bluuebunny/crossref_metadata_2025 huggingface dataset:
On the “contact” hyperfine interaction
Authors: Saslow Wayne M.
Published: May 2024

When Enrico Fermi analyzed the magnetic interaction between the electron and Na, Cs, and Rb nuclei in 1930, he used the Dirac equation to compute the energy of an electron interacting with a point charge and magnetic dipole (the nucleus) fixed at the origin. After the mathematical dust had settled, he found an interaction that appeared to act only at a single point: the center of the electron wavefunction; it has been called a contact interaction. In 1936, Casimir analyzed the magnetic interaction of proton and neutron spins in the ground state of the deuteron using the Schrödinger equation and classical electrodynamics. Using symmetries appropriate only to s states, and performing an integration by parts, he found that they, too, seemed to interact only at a single common point of the proton and neutron: their center-of-mass. When applied to hydrogen, his result agreed with Fermi's. We present an expanded version of Casimir's important but little-known calculation.
Psychological Safety in Elite Swimming: Fearful Versus Fearless Coaching Environments
Authors: Maughan Amelia B. , Jowett Sophia
Published: May 2024

Psychological safety has become a popular concept within organisational settings and recently has become a topic of interest within sport. The purpose of this paper was to explore the notion of psychological safety and its impact on athletes’ performance, as well as examine the role coaches played in creating psychologically safe environments. Semistructured interviews were conducted with five former female elite swimmers—all of whom had represented their country in Olympic Games and/or World Championships at least once. Obtained qualitative data were transcribed and analysed using reflexive thematic analysis. The analysis generated three main themes: (a) fearful coaching environment,  (b) fearless coaching environment, and  (c) team environment. All participants experienced both the presence and lack of psychological safety during their athletic careers. According to the participants, their coaches played a fundamental role in creating coaching environments that either invoked or suppressed fear. Swimming teams formed by peers also contributed to experiencing psychological safety (or lack of). This study highlights that an investigation of the content and functions of psychological safety within specific sport contexts can garner insightful knowledge that can have important theoretical and practical ramifications for coaches and coaching in sport.
Independent and Combined Associations of Physical Activity and Screen Time With Biomarkers of Inflammation in Children and Adolescents With Overweight/Obesity
Authors: Ding Yijian , Xu Xi
Published: May 2024

Purpose: Inflammation regulation is important for obesity management and prevention of obesity-related diseases. This cross-sectional study aimed to analyze the independent and combined associations of physical activity and screen time with biomarkers of inflammation in children and adolescents with overweight/obesity. Method: A total of 1289 children and adolescents with overweight/obesity were included from the 2015 to 2018 National Health and Nutrition Examination Survey. Multivariable linear regressions were conducted for the association analyses. Results: For the independent associations, a negative dose-dependent relationship was demonstrated between physical activity and inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) in adolescents with overweight/obesity (P < .001) but not children; screen time was not associated with hsCRP in both children and adolescents. No significant association was found between physical activity or screen time with other inflammatory biomarkers. For the combined associations, there was an interaction between physical activity and screen time on hsCRP in adolescents with overweight/obesity (P = .014). In addition, the negative association between physical activity and hsCRP was greater in boys compared with girls and in Hispanic and non-Hispanic Black individuals compared with non-Hispanic White individuals. Conclusion: This study demonstrated a combined association of physical activity and screen time with inflammatory biomarker hsCRP in adolescents with overweight/obesity.
Pseudo-bottle-brush decorated thin-film composite desalination membranes with ultrahigh mineral scale resistance
Authors: Ziemann Eric , Coves Tali , Oren Yaeli S. , Maman Nitzan , Sharon-Gojman Revital , Neklyudov Vadim , Freger Viatcheslav , Ramon Guy Z. , Bernstein Roy
Published: May 2024

High water recovery is crucial to inland desalination but is impeded by mineral scaling of the membrane. This work presents a two-step modification approach for grafting high-density zwitterionic pseudo-bottle-brushes to polyamide reverse osmosis membranes to prevent scaling during high-recovery desalination of brackish water. Increasing brush density, induced by increasing reaction time, correlated with reduced scaling. High-density grafting eliminated gypsum scaling and almost completely prevented silica scaling during desalination of synthetic brackish water at a recovery ratio of 80%. Moreover, scaling was effectively mitigated during long-term desalination of real brackish water at a recovery ratio of 90% without pretreatment or antiscalants. Molecular dynamics simulations reveal the critical dependence of the membrane’s silica antiscaling ability on the degree to which the coating screens the membrane surface from readily forming silica aggregates. This finding highlights the importance of maximizing grafting density for optimal performance and advanced antiscaling properties to allow high-recovery desalination of complex salt solutions.
Unlocking iron metal as a cathode for sustainable Li-ion batteries by an anion solid solution
Authors: Yu Mingliang , Wang Jing , Lei Ming , Jung Min Soo , Zhuo Zengqing , Yang Yufei , Zheng Xueli , Sandstrom Sean , Wang Chunsheng , Yang Wanli , Jiang De-en , Liu Tongchao , Ji Xiulei
Published: May 2024

