bluuebunny/crossref_metadata_2025 huggingface dataset:
Cecal volvulus as a rare complication of internal hernia after Roux-en-Y gastric bypass: a case report and literature review
Authors: Heck Marvin , Kensing Benjamin C , Ismael Hishaam N
Published: April 2024

This case report describes a rare instance of cecal volvulus resulting from an internal hernia through Petersen’s space, occurring 20 years after Roux-en-Y gastric bypass surgery, marking it as the second such case in English literature. An 81-year-old female presented with symptoms of bowel obstruction, and imaging findings concerning for cecal volvulus. Emergency surgery revealed necrotic bowel due to an internal hernia, necessitating a right hemicolectomy, with subsequent successful anastomosis and hernia defect closure. The incidence of internal hernias post-gastric bypass is notable, emphasizing the critical need for surgical vigilance. This case underscores the importance of considering internal hernias in differential diagnoses for bowel obstruction in post-bariatric surgery patients, highlighting the life-saving role of prompt surgical intervention in the management of cecal volvulus complications.
Sigmoid stenosis caused by diverticulosis mimicking advanced colorectal cancer
Authors: Shumarova Svetlana , Koichev Anton , Sokolov Manol
Published: April 2024

Stenosis is a rare complication of acute diverticulitis, difficult to differentiate from colon cancer. We present a 63-year-old woman with right lumbar pain radiating to the back. A sigmoid stenosis was detected by magnetic resonance imaging. Three biopsies were performed, all of which were negative for malignancy. From CT images with data of circumferentially thickened intestinal wall along 6 cm, stenosing the lumen enlarged regional lymph nodes. A sigmoid resection was performed and the results of histological examination showed complicated diverticulitis of the large intestine with exacerbation, abscending and spread of the inflammatory process with involvement of the pericolic tissues. Given the high risk of developing a malignant process in patients with acute diverticulitis and the slightest doubt should be followed by surgical treatment.
Integration of nitrate and abscisic acid signaling in plants
Authors: Xu Yiran , Qi Shengdong , Wang Yong , Jia Jingbo
Published: April 2024

To meet the demands of the new Green Revolution and sustainable agriculture, it is important to develop crop varieties with improved yield, nitrogen use efficiency, and stress resistance. Nitrate is the major form of inorganic nitrogen available for plant growth in many well-aerated agricultural soils, and acts as a signaling molecule regulating plant development, growth, and stress responses. Abscisic acid (ABA), an important phytohormone, plays vital roles in integrating extrinsic and intrinsic responses and mediating plant growth and development in response to biotic and abiotic stresses. Therefore, elucidating the interplay between nitrate and ABA can contribute to crop breeding and sustainable agriculture. Here, we review studies that have investigated the interplay between nitrate and ABA in root growth modulation, nitrate and ABA transport processes, seed germination regulation, and drought responses. We also focus on nitrate and ABA interplay in several reported omics analyses with some important nodes in the crosstalk between nitrate and ABA. Through these insights, we proposed some research perspectives that could help to develop crop varieties adapted to a changing environment and to improve crop yield with high nitrogen use efficiency and strong stress resistance.
A probabilistic graphical model for assessing equivocal evidence
Authors: Taroni Franco , Garbolino Paolo , Bozza Silvia
Published: April 2024

The Bayes’ theorem can be generalized to account for uncertainty on reported evidence. This has an impact on the value of the evidence, making the computation of the Bayes factor more demanding, as discussed by Taroni, Garbolino, and Bozza (2020). Probabilistic graphical models can however represent a suitable tool to assist the scientist in their evaluative task. A Bayesian network is proposed to deal with equivocal evidence and its use is illustrated through examples.
Potential climates and habitability on Gl 514 b: a super-Earth exoplanet with high eccentricity
Authors: Biasiotti L , Simonetti P , Vladilo G , Ivanovski S , Damasso M , Sozzetti A , Monai S
Published: April 2024

The recently discovered super-Earth Gl 514 b, orbiting a nearby M0.5-1.0 star at 7.6 pc, is one of the best benchmark exoplanets for understanding the potential climate states of eccentric planets. The elongated (e = 0.45$^{+0.15}_{-0.14}$) orbit of Gl 514 b, which only partially lies in the Conservative Habitable Zone, suggests a dynamically young system, where the spin-orbit tidal synchronization may not have yet occurred up to the present time. In the present work, we use a seasonal-latitudinal energy balance model, EOS-ESTM, to explore the potential impact of both constrained and unconstrained planetary, orbital, and atmospheric parameters on the Gl 514 b habitability, mapped in terms of surface temperature. We test three distinct CO2-dominated atmospheres by varying the CH4 concentration values (0 per cent, 0.1 per cent, and 1 per cent) and the total surface pressure. As a general trend, we find that habitable conditions are favoured by high-CH4 and high-pressure regimes. Habitability also increases for high-axis obliquities (at least until the appearance of an icebelt), long-rotation periods, and high-ocean fractional coverage. If the ocean fraction is low, then also the argument of periastron becomes relevant. Our results are robust against changes of the continental distribution. Thus, we conclude that Gl 514 b can potentially maintain temperate surface conditions with modest seasonal temperature variations under a wide variety of planetary, orbital, and atmospheric conditions. Despite no transit have been detected yet, the results found in this work should motivate the community to invest time in future observations.
Probing primordial black holes at high redshift with future gravitational wave detectors
Authors: Marcoccia Paolo , Nardini Germano , Pieroni Mauro
Published: April 2024

