bluuebunny/crossref_metadata_2025 huggingface dataset:
Nascent chain-mediated translation regulation in bacteria: translation arrest and intrinsic ribosome destabilization
Authors: Chiba Shinobu , Fujiwara Keigo , Chadani Yuhei , Taguchi Hideki
Published: January 2023

Proteins that exsert physiological functions during being translated have been discovered from prokaryotes to eukaryotes. These proteins, also called regulatory nascent chains, are common in interacting co-translationally with the ribosomes to stall them. In most cases, such a translational arrest is induced or released in response to changes in the intracellular environment. Cells take advantage of such an environmental sensitivity as a sensor to feedback-regulate gene expression. Recent studies reveal that certain nascent chains could also destabilize the translating ribosomes, leading to stochastic premature translation termination. In this review, we introduce several examples of bacterial nascent chain-based mechanisms of translation regulation by which bacteria regulate cellular functions.
Digitalization and law: innovating around the boundaries
Authors: Callegari Beniamino , Rai Ranvir S
Published: January 2023

Recent developments in digital technologies have challenged the ways in which service firms create, deliver, and capture value. Although research and practice suggest business model innovation as an effective response to digitalization, many firms are not willing to make radical changes in the architecture of the firm’s activities. In this study, we take an in-depth look at which factors influence the firm’s capability for technology-driven business model innovation in the legal industry context. As our empirical context, we have chosen the legal industry, notorious for its risk aversion and for practices that inhibit innovation, but where the focus on digitalization is increasing due to external pressures. We interviewed nine law firms in Norway, representing together the largest share of the country’s legal services market, four of them being traditional law firms and the rest being newly established yet large digital New Law organizations. We find that profitability acts both as an inhibitor of business model innovation for established firms and as a driver for New Law firms. However, the relatively high job satisfaction of Norwegian lawyers in comparison to their US-based counterparts dampens the pull of technological opportunities on business model innovation by making human capital more difficult to acquire by new entrants. Barring an unexpected profitability crisis, digitalization of the Norwegian law sector will not disrupt traditional law firms’ business models. However, New Law firms are accumulating the competences required to compete with the incumbents.
Rootstock increases the physiological defence of tomato plants againstPseudomonas syringaepv.tomatoinfection
Authors: Alfaro-Quezada Juan Felipe , Martínez Juan Pablo , Molinett Sebastian , Valenzuela Miryam , Montenegro Ivan , Ramírez Ingrid , Dorta Fernando , Ávila-Valdés Andrea , Gharbi Emna , Zhou Mingxi , Dailly Hélène , Quinet Muriel , Lutts Stanley , Seeger Michael
Published: January 2023

Climate change has intensified the infection of tomato plants by pathogens such as Pseudomonas syringae pv. tomato (Pst). Rootstocks may increase plant tolerance to leaf phytopathogens. The aim of this study was to evaluate the effects of the tolerant Poncho Negro (R) tomato rootstock on physiological defence and the role of hydrogen sulfide (H2S) in susceptible Limachino (L) tomato plant responses to Pst attack. Ungrafted (L), self-grafted (L/L), and grafted (L/R) plants were infected with Pst. Rootstock increased the concentration of antioxidant compounds including ascorbate in the scion. Tolerant rootstock induced an increase of H2S in the scion, which correlated with enhanced expression of the SlAPX2 gene. A high accumulation of salicylic acid was observed in Pst-inoculated grafted L/L and L/R plants, but this was higher in L/R plants. The increase of H2S during Pst infection was associated with a reduction of ethylene in L/R plants. Our study indicates that the Poncho Negro rootstock reduced the symptoms of bacterial speck disease in the Limachino tomato plants, conferring tolerance to Pst infection. This study provides new knowledge about the impact of rootstock in the defence of tomato plants against leaf pathogens that could be used in sustainable management of tomato cultivation.
The case of HD 106906 debris disc: a binary’s revenge
Authors: Farhat Mohammad A , Sefilian Antranik A , Touma Jihad R
Published: January 2023

Debris disc architecture presents [exo-]planetary scientists with precious clues for processes of planet formation and evolution, including constraints on planetary mass perturbers. This is particularly true of the disc in HD 106906, which in early HST, then follow up polarimetric observations, presented asymmetries and needle-like features that have been attributed to perturbations by a massive, and unusually distant external planetary companion. Here, we revisit the long-term secular dynamical evolution of the HD 106906 disc allowing for the combined gravitational action of the planetary companion and the inner stellar binary which holds the system together. We argue that the binary is strong enough to impose a dynamical break at the disc’s location, resulting in distinctive observational signatures which we render via simulated surface density maps and vertical structure profiles. Within uncertainties on the planet’s orbit, we show that the disc can go from being fully dominated by the inner binary to significantly so, and is hardly ever outside its reach. The extent of binary dominance impacts the disc’s mean eccentricity, a metric which we map as a function of the planet’s semimajor axis and orbital eccentricity, with and without radiation pressure. We can thus constrain the planet’s orbit to ease the tension between evident axisymmetry in the millimeter, and apparent asymmetry in scattered light. We discuss phase space structure, then inclination distribution, arguing for the relevance of our results to a variety of hierarchical systems, as we set the stage for generalizations that allow for disc self-gravity and collisional evolution.
VLBI astrometry on the white dwarf pulsar AR Scorpii
Authors: Jiang Pengfei , Cui Lang , Yang Jun , Zhang Bo , Xu Shuangjing , Shu Fengchun , Jiang Wu , Chen Wen , Li Guanghui , Xia Bo , Weston Stuart , Gulyaev Sergei , Cao Hongmin , Liu Xiang , An Tao
Published: January 2023

