bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of collagenase Clostridium histolyticum in men with ventral curvatures: an updated series
Authors: Larson Henry , Savage Joshua , Brearton Klint , Warner Riley , Ziegelmann Matthew , Kohler Tobias , Trost Landon
Published: December 2023

Background

The efficacy and safety of collagenase Clostridium histolyticum (CCH) have been demonstrated in the treatment of men with Peyronie’s disease (PD); however, the pivotal clinical trials excluded men with ventral penile curvature.

Aim

The study sought to evaluate outcomes of CCH treatment in men with ventral curvatures secondary to PD.

Methods

Men with PD treated with CCH were identified from a prospective database. Patients received up to 4 series of CCH injections using a progressively modified protocol over time. Results were compared between those with baseline ventral vs nonventral penile curvatures.

Outcomes

Changes in penile curvature, Peyronie’s Disease Questionnaire scores, International Index of Erectile Function scores, nonstandardized assessments, and adverse events.

Results

A total of 560 men with PD (85 ventral curvature, 475 nonventral curvature) were included in the analysis. Baseline median curvature was 60.0° (interquartile range, 48.8°-75.0°) in the ventral cohort and 65.0° (interquartile range, 45.0°-80.0°) in the nonventral cohort. Median change from baseline penile curvature was −25.0° in the ventral cohort vs −24.0° in the nonventral cohort (P = .08, between-group comparison), which corresponded to curvature reductions of 44.7% and 33.6%, respectively (P = .03). In the subset of patients who completed CCH treatment (ie, received 8 injections or discontinued early because of patient satisfaction with curvature reduction), median change from baseline was −35.0° in the ventral cohort vs −25.0° in the nonventral cohort (P < .05); median percent improvement was 48.3% and 37.5%, respectively (P = .11). Median change from baseline in Peyronie’s Disease Questionnaire and International Index of Erectile Function domain scores and adverse events were similar between cohorts, with the exception of possibly higher hematoma rates in the nonventral group (50% vs 37%; P = .05). No urethral injuries were sustained in either cohort.

Clinical Implications

Data support the use of CCH for the treatment of ventral as well as nonventral penile curvatures in men with PD.

Strengths and Limitations

Study strengths are the inclusion of a general clinical population of men with PD, the prospective design, and the relatively large series of men with ventral curvature. Limitations include the single-center and observational nature of the study.

Conclusion

CCH was safe and effective in the treatment of both ventral and nonventral penile curvatures in men with PD.
Urine immunofixation electrophoresis and serum free light chain analyses benefit diagnosis of multiple myeloma in orthopedic patients with normal serum total proteins, creatinine, calcium, and hemoglobin
Authors: Jia Zhongwei , Xia Jinxing , Lu Qiong
Published: December 2023

Background

A substantial number of patients with multiple myeloma (MM) who have bone destruction are initially admitted into the orthopedic service at the hospital. However, routine laboratory testing usually fails to identify these patients, thus delaying optimal therapy. Therefore, there is a clear medical need for early diagnosis of MM in these patients.

Methods

Between 2019 and 2021, 42 patients receiving treatment for orthopedic conditions had normal hemoglobin (Hb), total protein (TP), albumin (ALB), creatinine (CREA), and blood calcium (Ca) levels before their surgical procedure(s) but were subsequently pathologically confirmed to have MM, based on their presenting orthopedic symptoms. During the same period, 52 patients with orthopedic conditions were pathologically excluded from the diagnosis of MM and were recruited into our control group. Serum free light chain (sFLC) testing was performed in 94 consecutive patients in the orthopedic service using Siemens N Latex FLC kits. The levels of Hb, TP, ALB, CREA, and Ca were also measured. All 42 patients with MM were divided into group A (n = 25: κ proliferation) and group B (n = 17: λ proliferation) by the pathology department.

Results

There were no significant differences in levels of Hb, TP, ALB, CREA, and Ca between group A and group B and the control group. However, the sFLC κ/λ ratio of group A and B was also significantly different from that of the control group (P < .001). The results of serum immunofixation electrophoresis (IFE) testing demonstrated negative results in 14 cases (58.3%) in group A and 4 cases (25.0%) in group B.