Traditional cathode chemistry of Li-ion batteries relies on the transport of Li-ions within the solid structures, with the transition metal ions and anions acting as the static components. Here, we demonstrate that a solid solution of F
−
and PO
4
3−
facilitates the reversible conversion of a fine mixture of iron powder, LiF, and Li
3
PO
4
into iron salts. Notably, in its fully lithiated state, we use commercial iron metal powder in this cathode, departing from electrodes that begin with iron salts, such as FeF
3
. Our results show that Fe-cations and anions of F
−
and PO
4
3−
act as charge carriers in addition to Li-ions during the conversion from iron metal to a solid solution of iron salts. This composite electrode delivers a reversible capacity of up to 368 mAh/g and a specific energy of 940 Wh/kg. Our study underscores the potential of amorphous composites comprising lithium salts as high-energy battery electrodes.
Genetic regulation of cell type–specific chromatin accessibility shapes brain disease etiology
Authors: Zeng Biao , Bendl Jaroslav , Deng Chengyu , Lee Donghoon , Misir Ruth , Reach Sarah M. , Kleopoulos Steven P. , Auluck Pavan , Marenco Stefano , Lewis David A. , Haroutunian Vahram , Ahituv Nadav , Fullard John F. , Hoffman Gabriel E. , Roussos Panos
Published: May 2024

Nucleotide variants in cell type–specific gene regulatory elements in the human brain are risk factors for human disease. We measured chromatin accessibility in 1932 aliquots of sorted neurons and non-neurons from 616 human postmortem brains and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci (caQTLs). Only 10.4% of caQTLs are shared between neurons and non-neurons, which supports cell type–specific genetic regulation of the brain regulome. Incorporating allele-specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms that underlie disease risk. Using massively parallel reporter assays in induced excitatory neurons, we screened 19,893 brain QTLs and identified the functional impact of 476 regulatory variants. Combined, this comprehensive resource captures variation in the human brain regulome and provides insights into disease etiology.
A metabolic dependency of EBV can be targeted to hinder B cell transformation
Authors: Müller-Durovic Bojana , Jäger Jessica , Engelmann Christine , Schuhmachers Patrick , Altermatt Sabine , Schlup Yannick , Duthaler Urs , Makowiec Celia , Unterstab Gunhild , Roffeis Sarah , Xhafa Erta , Assmann Nadine , Trulsson Fredrik , Steiner Rebekah , Edwards-Hicks Joy , West James , Turner Lorinda , Develioglu Leyla , Ivanek Robert , Azzi Tarik , Dehio Philippe , Berger Christoph ,   Swiss Transplant Cohort Study#, Kuzmin Dmitry , Saboz Sophie , Mautner Josef , Löliger Jordan , Geigges Marco , Palianina Darya , Khanna Nina , Dirnhofer Stefan , Münz Christian , Bantug Glenn R. , Hess Christoph , Berger Christoph , Hess Christoph , Koller Michael , Rossi Simona , Stampf Susanne , Müller Nicolas J.
Published: May 2024

After infection of B cells, Epstein-Barr virus (EBV) engages host pathways that mediate cell proliferation and transformation, contributing to the propensity of the virus to drive immune dysregulation and lymphomagenesis. We found that the EBV protein EBNA2 initiates nicotinamide adenine dinucleotide (NAD) de novo biosynthesis by driving expression of the metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) in infected B cells. Virus-enforced NAD production sustained mitochondrial complex I activity, to match adenosine triphosphate (ATP) production with bioenergetic requirements of proliferation and transformation. In transplant patients, IDO1 expression in EBV-infected B cells, and a serum signature of increased IDO1 activity, preceded development of lymphoma. In humanized mice infected with EBV, IDO1 inhibition reduced both viremia and lymphomagenesis. Virus-orchestrated NAD biosynthesis is therefore a druggable metabolic vulnerability of EBV-driven B cell transformation, opening therapeutic possibilities for EBV-related diseases.
Pursuing a smoke-free generation
Authors: Gostin Lawrence O.
Published: May 2024

The United Kingdom may soon become a world leader in forging a smoke-free generation. Last month, the country passed a bill that bans the sale of cigarettes to anyone born in 2009 or later. The prime minister claims the policy will “phase out smoking in young people almost completely as early as 2040.” A final vote by Parliament is expected next month. Tobacco claims 8 million lives every year, and could claim a billion lives over this century—mostly in low- and middle-income countries. For every person that dies, at least 30 more suffer from smokingrelated chronic disease. The benefits of a tobacco-free society would be transformational.
Alvin
, the iconic submersible, plunges deeper than ever
Authors: Cornwall Warren
Published: May 2024

After $50 million upgrade, U.S. research sub can reach 99% of the ocean floor
A
Haemophilus ducreyi
strain lacking the
yfeABCD
iron transport system is virulent in human volunteers
Authors: Fortney Kate R. , Brothwell Julie A. , Batteiger Teresa A. , Duplantier Rory , Katz Barry P. , Spinola Stanley M.
Published: May 2024

