenic germline variants in BRCA1-Associated Protein 1 (BAP1) cause BAP1 tumor predisposition syndrome (BAP1-TPDS). Carriers run especially a risk of uveal (UM) and cutaneous melanoma, malignant mesothelioma, and clear cell renal carcinoma. Approximately half of increasingly reported BAP1 variants lack accurate classification. Correct interpretation of pathogenicity can improve prognosis of the patients through tumor screening with better understanding of BAP1-TPDS.

Methods

We edited five rare BAP1 variants with differing functional characteristics identified from patients with UM in HAP1 cells using CRISPR-Cas9 and assayed their effect on cell adhesion/spreading (at 4 h) and proliferation (at 48 h), measured as cell index (CI), using xCELLigence real-time analysis system.

Results

In BAP1 knockout HAP1 cultures, cell number was half of wild type (WT) cultures at 48 h (p = 0.00021), reaching confluence later, and CI was 78% reduced (p < 0.0001). BAP1-TPDS-associated null variants c.67+1G>T and c.1780_1781insT, and a likely pathogenic missense variant c.281A>G reduced adhesion (all p ≤ 0.015) and proliferation by 74%–83% (all p ≤ 0.032). Another likely pathogenic missense variant c.680G>A reduced both by at least 50% (all p ≤ 0.032), whereas cells edited with likely benign one c.1526C>T grew similarly to WT.

Conclusions

BAP1 is essential for optimal fitness of HAP1 cells. Pathogenic and likely pathogenic BAP1 variants reduced cell fitness, reflected in adhesion/spreading and proliferation properties. Further, moderate effects were quantifiable. Variant modelling in HAP1 with CRISPR-Cas9 enabled functional analysis of coding and non-coding region variants in an endogenous expression system.
Improving diagnostic precision in primary ovarian insufficiency using comprehensive genetic and autoantibody testing
Authors: Vogt Elinor Chelsom , Bratland Eirik , Berland Siren , Berentsen Ragnhild , Lund Agnethe , Björnsdottir Sigridur , Husebye Eystein , Øksnes Marianne
Published: November 2023

STUDY QUESTION

Is it possible to find the cause of primary ovarian insufficiency (POI) in more women by extensive screening?

SUMMARY ANSWER

Adding next generation sequencing techniques including a POI-associated gene panel, extended whole exome sequencing data, as well as specific autoantibody assays to the recommended diagnostic investigations increased the determination of a potential etiological diagnosis of POI from 11% to 41%.

WHAT IS KNOWN ALREADY

POI affects ∼1% of women. Clinical presentations and pathogenic mechanisms are heterogeneous and include genetic, autoimmune, and environmental factors, but the underlying etiology remains unknown in the majority of cases.

STUDY DESIGN, SIZE, DURATION

Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause consecutively referred to Haukeland University Hospital, Bergen, Norway, January 2019 to December 2021.

PARTICIPANTS/MATERIALS, SETTING, METHODS

In addition to standard recommended diagnostic investigations including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1) we used whole exome sequencing, including targeted analysis of 103 ovarian-related genes, and assays of autoantibodies against steroid cell antigens.

MAIN RESULTS AND THE ROLE OF CHANCE

We identified chromosomal aberrations in 8%, FMR1 premutations in 3%, genetic variants related to POI in 16%, and autoimmune POI in 3%. Furthermore in 11% we identified POI associated genetic Variants of unknown signifcance (VUS). A homozygous pathogenic variant in the ZSWIM7 gene (NM_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found.

LIMITATIONS, REASONS FOR CAUTION

Use of candidate genetic and autoimmune markers limit the possibility to discover new markers. To further investigate the genetic variants, family studies would have been useful. We found a relatively high proportion of genetic variants in women from Africa and lack of genetic diversity in the genomic databases can impact diagnostic accuracy.

WIDER IMPLICATIONS OF THE FINDINGS

Since no specific clinical or biochemical markers predicted the underlying cause of POI discussion of which tests should be part of diagnostic screening in clinical practice remains open. New technology has altered the availability and effectiveness of genetic testing, and cost-effectiveness analyses are required to aid sustainable diagnostics.

STUDY FUNDING/COMPETING INTEREST(S)

The study was supported by grants and fellowships from Stiftelsen Kristian Gerhard Jebsen, the Novonordisk Foundation, the Norwegian Research Council, University of Bergen, and the Regional Health Authorities of Western Norway. The authors declare no conflict of interest.

