bluuebunny/crossref_metadata_2025 huggingface dataset:
PROFILE OF CENTRAL AORTIC BLOOD PRESSURE, AUGMENTATION INDEX AND PULSE PRESSURE AMPLIFICATION IN PREECLAMPSIA AND UNCOMPLICATED HYPERTENSION IN PREGNANCY
Authors: Szczepaniak-chichel Ludwina , Lipski Dawid , Uruski Pawel , Tykarski Andrzej
Published: May 2024

Objective:

The objective of our study was to assess the differences in profile of central aortic blood pressure and other pulse wave analysis parameters of arterial stiffness between healthy pregnancy, uncomplicated pregnancy hypertension (HT) and women with preeclampsia (HT+PE).

Design and method:

In a prospective longitudinal study we have examined 241 pregnant women admitted between 2017 and 2023 to outpatient clinic and gave their consent to participate. On monthly visits throughout pregnancy, and 6-8 weeks, 6 months and 1 year postpartum on each occasion after at least 10 min rest brachial blood pressure was measured (OMRON®-705I) and assessment of aortic central blood pressure (AoBP), augmentation index (AIx, AIx75HR) and pulse pressure amplification (PPAmpl) was performed with applanation tonometry method (SphygmoCor® PVx) by a single investigator. Pharmacotherapy in hypertensive patients was managed in accordance with ESH/ESC guidelines.

Results:

We have recruited 201 women with hypertension (145 chronic; 56 pregnancy induced) and 40 normotensive pregnant controls. Preeclampsia developed in 49 of women with hypertension (HT+PE), on average in 32,8 week of gestation(range:20-39w.g.). Profiles of assessed central pulse wave analysis parameters are presented in Figure 1. Significant differences between the groups (p< 0.05) are marked on the graphs. Mean brachial BP was maintained below < 140/90 mmHg in each subgroup throughout pregnancy with antihypertensive treatment.

Conclusions:

AoSP was significantly lower in normotensive than in HT patients through whole pregnancy. In preeclampsia from 6thmonth AoSP was significantly higher and rising until delivery while in uncomplicated HT it was stable until 9thmonth. AIx was lower and PPAmpl higher in control group than in hypertensive patients through whole pregnancy however only in 4th and 6thmonth difference reached statistical significance. There is a turning point in trends of both -AIx and PPAmpl in preeclamptic patients, although in opposite direction, in between 23-26w.g.,at least a month before PE recognition. In addition there is significant difference between preeclamptic and uncomplicated HT in PPAmpl in 27-31w.g. and opposite trend between the groups in direction of changes of this parameter onwards. Observation of AIx and PPAmpl profile in pregnancy could be useful in earlier prediction of preeclampsia.
COMPARATIVE ASSESSMENT OF ECHOCARDIOGRAPHY INDICATORS IN PREGNANT WOMEN DEPENDING ON THE FORM OF ARTERIAL HYPERTENSION
Authors: Mokhinur Sadulloeva , Zakirova Feruza , Kuchkarov Husniddin , Jabborova Nafisakhon , Yenaliyeva Diana , Hazratkulov Rustam
Published: May 2024

Objective:

To identify the features of hemodynamic parameters in pregnant women with pre-existed/chronic arterial hypertension (CAH) and gestational arterial hypertension (GAH).

Design and method:

Study included 61 pregnant women with arterial hypertension. Women were divided into 2 groups: I group included women with CAH (n=31) and II group included women with GAH (n=30) according to the 2018 ESC during pregnancy. All women underwent a medical history taking, BP measurement, ECG, EchoCG, 24-hour BP monitoring. Statistical analysis of obtained data was carried out using STATISTICA 13 program.