We analyse the detection prospects for potential Primordial Black Hole Binary (PBHB) populations buried in the Stellar-Origin Black Hole Binary (SOBHB) population inferred by the LVK collaboration. We consider different PBHB population scenarios and several future Gravitational Wave (GW) detectors. To separate the PBHB component from the SOBHB one, we exploit the prediction that the PBHB merger rate does not decline as fast as the SOBHB one at high redshift. However, only a tiny fraction of PBHB events may be resolved individually, and the sub-threshold events may yield an undetectable Stochastic GW Background (SGWB). For this reason, we determine the statistical significance of the PBHB contributions in the number of resolvable events seen in future Earth-based detectors and the SGWB measured at LISA. We quantify them in the limit that SOBHB population uncertainties are small, as one may optimistically expect at the time that future detectors will operate. In general, we find the synergy between these probes will consistently help assess whether or not a sizeable PBHB population is present.
A High-Coverage Mesolithic Aurochs Genome and Effective Leveraging of Ancient Cattle Genomes Using Whole Genome Imputation
Authors: Erven Jolijn A M , Scheu Amelie , Verdugo Marta Pereira , Cassidy Lara , Chen Ningbo , Gehlen Birgit , Street Martin , Madsen Ole , Mullin Victoria E
Published: April 2024

Ancient genomic analyses are often restricted to utilizing pseudohaploid data due to low genome coverage. Leveraging low-coverage data by imputation to calculate phased diploid genotypes that enables haplotype-based interrogation and single nucleotide polymorphism (SNP) calling at unsequenced positions is highly desirable. This has not been investigated for ancient cattle genomes despite these being compelling subjects for archeological, evolutionary, and economic reasons. Here, we test this approach by sequencing a Mesolithic European aurochs (18.49×; 9,852 to 9,376 calBCE) and an Early Medieval European cow (18.69×; 427 to 580 calCE) and combine these with published individuals: two ancient and three modern. We downsample these genomes (0.25×, 0.5×, 1.0×, and 2.0×) and impute diploid genotypes, utilizing a reference panel of 171 published modern cattle genomes that we curated for 21.7 million (Mn) phased SNPs. We recover high densities of correct calls with an accuracy of >99.1% at variant sites for the lowest downsample depth of 0.25×, increasing to >99.5% for 2.0× (transversions only, minor allele frequency [MAF] ≥ 2.5%). The recovery of SNPs correlates with coverage; on average, 58% of sites are recovered for 0.25× increasing to 87% for 2.0×, utilizing an average of 3.5 million (Mn) transversions (MAF ≥2.5%), even in the aurochs, despite the highest temporal distance from the modern reference panel. Our imputed genomes behave similarly to directly called data in allele frequency-based analyses, for example consistently identifying runs of homozygosity >2 Mb, including a long homozygous region in the Mesolithic European aurochs.
Comparative Analysis of Maternal Gene Expression Patterns Unravels Evolutionary Signatures Across Reproductive Modes
Authors: Kagan Ferenc , Hejnol Andreas
Published: April 2024

Maternal genes have a pivotal role in regulating metazoan early development. As such their functions have been extensively studied since the dawn of developmental biology. The temporal and spatial dynamics of their transcripts have been thoroughly described in model organisms and their functions have been undergoing heavy investigations. Yet, less is known about the evolutionary changes shaping their presence within diverse oocytes. Due to their unique maternal inheritance pattern, a high degree is predicted to be present when it comes to their expression. Insofar only limited and conflicting results have emerged around it. Here, we set out to elucidate which evolutionary changes could be detected in the maternal gene expression patterns using phylogenetic comparative methods on RNAseq data from 43 species. Using normalized gene expression values and fold change information throughout early development we set out to find the best-fitting evolutionary model. Through modeling, we find evidence supporting both the high degree of divergence and constraint on gene expression values, together with their temporal dynamics. Furthermore, we find that maternal gene expression alone can be used to explain the reproductive modes of different species. Together, these results suggest a highly dynamic evolutionary landscape of maternal gene expression. We also propose a possible functional dichotomy of maternal genes which is influenced by the reproductive strategy undertaken by examined species.
Towards parsimonious generative modeling of RNA families
Authors: Calvanese Francesco , Lambert Camille N , Nghe Philippe , Zamponi Francesco , Weigt Martin
Published: April 2024

Generative probabilistic models emerge as a new paradigm in data-driven, evolution-informed design of biomolecular sequences. This paper introduces a novel approach, called Edge Activation Direct Coupling Analysis (eaDCA), tailored to the characteristics of RNA sequences, with a strong emphasis on simplicity, efficiency, and interpretability. eaDCA explicitly constructs sparse coevolutionary models for RNA families, achieving performance levels comparable to more complex methods while utilizing a significantly lower number of parameters. Our approach demonstrates efficiency in generating artificial RNA sequences that closely resemble their natural counterparts in both statistical analyses and SHAPE-MaP experiments, and in predicting the effect of mutations. Notably, eaDCA provides a unique feature: estimating the number of potential functional sequences within a given RNA family. For example, in the case of cyclic di-AMP riboswitches (RF00379), our analysis suggests the existence of approximately 1039 functional nucleotide sequences. While huge compared to the known <4000 natural sequences, this number represents only a tiny fraction of the vast pool of nearly 1082 possible nucleotide sequences of the same length (136 nucleotides). These results underscore the promise of sparse and interpretable generative models, such as eaDCA, in enhancing our understanding of the expansive RNA sequence space.
Multivalent DNAzyme agents for cleaving folded RNA
Authors: Dubovichenko Mikhail V , Batsa Michael , Bobkov Gleb A , Vlasov Gleb S , El-Deeb Ahmed A , Kolpashchikov Dmitry M
Published: April 2024