TRIAL REGISTRATION NUMBER

NCT04082169
Maybe it’s good to not have too much focus
Authors: Pechenik Jan A
Published: November 2023

I had no idea what I was getting into when I decided to go into marine biology as a graduate student. It has ended up being a wonderful career, with opportunities to work with wonderful people around the world, and to work with many wonderful students at a variety of grade levels. It has also opened up opportunities in completely unexpected directions and allowed me to explore a good variety of research questions, explore a variety of teaching methods at a variety of grade levels, write a few books, and even develop some games for middle-school students. Luck has certainly played a role in some of this, but my main advice is to always keep an eye open for opportunities of interest, within and outside of your normal field…and seize them if possible!
Uniqueness of Unbounded Component for Level Sets of Smooth Gaussian Fields
Authors: Severo Franco
Published: November 2023

For a large family of stationary continuous Gaussian fields $f$ on ${\mathbb {R}}^{d}$, including the Bargmann–Fock and Cauchy fields, we prove that there exists at most one unbounded connected component in the level set $\{f=\ell \}$ (as well as in the excursion set $\{f\geq \ell \}$) almost surely for every level $\ell \in {\mathbb {R}}$, thus proving a conjecture proposed by Duminil-Copin, Rivera, Rodriguez, and Vanneuville. As the fields considered are typically very rigid (e.g., analytic almost surely), there is no sort of finite energy property available and the classical approaches to prove uniqueness become difficult to implement. We bypass this difficulty using a soft shift argument based on the Cameron–Martin theorem.
Higher Levels of SARS-CoV-2 Genetic Variation in Immunocompromised Patients: A Retrospective Case-Control Study
Authors: Guilbaud Romane , Franco Yusti Anna-Maria , Leducq Valentin , Zafilaza Karen , Bridier-Nahmias Antoine , Todesco Eve , Soulie Cathia , Fauchois Antoine , Le Hingrat Quentin , Kramer Laura , Goulenok Tiphaine , Salpin Mathilde , Daugas Eric , Dorent Richard , Ottaviani Sébastien , Zalcman Gérard , Ghosn Jade , Choquet Sylvain , Cacoub Patrice , Amoura Zahir , Barroux Benoit , Pourcher Valérie , Spano Jean-Philippe , Louet Martine , Marcelin Anne-Geneviève , Calvez Vincent , Charpentier Charlotte , Descamps Diane , Marot Stéphane , Ferré Valentine Marie , Coppée Romain
Published: November 2023

Background

A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection lasts longer in immunocompromised hosts than in immunocompetent patients. Prolonged infection is associated with a higher probability of selection for novel SARS-CoV-2 mutations, particularly in the spike protein, a critical target for vaccines and therapeutics.

Methods

From December 2020 to September 2022, respiratory samples from 444 immunocompromised patients and 234 health care workers positive for SARS-CoV-2, diagnosed at 2 hospitals in Paris, France, were analyzed using whole-genome sequencing using Nanopore technology. Custom scripts were developed to assess the SARS-CoV-2 genetic diversity between the 2 groups and within the host.

Results

Most infections were SARS-CoV-2 Delta or Omicron lineages. Viral genetic diversity was significantly higher in infections of immunocompromised patients than those of controls. Minor mutations were identified in viruses sequenced from immunocompromised individuals, which became signature mutations for newer SARS-CoV-2 variants as the epidemic progressed. Two patients were coinfected with Delta and Omicron variants. The follow-up of immunocompromised patients revealed that the SARS-CoV-2 genome evolution differed in the upper and lower respiratory tracts.

Conclusions

This study found that SARS-CoV-2 infection in immunocompromised patients is associated with higher genetic diversity, which could lead to the emergence of new SARS-CoV-2 variants with possible immune evasion or different virulence characteristics.
Oiling the War Machine? The Fuel Dilemma and Warfighting Capability
Authors: Kim Inwook
Published: November 2023

Oil is a double-edged sword in modern warfare for its usage enables greater firepower and mobility in combats while imposing tremendous operational and strategic burden to run and defend Wartime Fuel Network. The tension between the two generates a fuel dilemma, a consequential trade-off between fuel-powered capability and fuel sustainability. States facing the dilemma address it with three fuel management practices: minimalism, control, and gamble. I describe promises and pitfalls of each measure with three illustrative case studies—the Japanese “gamble” during WWII, Chinese “control” in the Korean War, and Vietnamese “minimalism” during the Vietnam War. The theory and evidence have important implications for future research on military logistics, warfighting capability, and the study of conventional warfare.
Antimicrobial prescribing in a secondary care setting during the COVID-19 pandemic
Authors: Tadros Michael M , Boshra Marian S , Scott Michael , Fleming Glenda , Magee Fidelma , Hamed Mohammad I , Abuelhana Ahmed , Courtenay Aaron , Salem Heba F , Burnett Kathryn
Published: November 2023

Background

Increased antimicrobial resistance patterns lead to limited options for antimicrobial agents, affecting patient health and increasing hospital costs.