AR Scorpii (AR Sco), the only-known radio-pulsing white dwarf binary, shows unusual pulsating emission at the radio, infrared, optical, and ultraviolet bands. To determine its astrometric parameters at the radio band independently, we conducted multi-epoch Very Long Baseline Interferometry (VLBI) phase-referencing observations with the European VLBI Network at 5 GHz and the Chinese VLBI Network plus the Warkworth 30-m telescope (New Zealand) at 8.6 GHz. By using the differential VLBI astrometry, we provide high-precision astrometric measurements on the parallax ($\pi =8.52_{-0.07}^{+0.04}$ mas) and proper motion ($\mu _{\alpha }=9.48_{-0.07}^{+0.04}$ mas yr−1, $\mu _{\delta }=-51.32_{-0.38}^{+0.22}$ mas yr−1). The new VLBI results agree with the optical Gaia astrometry. Our kinematic analysis reveals that the Galactic space velocities of AR Sco are quite consistent with that of both intermediate polars and polars. Combined with the previous tightest VLBI constraint on the size, our parallax distance suggests that the radio emission of AR Sco should be located within the light cylinder of its white dwarf.
Parallelized gene cluster editing illuminates mechanisms of epoxyketone proteasome inhibitor biosynthesis
Authors: Huang Chuan , Zabala Daniel , de los Santos Emmanuel L C , Song Lijiang , Corre Christophe , Alkhalaf Lona M , Challis Gregory L
Published: January 2023

Advances in DNA sequencing technology and bioinformatics have revealed the enormous potential of microbes to produce structurally complex specialized metabolites with diverse uses in medicine and agriculture. However, these molecules typically require structural modification to optimize them for application, which can be difficult using synthetic chemistry. Bioengineering offers a complementary approach to structural modification but is often hampered by genetic intractability and requires a thorough understanding of biosynthetic gene function. Expression of specialized metabolite biosynthetic gene clusters (BGCs) in heterologous hosts can surmount these problems. However, current approaches to BGC cloning and manipulation are inefficient, lack fidelity, and can be prohibitively expensive. Here, we report a yeast-based platform that exploits transformation-associated recombination (TAR) for high efficiency capture and parallelized manipulation of BGCs. As a proof of concept, we clone, heterologously express and genetically analyze BGCs for the structurally related nonribosomal peptides eponemycin and TMC-86A, clarifying remaining ambiguities in the biosynthesis of these important proteasome inhibitors. Our results show that the eponemycin BGC also directs the production of TMC-86A and reveal contrasting mechanisms for initiating the assembly of these two metabolites. Moreover, our data shed light on the mechanisms for biosynthesis and incorporation of 4,5-dehydro-l-leucine (dhL), an unusual nonproteinogenic amino acid incorporated into both TMC-86A and eponemycin.
SMAP design: a multiplex PCR amplicon and gRNA design tool to screen for natural and CRISPR-induced genetic variation
Authors: Develtere Ward , Waegneer Evelien , Debray Kevin , De Saeger Jonas , Van Glabeke Sabine , Maere Steven , Ruttink Tom , Jacobs Thomas B
Published: January 2023

Multiplex amplicon sequencing is a versatile method to identify genetic variation in natural or mutagenized populations through eco-tilling or multiplex CRISPR screens. Such genotyping screens require reliable and specific primer designs, combined with simultaneous gRNA design for CRISPR screens. Unfortunately, current tools are unable to combine multiplex gRNA and primer design in a high-throughput and easy-to-use manner with high design flexibility. Here, we report the development of a bioinformatics tool called SMAP design to overcome these limitations. We tested SMAP design on several plant and non-plant genomes and obtained designs for more than 80–90% of the target genes, depending on the genome and gene family. We validated the designs with Illumina multiplex amplicon sequencing and Sanger sequencing in Arabidopsis, soybean, and maize. We also used SMAP design to perform eco-tilling by tilling PCR amplicons across nine candidate genes putatively associated with haploid induction in Cichorium intybus. We screened 60 accessions of chicory and witloof and identified thirteen knockout haplotypes and their carriers. SMAP design is an easy-to-use command-line tool that generates highly specific gRNA and/or primer designs for any number of loci for CRISPR or natural variation screens and is compatible with other SMAP modules for seamless downstream analysis.
SARS-CoV-2 seroprevalence in workers from a Colombian University Hospital
Authors: Moreno-Medina K , Sáenz Pérez L D , Villar J C , Váquiro Herrera E , Pérez Franco J E , Varón-Vega F A , Guanes Cortés R , Steevens Gualdrón A , Sarmiento Becerra M S
Published: January 2023

Background

Antibody (Ab) tests for SARS-CoV-2 virus allows for the estimation of incidence, level of exposure and duration of immunity acquired by a previous infection. In health workers, the hospital setting might convey a greater risk of infection.