Haemophilus ducreyi
causes the genital ulcer disease chancroid and painful cutaneous ulcers in children who live in the tropics. To acquire heme from the host,
H. ducreyi
expresses a TonB-dependent hemoglobin receptor, HgbA, which is necessary and sufficient for
H. ducreyi
to progress to the pustular stage of disease in a controlled human infection model. HgbA transports hemoglobin across the outer membrane; how heme is transported across the cytoplasmic membrane is unclear. In previous studies, transcripts encoding the YfeABCD heme transporter were upregulated in experimental lesions caused by
H. ducreyi
in human volunteers, suggesting the latter may have a role in virulence. Here we constructed a double deletion mutant, 35000HPΔ
yfeAB
Δ
yfeCD
, which exhibited growth defects relative to its parent 35000HP in media containing human hemoglobin as an iron source. Five human volunteers were inoculated at three sites on the skin overlying the deltoid with each strain. The results of the trial showed that papules formed at 100% (95% CI, 71.5, 100) at both 35000HP and 35000HPΔ
yfeAB
Δ
yfeCD
-inoculated sites (
P
= 1.0). Pustules formed at 60% (95% CI, 25.9, 94.1) at parent-inoculated sites and 53% (95% CI, 18.3, 88.4) at mutant-inoculated sites (
P
= 0.79). Thus, the ABC transporter encoded by
yfeAB
and
yfeCD
was dispensable for
H. ducreyi
virulence in humans. In the absence of YfeABCD,
H. ducreyi
likely utilizes other periplasmic binding proteins and ABC-transporters such as HbpA, SapABCDF, and DppBCDF to shuttle heme from the periplasm into the cytoplasm, underscoring the importance of redundancy of such systems in gram-negative pathogens.
Competitive fitness of asymptomatic bacteriuria
E. coli
strain 83972 against uropathogens in human urine
Authors: George Iris , Kalairaj Manivannan Sivaperuman , Zimmern Philippe E. , Ware Taylor H. , Subashchandrabose Sargurunathan
Published: May 2024

Urinary tract infection (UTI) is one of the most common bacterial infections worldwide. The main causative agent of UTI is uropathogenic
Escherichia coli
(UPEC). There is an immediate need for novel prophylactic and treatment strategies against UTI because of the increasing incidence of antimicrobial resistance among uropathogens. ABU 83972, an asymptomatic bacteriuria-causing
E. coli
strain
,
prevents UTI by suppressing the colonization of UPEC. However, the nature of competition and growth repression of UPEC by ABU 83972 is unclear and is the subject of our investigation. Here, we characterized the growth kinetics of ABU 83972 and uropathogens in human urine and laboratory media. Next, we performed a series of competitive co-culture experiments where ABU 83972 and uropathogens were inoculated at a 1:1 ratio in human urine and in various media, and their relative abundance was determined. In human urine, ABU 83972 outcompeted UPEC and additional uropathogens, reaching up to 90% of the total population after 24 hours of incubation. In contrast, UPEC outcompeted ABU 83972 in LB and M9 minimal media and exhibited superior colonization than ABU 83972 in the mouse urinary bladder. Since engineered living materials (ELMs) can be used to retain an organism of interest in a particular location, we developed ABU 83972-containing ELMs that effectively outcompeted UPEC in human urine. In summary, our work establishes that ABU 83972 outcompetes UPEC in a milieu- and cell-density-dependent manner, highlighting the importance of the metabolites and nutrients found in the human urine as determinants of the competitive fitness of ABU 83972.
SIV infection and ARV treatment reshape the transcriptional and epigenetic profile of naïve and memory T cells
in vivo
Authors: Rahmberg Andrew R. , Markowitz Tovah E. , Mudd Joseph C. , Ortiz Alexandra M. , Brenchley Jason M.
Published: May 2024

Human and simian immunodeficiency viruses (HIV and SIV) are lentiviruses that reverse transcribe their RNA genome with subsequent integration into the genome of the target cell. How progressive infection and administration of antiretrovirals (ARVs) longitudinally influence the transcriptomic and epigenetic landscape of particular T cell subsets, and how these may influence the genetic location of integration are unclear. Here, we use RNAseq and ATACseq to study the transcriptomics and epigenetic landscape of longitudinally sampled naïve and memory CD4+ and CD8+ T cells in two species of non-human primates prior to SIV infection, during chronic SIV infection, and after administration of ARVs. We find that SIV infection leads to significant alteration to the transcriptomic profile of all T cell subsets that are only partially reversed by administration of ARVs. Epigenetic changes were more apparent in animals with longer periods of untreated SIV infection and correlated well with changes in corresponding gene expression. Known SIV integration sites did not vary due to SIV status but did contain more open chromatin in rhesus macaque memory T cells, and the expression of proteasome-related genes at the pre-SIV timepoint correlated with subsequent viremia.

IMPORTANCE

Chronic inflammation during progressive human and simian immunodeficiency virus (HIV and SIV) infections leads to significant co-morbidities in infected individuals with significant consequences. Antiretroviral (ARV)-treated individuals also manifest increased levels of inflammation which are associated with increased mortalities. These data will help guide rational development of modalities to reduce inflammation observed in people living with HIV and suggest mechanisms underlying lentiviral integration site preferences.
Transmissible gastroenteritis virus induces inflammatory responses via RIG-I/NF-κB/HIF-1α/glycolysis axis in intestinal organoids and
in vivo
Authors: Zhang Yunhang , Yang Ning , Li Yang , Tan Chen , Cai Yifei , Rui Xue , Liu Yuanyuan , Fu Yuguang , Liu Guangliang
Published: May 2024