Conclusions

Some patients with orthopedic conditions who do not have typical MM laboratory results, such as those with abnormal Hb, TP, ALB, CREA, and Ca levels before their operation(s), actually have MM. MM should be highly suspected in patients with unexplained bone lesions and with an abnormal sFLC κ/λ ratio. Further tissue or bone marrow biopsy is needed in these patients even if serum and urine IFE results are negative and light chain ratio is normal.
Switching Style towards Ease in a Medieval Textbook of Medicine: Revison of Constantine the African’s Pantegni, Theorica in Twelfth-Century Manuscripts
Authors: Kaltio Outi
Published: December 2023

The Pantegni of Constantine the African (d. by 1098/9) was the first ever comprehensive medical textbook written in Latin. It was translated and modified from an Arabic original in Salerno and in the monastery of Monte Cassino in south Italy. This article demonstrates that a large-scale stylistic revision of the Pantegni, or more precisely of its section Theorica, was carried out in the first half of the twelfth century at the latest. The existence of the revised version suggests there was a desire for Constantine’s translation to meet altered expectations and practical needs. Based on collation of a chapter from Book V and additional sample passages in both the standard version and the revised version of the Theorica, it is argued that the latter was compiled in order to simplify and clarify Constantine’s expression and make his train of thought as lucid as possible.
Given by Lady Joan Ingoldisthorpe: The Caxton Cordyal (1479) from a Library at Pott Chapel (Pott Shrigley, Cheshire), c. 1493, Identified
Authors: Harding Robert J D
Published: December 2023

This paper describes a copy of William Caxton’s printing of the Cordyal of the four last and final thinges (Westminster: 24 March 1479) recently acquired by the Brotherton Library, University of Leeds. It bears a gift inscription from Lady Joan Ingoldisthorpe (d. 1494) to the Downes Chantry Chapel at Pott Shrigley, Cheshire, which possessed a small library of books, including several others printed by Caxton, previously known only through an early inventory. It discusses the book’s ownership and provenance, the reception of Caxton’s printings beyond London, the possible patronage of his edition of John Tiptoft, earl of Worcester’s translations of Cicero and Buonaccorso da Montemagno printed by Caxton in 1481, and the early provenance of the unique copy of the Sarum Missal printed in Paris by Guillaume Maynyal for Caxton in 1487 owned by the National Trust at Lyme Park in Cheshire.
Counterfeiting Periodicals in Seventeenth-Century Europe: Engravings, Music, and Binding of the Dutch Mercure galant in the Austrian National Library (1678–1679)
Authors: Schuwey Christophe
Published: December 2023

This article analyses in detail a collection of seven counterfeit volumes of the Mercure galant—the main cultural periodical and principal propaganda machine of the late seventeenth-century—kept in the Austrian National Library in Vienna. These counterfeits, which have never been studied before, reveal the efforts and strategies undertaken by the Dutch bookseller Abraham Wolfgang to copy the text, engravings and music in each monthly issue. Analysing this set also reveals the financial and material constraints faced by the Parisian publishers of the original Mercure. Finally, the binding and bookplate reveal important clues regarding the international distribution and readership of Le Mercure galant, as well as its transformation from a periodical to an historical account.
Stellar rotations and the disentanglement of the Galactic thin and thick discs
Authors: da Silva M P , Alves-Brito A , do Nascimento J D
Published: December 2023

The kinematics, mean α-elements, and ages of the stars reveal two distinct disc populations observed in the Solar neighbourhood. Although several studies have been carried out to characterize abundances of chemical elements and kinematic identifications in these populations, there are few studies that dealt with the analysis of stellar rotation and characteristics of populations focused on low-mass stars of the F and G types. In this work, we propose a new approach to classify stellar populations from the thin and thick disc for F and G dwarf stars by relating chemical abundance and rotation (v sin i) of these stars in the rotational–chemical–plane (v sin i–[α/Fe]–[Fe/H] plot). Our results show that the two rotational-chemical sequences disentangled, high- and low-[α/Fe] components, present properties (α-enhanced, ages, kinematics, space velocity gradients, local density ratio) closely linked to the stars of the chemically and kinematically defined as thin and thick disc components. This study has an impact on calibrations that relate ages to rotation (gyro-chronology) as well as age to chemical abundances (chemochronology), as well as sheds light on the understanding of the processes of Galactic disc formation.
A survey of molecular line emission towards Herbig Be star V645 Cyg
Authors: Gimalieva A D , Kirsanova M S , Salii S V , Kalenskii S V , Olofsson A O H , Topchieva A P
Published: December 2023

We present a survey of molecular line emission towards the molecular cloud surrounding Herbig Be star V645 Cyg. The survey was performed with the 20-m Onsala space telescope at 3 and 4 mm. We detected emission lines of 33 molecules and their isotopologues from diatomic molecules to four COMs up to seven atoms. Using detected lines, we estimated molecular column densities and abundances relative to molecular hydrogen in local thermodynamic equilibrium (LTE) approximation for all molecules except for methanol, for which we obtained physical parameters using a non-LTE model. Moreover, in the basement of the non-LTE model of methanol line emission, we consider that there is a weak maser effect in the additional spectral component of 51–40 E methanol line at 84.521 GHz. We compared the molecular abundances with values found in several astrochemical templates: molecular clouds, hot cores, and photodissociation regions, and found that signatures of these different types can be found towards V645 Cyg. We also obtained maps of the cloud in several molecular emission lines. The peaks of CO and CH3OH emission are shifted from the direction of the star, but the CS, HCO+, HNC, HCN, and N2H+ emission peaks are observed directly towards the star. Exploring the gas kinematics around V645 Cyg, we found that velocity structure in the ambient molecular cloud on the scale ≈1.6–2.0 pc is not the same as within ≈0.5 pc found previously by other authors.
AGN-driven outflows in the OH absorber galaxy IRAS 19154+2704
Authors: Hekatelyne C , Storchi-Bergmann Thaisa , Riffel Rogemar A , Kharb Preeti , Cassanta Claudia M , Robinson Andrew , Sales Dinalva A
Published: December 2023