Multivalent recognition and binding of biological molecules is a natural phenomenon that increases the binding stability (avidity) without decreasing the recognition specificity. In this study, we took advantage of this phenomenon to increase the efficiency and maintain high specificity of RNA cleavage by DNAzymes (Dz). We designed a series of DNA constructs containing two Dz agents, named here bivalent Dz devices (BDD). One BDD increased the cleavage efficiency of a folded RNA fragment up to 17-fold in comparison with the Dz of a conventional design. Such an increase was achieved due to both the improved RNA binding and the increased probability of RNA cleavage by the two catalytic cores. By moderating the degree of Dz agent association in BDD, we achieved excellent selectivity in differentiating single-base mismatched RNA, while maintaining relatively high cleavage rates. Furthermore, a trivalent Dz demonstrated an even greater efficiency than the BDD in cleaving folded RNA. The data suggests that the cooperative action of several RNA-cleaving units can significantly improve the efficiency and maintain high specificity of RNA cleavage, which is important for the development of Dz-based gene knockdown agents.
TTSBBC: triplex target site biomarkers and barcodes in cancer
Authors: Ylagan Maya , Xu Qi , Kowalski Jeanne
Published: April 2024

The technology of triplex-forming oligonucleotides (TFOs) provides an approach to manipulate genes at the DNA level. TFOs bind to specific sites on genomic DNA, creating a unique intermolecular triple-helix DNA structure through Hoogsteen hydrogen bonding. This targeting by TFOs is site-specific and the locations TFOs bind are referred to as TFO target sites (TTS). Triplexes have been observed to selectively influence gene expression, homologous recombination, mutations, protein binding, and DNA damage. These sites typically feature a poly-purine sequence in duplex DNA, and the characteristics of these TTS sequences greatly influence the formation of the triplex. We introduce TTSBBC, a novel analysis and visualization platform designed to explore features of TTS sequences to enable users to design and validate TTSs. The web server can be freely accessed at https://kowalski-labapps.dellmed.utexas.edu/TTSBBC/.
Perceptions of Heated Tobacco Products (HTPs) Versus Cigarettes and e-Cigarettes in Relation to Likelihood of Trying HTPs or Suggesting HTPs to Those who Smoke Cigarettes
Authors: Duan Zongshuan , Berg Carla J , Bar-Zeev Yael , Abroms Lorien C , Wang Yan , Khayat Amal , Cui Yuxian , LoParco Cassidy R , Levine Hagai
Published: April 2024

Introduction

Heated tobacco products (HTPs), like IQOS, are marketed as innovative, stylish, harm-reduction products distinct from cigarettes and e-cigarettes. Research is needed to better understand how adults who are newly introduced to HTPs perceive them relative to cigarettes and e-cigarettes, and the impact of these perceptions on use outcomes.

Aims and Methods

We analyzed 2021 cross-sectional survey data from 1914 adults who never used HTPs from the United States and Israel, two countries where IQOS has unique histories and markets. Exploratory factor analysis examined perceptions of HTPs (vs. cigarettes and e-cigarettes) across 12 perception measures (eg, innovative, trendy, harmful, addictive). Multivariable linear regression examined these factors in relation to self-reported likelihood to: (1) “try HTPs in the next year” (1 = not–7 = extremely) and (2) “suggest IQOS to a friend who smokes cigarettes” (1 = not–5 = very), controlling for demographics and past-month cigarette and e-cigarette use (10.1% dual use, 15.4% cigarette-only, 5.7% e-cigarette-only, 68.8% neither).

Results

Four factors were identified: HTPs’ health and utility (“health-utility”) and design and appeal (“design-appeal”) versus cigarettes and versus e-cigarettes, separately. More favorable perceptions of HTP versus e-cigarette design-appeal (B = 0.30, 95% CI = 0.18, 0.41) were associated with greater likelihood to try HTPs. More favorable perceptions of HTP versus cigarette design-appeal (B = 0.38, 95% CI = 0.26, 0.51) and health-utility (B = 0.25, 95% CI = 0.13, 0.36), and HTP versus e-cigarette design-appeal (B = 0.32, 95% CI = 0.20, 0.45) were associated with greater likelihood to suggest HTPs to smokers.

Conclusions

Monitoring perceptions of HTPs versus cigarettes and e-cigarettes is critical given the role of such perceptions in HTP use and their population-level impact.