Transmissible gastroenteritis virus (TGEV)-induced enteritis is characterized by watery diarrhea, vomiting, and dehydration, and has high mortality in newborn piglets, resulting in significant economic losses in the pig industry worldwide. Conventional cell lines have been used for many years to investigate inflammation induced by TGEV, but these cell lines may not mimic the actual intestinal environment, making it difficult to obtain accurate results. In this study, apical-out porcine intestinal organoids were employed to study TEGV-induced inflammation. We found that apical-out organoids were susceptible to TGEV infection, and the expression of representative inflammatory cytokines was significantly upregulated upon TGEV infection. In addition, retinoic acid-inducible gene I (RIG-I) and the nuclear factor-kappa B (NF-κB) pathway were responsible for the expression of inflammatory cytokines induced by TGEV infection. We also discovered that the transcription factor hypoxia-inducible factor-1α (HIF-1α) positively regulated TGEV-induced inflammation by activating glycolysis in apical-out organoids, and pig experiments identified the same molecular mechanism as the
ex vivo
results. Collectively, we unveiled that the inflammatory responses induced by TGEV were modulated via the RIG-I/NF-κB/HIF-1α/glycolysis axis
ex vivo
and
in vivo
. This study provides novel insights into TGEV-induced enteritis and verifies intestinal organoids as a reliable model for investigating virus-induced inflammation.

IMPORTANCE

Intestinal organoids are a newly developed culture system for investigating immune responses to virus infection. This culture model better represents the physiological environment compared with well-established cell lines. In this study, we discovered that inflammatory responses induced by TGEV infection were regulated by the RIG-I/NF-κB/HIF-1α/glycolysis axis in apical-out porcine organoids and in pigs. Our findings contribute to understanding the mechanism of intestinal inflammation upon viral infection and highlight apical-out organoids as a physiological model to mimic virus-induced inflammation.
Tripartite motif-containing protein 21 is involved in IFN-γ-induced suppression of hepatitis B virus by regulating hepatocyte nuclear factors
Authors: Won Juhee , Kang Hong Seok , Kim Na Yeon , Dezhbord Mehrangiz , Marakkalage Kamindu Gayashan , Lee Eun-Hwi , Lee Donghyo , Park Soree , Kim Dong-Sik , Kim Kyun-Hwan
Published: May 2024

The antiviral role of the tripartite motif-containing (TRIM) protein family , a member of the E3-ubiquitin ligase family, has recently been actively studied. Hepatitis B virus (HBV) infection is a major contributor to liver diseases; however, the host factors regulated by cytokine-inducible TRIM21 to suppress HBV remain unclear. In this study, we showed the antiviral efficacy of TRIM21 against HBV in hepatoma cell lines, primary human hepatocytes isolated from patient liver tissues, and mouse model. Using TRIM21 knock-out cells, we confirmed that the antiviral effects of interferon-gamma, which suppress HBV replication, are diminished when TRIM21 is deficient. Northern blot analysis confirmed a reduction of HBV RNA levels by TRIM21. Using Luciferase reporter assay, we also discovered that TRIM21 decreases the activity of HBV enhancers, which play a crucial role in covalently closed circular DNA transcription. The participation of the RING domain and PRY-SPRY domain in the anti-HBV effect of TRIM21 was demonstrated through experiments using deletion mutants. We identified a novel interaction between TRIM21 and hepatocyte nuclear factor 4α (HNF4α) through co-immunoprecipitation assay. More specifically, ubiquitination assay revealed that TRIM21 promotes ubiquitin-mediated proteasomal degradation of HNF4α. HNF1α transcription is down-regulated as a result of the degradation of HNF4α, an activator for the HNF1α promoter. Therefore, the reduction of key HBV enhancer activators, HNF4α and HNF1α, by TRIM21 resulted in a decline in HBV transcription, ultimately leading to the inhibition of HBV replication.

IMPORTANCE

Despite extensive research efforts, a definitive cure for chronic hepatitis B remains elusive, emphasizing the persistent importance of this viral infection as a substantial public health concern. Although the risks associated with hepatitis B virus (HBV) infection are well known, host factors capable of suppressing HBV are largely uncharacterized. This study elucidates that tripartite motif-containing protein 21 (TRIM21) suppresses HBV transcription and consequently inhibits HBV replication by downregulating the hepatocyte nuclear factors, which are host factors associated with the HBV enhancers. Our findings demonstrate a novel anti-HBV mechanism of TRIM21 in interferon-gamma-induced anti-HBV activity. These findings may contribute to new strategies to block HBV.
Aberrant RNA polymerase initiation and processivity on the genome of a herpes simplex virus 1 mutant lacking ICP27
Authors: Birkenheuer Claire H. , Baines Joel D.
Published: May 2024

Within the first 15 minutes of infection, herpes simplex virus 1 immediate early proteins repurpose cellular RNA polymerase (Pol II) for viral transcription. An important role of the viral-infected cell protein 27 (ICP27) is to facilitate viral pre-mRNA processing and export viral mRNA to the cytoplasm. Here, we use precision nuclear run-on followed by deep sequencing (PRO-seq) to characterize transcription of a viral ICP27 null mutant. At 1.5 and 3 hours post infection (hpi), we observed increased total levels of Pol II on the mutant viral genome and accumulation of Pol II downstream of poly A sites indicating increased levels of initiation and processivity. By 6 hpi, Pol II accumulation on specific mutant viral genes was higher than that on wild-type virus either at or upstream of poly A signals, depending on the gene. The PRO-seq profile of the ICP27 mutant on late genes at 6 hpi was similar but not identical to that caused by treatment with flavopiridol, a known inhibitor of RNA processivity. This pattern was different from PRO-seq profiles of other
α
gene mutants and upon inhibition of viral DNA replication with PAA. Together, these results indicate that ICP27 contributes to the repression of aberrant viral transcription at 1.5 and 3 hpi by inhibiting initiation and decreasing RNA processivity. However, ICP27 is needed to enhance processivity on most late genes by 6 hpi in a mechanism distinguishable from its role in viral DNA replication.