We present a two-dimensional study of the gas distribution, excitation, and kinematics of the OH absorber galaxy IRAS 19154+2704 using Gemini Multi-Object Spectrograph integral field unit observations. Its continuum image shows a disturbed morphology indicative of a past or ongoing interaction. The ionized gas emission presents two kinematic components: a narrow (σ ≲ 300 km s−1) component that may be tracing the gas orbiting in the galaxy potential and a broad (σ ≳ 500 km s−1) component, which is produced by an active galactic nucleus (AGN)-driven outflow, with velocities reaching −500 km s−1, which may exceed the escape velocity of the galaxy. The emission-line ratios and Baldwin–Phillips–Terlevich diagrams confirm that the gas excitation in the inner ∼2 kpc is mainly due to the AGN, while in regions farther away, a contribution from star formation is observed. We estimate a mass-outflow rate of $\dot{M}_{\rm out}=4.0\pm 2.6$ M⊙ yr−1 at a distance of 850 pc from the nucleus. The corresponding outflow kinetic power, $\dot{E}_{\rm out} = (2.5\pm 1.6)\times 10^{42}$ erg s−1, is only 3 × 10−4 Lbol (the AGN luminosity), but the large mass-outflow rate, if kept for an ∼10 Myr AGN life cycle, will expel ≈108 M⊙ in ionized gas alone. This is the sixth of a series of papers in which we have investigated the kinematics of ultra-luminous infrared galaxies, most of which are interacting galaxies showing OH megamasers. IRAS 19154 shows the strongest signatures of an active AGN, supporting an evolutionary scenario: interactions trigger AGN that fully appears in the most advanced stages of the interaction.
Semi-reference based cell type deconvolution with application to human metastatic cancers
Authors: Lu Yingying , Chen Qin M , An Lingling
Published: December 2023

Bulk RNA-seq experiments, commonly used to discern gene expression changes across conditions, often neglect critical cell type-specific information due to their focus on average transcript abundance. Recognizing cell type contribution is crucial to understanding phenotype and disease variations. The advent of single-cell RNA sequencing has allowed detailed examination of cellular heterogeneity; however, the cost and analytic caveat prohibits such sequencing for a large number of samples. We introduce a novel deconvolution approach, SECRET, that employs cell type-specific gene expression profiles from single-cell RNA-seq to accurately estimate cell type proportions from bulk RNA-seq data. Notably, SECRET can adapt to scenarios where the cell type present in the bulk data is unrepresented in the reference, thereby offering increased flexibility in reference selection. SECRET has demonstrated superior accuracy compared to existing methods using synthetic data and has identified unknown tissue-specific cell types in real human metastatic cancers. Its versatility makes it broadly applicable across various human cancer studies.
Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression
Authors: Appin Christina L , Hong Chibo , Suwala Abigail K , Hilz Stephanie , Mathur Radhika , Solomon David A , Smirnov Ivan V , Stevers Nicholas O , Shai Anny , Wang Albert , Berger Mitchel S , Chang Susan M , Phillips Joanna J , Costello Joseph F
Published: December 2023

Background

The TERT promoter mutation (TPM) is acquired in most IDH-wildtype glioblastomas (GBM) and IDH-mutant oligodendrogliomas (OD) enabling tumor cell immortality. Previous studies on TPM clonality show conflicting results. This study was performed to determine whether TPM is clonal on a tumor-wide scale.

Methods

We investigated TPM clonality in relation to presumed early events in 19 IDH-wildtype GBM and 10 IDH-mutant OD using 3-dimensional comprehensive tumor sampling. We performed Sanger sequencing on 264 tumor samples and deep amplicon sequencing on 187 tumor samples. We obtained tumor purity and copy number estimates from whole exome sequencing. TERT expression was assessed by RNA-seq and RNAscope.

Results

We detected TPM in 100% of tumor samples with quantifiable tumor purity (219 samples). Variant allele frequencies (VAF) of TPM correlate positively with chromosome 10 loss in GBM (R = 0.85), IDH1 mutation in OD (R = 0.87), and with tumor purity (R = 0.91 for GBM; R = 0.90 for OD). In comparison, oncogene amplification was tumor-wide for MDM4- and most EGFR-amplified cases but heterogeneous for MYCN and PDGFRA, and strikingly high in low-purity samples. TPM VAF was moderately correlated with TERT expression (R = 0.52 for GBM; R = 0.65 for OD). TERT expression was detected in a subset of cells, solely in TPM-positive samples, including samples equivocal for tumor.