Aims

To describe the frequency of immunoglobulin G (IgG) Abs (IgG-Abs) to the SARS-CoV-2 virus among workers at a third-level university hospital in Colombia.

Methods

In this cross-sectional study, we included medical and non-medical personnel with at least one real-time polymerase chain reaction (RT–PCR)/antigen test between March 2020 and March 2021. In April 2021, an IgG-Ab test against SARS-CoV-2 was conducted for all participants and replicated 2 weeks later in a random sample (10%). The frequency of IgG-Abs is presented based on status (positive/negative) and time elapsed since RT–PCR/antigen test (<3 months, 3–6 months, >6 months).

Results

We included 1021 workers (80% women, median age 34 years (interquartile range 28–42), 73% medical personnel, 23% with previous positive RT–PCR/antigen). The overall seroprevalence was 35% (95% CI 31.6–37.4, 35% in medical and 33% in non-medical personnel). For those with a previous positive RT–PCR/antigen test, the seroprevalence was 90% (<3 months), 82% (3–6 months) and 48% (>6 months). In participants with a previous negative RT–PCR/antigen test, the seroprevalence was 17% (<3 months), 21% (3–6 months) and 29% (>6 months).

Conclusions

High IgG-Ab positivity was found in hospital personnel, regardless of work activities. The prevalence of detectable Abs differed by previous RT–PCR/antigen status and time elapsed since the diagnostic test.
Predictors of combat training attrition in Israel Defense Forces soldiers
Authors: Gendler S , Talmy T , Shapiro M , Tzur D , Kedem R , Landau R , Zubkov K
Published: January 2023

Background

Attrition from combat service carries significant organizational and personal ramifications, but predicting factors associated with attrition remains challenging.

Aims

To evaluate medical and psychosocial factors associated with attrition from basic combat training (BCT) in the Israel Defense Forces (IDF). In addition, we identify subsets of the recruit population which exhibit certain trends in terms of medical corresponding with a high risk of attrition.

Methods

A cross-sectional study of IDF combat trainees undergoing infantry BCT between 2012 and 2017. Data were collected from the soldiers’ electronic medical and administrative records. We used multivariable logistic regression and the SAS® decision-tree tool to analyse key predictive factors for attrition.

Results

A total of 46 472 soldiers enlisted to BCT during the research period. The mean body mass index (BMI) was 21.8 (SD 3.54). The overall attrition rate was 10%. The following factors were associated with attrition from BCT: ethnicity (P < 0.01), BMI (P < 0.01), pre-enlisting motivation score (P < 0.01) and the number of mental health officer visits (P < 0.01). Using a decision-tree model, we found a high attrition rate among soldiers who had >5.2 to primary care physician visits (11% attrition rate versus 3%) or more than 11 sick leave days (59% versus 19%).

Conclusions

This study sheds light on unique measures relating to attrition. Attrition is associated with several demographic and psychosocial factors. Early prediction of motivation and monitoring of healthcare utilization may enable early identification and focused interventions targeting soldiers at high risk for attrition. These findings need to be further translated into actionable directives and further investigations.
Characterization of a Novel Pathogen in Immunocompromised Patients:Elizabethkingia anophelis—Exploring the Scope of Resistance to Contemporary Antimicrobial Agents and β-lactamase Inhibitors
Authors: Yasmin Mohamad , Rojas Laura J , Marshall Steven H , Hujer Andrea M , Cmolik Anna , Marshall Emma , Boucher Helen W , Vila Alejandro J , Soldevila Maxime , Diene Seydina M , Rolain Jean-Marc , Bonomo Robert A
Published: January 2023

Background

Elizabethkingia anophelis is an emerging Gram-negative nonlactose fermenter in the health care setting, where it causes life-threatening infections in immunocompromised patients. We aimed to characterize the molecular mechanisms of antimicrobial resistance and evaluate the utility of contemporary antibiotics with the intent to offer targeted therapy against an uncommonly encountered pathogen.

Methods

Whole-genome sequencing (WGS) was conducted to accurately identify isolate species and elucidate the determinants of β-lactam resistance. Antimicrobial susceptibility testing was performed using broth microdilution and disk diffusion assays. To assess the functional contribution of the major metallo-β-lactamase (MBL) encoding genes to the resistance profile, blaBlaB was cloned into pBCSK(-) phagemid vector and transformed into Escherichia coli DH10B.

Results

WGS identified the organism as E. anophelis. MBL genes blaBlaB-1 and blaGOB-26 were identified, in addition to blaCME-2, which encodes for an extended-spectrum β-lactamase (ESBL). Plasmids were not detected. The isolate was nonsusceptible to all commonly available β-lactams, carbapenems, newer β-lactam β-lactamase inhibitor combinations, and to the combination of aztreonam (ATM) with ceftazidime-avibactam (CAZ-AVI). Susceptibility to the novel siderophore cephalosporin cefiderocol was determined. A BlaB-1 transformant E. coli DH10B isolate was obtained and demonstrated increased minimum inhibitory concentrations to cephalosporins, carbapenems, and CAZ-AVI, but not ATM.