Implications

This study examined the relationship of perceptions of HTPs relative to cigarettes and e-cigarettes, with regard to adults’ self-reported likelihood to use HTP or to suggest HTPs to those who smoke cigarettes. Favorable perceptions of HTPs’ design and appeal versus e-cigarettes correlated with greater likelihood to try HTPs. Favorable perceptions of HTPs’ design and appeal, as well as health and utility, versus cigarettes and e-cigarettes correlated with greater likelihood to suggest HTPs to those who smoke. Findings underscore the need for ongoing surveillance of HTP marketing and consumer perceptions to inform regulatory efforts and estimate the population-level impact of HTPs and other tobacco products.
Mapping the evidence of novel plant-based foods: a systematic review of nutritional, health, and environmental impacts in high-income countries
Authors: Nájera Espinosa Sarah , Hadida Genevieve , Jelmar Sietsma Anne , Alae-Carew Carmelia , Turner Grace , Green Rosemary , Pastorino Silvia , Picetti Roberto , Scheelbeek Pauline
Published: April 2024

Context

Shifting from current dietary patterns to diets rich in plant-based (PB) foods and lower in animal-based foods (ABFs) is generally regarded as a suitable strategy to improve nutritional health and reduce environmental impacts. Despite the recent growth in supply of and demand for novel plant-based foods (NPBFs), a comprehensive overview is lacking.

Objectives

This review provides a synthesis of available evidence, highlights challenges, and informs public health and environmental strategies for purposeful political decision-making by systematically searching, analyzing, and summarizing the available literature.

Data Sources

Five peer-reviewed databases and grey literature sources were rigorously searched for publications.

Data Extraction

Study characteristics meeting the inclusion criteria regarding NPBF nutrient composition and health and environmental outcomes in high-income countries were extracted.

Data analysis

Fifty-seven peer-reviewed and 36 grey literature sources were identified; these were published in 2016–2022. NPBFs typically have substantially lower environmental impacts than ABFs, but the nutritional contents are complex and vary considerably across brands, product type, and main primary ingredient. In the limited evidence on the health impacts, shifts from ABFs to PB meats were associated with positive health outcomes. However, results were mixed for PB drinks, with links to micronutrient deficiencies.

Conclusion

If carefully selected, certain NPBFs have the potential to be healthier and nutrient-rich alternatives to ABFs and typically have smaller environmental footprints. More disaggregated categorization of various types of NPBFs would be a helpful step in guiding consumers and key stakeholders to make informed decisions. To enable informed policymaking on the inclusion of NPBFs in dietary transitions as part of a wider net-zero and health strategy, future priorities should include nutritional food standards, labelling, and subdivisions or categorizations of NPBFs, as well as short- and long-term health studies evaluating dietary shifts from ABFs to NPBFs and standardized environmental impact assessments, ideally from independent funders.
Combination of Antistaphylococcal β-Lactam With Standard Therapy Compared to Standard Therapy Alone for the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia: A Post Hoc Analysis of the CAMERA2 Trial Using a Desirability of Outcome Ranking Approach
Authors: Petersiel Neta , Davis Joshua S , Meagher Niamh , Price David J , Tong Steven Y C ,   Combination Antibiotics for MEthicillin Resistant Staphylococcus aureus (CAMERA2) Study Group, Lye David C , Yahav Dafna , Sud Archana , Robinson J Owen , Nelson Jane , Archuleta Sophia , Roberts Matthew A , Cass Alan , Paterson David L , Foo Hong , Paul Mical , Guy Stephen D , Tramontana Adrian R , Walls Genevieve B , McBride Stephen , Bak Narin , Ghosh Niladri , Rogers Benjamin A , Ralph Anna P , Davies Jane , Ferguson Patricia E , Dotel Ravindra , McKew Genevieve L , Gray Timothy J , Holmes Natasha E , Smith Simon , Warner Morgyn S , Kalimuddin Shirin , Young Barnaby E , Runnegar Naomi , Andresen David N , Anagnostou Nicholas A , Johnson Sandra A , Chatfield Mark D , Cheng Allen C , Fowler Vance G , Howden Benjamin P , Meagher Niamh , Price David J , van Hal Sebastiaan J , Sullivan Matthew V N O
Published: April 2024

Background

Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints.

Methods

We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an antistaphylococcal β-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy.

Results

Participants assigned combination therapy had a 54.5% (95% confidence interval [CI], 48.9%–60.1%; P = .11) probability and a 1.2-fold odds (95% CI, .95–1.50; P = .12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI, 49.5%–61.7%) and 55.3% (95% CI, 49.2%–61.4%) probability of having a worse outcome than participants in the standard treatment group, respectively.

Conclusions

When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a β-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteremia.
Masqueraders Around Disaster: Clinical Features of Scrub Typhus in Fukushima, Japan
Authors: Narita Masashi , Monma Naota , Chiba Kazuki , Suzuki Rie , Fujita Shohei , Hoshino Chisho , Nakamura Kiwamu , Sekikawa Yoshiyuki , Ikeda Hiroshi , Inoue Minoru , Shimbo Takuro , Yamamoto Seigo , Ando Shuji , Takada Nobuhiro , Fujita Hiromi
Published: April 2024

Background

Scrub typhus (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment.

Methods

We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan.

Results

Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55).