Conclusions

On a tumor-wide scale, TPM is among the earliest events in glioma evolution. Intercellular heterogeneity of TERT expression, however, suggests dynamic regulation during tumor growth. TERT expression may be a tumor cell-specific biomarker.
Developing a computable phenotype for glioblastoma
Authors: Yan Sandra , Melnick Kaitlyn , He Xing , Lyu Tianchen , Moor Rachel S F , Still Megan E H , Mitchell Duane A , Shenkman Elizabeth A , Wang Han , Guo Yi , Bian Jiang , Ghiaseddin Ashley P
Published: December 2023

Background

Glioblastoma is the most common malignant brain tumor, and thus it is important to be able to identify patients with this diagnosis for population studies. However, this can be challenging as diagnostic codes are nonspecific. The aim of this study was to create a computable phenotype (CP) for glioblastoma multiforme (GBM) from structured and unstructured data to identify patients with this condition in a large electronic health record (EHR).

Methods

We used the University of Florida (UF) Health Integrated Data Repository, a centralized clinical data warehouse that stores clinical and research data from various sources within the UF Health system, including the EHR system. We performed multiple iterations to refine the GBM-relevant diagnosis codes, procedure codes, medication codes, and keywords through manual chart review of patient data. We then evaluated the performances of various possible proposed CPs constructed from the relevant codes and keywords.

Results

We underwent six rounds of manual chart reviews to refine the CP elements. The final CP algorithm for identifying GBM patients was selected based on the best F1-score. Overall, the CP rule “if the patient had at least 1 relevant diagnosis code and at least 1 relevant keyword” demonstrated the highest F1-score using both structured and unstructured data. Thus, it was selected as the best-performing CP rule.

Conclusions

We developed and validated a CP algorithm for identifying patients with GBM using both structured and unstructured EHR data from a large tertiary care center. The final algorithm achieved an F1-score of 0.817, indicating a high performance, which minimizes possible biases from misclassification errors.
Responses to Real-World and Hypothetical E-Cigarette Flavor Bans Among US Young Adults Who Use Flavored E-Cigarettes
Authors: Tam Jamie , Jimenez-Mendoza Evelyn , Buckell John , Sindelar Jody , Meza Rafael
Published: December 2023

Introduction

E-cigarette flavor bans could reduce or exacerbate population health harms. To determine how US e-cigarette flavor restrictions might influence tobacco use behavior, this study assesses responses to real-world and hypothetical flavor bans among young adults who use flavored e-cigarettes.

Aims and Methods

An online, national survey of young adults ages 18–34 who use flavored e-cigarettes was conducted in 2021 (n = 1253), oversampling states affected by e-cigarette flavor restrictions. Participants were asked about their responses to real-world changes in the availability of flavored e-cigarettes. Unaffected participants were asked to predict their responses under a hypothetical federal e-cigarette flavor ban.

Results

The most common response to real-world changes in flavored e-cigarettes availability was to continue vaping (~80%). Among those who exclusively vaped, 12.5% switched to combustible tobacco. Quitting all forms of tobacco was selected by 5.3% of those exclusively vape versus 4.2% who dual use. Under a hypothetical federal ban, more than half of respondents stated they would continue vaping; 20.9% and 42.5% of those who exclusively vape versus dual use would use combustible tobacco. Quitting all tobacco products was endorsed by 34.5% and 17.2% of those who exclusively vape versus dual use.

Conclusions

Young adults who vape flavored e-cigarettes have mixed responses to e-cigarette flavor bans. Under both real-world and hypothetical e-cigarette flavor bans, most who use flavored e-cigarettes continue vaping. Under a real-world ban, the second most common response among those who exclusively vape is to switch to smoking; under a hypothetical federal ban, it is to quit all tobacco.

Implications

This is the first national survey to directly ask young adults who use flavored e-cigarettes about their responses to real-world changes in flavored e-cigarette availability due to state and local flavor restrictions. The survey also asked individuals to predict their responses under a hypothetical federal e-cigarette flavor ban. Most who use flavored e-cigarettes would continue vaping following e-cigarette flavor restrictions, but many would switch to or continue using combustible tobacco, highlighting potential negative public health consequences of these policies. Policymakers must consider the impact of e-cigarette flavor bans on both e-cigarette and cigarette use.
Effect of carotenoid supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose–response meta-analysis of randomized controlled trials
Authors: Behzadi Mehrdad , Akbarzadeh Marzieh , Mohammadi Sartang Mohsen , Rabiee Mohammadreza , Bideshki Mohammad Vesal
Published: December 2023

Context

Hypertension (HTN) is regarded as a serious public health issue throughout the world. High blood pressure (BP) may be improved by carotenoid supplementation; however, randomized controlled trials (RCTs) provide conflicting evidence.