Objectives

To investigate the antimicrobial prescribing patterns at two district hospitals in Northern Ireland before and during the COVID-19 pandemic.

Methods

A mixed prospective-retrospective study was designed to compare pre- and during pandemic antimicrobial prescribing data in both hospitals using a Global Point Prevalence Survey.

Results

Of the 591 patients surveyed in both hospitals, 43.8% were treated with 402 antimicrobials. A total of 82.8% of antimicrobial prescriptions were for empirical treatment. No significant difference existed in numbers of patients treated or antimicrobials used before and during the pandemic. There was a slight decrease of 3.3% in the compliance rate with hospital antimicrobial guidelines during the pandemic when compared with the pre-pandemic year of 2019, when it was 69.5%. Treatment based on patients’ biomarker data also slightly decreased from 83.5% pre-pandemic (2019) to 81.5% during the pandemic (2021).

Conclusions

There was no overall significant impact of the pandemic on the antimicrobial prescribing patterns in either hospital when compared with the pre-pandemic findings. The antimicrobial stewardship programmes would appear to have played an important role in controlling antimicrobial consumption during the pandemic.
Determining mating type and ploidy in Rhodotorula toruloides and its effect on growth on sugars from lignocellulosic biomass
Authors: Lopes Daiane Dias , Dien Bruce S , Hector Ronald E , Singh Vijay , Thompson Stephanie R , Slininger Patricia J , Boundy-Mills Kyria , Jagtap Sujit S , Rao Christopher V
Published: November 2023

Rhodotorula toruloides is being developed for the use in industrial biotechnology processes because of its favorable physiology. This includes its ability to produce and store large amounts of lipids in the form of intracellular lipid bodies. Nineteen strains were characterized for mating type, ploidy, robustness for growth, and accumulation of lipids on inhibitory switchgrass hydrolysate (SGH). Mating type was determined using a novel polymerase chain reaction (PCR)-based assay, which was validated using the classical microscopic test. Three of the strains were heterozygous for mating type (A1/A2). Ploidy analysis revealed a complex pattern. Two strains were triploid, eight haploid, and eight either diploid or aneuploid. Two of the A1/A2 strains were compared to their parents for growth on 75%v/v concentrated SGH. The A1/A2 strains were much more robust than the parental strains, which either did not grow or had extended lag times. The entire set was evaluated in 60%v/v SGH batch cultures for growth kinetics and biomass and lipid production. Lipid titers were 2.33–9.40 g/L with a median of 6.12 g/L, excluding the two strains that did not grow. Lipid yields were 0.032–0.131 (g/g) and lipid contents were 13.5–53.7% (g/g). Four strains had significantly higher lipid yields and contents. One of these strains, which had among the highest lipid yield in this study (0.131 ± 0.007 g/g), has not been previously described in the literature.

The yeast Rhodotorula toruloides was used to produce oil using sugars extracted from a bioenergy grass.
Digital PCR to Measure SARS-CoV-2 RNA, Variants, and Outcomes in Youth
Authors: Hijano Diego R , Ferrolino Jose A , Gu Zhengming , Brazelton Jessica N , Zhu Haiqing , Suganda Sri , Glasgow Heather L , Dallas Ronald H , Allison Kim J , Maron Gabriela ,   St. Jude COVID-19 Patients Study Team, Turner Paige , Peterson Megan , Ross Hailey S , Burton Madeline , Pardasani Sapna , Hankins Jane S , Takemoto Clifford , Inaba Hiroto , Helmig Sara , Vinitsky Anna , Hines Melissa R , Suliman Ali Y , Thomas Paul G , Allen E Kaitlynn , Wolf Joshua , Hakim Hana , Patel Nehali , Knapp Katherine , Adderson Elisabeth E , Darji Himani , Tang Li , Fabrizio Thomas P , Webby Richard J , Hayden Randall T
Published: November 2023

Background

The role of SARS-CoV-2 viral load in predicting contagiousness, disease severity, transmissibility, and clinical decision-making continues to be an area of great interest. However, most studies have been in adults and have evaluated SARS-CoV-2 loads using cycle thresholds (Ct) values, which are not standardized preventing consistent interpretation critical to understanding clinical impact and utility. Here, a quantitative SARS-CoV-2 reverse-transcription digital PCR (RT-dPCR) assay normalized to WHO International Units was applied to children at risk of severe disease diagnosed with COVID-19 at St. Jude Children’s Research Hospital between March 28, 2020, and January 31, 2022.

Methods

Demographic and clinical information from children, adolescents, and young adults treated at St. Jude Children’s Research Hospital were abstracted from medical records. Respiratory samples underwent SARS-CoV-2 RNA quantitation by RT-dPCR targeting N1 and N2 genes, with sequencing to determine the genetic lineage of infecting virus.