Results:

Analysis showed, CAH was more common in women whose average age exceeded 30 years, while GAH in those under 30 years of age (32.7±4.8 years and 27.2±5.7 years, in groups I and II, p=0.0001). They also differed in number of pregnancies 3.3±1.2 and 2.5±1.35, p 0.0174 and births 2.7±1.05 and 2.13±1.0, p 0.0341. Groups had similar SBP values 153.8±16.4 mmHg and 150.2±8.1 mmHg, p 0.2840, but differed in DBP 96.4±7.6 mmHg and 88.6±5.9 mmHg, p 0.0002. Statistically significant high DBP rates in I group, in our opinion, are associated with greater activation of renin-angiotensin-aldosterone system in CAH, whereas in GAH, hormonal and immunological mechanisms are more important. EchoCG indicators were within normal values, but had own characteristics. So in I group, IVST was 0.98±0.14 cm; PWT was 0.93±0.12 cm; LV mass was 166.96±49.6 g; LV index mass was 90.97±22.94; EDV was 108.45±23.72 ml; EF was 64.9±4.9%. In II group IVST was 0.94±0.12 cm, p 0.2364; PWT was 0.92±0.10 cm, p 0, 7254, LV mass was 154.1±30.8 g, p 0.2304; LV index mass was 82.56±17.14, p 0.1110; EDV was 102.63±17.42 ml, p 0.2805; EF was 65.6±3.8%, p 0.5839. Among women included in the study, there were no women with left ventricular diastolic dysfunction in both groups, E/A = 1.3±0.2.

Conclusions:

Preliminary results show that women with CAH have an older age and higher DBP compared with pregnant women with HAG. The next stage of the study will be a comparative assessment of development of such end points as preeclampsia and eclampsia in pregnant women with CAH and GAH.
Pars Plana Vitrectomy With External Drainage for Nonexudative Retinal Detachment
Authors: Scupola Andrea , Fossataro Claudia , Sammarco Maria Grazia , Fossataro Federica , Savino Gustavo , Rizzo Stanislao
Published: May 2024

Purpose:

To describe a surgical technique for retinal detachment with undetected retinal breaks, which combines pars plana vitrectomy and external subretinal fluid (SRF) drainage.

Methods:

In this retrospective observational study, patients with a diagnosis of retinal detachment with undetected retinal breaks were enrolled. Standard three-port 25-gauge (G) core and peripheral pars plana vitrectomy was performed. Perfluorocarbon liquid was injected into the vitreous cavity to obtain posterior retinal flattening. Trans-scleral 27-G needle external drainage was performed approximately at 8 mm from limbus to drain SRF subconjunctivally. Prophylactic peripheral endolaser was performed on 360°. Sulfur hexafluoride 20% was used as tamponade.

Results:

In 14 of 15 patients, complete SRF drainage was obtained. In only one case, SRF did not leak out in the subconjunctival space. Neither intraoperative nor postsurgical complications were recorded. Flat retina with no SRF was observed in all samples, and no retinal detachment relapses were reported at each follow-up.

Conclusion:

External drainage combined with pars plana vitrectomy may represent a valid and safe option to drain SRF in retinal detachment cases with undetected retinal breaks. The advantages of the technique include the absence of dispersion of retinal pigment epithelium cells in the vitreous chamber, prompt dry retina, and low risk of postoperative retinal folds.
Bilateral Dacryocystoceles in Congenital Arhinia
Authors: Lin Lisa Y. , Chiou Carolina A. , Lee Nahyoung Grace
Published: May 2024

Congenital arhinia is a rare anomaly characterized by a syndrome called Bosma arhinia microphthalmia syndrome. A 22-year-old woman with a history of congenital arhinia presented with bilateral discharge and enlarged bilateral lacrimal sacs, with imaging consistent with bilateral dacryocystoceles and complete absence of nasal structures. This is the first case in the literature that describes surgical management of bilateral dacryocystoceles in a patient with Bosma arhinia microphthalmia syndrome.
Investigating neuroepigenetic alterations in chronic low back pain with positron emission tomography
Authors: Yoo Chi-Hyeon , Rani Nisha , Shen Shiqian , Loggia Marco L. , Gaynor Kate , Moore Katelyn E. , Bagdasarian Frederick A. , Lin Yu-Shiuan , Edwards Robert R. , Price Julie C. , Hooker Jacob M. , Wey Hsiao-Ying
Published: May 2024