Objective

The aim of this study was to evaluate the effects of carotenoid supplementation on BP in RCTs by systematically review and meta-analysis.

Data Sources

A comprehensive literature search was performed in the Scopus, PubMed, and Web of Science databases until October 2023, with no limitation on the date or language of publication.

Data Extraction

Studies that evaluated the net effects of carotenoids in the form of supplements on BP in adults were selected. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated on the basis of a fixed or random-effects model. Sensitivity analysis, meta-regression, publication bias, and heterogeneity were assessed using standard methods. Cochrane quality assessments were used to evaluate the included studies' bias risks. Evidence certainty was calculated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework).

Data Analysis

Reports on a total of 19 RCTs involving 1151 participants were included in this review. Carotenoid supplementation significantly reduced the systolic BP (SBP) (WMD, –2.492 mmHg; 95%CI, –4.52, –0.47; P = 0.016) and diastolic BP (DBP) (WMD, –1.60 mmHg; 95%CI, –2.73, –0.47; P = 0.005). Greater effects were observed in Asian participants, those aged >50 years, nonhealthy participants, and participants with a baseline SBP ≥130 mmHg and DBP ≥80 mmHg, at dose >10 mg. Dose–response analysis showed that carotenoid supplementation decreased SBP and DBP levels at doses of, respectively, 0–25 and 0–20 mg/d. Evidence for all SBP, DBP, and heart rate values was high quality.

Conclusions

Carotenoid supplementation had a beneficial effect on BP parameters, especially in nonhealthy study participants with high BP baseline levels.

PROSPERO registration no

CRD42023402740.
What is a real black hole?
Authors: Sugawara Hirotaka
Published: December 2023

Four dimensional Einstein equation with non-vanishing energy momentum tensor is solved to give a solution where the event horizon of a celestial body is outside of the body, which corresponds to a black hole by definition. There is no singularity at the center of the object unlike the case of Schwarzschild solution. We do not have the gravitational collapse. We do not have the gravitational collapse thus avoiding the Penrose-Hawking singularity theorems. The main feature of our black hole solution is that it has the horizon inside the black hole in addition to the usual outside horizon. This inner horizon singularity is not removable by a coordinate transformation because the determinant of metric tensor is singular at this point but there is no singularity neither in the density nor in the pressure indicating there is no gravitational collapse.
Recent progress in functional metal–organic frameworks for bio-medical application
Authors: Chai Wenwen , Chen Xiaochen , Liu Jing , Zhang Liyan , Liu Chunyu , Li Li , Honiball John Robert , Pan Haobo , Cui Xu , Wang Deping
Published: December 2023

Metal–organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.
Transcriptomic features of systemic lupus erythematosus patients in flare and changes during acute in-hospital treatment
Authors: Liu Zhongyi , Shao Li , Hou Fei , Li Weiyang , Wang Yong-Fei , Feng Hong , Wang Frank Qingyun , Lei Yao , Zheng Lichuan , Liang Rui , Li Jian , Guo Xianghua , Zhang Lili , Zhang Yanfang , Yang Jing , Qin Xiao , Wei Wei , Yang Xingtian , Dang Xiao , Ma Wen , She Chun Hing , Kong Qingsheng , Yang Jing , Ban Bo , Lau Yu Lung , Song Qin , Yang Wanling
Published: December 2023

Objectives

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies.

Methods

RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment.

Results

Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts.

Conclusions

In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development.
Alpine Extremophytes in Evolutionary Turmoil: Complex Diversification Patterns and Demographic Responses of a Halophilic Grass in a Central Asian Biodiversity Hotspot
Authors: Wróbel Anna , Klichowska Ewelina , Nowak Arkadiusz , Nobis Marcin
Published: December 2023

Diversification and demographic responses are key processes shaping species evolutionary history. Yet we still lack a full understanding of ecological mechanisms that shape genetic diversity at different spatial scales upon rapid environmental changes. In this study, we examined genetic differentiation in an extremophilic grass Puccinellia pamirica and factors affecting its population dynamics among the occupied hypersaline alpine wetlands on the arid Pamir Plateau in Central Asia. Using genomic data, we found evidence of fine-scale population structure and gene flow among the localities established across the high-elevation plateau as well as fingerprints of historical demographic expansion. We showed that an increase in the effective population size could coincide with the Last Glacial Period, which was followed by the species demographic decline during the Holocene. Geographic distance plays a vital role in shaping the spatial genetic structure of P. pamirica alongside with isolation-by-environment and habitat fragmentation. Our results highlight a complex history of divergence and gene flow in this species-poor alpine region during the Late Quaternary. We demonstrate that regional climate specificity and a shortage of nonclimate data largely impede predictions of future range changes of the alpine extremophile using ecological niche modeling. This study emphasizes the importance of fine-scale environmental heterogeneity for population dynamics and species distribution shifts.
Dietary of different forms of Humulus scandens on growth performance and intestinal bacterial communities in piglets
Authors: Hao Lihong , Wang Cheng , Wang Huaizhong , Zhou Meng , Wang Yong , Hu Hongmei
Published: December 2023