Results

Four hundred and sixty-two patients aged 0–24 years (median 11 years old) were included during the study period. Most patients were infected by the omicron variant (43.72%), followed by ancestral strain (22.29%), delta (13.20%), and alpha (2.16%). Viral load at presentation ranged from 2.49 to 9.14 log10 IU/mL, and higher viral RNA loads were associated with symptoms (OR 1.32; CI 95% 1.16–1.49) and respiratory disease (OR 1.23; CI 95% 1.07–1.41). Viral load did not differ by SARS-CoV-2 variant, vaccination status, age, or baseline diagnosis.

Conclusions

SARS-CoV-2 RNA loads predict the presence of symptomatic and respiratory diseases. The use of standardized, quantitative methods is feasible, allows for replication, and comparisons across institutions, and has the potential to facilitate consensus quantitative thresholds for risk stratification and treatment.
Rupture of the bilateral and simultaneous tendon of the pectoralis major muscle. Description of three cases
Authors: de Castro Pochini Alberto , Ejnisman Benno , Andreoli Carlos V , Lara Paulo H S , Ribeiro Leandro M , Cohen Moises , Belangero Paulo S , Hipolide Debora C
Published: November 2023

Pectoralis major muscle tendon ruptures associated with physical activity or effort are no longer uncommon in the medical literature. Treatment has also evolved significantly in the last 20 years. However, simultaneous bilateral rupture has only been described in a few cases. This article reports three cases with simultaneous bilateral rupture and describes the examinations and treatment performed. Bilateral lesions, although infrequent, also require early diagnosis and treatment in the acute phase. The chronic phase requires tendon grafting for full correction and a slow rehabilitation process.
Importance of optimizing duration of adjuvant immune checkpoint inhibitor therapy to treat postoperative hepatocellular carcinoma after conversion therapy: a case report
Authors: Li Jian-Rong , Yang Da-Long , Wang Jin-Ming , Tian Wei , Wei Wei , Luo Cheng-Piao , Qi Lu-Nan , Ma Liang , Zhong Jian-Hong
Published: November 2023

Patients with hepatocellular carcinoma at high risk of recurrence after hepatic resection or local ablation often undergo adjuvant immunotherapy with immune checkpoint inhibitors for 1 year in randomized controlled trials, but the appropriateness of this duration is controversial, especially given the risk of adverse events. Here we report the case of a 52-year-old Chinese man with initially unresectable multinodular recurrent hepatocellular carcinoma who underwent two cycles of transarterial chemoembolization, followed by hepatic resection and 24 months of adjuvant therapy with the PD-1 inhibitor tislelizumab. The patient achieved a recurrence-free survival time of 24 months, but he experienced elevated alpha fetoprotein, Grade 2 hypothyroidism and pruritus while on adjuvant therapy. This case highlights the need to optimize the duration of adjuvant immunotherapy after curative treatment for hepatocellular carcinoma in order to minimize risk of not only recurrence but also adverse events.
A case of primary conjunctival follicular lymphoma presenting as nasolacrimal obstruction
Authors: Amir Amaar , Amir Baraa , Sheikh Salwa
Published: November 2023

We herein report a 76-year-old male who presented to the ophthalmology clinic after complaining from excessive lacrimation for ~6 months prior to presentation. He reports previously undergoing a nasolacrimal recanalization procedure in attempts to resolve his symptoms, but reported no improvement. On examination, a mass on the nasal conjunctiva around the medial canthus of the right eye was noted and subsequently excised. The findings support the diagnosis of low-grade follicular lymphoma. The patient was referred to radiation oncology for radiation therapy and received a total dose of 2400 cGy. Most ocular adnexal lymphomas are B-cell in origin, with follicular lymphomas being one of the rarest forms of such lymphomas. The most common translocation reported in over 85% of follicular lymphomas of the ocular adnexa is t(14; 18) (q32; q21). Traditional treatment options typically include a mix of chemical, surgical, and radio-oncological interventions.
Reduced splenic function can mimic artemisinin resistance in severe malaria
Authors: Roussel Camille , Serris Alexandra , Henry Benoît , Lafon Desmurs Barthelemy , Sitterlé Emilie , Bougnoux Marie Elisabeth , Argy Nicolas , Larréché Sébastien , De Montalembert Mariane , Ioos Vincent , Tantaoui Ilhame , Chambrion Charlotte , Fricot Aurélie , Rouzaud Claire , Lanternier Fanny , Lortholary Olivier , Houzé Sandrine , Jauréguiberry Stéphane , Thellier Marc , Ndour Papa Alioune , Buffet Pierre
Published: November 2023