IMPORTANCE

We developed and validated the use of a processivity index for precision nuclear run-on followed by deep sequencing data. The processivity index calculations confirm infected cell protein 27 (ICP27) induces downstream of transcription termination on certain host genes. The processivity indices and whole gene probe data implicate ICP27 in transient immediate early gene-mediated repression, a process that also requires ICP4, ICP22, and ICP0. The data indicate that ICP27 directly or indirectly regulates RNA polymerase (Pol II) initiation and processivity on specific genes at specific times post infection. These observations support specific and varied roles for ICP27 in regulating Pol II activity on viral genes in addition to its known roles in post transcriptional mRNA processing and export.
Improved protein splicing through viral passaging
Authors: Hume Adam J. , Deeney Dylan J. , Smetana John S. , Turcinovic Jacquelyn , Connor John H. , Belfort Marlene , Mühlberger Elke , Lennon Christopher W.
Published: May 2024

In
tervening pro
teins
(inteins) are translated as subdomains within host proteins and removed through an intein-driven splicing reaction where the flanking sequences (exteins) are joined with a peptide bond. Previously, we developed a self-removing translation reporter for labeling Ebola virus (EBOV). In this reporter, an intein (RadA) containing the fluorescent protein ZsGreen (ZsG) is inserted within the EBOV protein VP30. Upon VP30-RadA-ZsG expression from the viral genome, RadA-ZsG is removed from VP30 through the protein splicing activity of RadA, generating functional, non-tagged VP30 and functional ZsGreen. While incorporation of our VP30-RadA-ZsG fusion reporter into recombinant EBOV (rEBOV-RadA-ZsG) resulted in an infectious virus that expresses ZsG upon infection of cells, this virus displayed a replication defect compared to wild-type EBOV, which might be the result of insufficient RadA splicing. Here, we demonstrate that the serial passaging of rEBOV-RadA-ZsG in human cells led to an increase in replication efficiency compared to unpassaged rEBOV-RadA-ZsG. Sequencing of passaged viruses revealed intein-specific mutations. These mutations improve intein activity in both prokaryotic and eukaryotic systems, as well as in multiple extein contexts. Taken together, our findings offer a novel means to select for inteins with enhanced catalytic properties that appear independent of extein context and expression system.

IMPORTANCE

In
tervening pro
teins
(inteins) are self-removing protein elements that have been utilized to develop a variety of innovative protein engineering technologies. Here, we report the isolation of inteins with improved catalytic activity through viral passaging. Specifically, we inserted a highly active intein within an essential protein of Ebola virus and serially passaged this recombinant virus, which led to intein-specific hyper-activity mutations. The identified mutations showed improved intein activity within both bacterial and eukaryotic expression systems and in multiple extein contexts. These results present a new strategy for developing inteins with improved splicing activity.
Disseminated tuberculosis in PLWHIV presenting as primary adrenal insufficiency
Authors: Kumar Abhinav , Verma Vishesh , Samdarshi Samir , Muthukrishnan Jayraman
Published: May 2024

A woman in her 40s presented with a history of fatigue, symptoms of light-headedness on getting up from a sitting position and hyperpigmentation of the skin and mucous membranes. During the evaluation, she was diagnosed with primary adrenal insufficiency. Radiological imaging and microbiological evidence revealed features of disseminated tuberculosis involving the lungs and the adrenals. She was found to have an HIV infection. This patient was prescribed glucocorticoid and mineralocorticoid replacement therapy and was administered antituberculous and antiretroviral treatment.
NSAID-induced corneal melt as the first presentation of Sjögren’s syndrome
Authors: Hammad Mustafa , Ahmed Lubna , Seifelnasr Mohamed
Published: May 2024

A non-diabetic woman in her 80s presented 1 week following uncomplicated left eye cataract surgery complaining of decreased vision, gritty sensation and photophobia in the same eye. Postoperative treatment included G. Acular (Ketorolac Tromethamine 0.5%, NSAID: non-steroidal anti-inflammatory drug) and G. Tobradex (Tobramycin 0.3% and Dexamethasone 0.1%, antibiotic and steroid, respectively) each prescribed four times a day for 2 weeks. On examination, the patient had a corneal epithelial defect which progressed to a full-thickness perforation despite ceasing the NSAID drops. Cyanoacrylate glue application with a plastic drape patch failed to seal the perforation, and a full-thickness tectonic corneal transplant was performed. On investigation, the patient had positive anti-RO and anti-LA antibodies, suggesting a diagnosis of Sjögren’s syndrome. We advocate for careful preoperative assessment prior to cataract surgery, patient education, close follow-up and cautious medication use postoperatively including avoiding NSAID drops in patients with risk factors for postoperative dry eye disease.
Diagnostic and therapeutic challenges in a recurrent endometrial carcinoma in lung, 15 years after primary treatment
Authors: Upadhyay Amitabh Kumar , Kumar Manoj , Prakash Aaditya , Kumar Abhishek
Published: May 2024