The present study was aimed at elucidating the effects of feeding different forms of Humulus scandens (Hu) on performance and bacterial communities in piglets. A total of 160 piglets were divided into four groups: (1) a control (CG, basal diet); (2) a basal diet with Hu pulp (HS), basal diet + Hu pulp; (3) a basal diet with Hu juice (HSJ), basal diet + Hu juice; and (4) a basal diet with Hu residue (HSR), basal diet + Hu residue. Results showed that HS, HSJ, and HSR supplementation led to rich average daily gain (ADG) and poor feed conversion ratio (FCR) during 28 to 70 d of age, increased 120 d body weight (BW), average daily feed intake (ADFI) and ADG and decreased FCR during 71 to 120 d of age. Three experiment groups presented greater (P < 0.05) IgA, IgG, and IgM and lower (P < 0.05) glucose, and blood urea nitrogen. The content of diamine oxidase significantly decreased (P < 0.05) in HS group. The crude  protein and crude fiber digestibility were improved (P < 0.05) in HS group and the Ca digestibility was increased (P < 0.05) in HS and HSJ groups. HSR supplementation improved the abundance of Firmicutes and decreased the abundance of Bacteroidetes. Hu supplementation with different forms increased the proportion of Lactobacillus in cecum content. These results indicated that supplemental feeding of Hu with different forms improved serum immunity, nutrient digestibility, and bacterial communities in piglets, promoting growth and development, which may be regarded as a reference for developing novel feed resources for piglets.
Reducing ophthalmic surgical waste through electronic instructions for use: a multisociety position paper
Authors: Schehlein Emily M. , Hovanesian John , Shukla Aakriti Garg , Talley Rostov Audrey , Findl Oliver , Chang David F.
Published: December 2023

Every ophthalmic surgical supply, including intraocular lenses (IOLs), IOL cartridges, and ophthalmic viscosurgical device syringes, is packaged with instructions for use (IFU). These pamphlets are printed in multiple languages and, in the case of an IOL, significantly increase the size and weight of the packaging. To eliminate this significant and unnecessary source of waste, we recommend that manufacturers move to Quick Response codes that link to online electronic IFU (e-IFU) as a sensible alternative. In addition to reducing carbon emissions and manufacturing costs, e-IFU can be updated more easily and accessed by surgeons in the clinic, where IOL models and powers are selected. Varying and inconsistent IFU requirements between different countries are a barrier to wider adoption of e-IFU by the ophthalmic surgical industry. Regulatory agencies in every country should allow and encourage e-IFU. This position paper has been endorsed by the 3 major societies that sponsor EyeSustain, a consortium of global societies dedicated to advancing sustainability in ophthalmology.
20(S)-Ginsenoside Rh1 alleviates sevoflurane-induced ototoxicity by reducing oxidative stress levels
Authors: Lin Jin , Gang Li , Wen Li , Zi He Ying , Xia Shen
Published: December 2023

Context

Sevoflurane is an inhalational anesthetic widely used in pediatric surgery. However, animal studies have shown that multiple sevoflurane exposures during the neonatal period led to ototoxicity. 20(S)-Ginsenoside Rh1, a ginsenoside extract, protects against cisplatin-induced ototoxicity by scavenging free radicals.

Objective

This study aimed to assess the effects of Rh1 on sevoflurane-induced ototoxicity.

Materials and methods

Neonatal cochlear explants and House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were cultured and randomly divided into three groups: the control group, the sevoflurane group and the Rh1 pretreatment group. We pretreated cochlear explants or HEI-OC1 cells with 100 μM Rh1 2 hours before performing sevoflurane exposure. Immunofluorescence was used to detect hair cells and spiral ganglion neurons. Cell Counting Kit-8 assay was used to determine cell viability. Annexin V-fluorescein isothiocyanate and propidium iodide were used to evaluate apoptosis. CellROX-Green and MitoSOX-Red probes were used to measure the amount of reactive oxygen species (ROS). Tetramethylrhodamine methyl ester labeling was used to examine mitochondrial membrane potential.

Results

Rh1 attenuated spiral ganglion neuron nerve fibers and synapses degeneration in cochlear explants after sevoflurane exposure. Rh1 significantly increased the viability of HEI-OC1 cells, reduced reactive oxygen species accumulation in HEI-OC1 cells, and prevented mitochondrial damage in HEI-OC1 cells after sevoflurane exposure.