We describe severe post-treatment episodes that complicate Plasmodium falciparum malaria in patients with hyposplenism, characterized by prolonged circulation of red cells containing dead parasites (hearse red cells), persistent or recurrent fever, profound anaemia, and inflammation. Asplenia-related Post-antimalarial Inflammation & Hemolysis (APIH) mimics concomitant infection and parasite resistance to drugs.
A Highly Integrated AFM-SEM Correlative Analysis Platform
Authors: Alipour A , Arat K T , Alemansour H , Montes L , Gardiner J , Diederichs J , Colvin B , Amann A , Jensen K , Neils W , Spagna S , Stühn L , Seibert S , Frerichs H , Wolff M , Schwalb C H
Published: November 2023

We describe the first truly correlative atomic force micro­scopy-scanning electron microscopy (AFM-SEM) platform designed from first principles and from the ground up for the study of sample properties under a wide range of magnifications. Combining these two microscopy techniques, “in situ,” into a highly integrated workstation opens unprecedented measurement capabilities at the nanoscale, while simplifying experiment workflows to yield a higher level of data throughput. Unlike SEM, the AFM offers true three-dimensional topo­graphy images, something SEM can only provide indirectly. This allows for the characterization of nano-mechanical properties, as well as for magnetic and electrical characterization of samples, which are increasingly of interest in material science, multi-component technologies (that is, solar cell and battery research), and pharmaceutical investigations. On the other hand, the SEM’s wide field-of-view is critical in identifying regions of interest with feature sizes of less than a micron, which are notoriously difficult to find over large spatial scales in conventional AFM systems. In addition, the SEM’s ability to visualize the AFM tip facilitates its navigation to aid the characterization of samples with challenging three-dimensional topographies. In this paper, we describe the major elements of the system design and demonstrate how correlative microscopy can help the characterization of samples with challenging morphologies such as the edge of a razor blade or the nanomechanical analysis of platinum nanopillars.
Periop 101: Improving Perioperative Nursing Knowledge and Competence in Labor and Delivery Nurses Through an Evidence-Based Education and Training Program
Authors: Stucky Christopher H , Knight Albert R , Dindinger Rebeccah A , Maio Shannon , House Sherita , Wymer Joshua A , Barker Amber J
Published: November 2023

Introduction

To reach the highest levels of health care quality, all nurses providing intraoperative care to surgical patients should have a firm grasp of the complex knowledge, skills, and guidelines undergirding the perioperative nursing profession. In military treatment facilities, either perioperative registered nurses or labor and delivery (L&D) nurses provide skilled intraoperative nursing care for cesarean deliveries. However, L&D and perioperative nurses occupy vastly different roles in the continuum of care and may possess widely differing levels of surgical training and experience.

Materials and Methods

The purpose of this project was to improve surgical care quality by standardizing and strengthening L&D nurse perioperative training, knowledge, and competence. Our population, intervention, comparative, and outcome question was, “For labor and delivery nurses of a regional military medical center (P), does implementing an evidence-based training program (I), as compared to current institutional nursing practices (C), increase nursing knowledge and perioperative nursing competence (O)?” We implemented Periop 101: A Core Curriculum—Cesarean Section training for 17 L&D nurses, measured knowledge using product-provided testing, and assessed competence using the Perceived Perioperative Competence Scale-Revised.

Results

We found that perioperative nursing knowledge and competence significantly improved and were less varied among the nurses after completing the training program. Nurses demonstrated the greatest knowledge area improvements in scrubbing, gowning, and gloving; wound healing; and sterilization and disinfection, for which median scores improved by more than 100%. Nurses reported significantly greater perceived competence across all six domains of the Perioperative Competence Scale-Revised, with the largest improvements realized in foundational skills and knowledge, leadership, and proficiency.

Conclusions

We recommend that health care leaders develop policies to standardize perioperative education, training, and utilization for nurses providing intraoperative care to reduce clinician role ambiguity, decrease inefficiencies, and enhance care.
Perioperative Pressure Injury Prevention Program in a Military Medical Treatment Facility: A Quality Improvement Project
Authors: Romito Kenneth , Talbot Laura A , Metter E. Jeffrey , Smith Amber L , Hartmann J. Michael , Bradley David F
Published: November 2023

Introduction

The incidence of perioperative pressure injuries (PPIs) at a military medical treatment facility (MTF) increased from three PPI events in 2018 to five PPI events in the first half of 2019. The purpose of this quality improvement initiative was to determine whether an evidence-based PPI prevention program introduced during the second half of 2019 reduced pressure injuries compared to the previous 1.5 years that followed the standard of care for perioperative patient positioning.

Methods

We used a multidisciplinary quality improvement PPI prevention approach that included education, Scott Triggers® patient risk assessment, application of a five-layer silicone dressing to at-risk surgical position sites, and feedback via multidisciplinary postoperative rounding.