Conclusions

Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common.
A GDSL-motif Esterase/Lipase Affects Wax and Cutin Deposition and Controls Hull-Caryopsis Attachment in Barley
Authors: Campoli Chiara , Eskan Mhmoud , McAllister Trisha , Liu Linsan , Shoesmith Jennifer , Prescott Alan , Ramsay Luke , Waugh Robbie , McKim Sarah M
Published: April 2024

The cuticle covering aerial organs of land plants is well known to protect against desiccation. Cuticles also play diverse and specialized functions, including organ separation, depending on plant and tissue. Barley shows a distinctive cuticular wax bloom enriched in β-diketones on leaf sheaths, stem nodes and internodes and inflorescences. Barley also develops a sticky surface on the outer pericarp layer of its grain fruit leading to strongly adhered hulls, ‘covered grain’, important for embryo protection and seed dispersal. While the transcription factor-encoding gene HvNUDUM (HvNUD) appears essential for adherent hulls, little is understood about how the pericarp cuticle changes during adhesion or whether changes in pericarp cuticles contribute to another phenotype where hulls partially shed, called ‘skinning’. To that end, we screened barley lines for hull adhesion defects, focussing on the Eceriferum (= waxless, cer) mutants. Here, we show that the cer-xd allele causes defective wax blooms and compromised hull adhesion, and results from a mutation removing the last 10 amino acids of the GDS(L) [Gly, Asp, Ser, (Leu)]-motif esterase/lipase HvGDSL1. We used severe and moderate HvGDSL1 alleles to show that complete HvGDSL1 function is essential for leaf blade cuticular integrity, wax bloom deposition over inflorescences and leaf sheaths and pericarp cuticular ridge formation. Expression data suggest that HvGDSL1 may regulate hull adhesion independently of HvNUD. We found high conservation of HvGDSL1 among barley germplasm, so variation in HvGDSL1 unlikely leads to grain skinning in cultivated barley. Taken together, we reveal a single locus which controls adaptive cuticular properties across different organs in barley.
Multiple genetic variants at the SLC30A8 locus affect local super‐enhancer activity and influence pancreatic β‐cell survival and function
Authors: Hu Ming , Kim Innah , Morán Ignasi , Peng Weicong , Sun Orien , Bonnefond Amélie , Khamis Amna , Bonàs‐Guarch Sílvia , Froguel Philippe , Rutter Guy A.
Published: April 2024

Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), at the C‐terminus of the secretory granule‐enriched zinc transporter, ZnT8. Although this protein‐coding variant was previously thought to be the sole driver of T2D risk at this locus, recent studies have provided evidence for lowered expression of SLC30A8 mRNA in protective allele carriers. In the present study, we examined multiple variants that influence SLC30A8 allele‐specific expression. Epigenomic mapping has previously identified an islet‐selective enhancer cluster at the SLC30A8 locus, hosting multiple T2D risk and cASE associations, which is spatially associated with the SLC30A8 promoter and additional neighboring genes. Here, we show that deletion of variant‐bearing enhancer regions using CRISPR‐Cas9 in human‐derived EndoC‐βH3 cells lowers the expression of SLC30A8 and several neighboring genes and improves glucose‐stimulated insulin secretion. While downregulation of SLC30A8 had no effect on beta cell survival, loss of UTP23, RAD21, or MED30 markedly reduced cell viability. Although eQTL or cASE analyses in human islets did not support the association between these additional genes and diabetes risk, the transcriptional regulator JQ1 lowered the expression of multiple genes at the SLC30A8 locus and enhanced stimulated insulin secretion.
PPAR‐γ regulates the polarization of M2 macrophages to improve the microenvironment for autologous fat grafting
Authors: Zhang Ya‐An , Li Fang‐Wei , Dong Yun‐Xian , Xie Wen‐Jie , Wang Hai‐Bin
Published: April 2024

The unpredictable survival rate of autologous fat grafting (AFG) seriously affects its clinical application. Improving the survival rate of AFG has become an unresolved issue in plastic surgery. Peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) regulates the adipogenic differentiation of adipocytes, but the functional mechanism in AFG remains unclear. In this study, we established an animal model of AFG and demonstrated the superior therapeutic effect of PPAR‐γ regulation in the process of AFG. From day 3 after fat grafting, the PPAR‐γ agonist rosiglitazone group consistently showed better adipose integrity, fewer oil cysts, and fibrosis. Massive macrophage infiltration was observed after 7 days. At the same time, M2 macrophages begin to appear. At day 14, M2 macrophages gradually became the dominant cell population, which suppressed inflammation and promoted revascularization and fat regeneration. In addition, transcriptome sequencing showed that the differentially expressed genes in the Rosiglitazone group were associated with the pathways of adipose regeneration, differentiation, and angiogenesis; these results provide new ideas for clinical treatment.
Recommendations for managing patients with hypothyroidism
Authors: Hardy Cheyenne
Published: April 2024

The American Thyroid Association recommends levothyroxine monotherapy for treating hypothyroidism, a condition that affects 4.6% of the US population. However, up to 15% of these patients experience residual symptoms despite normalized thyroid-stimulating hormone levels, and may benefit from an endocrinology referral. Additional high-quality studies are needed to further evaluate patient preferences, as well as to investigate long-term outcomes of combination therapy and continue exploring therapeutic options for hypothyroidism management among specific patient subgroups.
Glucagon-like peptide 1 agonists for type 2 diabetes, weight loss, or both?
Authors: Keedy Chelsea A. , Bland Christopher M.
Published: April 2024

Glucagon-like peptide 1 agonists (GLP1s) and the novel glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 agonist are effective drugs for reducing A1C and weight in patients with type 2 diabetes. However, clinicians may find it difficult to discern which drug to prescribe in specific clinical scenarios. This article discusses evidence-based clinical use of these drugs.
FDA Issues Warning About ‘Gas Station Heroin’
Authors: Roush Karen
Published: April 2024