Discussion and conclusion

These findings suggest that Rh1 is a promising drug for preventing sevoflurane-induced ototoxicity.
The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis
Authors: Zhang Qing , Li Meng Ke , Hu Xin Yuan , Wang Ying Ying , Zhao Pan Pan , Cheng Lin Na , Yu Rong Hua , Zhang Xu Dong , Chen Song , Zhu Zun Min , de Bock Charles E. , Thorne Rick F.
Published: December 2023

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vavi-Cre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hemopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine haematopoiesis.
Mechanism of action of Buqing Granule against Diabetic retinopathy based on network pharmacology and animal experiments
Authors: Yang Yifan , Yuan Ling , Li Xiangyang , Liu Qian , Jiang Wenjie , Jiao Taiqiang , Li Jiaqing , Ye Mengyi , Niu Yang , Nan Yi
Published: December 2023

Objective

For this study, network pharmacology and animal experiments were used together to get a better idea of how BQKL works at the molecular level to treat DR.

Methods

In this study, we obtained the relevant action target information of BQKL from the TCMSP and also combined the GeneCards, OMIM, TTD, and PharmGKB databases with the GEO database to obtain the relevant target information of DR. The intersection of these targets was determined using a Venn diagram to identify the target of action for the treatment of DR with BQKL. The target proteins of BQKL for DR were then uploaded to the String database. The resultant data were imported into Cytoscape 3.9.0 to construct PPI networks and identify key targets of action. The DAVID database was used to do a GO and KEGG pathway enrichment analysis of target genes for treating DR with BQKL. Molecular docking was performed to validate the core action targets with the core compounds of BQKL. In addition, we induced DR production in rats by a high-fat, high-sugar diet and intraperitoneal injection of STZ and validated the results obtained from the network pharmacological analysis by changes in body weight and blood glucose, serum levels of biochemical markers, HE staining, immunohistochemistry, qRT-PCR, and Western blot experiments in rats.

Results

In this study, quercetin, kaempferol, β-sitosterol, lignanserin, and stigmasterol were identified as the key components, TP53, AKT1, JUN, CASPASE3, MAPK3, and MAPK1 as the key targets, and PI3K-Akt, AGE-RAGE, and MAPK signaling pathways as the main pathways involved. The results of animal experiments showed that BQKL could not only effectively reduce the degree of blood glucose, blood lipids, and oxidative damage in diabetic rats but also slow down the development process of DR. At the same time, it can significantly up-regulate the expression of AKT1, MAPK1, and MAPK3 and down-regulate the expression of CASPASE3, c-JUN, and TP53 in retinal tissue.

Conclusion

BQKL ameliorates oxidative stress, apoptosis, and inflammation due to hyperglycemia-related stress by regulating key targets of CASPASE3, AKT1, c-JUN, TP53, MAPK1, and MAPK3, thereby delaying the onset and progression of DR.
“I found out about Zika virus after she was born.” Women’s experiences of risk communication during the Zika virus epidemic in Brazil, Colombia, and Puerto Rico
Authors: Miranda María Consuelo , Sánchez Claudia Hormiga , Souto Ester Paiva , Pérez Edna Acosta , Matta Gustavo Corrêa , Daza Marcela , Gama Gabriela Lopes , Pimentel Camila , Mercado Marcela , Niño Angélica María Amado , Leegstra Luz Marina , Marbán Castro Elena , Manders Olivia C. , Maxwell Lauren
Published: December 2023

Introduction

Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women’s perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development.

Methods

We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women’s experiences of ZIKV test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews.

Findings

Participants in Brazil and Colombia reported that the healthcare system’s lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy.

Conclusion

Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families’ preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication.
Activated PI3Kδ specifically perturbs mouse Treg homeostasis and function leading to immune dysregulation
Authors: Singh Akhilesh K. , Qureshah Fahd Al , Drow Travis , Hou Baidong , Rawlings David J
Published: December 2023

Foxp3+regulatory T cells (Treg) are required for maintaining immune tolerance and preventing systemic autoimmunity. PI3Kδ is required for normal Treg development and function. However, the impacts of dysregulated PI3Kδ signaling on Treg function remain incompletely understood. Here, we used a conditional mouse model of activated PI3Kδ syndrome (APDS) to investigate the role of altered PI3Kδ signaling specifically within the Treg compartment. Aged mice expressing a PIK3CD gain-of-function mutation (aPIK3CD) specifically within the Treg compartment exhibited weight loss and evidence for chronic inflammation as demonstrated by increased memory/effector CD4+and CD8+T cells with enhanced IFN-γ secretion, spontaneous germinal center responses and production of broad-spectrum autoantibodies. Intriguingly, aPIK3CD facilitated Treg precursor development within the thymus and an increase in peripheral Treg numbers. Peripheral Treg, however, exhibited an altered phenotype including increased PD1 expression and reduced competitive fitness. Consistent with these findings, Treg specific-aPIK3CD mice mounted an elevated humoral response following immunization with a T-cell dependent antigen, that correlated with a decrease in follicular Treg. Taken together, these findings demonstrate that an optimal threshold of PI3Kδ activity is critical for Treg homeostasis and function, suggesting that PI3Kδ signaling in Treg might be therapeutically targeted to either augment or inhibit immune responses.
Simple syntactic rules through rapid synaptic changes
Authors: Sun Lin , Manohar Sanjay G
Published: December 2023