Conclusions

Using WGS, we accurately identified and characterized an extensively drug-resistant E. anophelis in an immunocompromised patient. Rapid evaluation of the genetic background can guide accurate susceptibility testing to better inform antimicrobial therapy selection.
Apoplast-Localized β-Glucosidase Elevates Isoflavone Accumulation in the Soybean Rhizosphere
Authors: Matsuda Hinako , Yamazaki Yumi , Moriyoshi Eiko , Nakayasu Masaru , Yamazaki Shinichi , Aoki Yuichi , Takase Hisabumi , Okazaki Shin , Nagano Atsushi J , Kaga Akito , Yazaki Kazufumi , Sugiyama Akifumi
Published: January 2023

Plant specialized metabolites (PSMs) are often stored as glycosides within cells and released from the roots with some chemical modifications. While isoflavones are known to function as symbiotic signals with rhizobia and to modulate the soybean rhizosphere microbiome, the underlying mechanisms of root-to-soil delivery are poorly understood. In addition to transporter-mediated secretion, the hydrolysis of isoflavone glycosides in the apoplast by an isoflavone conjugate–hydrolyzing β-glucosidase (ICHG) has been proposed but not yet verified. To clarify the role of ICHG in isoflavone supply to the rhizosphere, we have isolated two independent mutants defective in ICHG activity from a soybean high-density mutant library. In the root apoplastic fraction of ichg mutants, the isoflavone glycoside contents were significantly increased, while isoflavone aglycone contents were decreased, indicating that ICHG hydrolyzes isoflavone glycosides into aglycones in the root apoplast. When grown in a field, the lack of ICHG activity considerably reduced isoflavone aglycone contents in roots and the rhizosphere soil, although the transcriptomes showed no distinct differences between the ichg mutants and wild-types (WTs). Despite the change in isoflavone contents and composition of the root and rhizosphere of the mutants, root and rhizosphere bacterial communities were not distinctive from those of the WTs. Root bacterial communities and nodulation capacities of the ichg mutants did not differ from the WTs under nitrogen-deficient conditions either. Taken together, these results indicate that ICHG elevates the accumulation of isoflavones in the soybean rhizosphere but is not essential for isoflavone-mediated plant–microbe interactions.
The gauge-invariant formulation of the local expansion rate driven by the local average density in an inhomogeneous universe
Authors: Tomonaga Masanori , Kasai Masumi , Futamase Toshifumi
Published: January 2023

The Hubble tension casts a blight on the standard cosmology. As a possible solution to the problem, the local variation of the expansion rate has been proposed where the spatial averaging over a finite domain was introduced in order to restore the local Friedmannian behavior in an inhomogeneous cosmology. So far, however, the approaches are limited to the particular choices of the gauges, and it has been unclear whether the results are gauge invariant. In this paper, we present the gauge-invariant formulation of the local expansion rate, which is driven by the spatial average of the gauge-invariant inhomogeneous density. We show that the local cosmological parameters in the finite domain may change from the global parameters, and the relations between them are expressed by the gauge-invariant averaged density.
The Brain Medicine Fellowship: A Competency-Based Training Program to Treat Complex Brain Disorders
Authors: Levitt Sarah , Henri-Bhargava Alex , Hogan David B. , Shulman Kenneth , Mitchell Sara B.
Published: January 2023

Problem

Complex brain disorders involve symptoms in the domains of affect, behavior, and cognition. It is increasingly recognized that there is a need for a novel type of physician who can treat individuals with these conditions in an interdisciplinary fashion to best address their complexity. Few training programs have focused on the education of such practitioners.

Approach

The authors outline the development and practices of the Brain Medicine Fellowship, an innovative, competency-based fellowship program at the University of Toronto Temerty Faculty of Medicine that accepts trainees from multiple brain medicine–related specialty training programs to develop expertise in integrative assessment and treatment of complex brain disorders. The authors describe how brain medicine competencies were generated, the current assessment process, and the seminal clinical experience associated with the fellowship—the Brain Medicine Clinic—and explain how it exemplifies brain medicine in action.

Outcomes

The first fellow was registered from July 2019 to December 2020. As of December 2022, 3 fellows have entered the program, with 3 more anticipated to begin in July 2023. More than 26 supervisors are associated with the fellowship, who offer a diversity of experiences for fellows to choose from in developing their individualized learning plans. The Brain Medicine Fellowship not only fosters the development of a novel type of clinician (a brain medicine specialist) but also is innovative in its educational design as one of the first nonsurgical fellowships to implement competency-based medical education and has resulted in original clinical programming in the form of the Brain Medicine Clinic, which benefits patients and their caregivers.