Endometrial carcinoma (EC) is the sixth most common cancer in females. Most ECs are detected in stage 1 and have a 5-year survival rate of more than 90%. Recurrence rates are highest within 5 years after treatment and are exceptionally rare after 10 years. Here, we describe a woman in her late 70s with endometrial cancer who was treated in 2008 and was diagnosed with a relapse in her left lung in 2023. Due to her advanced age and comorbidities, she was deemed inoperable. However, she received sequential chemotherapy and radiotherapy with a good partial response. She has now been started on hormonal therapy with an alternate megestrol and tamoxifen regime. There is a lack of follow-up imaging guidelines to detect late relapse, a dilemma in preferred treatment sequencing at relapse and an enigma in selecting chemotherapy or hormonal therapy.
Intralesional leiomyosarcoma malignant transformation from a biopsied benign angioleiomyoma of the proximal anterior tibia
Authors: Ward Thomas Robert William , Eastley Nicholas C , Sheikh Nomaan , Ashford Robert U
Published: May 2024

We present a novel case of a malignant transformation of an extremity soft tissue angioleiomyoma to leiomyosarcoma in a man in his late 70s who presented with a painful and increasing lump on his anterior tibia. Initial imaging and biopsy showed a benign angioleiomyoma which was excised for symptomatic reasons. An analysis of the resulting specimen revealed a 50×42×15 mm smooth muscle neoplasm consistent with angioleiomyoma with a 22×11 mm entirely intralesional nodular component in keeping with a grade 1 leiomyosarcoma. The malignant constituent of the lesion was entirely encased in benign angioleiomyoma negating the need for further surgery. Systemic staging investigation revealed no evidence of metastatic disease spread final staging as per the eighth edition of theAmerican Joint Committee on Cancer(AJCC) Staging T1N0M0 R0 Stage 1 a.
From evidence to tailored decision-making: a qualitative research of barriers and facilitating factors for the implementation of non-clinical interventions to reduce unnecessary caesarean section in Romania
Authors: Berdzuli Nino , Llop-Gironés Alba , Farcasanu Dana , Butu Cassandra , Grbic Miljana , Betran Ana Pilar
Published: May 2024

Objective

To improve understanding of the drivers of the increased caesarean section (CS) rate in Romania and to identify interventions to reverse this trend, as well as barriers and facilitators.

Design

A formative research study was conducted in Romania between November 2019 and February 2020 by means of in-depth interviews and focus-group discussions. Romanian decision-makers and high-level obstetricians preselected seven non-clinical interventions for consideration. Thematic content analysis was carried out.

Participants

88 women and 26 healthcare providers and administrators.

Settings

Counties with higher and lower CS rates were selected for this research—namely Argeș, Bistrița-Năsăud, Brașov, Ialomița, Iași, Ilfov, Dolj and the capital city of București (Bucharest).

Results

Women wanted information, education and support. Obstetricians feared malpractice lawsuits; this was identified as a key reason for performing CSs. Most obstetrics and gynaecology physicians would oppose policies of mandatory second opinions, financial measures to equalise payments for vaginal and CS births and goal setting for CS rates. In-service training was identified as a need by obstetricians, midwives and nurses. In addition, relevant structural constraints were identified: perceived lower quality of care for vaginal birth, a lack of obstetricians with expertise in managing complicated vaginal births, a lack of anaesthesiologists and midwives, and family doctors not providing antenatal care. Finally, women expressed the need to ensure their rights to dignified and respectful healthcare through pregnancy and childbirth.

Conclusion

Consideration of the views, values and preferences of all stakeholders in a multifaceted action tailored to Romanian determinants is critical to address relevant determinants to reduce unnecessary CSs. Further studies should assess the effect of multifaceted interventions.
Aspirin versus metformin in pregnancies at high risk of preterm pre-eclampsia in China (AVERT): protocol for a multicentre, double-blind, 3-arm randomised controlled trial
Authors: Liu Jiao , Shen Lixia , Nguyen-Hoang Long , Zhou Qiongjie , Wang Chi Chiu , Lu Xiaohong , Sahota Daljit , Chong Ka Chun , Ying Hao , Gu Weirong , Zhou Rong , Yang Huixia , Jiang Yanmin , Chen Dunjin , Li Xiaotian , Poon Liona
Published: May 2024

Introduction

Pre-eclampsia (PE) affects about 5% of Chinese pregnant women and is a major cause of maternal and perinatal morbidity and mortality. The first trimester screening model developed by the Fetal Medicine Foundation, which uses the Bayes theorem to combine maternal characteristics and medical history together with measurements of biomarkers, has been proven to be effective and has superior screening performance to that of the traditional risk factor-based approach for the prediction of PE. Prophylactic use of low-dose aspirin in women at risk for PE has resulted in a lower incidence of preterm-PE. However, there is no consensus on the preferred aspirin dosage for the prevention of preterm-PE. Evidence has also suggested that metformin has the potential benefit in preventing PE in pregnant women who are at high risk of the disorder.