The highly addictive dietary supplement mimics opioid effects.
Armed Conflicts and Increasing Violence Against Health Care
Authors: Molyneux Jacob
Published: April 2024

The Geneva Conventions remain an invaluable, universal standard.
An Introduction to Implementing and Conducting the Study
Authors: Capili Bernadette , Anastasi Joyce K.
Published: April 2024

Editor's note: This is the 21st article in a series on clinical research by nurses. The series is designed to be used as a resource for nurses to understand the concepts and principles essential to research. Each column will present the concepts that underpin evidence-based practice—from research design to data interpretation. To see all the articles in the series, go to https://links.lww.com/AJN/A204.
Reconnecting
Authors: Sackin Henry
Published: April 2024

A briefly renewed friendship, 60 years later
Evaluation of Sleep in Pregnant Inpatients Compared With Outpatients
Authors: Panelli Danielle M. , Miller Hayley E. , Simpson Samantha L. , Hurtado Janet , Shu Chi-Hung , Boncompagni Ana C. , Chueh Jane , Barwick Fiona , Carvalho Brendan , Sultan Pervez , Aghaeepour Nima , Druzin Maurice L.
Published: April 2024

OBJECTIVE:

To evaluate whether antepartum hospitalization was associated with differences in sleep duration or disrupted sleep patterns.

METHODS:

This was a prospective cohort study with enrollment of pregnant people aged 18–55 years with singleton gestations at 16 weeks of gestation or more between 2021 and 2022. Each enrolled antepartum patient was matched by gestational age to outpatients recruited from obstetric clinics at the same institution. Participants responded to the ISI (Insomnia Severity Index) and wore actigraph accelerometer watches for up to 7 days. The primary outcome was total sleep duration per 24 hours. Secondary outcomes included sleep efficiency (time asleep/time in bed), ISI score, clinical insomnia (ISI score higher than 15), short sleep duration (less than 300 minutes/24 hours), wakefulness after sleep onset, number of awakenings, and sleep fragmentation index. Outcomes were evaluated with multivariable generalized estimating equations adjusted for body mass index (BMI), sleep aid use, and insurance type, accounting for gestational age correlations. An interaction term assessed the joint effects of time and inpatient status.

RESULTS:

Overall 58 participants were included: 18 inpatients and 40 outpatients. Inpatients had significantly lower total sleep duration than outpatients (mean 4.4 hours [SD 1.6 hours] inpatient vs 5.2 hours [SD 1.5 hours] outpatient, adjusted β=−1.1, 95% CI, −1.8 to −0.3, P=.01). Awakenings (10.1 inpatient vs 13.8, P=.01) and wakefulness after sleep onset (28.3 inpatient vs 35.5 outpatient, P=.03) were lower among inpatients. There were no differences in the other sleep outcomes, and no interaction was detected for time in the study and inpatient status. Inpatients were more likely to use sleep aids (39.9% vs 12.5%, P=.03).

CONCLUSION:

Hospitalized pregnant patients slept about 1 hour/day less than outpatients. Fewer awakenings and reduced wakefulness after sleep onset among inpatients may reflect increased use of sleep aids in hospitalized patients.
The Impact of the Apolipoprotein E Genotype on Cardiovascular Disease and Cognitive Disorders
Authors: McMaster Matthew W. , Shah Avisha , Kangarlu John , Cheikhali Ryan , Frishman William H. , Aronow Wilbert S.
Published: April 2024

Apolipoprotein E (ApoE) plays a critical role in cholesterol transport and protection against the development of atherosclerotic cardiovascular disease (ASCVD). Humans have 3 prevalent isoforms of ApoE: apolipoprotein E2 (ApoE2), apolipoprotein E3 (ApoE3), and apolipoprotein E4 (ApoE4). The E4 allele has been associated with higher ASCVD risk. While E4 patients do have higher cholesterol levels, they do not have enough to account for the substantially elevated ASCVD risk relative to E2 and E3 patients. ASCVD risk calculators would underestimate the true effect of E4 if the difference was caused entirely by a difference in cholesterol level. This article reviews the function of ApoE in atherosclerosis, and how each isoform functions differently. We review what is known about the molecular mechanisms through which ApoE prevents endothelial dysfunction and damage, how ApoE stimulates macrophage efflux of cholesterol from atherogenic lesions, and the ways in which ApoE decreases inflammation throughout atherosclerosis. The impact of ApoE on Alzheimer’s disease and a discussion of why it is possibly unrelated to ASCVD prevention are included. Clinical applications to hyperlipidemia management and ASCVD prevention in specific patient populations are discussed.
Thymoquinone ameliorates symptoms of Parkinson’s disease in a 6-OHDA rat model by downregulation of miR-204-3p
Authors: Pala Mukaddes , Meral Ismail , Pala Acikgoz Nilgün , Mengi Murat , Erdim Gokce Meryem Betül , Unsal Rumeysa , Polat Yalcin , Akbas Fahri , Gorucu Yilmaz Senay
Published: April 2024