Next Steps

The development of the Brain Medicine Fellowship continues with competency refinement and translation into entrustable professional activities and constituent milestones. A comprehensive program evaluation will be completed by 2025.
Epidemiology of Merkel cell carcinoma in Tuscany (Italy), 2006–2021
Authors: Fidanzi Cristian , Troaca Silviu Flavius , Fanelli Giuseppe Nicolò , Romanelli Marco , Dini Valentina , Viacava Paolo , Marconcini Riccardo , Morganti Riccardo , D’Erme Angelo Massimiliano , Bagnoni Giovanni , Janowska Agata
Published: January 2023

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that still has a poor prognosis. MCC incidence has increased in recent years worldwide. The aim of our study was to perform an epidemiological retrospective study and to evaluate the impact of MCC clinical and pathological features on overall survival (OS) in a specific geographical area. We retrospectively collected 94 pathology reports from 2006 to 2021 that were present in the pathology archives of the University Hospital of Pisa and of the Hospital of Livorno. Laterality was different according to the site, and almost half of the lesions were T1 and nearly half of the patients had a clinical stage III. We reported a dramatic increase in MCC diagnoses in the last 5 years compared with the previous years, with a crude incidence rate of 1,15/100000 inhabitants, almost doubling the last reported data in Italy. Surgical margins status and ulceration were not related to OS. We have noticed some patients with a rapidly progressing disease and others showing a slow disease progression which should prompt the investigation of specific biomarkers or other features that could elucidate this striking difference in progression-free survival and could potentially identify different subtypes of MCC. Considering the generally low incidence of MCC worldwide, larger cohorts would be necessary to validate our data and to obtain a better prognostic stratification.
Parental Perspectives on the Impact of the COVID-19 Pandemic on Infant, Child, and Adolescent Development
Authors: Raffa Brittany J. , Heerman William J. , Lampkin Jacarra , Perrin Eliana M. , Flower Kori B. , Delamater Alan M. , Yin H. Shonna , Rothman Russell L. , Sanders Lee , Schilling Samantha
Published: January 2023

Objective:

The purpose of this study is to understand how families from diverse sociodemographic backgrounds perceived the impact of the pandemic on the development of their children.

Methods:

We used a multimethod approach guided by Bronfenbrenner's Ecological Systems Theory, which identifies 5 developmental systems (micro, meso, exo, macro, and chrono). Semistructured interviews were conducted in English or Spanish with parents living in 5 geographic regions of the United States between July and September 2021. Participants also completed the COVID-19 Exposure and Family Impact Survey.

Results:

Forty-eight families participated, half of whose preferred language was Spanish, with a total of 99 children ages newborn to 19 years. Most qualitative themes pertained to developmental effects of the microsystem and macrosystem. Although many families described negative effects of the pandemic on development, others described positive or no perceived effects. Some families reported inadequate government support in response to the pandemic as causes of stress and potential negative influences on child development. As context for their infant's development, families reported a variety of economic hardships on the COVID-19 Exposure and Family Impact Survey, such as having to move out of their homes and experiencing decreased income.

Conclusion:

In addition to negative impacts, many parents perceived positive pandemic-attributed effects on their child's development, mainly from increased time for parent-child interaction. Families described economic hardships that were exacerbated by the pandemic and that potentially affect child development and insufficient government responses to these hardships. These findings hold important lessons for leaders who wish to design innovative solutions that address inequities in maternal, family, and child health.
Confounding by Conception Seasonality in Studies of Temperature and Preterm Birth: A Simulation Study
Authors: Huang Mengjiao , Strickland Matthew J. , Richards Megan , Warren Joshua L. , Chang Howard H. , Darrow Lyndsey A.
Published: January 2023

Background:

Seasonal patterns of conception may confound acute associations between birth outcomes and seasonally varying exposures. We aim to evaluate four epidemiologic designs (time-stratified case-crossover, time-series, pair-matched case-control, and time-to-event) commonly used to study acute associations between ambient temperature and preterm births.

Methods:

We conducted simulations assuming no effect of temperature on preterm birth. We generated pseudo-birth data from the observed seasonal patterns of birth in the United States and analyzed them in relation to observed temperatures using design-specific seasonality adjustments.

Results:

Using the case-crossover approach (time-stratified by calendar month), we observed a bias (among 1,000 replicates) = 0.016 (Monte-Carlo standard error 95% CI: 0.015–0.018) in the regression coefficient for every 10°C increase in mean temperature in the warm season (May–September). Unbiased estimates obtained using the time-series approach required accounting for both the pregnancies-at-risk and their weighted probability of birth. Notably, adding the daily weighted probability of birth from the time-series models to the case-crossover models corrected the bias in the case-crossover approach. In the pair-matched case-control design, where the exposure period was matched on gestational window, we observed no bias. The time-to-event approach was also unbiased but was more computationally intensive than others.

Conclusions:

Most designs can be implemented in a way that yields estimates unbiased by conception seasonality. The time-stratified case-crossover design exhibited a small positive bias, which could contribute to, but not fully explain, previously reported associations.
Does the addition of serum antimüllerian hormone concentrations to the Framingham Risk Score and Pooled Cohort Equations improve the prediction of cardiovascular disease?
Authors: Amiri Mina , Ahmadi Narjes , Hadaegh Farzad , Mousavi Maryam , Azizi Fereidoun , Ramezani Tehrani Fahimeh
Published: January 2023

Objective

The current study aimed to examine the added value of serum antimüllerian hormone (AMH) concentration to the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) in predicting the risk of cardiovascular disease (CVD) in women of reproductive age.