Method and analysis

We present a protocol (V.2.0, date 17 March 2022) for the AVERT trial, which is a multicentre, double-blinded, 3-arm randomised controlled trial (RCT) that uses an effective PE screening programme to explore the optimal dosage of aspirin and the role of metformin for the prevention of PE among high-risk pregnant women in China. We intend to recruit 66 000 singleton pregnancies without treatment of low-dose aspirin and metformin at 11–13 weeks’ gestation and all eligible women attending for their first trimester routine scan will be invited to undergo screening for preterm-PE by the combination of maternal factors, mean arterial pressure and placental growth factor. Women found to be at high risk of developing preterm-PE will be invited to take part in the RCT. This study will compare the incidence of preterm-PE with delivery at <37 weeks’ gestation, as the primary outcome, of three different interventional groups: (1) aspirin 75 mg daily, (2) aspirin 150 mg daily and (3) aspirin 75 mg with metformin 1.5 g daily. 957 participants per treatment group are required to detect a significant difference of 59% in the reduction of the incidence of preterm-PE with 80% power and type I error of 5%. Pregnancy and neonatal outcomes will be collected and analysed.

Ethics and dissemination

Ethical approval for the study was obtained from the Joint Chinese University of Hong Kong–New Territories East Cluster Clinical Research Ethics Committee (CREC Ref. No. 2021.406) in Hong Kong and the Ethics Committee of each participating hospital in Mainland China. The study is registered at ClinicalTrials.gov. The results of the AVERT trial will be disseminated at international academic conferences and published in high-impact factor journals.

Trial registration number

NCT05580523
.
Multicentre, randomised, double-blind, placebo-controlled, proof of concept study of LSALT peptide as prevention of acute respiratory distress syndrome and acute kidney injury in patients infected with SARS-CoV-2 (COVID-19)
Authors: Somayaji Ranjani , Luke David R , Lau Arthur , Guner Rahmet , Tabak Ŏ Fehmi , Hepokoski Mark , Gardetto Nancy , Conrad Steven A , Kumar Sunil D , Ghosh Kalyan , Robbins Stephen M , Senger Donna L , Sun Daisy , Lim Rachel K S , Liu Jonathan , Eser Fatma , Karaali Ridvan , Tremblay Alain , Muruve Daniel
Published: May 2024

Objective

Dipeptidase-1 (DPEP-1) is a recently discovered leucocyte adhesion receptor for neutrophils and monocytes in the lungs and kidneys and serves as a potential therapeutic target to attenuate inflammation in moderate-to-severe COVID-19. We aimed to evaluate the safety and efficacy of the DPEP-1 inhibitor, LSALT peptide, to prevent specific organ dysfunction in patients hospitalised with COVID-19.

Design

Phase 2a randomised, placebo-controlled, double-blinded, trial.

Setting

Hospitals in Canada, Turkey and the USA.

Participants

A total of 61 subjects with moderate-to-severe COVID-19.

Interventions

Randomisation to LSALT peptide 5 mg intravenously daily or placebo for up to 14 days.

Primary and secondary outcome measures

The primary endpoint was the proportion of subjects alive and free of respiratory failure and/or the need for renal replacement therapy (RRT). Numerous secondary and exploratory endpoints were assessed including ventilation-free days, and changes in kidney function or serum biomarkers.

Results

At 28 days, 27 (90.3%) and 28 (93.3%) of subjects in the placebo and LSALT groups were free of respiratory failure and the need for RRT (p=0.86). On days 14 and 28, the number of patients still requiring more intensive respiratory support (O2≥6 L/minute, non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation) was 6 (19.4%) and 3 (9.7%) in the placebo group versus 2 (6.7%) and 2 (6.7%) in the LSALT group, respectively (p=0.14; p=0.67). Unadjusted analysis of ventilation-free days demonstrated 22.8 days for the LSALT group compared with 20.9 in the placebo group (p=0.4). LSALT-treated subjects had a significant reduction in the fold expression from baseline to end of treatment of serum CXCL10 compared with placebo (p=0.02). Treatment-emergent adverse events were similar between groups.

Conclusion

In a Phase 2 study, LSALT peptide was demonstrated to be safe and tolerated in patients hospitalised with moderate-to-severe COVID-19.

Trial registration number

NCT04402957.
Characteristics of patients who seek medical attention for headache and those who do not: cross-sectional survey and linked medical claims data analysis in Japan
Authors: Igarashi Hisaka , Sano Hiromi , Kondo Hiroyuki , Shibasaki Yoshiyuki , Koga Nobuyuki
Published: May 2024

Objective

To describe the characteristics of patients who sought medical attention for headache and those who did not.

Design

This observational study used a cross-sectional online survey and linked medical claims data.

Setting

Data from an online self-administered questionnaire survey conducted in November 2020 as well as linked medical claims data spanning December 2017 and November 2020 were provided by DeSC Healthcare Inc.

Participants

Of 21 480 respondents aged 19–74 years whose sex and age data matched the claims data, 7311 reported experiencing headache.

Measures

Outcomes included participant characteristics, status of medical attention seeking, medication use, quality of life (QOL) measured by Migraine-Specific QOL (MSQ) questionnaire V.2.1 and headache intensity.

Results

Of the 7311 respondents with headache, 735 sought medical attention and 6576 did not. Compared with those who did not seek medical attention, those who sought medical attention had more frequent headaches (median: 5 days/3 months vs 10 days/3 months in those who did not vs those who sought medical attention, respectively) had lower MSQ score (mean (SD) MSQ total score: 87.6 (13.0) vs 77.1 (18.1)) and were likely to experience moderately severe to severe headache (19.0% (1252/6576) vs 41.2% (303/735)) without headache medication. The inability to tolerate headache (36.5% (268/735)) was a common reason for seeking medical attention. Since the pain was not severe enough, 35.3% (2323/6576) of patients did not seek medical attention. Furthermore, a subgroup of respondents experiencing headache for ≥15 days were uncertain about which hospital or department to attend.