microRNAs (miRNAs) play a significant role in the pathophysiology of Parkinson’s disease. In this study, we evaluated the neuroprotective effect of thymoquinone on the expression profiles of miRNA and cognitive functions in the 6-hydroxydopamine (6-OHDA)-induced Parkinson’s model. Male adult Wistar albino rats (200–230 g, n = 36) were randomly assigned to six groups: Sham, thymoquinone (10 mg/kg, p.o.), 6-OHDA, 6-OHDA + thymoquinone (10 mg/kg), 6-OHDA + thymoquinone (20 mg/kg), and 6-OHDA + thymoquinone (50 mg/kg). Behavioral changes were detected using the open field and the elevated plus maze tests. The mature 728 miRNA expressions were evaluated by miRNA microarray (GeneChip miRNA 4.0). Ten miRNAs were selected (rno-miR-212-5p, rno-miR-146b-5p, rno-miR-150-5p, rno-miR-29b-2-5p, rno-miR-126a-3p, rno-miR-187-3p, rno-miR-34a-5p, rno-miR-181d-5p, rno-miR-204-3p, and rno-miR-30c-2-3p) and confirmed by real-time PCR. Striatum samples were stained with hematoxylin-eosin to determine the effect of dopaminergic lesions. One-way ANOVA test and independent sample t-test were used for statistical analyses. rno-miR-204-3p was upregulated at 6-OHDA and downregulated at the 50 mg/kg dose of thymoquinone. In conclusion, thymoquinone at a dose of 50 mg/kg ameliorates symptoms of Parkinson’s disease in a 6-OHDA rat model by downregulation of miR-204-3p. Also, the results showed that thymoquinone can improve locomotor activity and willing exploration and decreased anxiety. Therefore, thymoquinone can be used as a therapeutic agent.
Endophthalmitis after cataract surgery and effect of different intracameral antibiotic regimes in Sweden 2011-2017: national registry study
Authors: Friling Emma , Bro Tomas , Lundström Mats , Montan Per
Published: April 2024

Purpose:

To study the incidence, predictive factors, etiology, and visual consequences of postoperative endophthalmitis (PE) in relation to 3 intracameral (IC) antibiotic regimes.

Setting:

Swedish National Cataract Register entries from 2011 through 2017.

Design:

Observational retrospective study.

Methods:

PE incidence, influencing factors, bacteriology, and visual outcome were analyzed regarding the 3 major prophylactic IC protocols.

Results:

The overall incidence of PE was 0.023% or 177 cases in 764 513 cataract procedures. Analyzed per IC regime, the rates of PE were 0.024% (126 cases in 514 916 surgeries) for cefuroxime, 0.020% (25 cases in 122 340 surgeries) for moxifloxacin, and 0.017% (20 cases in 121 045 surgeries) for combined cefuroxime–ampicillin. Incidences were not statistically significantly different from one another. Gram-positive bacteria caused 89.0% of culture positive cases. Enterococci as pathogens were significantly more frequent with IC cefuroxime than with moxifloxacin, P = .006, or cefuroxime–ampicillin, P < .001, while streptococci other than enterococci were more common with moxifloxacin than with cefuroxime, P < .001. Bacterial susceptibility to the given antibiotics was demonstrated in 21.3% of PE cases treated with cefuroxime, which was statistically significantly lower than proportions found with cefuroxime–ampicillin, 60.0%, P = .015, or with moxifloxacin, 88.2%, P < .001. Visual outcome worse than 20/200 was similar in the groups ranging from 42.0% to 53.7%.

Conclusions:

No statistically significant differences in PE incidence or visual outcome results between treatment groups were demonstrated. However, differences in etiology and bacterial sensitivity were found between the prophylactic IC treatments.
Refining glaucoma diagnosis and treatment in cataract surgery candidates: contribution of preoperative OCT retinal nerve fiber layer
Authors: Goldberg Mordechai , Zadok David , Assayag Elishai , Ziv-On Elad , Zaitar Rand , Porat-Rein Adi , Brosh Kobi , Weill Yishay , Abulafia Adi
Published: April 2024

Purpose:

To evaluate the clinical significance of preoperative spectral domain optical coherence tomography (OCT) of the retinal nerve fiber layer (RNFL) thickness in identifying glaucoma and better managing patients scheduled for routine cataract surgery.

Setting:

Department of Ophthalmology, Shaare Zedek Medical Center, Jerusalem, Israel.

Design:

Retrospective cohort study.

Methods:

Consecutive patients scheduled for cataract surgery were enrolled from February 2022 to August 2022. Participants underwent routine OCT RNFL studies which were evaluated by a glaucoma specialist. Findings were compared with those of preoperative fundus biomicroscopic examinations conducted by the referring ophthalmologist. The main outcomes were the incidence of newly detected glaucoma based on OCT RNFL findings and the consequent changes in patient management.

Results:

In total, 486 patients met the inclusion criteria of whom 112 (23%) had abnormal RNFL. 31 patients (6.4%) had abnormal OCT RNFL findings attributed to comorbidities other than glaucoma, and 81 patients (16.7%) were suspected to have glaucoma based on their OCT RNFL findings, from which 44 patients (9%) were newly diagnosed with glaucoma or as glaucoma suspects, resulting in management modifications that included routine glaucoma follow-up (25 patients, 5.1%), initiation of intraocular pressure-lowering treatment (12 patients, 2.5%), and conversion to combined cataract-glaucoma surgery (7 patients, 1.4%).