Syntax is a central organizing component of human language but few models explain how it may be implemented in neurons. We combined two rapid synaptic rules to demonstrate how neurons can implement a simple grammar without accounting for the hierarchical property of syntax. Words bind to syntactic roles (e.g. “dog” as subject or object) and the roles obey ordering rules (e.g. subject → verb → object), guided by predefined syntactic knowledge. We find that, like humans, the model recalls sentences better than shuffled word-lists, and when given the permitted role orderings, and a set of words, the model can select a grammatical ordering and serialize the words to form a sentence influenced by the priming effect (e.g. producing a sentence in the passive voice after input of a different sentence also in the passive voice). The model also supports languages reliant on affixes, rather than word order, to define grammatical roles, exhibits syntactic priming and demonstrates typical patterns of aphasia when damaged. Crucially, it achieves these using an intuitive representation where words fill roles, allowing structured cognition.
Virus-encoded glycosyltransferases hypermodify DNA with diverse glycans
Authors: Pyle Jesse D. , Lund Sean R. , O’Toole Katherine H. , Saleh Lana
Published: December 2023

Enzymatic modification of DNA nucleobases can coordinate gene expression, protection from nucleases, or mutagenesis. We recently discovered a new clade of phage-specific cytosine methyltransferase (MT) and 5-methylpyrimidine dioxygenase (5mYOX,e.g.,TET) enzymes that produce 5-hydroxymethylcytosine (5hmC) as a precursor for additional post-replicative enzymatic hypermodifications on viral genomes. Here, we identify phage MT- and 5mYOX-dependent glycosyltransferase (GT) enzymes that catalyze linkage of diverse glycans directly onto 5hmC reactive nucleobase substrates. Using targeted bioinformatic mining of the phage metavirome databases, we discovered thousands of new biosynthetic gene clusters (BGCs) containing enzymes with predicted roles in cytosine sugar hypermodification. We developed a pathway reassembly platform for high-throughput functional screening of GT-containing BGCs, relying on the endogenousE. colimetabolome as a substrate pool. We successfully reconstituted a subset of phage BGCs and isolated novel and highly diverse sugar modifications appended to 5hmC, including mono-, di-, or tri-saccharide moieties comprised of hexose, N-acetylhexosamine or heptose sugars. Structural predictions and sugar product analyses suggest that phage GTs are related to host lipopolysaccharide, teichoic acid, and other small molecule biosynthesis enzymes and have been repurposed for DNA substrates. An expanded metagenomic search revealed hypermodification BGCs within gene neighborhoods containing phage structural proteins and putative genome defense systems. These findings enrich our knowledge of secondary modifications on DNA and the origins of corresponding sugar writer enzymes. Post-replicative cytosine hypermodification by virus-encoded GTs is discussed in the context of genome defense, DNA partitioning and virion assembly, and host-pathogen co-evolution.
Chromatin Remodeling and Epigenetic Modifications in Planar Cell Migration
Authors: Forman Jack , Hine Briar , Kaonis Samantha , Ghosh Soham
Published: December 2023

The cell nucleus plays a critical role in cell migration by its deformability under forces, by acting as a piston that activates mechanosensitive channels, and also by serving as a ruler tailoring cell response to spatial constraints. Cell nuclear mechanics determine the mechanobiology of static and migrating cells. Here, we report that intranuclear chromatin architecture plays a previously unknown role during cell migration on planar substrates. By inhibiting histone deacetylation, which compacts chromatin, and a methyltransferase, which affects chromatin remodeling and chromatin compaction, we showed that cell migration speed and persistence drastically slowed wound closure efficiency in an in vitro scratch wound assay. Chromatin remodeling was visualized and quantified during cell migration, which may be intertwined with nuclear mechanics and shape. Inhibition disrupts remodeling and other unknown roles in chromatin, thus affecting the speed and persistence of cell migration. Interestingly, cytoskeletal stress fiber formation and cell shape were not visibly affected by chromatin modifications, suggesting an exclusive nuclear mechanobiological role in cell migration. These findings provide new insights into how aging and other degenerative conditions affect the plasticity of chromatin architecture and hence its effect on cell migration efficiency.