Methods

Women 30 years and older were considered eligible for this population-based prospective study. The univariate and multivariate Cox proportional hazard models were used to evaluate the association between the serum concentrations of AMH and the risk of CVD.

Results

In the enhanced model, which integrated AMH into FRS and PCE and was adjusted for family history of premature CVD, AMH showed a significant association with the risk of CVD during a 19-year follow-up of 800 women (hazard ratio, 0.77 [95% CI, 0.60-0.99] and hazard ratio, 0.64 [95% CI, 0.48-0.84], respectively). According to the likelihood-ratio test, the addition of AMH measurements to FRS and PCE could significantly improve the risk prediction of CVD (P = 0.02 and P < 0.001, respectively); however, the integration of this biomarker did not improve the classification of risk categories.

Conclusions

The present findings revealed that the addition of serum AMH concentrations to FRS and PCE could potentially improve the risk prediction of CVD.
Migraine and sleep quality: does the association change in midlife women?
Authors: Faubion Stephanie S. , Ghaith Summer , Kling Juliana M. , Mara Kristin , Enders Felicity , Starling Amaal J. , Kapoor Ekta
Published: January 2023

Objective

The aim of this study was to compare the association between migraine and sleep quality in premenopausal versus perimenopausal women.

Methods

A cross-sectional analysis from the Data Registry on the Experiences of Aging, Menopause and Sexuality was conducted using questionnaire data from premenopausal and perimenopausal women seen at women's health clinics at 3 geographic locations from 2015 to 2021. Sleep quality and duration were assessed with the Pittsburgh Sleep Quality Index. Associations between poor sleep quality (Pittsburgh Sleep Quality Index >5) and self-reported migraine history (Y/N) were evaluated using a multivariable logistic regression model, adjusting for body mass index, anxiety, depression, and vasomotor symptoms.

Results

Of 2,067 women (mean age 43.2 years) included in the analysis, 594 (28.7%) reported a migraine history. Women were mostly white (92.2%), partnered (75.1%), and educated (86% with at least some college); 46.5% (n = 962) were premenopausal, 53.5% (n = 1,105) were perimenopausal, and 71.2% met the criteria for poor sleep. In univariate analysis, migraine history predicted poor sleep in both premenopausal and perimenopausal women (P = 0.005 and P = 0.004, respectively). However, in multivariable analysis, migraine history remained associated with poor sleep in premenopausal women (P = 0.044), but not in perimenopausal women (P = 0.46).

Conclusions

A migraine history was associated with poor sleep in premenopausal women. The relationship in perimenopausal women seemed to be influenced by confounding factors that are more prevalent during the menopause transition and are known to affect the frequency of migraine and sleep disturbances, such as anxiety, depression, and vasomotor symptoms. These conditions may need to be the focus of management in migraineurs with sleep disturbances during the menopause transition.
Revisiting malignant hypertension: rationale and design of the ‘HAMA cohort’, on behalf of the ESH working group ‘hypertension and the kidney’
Authors: Boulestreau Romain , Lorthioir Aurélien , Persu Alexandre , Sarafidis Pantelis , Cremer Antoine , Tharaux Pierre-Louis , Rubin Sebastien , Maier Benjamin , Mazighi Mikael , Paques Michel , Bonnin Sophie , Dreau Herve , Debeugny Stéphane , Halimi Jean Michel , Gosse Philippe
Published: January 2023

Background:

Malignant hypertension has not disappeared and is associated with a poor prognosis. Yet, so far, it has received limited attention from the medical community. Guidelines are mainly based on expert consensus and low quality evidences.

Method:

We set up a prospective, multicenter, observational cohort of patients with malignant hypertension. We collect at admission medical history, demographic data, ongoing treatment, clinical parameters, symptoms, care pathways, target organ status and at discharge and during follow up treatment administrated, adverse events, blood pressure level, target organ status. We aim to recruit 500 patients with malignant hypertension in 5 years, with a 5-year follow-up. Our primary objective is to assess the 5 years prognosis of these patients.

Discussion:

The HAMA (Hypertension Arterielle MAligne, meaning malignant hypertension) registry aims to describe the epidemiology and to assess the prognosis of malignant hypertension in a contemporary multidisciplinary cohort, with emphasis on the diversity of current management and care pathway among the different medical specialties. It may help improving our pathophysiological knowledge, and pave the way to update the definition of this particular form of hypertension. The multidisciplinary network developed in the wake of this project is expected to facilitate the set up therapeutic trials, laying the ground for evidence-based recommendations.
Radiation Protection among South African Diagnostic Radiographers—A Mixed Method Study
Authors: Lewis Shantel , Downing Charlene , Hayre Christopher M.
Published: January 2023