Conclusions

Patients typically seek help when the pain becomes unbearable. Still, some of them did not seek medical attention while they were experiencing headache for ≥15 days per month. Therefore, it is important to raise awareness and encourage seeking early medical attention before symptoms and associated burdens become too severe to be managed effectively.
Global trends in chronic kidney disease-related mortality: a systematic review protocol
Authors: Tungsanga Somkanya , Ghimire Anukul , Hariramani Vinash K , Abdulrahman Abdullah , Khan Ana S , Ye Feng , Kung Janice Y , Klarenbach Scott , Thompson Stephanie , Collister David , Srisawat Nattachai , Okpechi Ikechi G , Bello Aminu K
Published: May 2024

Introduction

In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic.

Methods and analysis

We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics.

Ethics and dissemination

A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences.

PROSPERO registration number

CRD42023416084.
Peroperative administration of tranexamic acid in Roux-en-Y and one-anastomosis gastric bypass to reduce haemorrhage in patients with morbid obesity: protocol for randomised controlled trial (PATRY trial)
Authors: 't Hart Judith W H , Noordman Bo J , Palsgraaf-Huisbrink Jeannine , Dunkelgrun Martin , Zengerink Hans F , Birnie Erwin , van Det Marc J , Boerma Evert-Jan G , de Castro Steve M M , Hazebroek Eric J , Langenhoff Barbara S , Verhoef Cornelis , Apers Jan A
Published: May 2024

Introduction

By implementation of Enhanced Recovery After Bariatric Surgery protocols and day-care surgery, early discharge poses a challenge if excessive bleeding occurs after bariatric surgery. Tranexamic acid (TXA) has demonstrated efficacy in other surgical fields and in bariatric pilot studies. This trial aims to assess the efficacy of peroperative administration of TXA in reducing haemorrhage in patients undergoing gastric bypass surgery.

Method and analysis

This is a multicentre, phase III, double-blind randomised controlled trial in six high-volume bariatric centres in the Netherlands. A total of 1524 eligible patients, aged 18 years or older, undergoing primary gastric bypass surgery (either Roux-en-Y gastric bypass or one-anastomosis gastric bypass) will be randomised between TXA and placebo (1:1, variable block, stratified for centre, day-care/overnight stay and type of surgery) after obtaining informed consent (2.5% less haemorrhage, power 80%, 2-sided-α 0.05 and 10% dropout). Exclusion criteria are pregnancy, amedical history of acute bleeding (without cause), venous thrombotic events (VTEs), epilepsy, anticoagulant use and iatrogenic bleeding during surgery (aside from staple line). The primary outcome is postoperative haemorrhage requiring intervention within 30 days postoperatively. Secondary outcome measures are staple line reinforcement, blood loss, duration of surgery, postoperative haemoglobin, vital parameters, minor and major complications, side effects of TXA (nausea, hypotension and VTE), length of hospital stay and directly made costs.

Ethics and dissemination

Written informed consent will be obtained from all participants. The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 7 February 2023 (registration number: R22.102). Results will be disseminated through peer-reviewed publications and conferences.

Trial registration number

NCT05464394
Prescriber decision-making on antithrombotic therapy after endovascular intervention for peripheral artery disease: a protocol for a discrete choice experiment
Authors: Zhu Alison , Tang Robert , Rajendran Saissan , Hajian Hamid , Aitken Sarah Joy
Published: May 2024

Introduction

Peripheral artery disease (PAD) is a major risk factor for cardiovascular morbidity and mortality, despite surgical and endovascular treatments. Emerging evidence supports the use of immediate antithrombotic medications after endovascular intervention for PAD, however, there is a lack of consensus regarding choice and duration of antithrombotic therapy. Prescriber decision-making is a complex process, with prior studies demonstrating patient factors can influence variability in antithrombotic therapy for PAD. However, it remains unclear the relative contribution of these factors. This paper describes a planned study that aims to (1) determine the influence of patient factors on clinician preference for antithrombotic therapy following endovascular intervention and (2) compare differences in prescribing preferences between consultant vascular surgeons and trainees.

Methods and analysis

This cross-sectional survey will evaluate antithrombotic prescribing choices using a discrete choice experiment (DCE) that has been developed and piloted for this study. A list of attributes and levels was generated using a mixed-methods approach. This included an extensive literature review and semistructured interviews with prescribing clinicians. Following final selection of included attributes, specialised software was used to construct a D-efficient design for the DCE questionnaire. The electronic questionnaire will be administered to vascular trainees and consultant surgeons across Australia. These data will be analysed using multinomial logistic regression, treating the decision to prescribe antithrombotic therapy as a function of both the attributes of the two alternatives, as well as characteristics of the respondent. Latent class analysis will be used to explore heterogeneity of responses.

Ethics and dissemination

Ethics approval was obtained from the University of Sydney Human Ethics committee (2023/474). The results of this study will be published in peer-reviewed journals and presented at national vascular surgical conferences. These results will be used to improve understanding how clinicians make prescribing decisions and to inform future strategy to enhance guideline-directed prescribing.