Conclusions:

OCT RNFL for cataract surgery candidates proved valuable in detecting glaucoma that had not been revealed by standard fundus biomicroscopic examination. The additional information provided by OCT RNFL can potentially enhance patient management and optimize outcomes.
A Longitudinal Multiinstitutional Study of Vulvar Lichen Sclerosus: From Childhood to Perimenopause
Authors: Di Giuseppe Jacopo , Delli Carpini Giovanni , Giannella Luca , Terenzi Tomas , Fichera Mariasole , Ragno Federica , Campanati Anna , Boero Veronica , Caia Carlotta , Pesce Elisa , Vercellini Paolo , Gardella Barbara , Dominoni Mattia , Spinillo Arsenio , Sopracordevole Francesco , Clemente Nicolò , Del Fabro Anna , Rossi Riccardo , Corazza Monica , Borghi Alessandro , Martinello Ruby , Greco Pantaleo , Rizzo Giuseppe , Criscuolo Anna Angela , Mappa Ilenia , Matteini Enrico , Botti Elisabetta , Campione Elena , Bianchi Luca , Ciavattini Andrea
Published: April 2024

Objective

The main outcome of this study was the evaluation of clinical characteristics, comorbidities, and therapeutic approaches in patients with vulvar lichen sclerosus (VLS) aged from childhood to perimenopause. Secondly, it was intended to compare these characteristics according to the menarchal status.

Methods

Patients less than 45 years of age with a diagnosis of VLS from January 2002 to June 2022 in 10 referral centers were included in this retrospective longitudinal study. The univariate analysis compared the dependent variables according to menarchal status.

Results

One hundred eighty-six patients met the inclusion criteria. At diagnosis, between 25% and 40% of premenarchal patients reported signs related to subepithelial hemorrhage. A significantly greater presence of bleeding (p < .005), easy bruising (p = .028), fissures (p = .008), petechiae/splinter hemorrhages (p < .001), and bleeding/blistering or open sores (p = .011) was observed in premenarchal patients with respect to the postmenarchal group. The perineum (p = .013) and the perianal region (p < .001) were significantly more involved in the premenarchal group. Topical calcineurin inhibitors were more used in the premenarchal population (p = .004), whereas vitamin E oil and moisturizers were more used in the postmenarchal population (p = .047).

Conclusions

Vulvar lichen sclerosus is a chronic condition that can cause vulvar changes that result in severe morbidity and affects sexual function and quality of life, even before menopause. Vulvar lichen sclerosus continues to be misdiagnosed in this population. This may lead to an average delay from symptom onset to diagnosis. Evaluating clinical manifestations of VLS in premenarchal and postmenarchal age allowed us to find different clinical characteristics between the 2 periods suggestive of the diagnosis.
Efficacy of a Triticum vulgare Extract as a Treatment of Cervical Ectropion: A Prospective Observational Cohort Study
Authors: Manna Paolo , Gallo Alessandra , Bitonti Giovanna , Venturella Roberta , Di Carlo Costantino
Published: April 2024

Objectives

To assess the effectiveness of a topical treatment for cervical ectropion with vaginal ovules containing aqueous extract of Triticum vulgare.

Methods

Prospective observational cohort study conducted between November 2020 and November 2022 at the colposcopy clinics of 2 different hospitals. Sexually active patients with a colposcopic diagnosis of cervical ectropion, awaiting ablative procedure, were included in the study and prescribed medical therapy with vaginal T. vulgare ovules (group 1) or wait-and-see therapy (group 2). At both enrollment and 2-month follow-up, a symptomatologic evaluation recording the intensity of postcoital bleeding, leucorrhea, and dyspareunia was performed with a Visual Analog Scale (VAS) questionnaire, and a colposcopic examination was performed, calculating the size of the ectropion area.

Results

A total of 116 patients (58 in group 1 and 58 in group 2) were included. Topical treatment with vaginal ovules containing aqueous extract of T. vulgare for 2 months resulted in significant decrease of symptoms related to cervical ectropion and significant reduction of the size of the ectropion area.

Conclusions

Our results support the efficacy of topical treatment with vaginal ovules containing aqueous extract of T. vulgare for symptomatic cervical ectropion; our study also suggests that expectant management, despite being widely practiced, seems to lead to a worsening of the natural history of ectropion.
Fibroblast growth factor 23 is pumping iron: C-terminal-fibroblast growth factor 23 cleaved peptide and its function in iron metabolism
Authors: Courbon Guillaume , David Valentin
Published: April 2024

Purpose of review

Iron deficiency regulates the production of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) but also its cleavage, to generate both intact (iFGF23) and C-terminal (Cter)-FGF23 peptides. Novel studies demonstrate that independently of the phosphaturic effects of iFGF23, Cter-FGF23 peptides play an important role in the regulation of systemic iron homeostasis. This review describes the complex interplay between iron metabolism and FGF23 biology.

Recent findings

C-terminal (Cter) FGF23 peptides antagonize inflammation-induced hypoferremia to maintain a pool of bioavailable iron in the circulation. A key mechanism proposed is the down-regulation of the iron-regulating hormone hepcidin by Cter-FGF23.

In this manuscript, we discuss how FGF23 is produced and cleaved in response to iron deficiency, and the principal functions of cleaved C-terminal FGF23 peptides. We also review possible implications anemia of chronic kidney disease (CKD).