Worldwide, radiographers’ radiation protection practices vary. In South Africa, evidence of diagnostic radiographers’ suboptimal radiation protection practices has been reported, but the reasons for these practices and suggestions to improve practices were lacking. Therefore, this study explored radiation protection among South African diagnostic radiographers. This study used an explanatory, sequential, mixed-method approach. Data were collected in three phases. Phase I, the quantitative phase, used an online questionnaire and respondents from Phase I interested in participating in Phase II, the qualitative phase, were interviewed, yielding 13 in-depth semi-structured telephone interviews. In Phase III, eight radiography managers co-constructed change strategies to optimize radiation protection in South Africa in two focus group interviews. Radiation protection was suboptimal despite diagnostic radiographers having a good attitude, subjective norm and perceived behavioral control toward radiation protection and optimal radiation protection knowledge. Varying attitudes to radiation protection, lack of resources, and support from radiography management and healthcare teams contributed to suboptimal radiation protection practices. Radiography managers suggested increasing radiation protection awareness, ameliorating the diminished stature of the radiographer in the healthcare team, and increasing the availability of optimal quality resources. South African diagnostic radiographers’ radiation protection knowledge was optimal, but the implementation of radiation protection varied and was influenced by multiple factors. A radiation protection culture supported by management is advocated to optimize radiation protection. However, ultimately radiation protection practices are incumbent on the individual radiographers’ choice to practice radiation protection.
Mechanisms of continual efferocytosis by macrophages and its role in mitigating atherosclerosis
Authors: Kumar Dhananjay , Pandit Rajan , Yurdagul Arif
Published: January 2023

Atherosclerotic cardiovascular disease is the leading cause of death worldwide. Rupture-prone atheromas that give rise to myocardial infarction and stroke are characterized by the presence of a necrotic core and a thin fibrous cap. During homeostasis, cellular debris and apoptotic cells are cleared quickly through a process termed “efferocytosis”. However, clearance of apoptotic cells is significantly compromised in many chronic inflammatory diseases, including atherosclerosis. Emerging evidence suggests that impairments in efferocytosis drive necrotic core formation and contribute significantly to plaque vulnerability. Recently, it has been appreciated that successive rounds of efferocytosis, termed “continual efferocytosis”, is mechanistically distinct from single efferocytosis and relies heavily on the metabolism and handling of apoptotic cell-derived cargo. In vivo, selective defects in continual efferocytosis drive secondary necrosis, impair inflammation resolution, and worsen atherosclerosis. This Mini Review focuses on our current understanding of the cellular and molecular mechanisms of continual efferocytosis and how dysregulations in this process mediate nonresolving inflammation. We will also discuss possible strategies to enhance efferocytosis when it fails.
Capsular Bag Insufficiency Disorder: A Perspective
Authors: Darian-Smith Erica , Safran Steven G. , Coroneo Minas T
Published: January 2023

To look at the pathophysiology behind and devise a classification system for the causes of zonular apparatus-capsular bag (ZACB) insufficiency. We will also discuss dystrophic bag syndrome, providing clinical cases and addressing where it lies on the ZACB spectrum. There has been interest in the emergence of in-the-bag IOL subluxation, the prevalence of which is increasing. There has also been a recent report of ’dead bag syndrome’ which we believe is part of the same disease spectrum. We put these phenomena into perspective and provide classification system based on the possible causes of what we have termed ZACB insufficiency. The basic aspects of capsular bag-IOL-ocular pathophysiology are summarised with a focus on functional aspects and the consequences for IOL fastening. Within this framework, dystrophic bag syndrome is a form of primary capsular ZACB insufficiency. The contribution of factors such as intraocular drugs may suggest a reconsideration of agents used and their mode of application.
Comparison of biometry measurements and intraocular lens power prediction between 2 SS‐OCT–based biometers
Authors: Sorkin Nir , Zadok Tal , Barrett Graham D. , Chasid Otzem , Abulafia Adi
Published: January 2023

Purpose:

To evaluate the agreement in biometry measurements and intraocular lens (IOL) power prediction between the Eyestar 900 and the IOLMaster 700.

Setting:

Institutional.

Design:

Retrospective comparative study.

Methods:

Patients were evaluated before cataract surgery using both devices on the same visit. Axial length, anterior and posterior keratometry, anterior chamber depth, corneal diameter (CD), central corneal thickness, and lens thickness were recorded by both devices. The agreement in measurements and in IOL power calculations was evaluated using the Barrett Universal II (BU-II) formula with either predicted or measured posterior keratometry.

Results:

In total, 402 eyes of 402 consecutive patients were included. The mean age was 72.0 ± 9.2 years. Clinically, mean differences in measured variables were small, albeit slightly larger for posterior flat and steep keratometry (0.43 diopters [D] and 0.42 D, respectively). The measurement correlation and agreement between the devices were good for all variables with slightly lower agreement in CD measurements. Consistent bias was seen in measurements of posterior flat and steep keratometry. Good agreement was also found in anterior and posterior astigmatism measurements. Good IOL power calculation agreement was found using either predicted posterior keratometry (95% limits of agreement [LoA] of −0.40 to +0.30 D) or measured posterior keratometry (95% LoA of −0.45 to +0.40 D). The agreement was within ±0.5 D in 394 eyes (98.0%) using predicted posterior keratometry and in 386 eyes (96.0%) using measured posterior keratometry.