Results

There was an observed decrease in the rate of PPIs from 0.62 to 0.00 per 1,000 patient surgeries during the 26-month period that this protocol was implemented.

Conclusion

This project was conducted at a major MTF using a multidisciplinary PPI prevention approach that may be of value in reducing PPIs in other settings. This approach seems worthy of further investigation and may be applicable to other military MTFs and in deployed settings.
Military Nursing Evidence-Based Practice Summit: A Descriptive Analysis of EBP Barriers and Solutions Within the Military Healthcare System
Authors: King Heather C , White Tonya , Leyden Christine , Martinez Stephanie , Yauger Young J
Published: November 2023

Background

Evidence-based practice (EBP) is an innovative systematic problem-solving methodology that incorporates the best research evidence into clinical practice to improve patient outcomes, job satisfaction, and reduced healthcare costs. Although there are significant advances to implement EBP into military healthcare and operational settings, many barriers and challenges still exist. Civilian healthcare organizations have examined barriers and solutions to integrate EBP into clinical practice, but limited data exists to identify barriers and solutions to integrate EBP into military healthcare settings. Advancing the implementation of EBPs within military healthcare settings has the power to transform the administrative processes of healthcare management and most importantly, the delivery of healthcare for service members and beneficiaries. The purpose of this article is to present findings from a qualitative descriptive research study which analyzed data obtained during an EBP military summit.

Methods

A qualitative descriptive research study was used to examine EBP barriers and solutions to implement EBP in military healthcare settings. Participants attended a virtual 1-day military EBP summit (n = 182). As part of the summit, participants were invited to voluntarily participate in focus groups. Focus groups were conducted to gain an understanding of EBP barriers and solutions from military and civilian nurses and medics with interest and experience conducting EBP within military healthcare settings (n = 42). Focus group discussions were transcribed and analyzed by the study team.

Results

The study analysis identified six themes: leadership, command culture, EBP barriers (specific to MTF/operational environments), communication, infrastructure support, and outcome measures. Sub-themes identified additional dimensions military-specific barriers and solutions within the six identified themes.

Conclusions

The results of this research study identify actionable tasks and recommendations to advance EBP within the military healthcare system. EBP is currently underutilized in the military healthcare system, and supportive implementation of EBP can be accomplished through enhanced leadership engagement, changing command culture, addressing EBP barriers, infrastructure, communication planning, and integration of existing national clinical and financial outcome measures. Given the critical need to further transition of military healthcare to evidence-based data driven decisions, the knowledge gained from this study can optimize readiness and advance healthcare delivered to service members and beneficiaries within the military healthcare system.
Key Factors to Consider When Implementing an Advanced Practice Registered Nurse-Led Heart Failure Clinic
Authors: Anderson Amanda J , Anderson Jeanette M , Cengiz Adem , Yoder Linda H
Published: November 2023

Advanced practice registered nurses (APRNs) such as clinical nurse specialists and nurse practitioners excel at chronic disease management. Development of an APRN-led heart failure (HF) clinic is an ideal way to manage complex HF patients. However, there are important factors to consider when implementing an APRN-led HF clinic. The purpose of this paper is to provide a consolidation of recommendations to consider when developing and implementing an APRN-led HF clinic. A review of applicable literature within the last 10 years was conducted to determine the key factors to be considered when developing organizational structures and processes for an APRN-led HF clinic. The increasing need for primary care and internal medicine providers supports using APRNs to fill the gap and provide disease management for HF patients. Also, APRNs can impact the overall costs of HF treatment by optimizing postdischarge care and preventing hospitalizations and readmissions. Multiple studies supported implementation of APRN-led HF clinics for disease management to provide complex treatment strategies and comprehensive care to these patients.
Does Non-Measurability Favour Imprecision?
Authors: Dorr Cian
Published: November 2023

In a recent paper, Yoaav Isaacs, Alan Hájek, and John Hawthorne argue for the rational permissibility of ’credal imprecision’ by appealing to certain propositions associated with non-measurable spatial regions: for example, the proposition that the pointer of a spinner will come to rest within a certain non-measurable set of points on its circumference. This paper rebuts their argument by showing that its premises lead to implausible consequences in cases where one is trying to learn, by making multiple observations, whether a certain outcome is associated with a non-measurable region or a measurable one.
ChannelsDB 2.0: a comprehensive database of protein tunnels and pores in AlphaFold era
Authors: Špačková Anna , Vávra Ondřej , Raček Tomáš , Bazgier Václav , Sehnal David , Damborský Jiří , Svobodová Radka , Bednář David , Berka Karel
Published: November 2023