Conclusions:

The Eyestar 900 and the IOLMaster 700 show strong agreement in biometry measurements and IOL power prediction by the BU-II formula using either standard or total corneal keratometry and can be used interchangeably.
Decrease in in vivo coagulant potential of emicizumab in a patient with hemophilia A and inhibitor complicated with infectious mononucleosis
Authors: Furukawa Shoko , Ogiwara Kenichi , Yada Koji , Takeyama Masahiro , Niino Tomomi , Shima Midori , Keiji Nogami
Published: January 2023

Emicizumab prophylaxis significantly reduces bleeding episodes in patients with hemophilia A (PwHA). There is little information on coagulant potentials in emicizumab-treated PwHA with infection, however. We encountered an emicizumab-treated PwHA with inhibitor, complicated with Epstein–Barr virus-associated infectious mononucleosis (IM) in phase 1/2 study (ACE001JP/ACE002JP). Although it was a typical clinical course of IM, activated partial thromboplastin time was mildly prolonged but rotational thromboelastometry revealed severely impaired coagulant potential. The blood concentration of emicizumab decreased moderately in the low concentration range, resulting in an increased risk of bleeding and possibly leading to severe ileocecal bleeds requiring coil embolization. The blood concentrations of factors IX/X little decreased and antiemicizumab antibodies did not develop, however. After the influence by IM resolved, his coagulant potentials gradually recovered with the recovery of emicizumab concentration, and parameters by global coagulation assays improved. An IM case for emicizumab-treated PwHA may need to monitor using global coagulation assays.
Psychological complications among patients with congenital bleeding disorders
Authors: Asad Fatemeh , Jahangarad Sara , Dorgalaleh Akbar
Published: January 2023

Congenital bleeding disorders (CBDs), including inherited platelet function disorders and rare and common bleeding disorders, are a heterogeneous group of bleeding disorders with a wide range of clinical presentations, including psychological complications. Due to the chronic nature of CBDs, psychological complications are relatively common in these patients, which can affect treatment adherence, quality of life, and even the frequency of bleeding episodes. Chronic pain causes many psychological problems in CBDs, disrupting their social interactions, affecting all aspects of their lives, including their emotional functioning and behavior, and eventually leading to social exclusion. About one-third of patients with severe hemophilia A suffer from anxiety, 64% from depression, and 60% from other minor psychological complications such as withdrawal/depression, anxiety/depression, attention problems, and emotional problems. Anxiety, depression, and uncontrolled pain interfere with treatment adherence. For this reason, psychological interventions are needed in people with CBDs. Psychological interventions increase quality of life and treatment adherence. Therefore, early recognition of psychological complications in CBD patients may increase treatment adherence, leading to a reduction in bleeding episodes and thus an improvement in quality of life.
Cangrelor for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia: it is not so easy
Authors: Godier Anne , Boucebci Karim-John , Delhaye Nathalie , Gendron Nicolas , Achouh Paul , Hamada Sophie Rym
Published: January 2023

Anticoagulation management for cardiopulmonary bypass (CPB) is challenging in patients with acute heparin-induced thrombocytopenia (HIT). The strategy of combining cangrelor intraoperatively with heparin for CPB anticoagulation is of increasing interest but exposes to specific unresolved problems.

We report the case of a patient requiring surgical pulmonary embolectomy for pulmonary embolism at the very acute phase of HIT, with a high titre of anti-PF4/heparin antibodies and severe thrombocytopenia. For CPB management, cangrelor was administered in combination with heparin prescribed and monitored as usual. Surgery was successfully performed, but postoperatively, the patient developed a new thrombotic event. We discussed the specific problems associated with such strategy, including the dose of cangrelor and its monitoring, the management of the cell-saver, the risk of heparin rebound and the risk of platelet transfusion. These issues must be addressed before considering the combination of cangrelor and unfractionated heparin as a standard of care for CBP.
Factor VII Padua in Iran: clinical and laboratory findings of three unrelated patients
Authors: Shams Mahmood , Hassani Saeed , Dorgalaleh Akbar , Zamani Fatemeh , Ahmadi Abbas
Published: January 2023

The congenital factor VII (FVII) deficiency with an estimated incidence of one per 300 000 is the most common rare congenital bleeding disorder. The heterogeneous clinical pictures, including asymptomatic to life-threatening manifestations, are seen in patients with FVII deficiency. A variety of gene variants throughout the FVII (F7) gene have been reported so far. In this setting, very rare FVII Padua polymorphism provokes an interesting condition in which results of prothrombin time and FVII activity are different based on the thromboplastin sources used in these tests. The current study aimed to report the phenotype and genotyping of patients with Padua variant. During the workup of the laboratory for FVII deficiency for diagnosis of FVII Padua, all patients with FVII deficiency who had prolonged prothrombin time, normal activated partial thromboplastin time, and variable FVII activity results using different sources of thromboplastin were included. Demographic data and clinical findings were recorded. For the molecular study, the F7 gene sequencing was performed using the Sanger sequencing technique. Five patients with FVII Padua and a history of mild-to-moderate bleeding, including easy bruising, epistaxis, gingivorrhagia, and bleeding after surgical challenges (including dental extraction and tonsillectomy), were detected during the study. DNA sequencing revealed a heterozygote CGG to CAG (Arg364Gln) variant in exon 9 at nucleotide position 1091, consistent with the genetic variant of FVII Padua. Timely diagnosis of FVII Padua is vital to avoid unnecessary exposure of patients to replacement therapy.