ChannelsDB 2.0 is an updated database providing structural information about the position, geometry and physicochemical properties of protein channels—tunnels and pores—within deposited biomacromolecular structures from PDB and AlphaFoldDB databases. The newly deposited information originated from several sources. Firstly, we included data calculated using a popular CAVER tool to complement the data obtained using original MOLE tool for detection and analysis of protein tunnels and pores. Secondly, we added tunnels starting from cofactors within the AlphaFill database to enlarge the scope of the database to protein models based on Uniprot. This has enlarged available channel annotations ∼4.6 times as of 1 September 2023. The database stores information about geometrical features, e.g. length and radius, and physico-chemical properties based on channel-lining amino acids. The stored data are interlinked with the available UniProt mutation annotation data. ChannelsDB 2.0 provides an excellent resource for deep analysis of the role of biomacromolecular tunnels and pores. The database is available free of charge: https://channelsdb2.biodata.ceitec.cz.
DriverDBv4: a multi-omics integration database for cancer driver gene research
Authors: Liu Chia-Hsin , Lai Yo-Liang , Shen Pei-Chun , Liu Hsiu-Cheng , Tsai Meng-Hsin , Wang Yu-De , Lin Wen-Jen , Chen Fang-Hsin , Li Chia-Yang , Wang Shu-Chi , Hung Mien-Chie , Cheng Wei-Chung
Published: November 2023

Advancements in high-throughput technology offer researchers an extensive range of multi-omics data that provide deep insights into the complex landscape of cancer biology. However, traditional statistical models and databases are inadequate to interpret these high-dimensional data within a multi-omics framework. To address this limitation, we introduce DriverDBv4, an updated iteration of the DriverDB cancer driver gene database (http://driverdb.bioinfomics.org/). This updated version offers several significant enhancements: (i) an increase in the number of cohorts from 33 to 70, encompassing approximately 24 000 samples; (ii) inclusion of proteomics data, augmenting the existing types of omics data and thus expanding the analytical scope; (iii) implementation of multiple multi-omics algorithms for identification of cancer drivers; (iv) new visualization features designed to succinctly summarize high-context data and redesigned existing sections to accommodate the increased volume of datasets and (v) two new functions in Customized Analysis, specifically designed for multi-omics driver identification and subgroup expression analysis. DriverDBv4 facilitates comprehensive interpretation of multi-omics data across diverse cancer types, thereby enriching the understanding of cancer heterogeneity and aiding in the development of personalized clinical approaches. The database is designed to foster a more nuanced understanding of the multi-faceted nature of cancer.
StemDriver: a knowledgebase of gene functions for hematopoietic stem cell fate determination
Authors: Luo Yangyang , Guo Jingjing , Wen Jianguo , Zhao Weiling , Huang Kexin , Liu Yang , Wang Grant , Luo Ruihan , Niu Ting , Feng Yuzhou , Xu Haixia , Kim Pora , Zhou Xiaobo
Published: November 2023

StemDriver is a comprehensive knowledgebase dedicated to the functional annotation of genes participating in the determination of hematopoietic stem cell fate, available at http://biomedbdc.wchscu.cn/StemDriver/. By utilizing single-cell RNA sequencing data, StemDriver has successfully assembled a comprehensive lineage map of hematopoiesis, capturing the entire continuum from the initial formation of hematopoietic stem cells to the fully developed mature cells. Extensive exploration and characterization were conducted on gene expression features corresponding to each lineage commitment. At the current version, StemDriver integrates data from 42 studies, encompassing a diverse range of 14 tissue types spanning from the embryonic phase to adulthood. In order to ensure uniformity and reliability, all data undergo a standardized pipeline, which includes quality data pre-processing, cell type annotation, differential gene expression analysis, identification of gene categories correlated with differentiation, analysis of highly variable genes along pseudo-time, and exploration of gene expression regulatory networks. In total, StemDriver assessed the function of 23 839 genes for human samples and 29 533 genes for mouse samples. Simultaneously, StemDriver also provided users with reference datasets and models for cell annotation. We believe that StemDriver will offer valuable assistance to research focused on cellular development and hematopoiesis.
PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs
Authors: Zeng Haonan , Zhang Wenjing , Lin Qing , Gao Yahui , Teng Jinyan , Xu Zhiting , Cai Xiaodian , Zhong Zhanming , Wu Jun , Liu Yuqiang , Diao Shuqi , Wei Chen , Gong Wentao , Pan Xiangchun , Li Zedong , Huang Xiaoyu , Chen Xifan , Du Jinshi ,   The PigGTEx Consortium, Zhao Fuping , Zhao Yunxiang , Ballester Maria , Crespo-Piazuelo Daniel , Amills Marcel , Clop Alex , Karlskov-Mortensen Peter , Fredholm Merete , Li Pinghua , Huang Ruihua , Tang Guoqing , Li Mingzhou , Liu Xiaohong , Chen Yaosheng , Zhang Qin , Li Jiaqi , Yuan Xiaolong , Ding Xiangdong , Fang Lingzhao , Zhang Zhe
Published: November 2023

To fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.
Exploiting public databases of genomic variation to quantify evolutionary constraint on the branch point sequence in 30 plant and animal species
Authors: Nosková Adéla , Li Chao , Wang Xiaolong , Leonard Alexander S , Pausch Hubert , Kadri Naveen Kumar
Published: November 2023

The branch point sequence is a degenerate intronic heptamer required for the assembly of the spliceosome during pre-mRNA splicing. Disruption of this motif may promote alternative splicing and eventually cause phenotype variation. Despite its functional relevance, the branch point sequence is not included in most genome annotations. Here, we predict branch point sequences in 30 plant and animal species and attempt to quantify their evolutionary constraints using public variant databases. We find an implausible variant distribution in the databases from 16 of 30 examined species. Comparative analysis of variants from whole-genome sequencing shows that variants submitted from exome sequencing or false positive variants are widespread in public databases and cause these irregularities. We then investigate evolutionary constraint with largely unbiased public variant databases in 14 species and find that the fourth and sixth position of the branch point sequence are more constrained than coding nucleotides. Our findings show that public variant databases should be scrutinized for possible biases before they qualify to analyze evolutionary constraint.
Economics as intervention: Expert struggles over quantitative easing at the Bank of England
Authors: Cassar Dylan
Published: November 2023

How does a technocratic entity, such as a central bank, craft a key policy intervention when faced with limits to established frameworks of governance? This article explores the Bank of England’s turn to unconventional policy in 2009 drawing on a set of eighteen in-depth interviews with former members of the Monetary Policy Committee, Executive team, and staff economists, and a corpus of documents. Adopting Goffman’s ‘framing analysis’, it argues that the limits to established governance led to the temporary replacement of the New Keynesian frame with a Monetarist frame, as a result of expert struggles, with consequential outcomes on the policy intervention. As the backstage dissensus spilled over onto the frontstage, manifesting as limits to knowledge, the Bank’s ‘expert authority’ was threatened. The Bank engaged in ‘manufactured consensus’—a backstage compromise between competing frames forged into a frontstage consensus via a hybrid frame—which proved to be a fragile strategy. By throwing light on the backstage–frontstage relations of technocratic organizations, I claim that an intervention may be shaped both by internal processes as well as by the ways in which the organization seeks to handle the external demands to which those very same internal processes may give rise.
Variations in gender identity and sexual orientation of university students
Authors: Yoshida Tomoko , Matsubara Keiko , Ogata-Kawata Hiroko , Miyado Mami , Ishiwata Keisuke , Nakabayashi Kazuhiko , Hata Kenichiro , Kageyama Ikuko , Tamaoka Satoshi , Shimada Yukiko , Fukami Maki , Sasaki Shoko
Published: November 2023

Background

Previous studies have shown that a small percentage of people in the general population have atypical gender identity and/or sexual orientation.

Aim

This study aimed to explore variations in gender identity and sexual orientation in university students and determine genetic factors associated with these variations.

Methods

Deviations from complete gender congruence and exclusive heterosexual orientation in 736 Japanese university students were quantitatively assessed with self-assessment questionnaires. Next, we conducted genetic tests for 80 participants who showed relatively low gender identity scores and/or atypical sexual orientation. These genetic tests consisted of repeat number analysis of the androgen receptor gene (AR) and a SKAT-O: an optimal unified sequence kernel association test, which is an exome-based rare variant association study. The results of the genetic tests were compared with the Japanese reference data and the results of our 637 control samples.

Outcomes

We calculated the gender identity and sexual orientation scores of all participants and analyzed the molecular data of 80 selected participants.

Results

The gender identity scores of 736 participants were broadly distributed: only ~15% of natal males and ~5% of natal females had the maximum score that corresponds to complete gender congruence. The sexual orientation scores also varied: ~80% of natal males and ~60% of natal females showed exclusive heterosexual orientation. We found no association between gender characteristics and AR repeat numbers. The SKAT-O showed that rare damaging variants of TDRP and 3 other genes were more common in the 80 participants than in the control group.

Clinical Implications

Our data support the view that gender is a phenotypic continuum rather than a binary trait.

Strength and Limitations

This study quantitatively assessed the gender characteristics of a large cohort of university students. Moreover, we conducted systematic screening for genetic factors associated with gender variations. The weaknesses of the study were the limited analytic power of the questionnaires, the relatively small sample for molecular analyses, and incomplete clinical information and relatively advanced ages of the control group.

Conclusion

This study revealed significant variations in gender identity and sexual orientation in university students, which may be partly associated with variants in TDRP or other genes.