Epigenetics has gained considerable interest as potential mediators of molecular alterations that could underlie the prolonged sensitization of nociceptors, neurons, and glia in response to various environmental stimuli. Histone acetylation and deacetylation, key processes in modulating chromatin, influence gene expression; elevated histone acetylation enhances transcriptional activity, whereas decreased acetylation leads to DNA condensation and gene repression. Altered levels of histone deacetylase (HDAC) have been detected in various animal pain models, and HDAC inhibitors have demonstrated analgesic effects in these models, indicating HDACs' involvement in chronic pain pathways. However, animal studies have predominantly examined epigenetic modulation within the spinal cord after pain induction, which may not fully reflect the complexity of chronic pain in humans. Moreover, methodological limitations have previously impeded an in-depth study of epigenetic changes in the human brain. In this study, we employed [11C]Martinostat, an HDAC-selective radiotracer, positron emission tomography to assess HDAC availability in the brains of 23 patients with chronic low back pain (cLBP) and 11 age-matched and sex-matched controls. Our data revealed a significant reduction of [11C]Martinostat binding in several brain regions associated with pain processing in patients with cLBP relative to controls, highlighting the promising potential of targeting HDAC modulation as a therapeutic strategy for cLBP.
Inflammation-based markers, especially the uric acid/albumin ratio, are associated with non-dipper pattern in newly diagnosed treatment-naive hypertensive patients
Authors: Toprak Kenan , Özen Kaya , Karataş Mesut , Dursun Ayten
Published: May 2024

Objective

Physiologically, at night, blood pressure (BP) is expected to decrease by at least 10% in hypertensive individuals. The absence of this decrease, called non-dipper hypertension, is associated with increased end-organ damage and cardiovascular mortality and morbidity in hypertensive individuals. It is known that increased inflammatory process plays an important role in the etiopathogenesis of non-dipper hypertension pattern. In recent years, it has been shown that inflammation-based markers (IBMs) obtained by combining various inflammation-related hematological and biochemical parameters in a single fraction have stronger predictive value than single inflammatory parameters. However, until now, there has not been a study investigating the relationship of these markers with dipper/non-dipper status in newly diagnosed hypertensive patients.

Methods

Based on ambulatory BP monitoring, 217 dipper and 301 non-dipper naive hypertensive subjects were included in this study. All subjects’ IBM values were compared between dipper and non-dipper hypertensive individuals.

Results

IBMs [C-reactive protein/albumin ratio (CAR), monocyte/high-density lipoprotein cholesterol ratio (MHR), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio, systemic immune-inflammation index (SII), uric acid/albumin ratio (UAR)] were significantly higher in the non-dipper group. CAR, MHR, NLR, SII, and UAR were determined as independent predictors for non-dipper pattern (P < 0.05, for all). Also, UAR’s diagnostic performance for non-dipper pattern was found to be superior to other IBMs (area under the curve: 0.783, 95% confidence interval: 0.743–0.822; P < 0.001).

Conclusion

These findings suggest an association between elevated IBMs, particularly UAR, and the non-dipper hypertension pattern observed in our study.
Changes in corneal epithelial irregularity following treatment with artificial tears
Authors: Tan Jacqueline , Chidi-Egboka Ngozi , Jia Tianni , Showyin Jared , Stapleton Fiona
Published: May 2024

Significance

Dry eye sufferers have a highly irregular corneal epithelial surface compared with those without dry eye. This study demonstrated that corneal epithelial thickness irregularity can be significantly reduced after as little as 48 hours following treatment with regular use of topical ocular lubricants.

Purpose

This study aimed to compare changes in corneal epithelial thickness irregularity factor (EIF) and ocular symptoms in a population with symptoms of dry eye before and up to 4 weeks after treatment with two commercially available lubricating eye drops versus saline.

Methods

We conducted a prospective single-center, investigator-masked, randomized, parallel-group dispensing study. Participants with moderate to severe symptoms of dry eye (Ocular Surface Disease Index score >23 at baseline) were enrolled and randomly assigned to receive either 0.15% hyaluronic acid + hydroxypropyl guar, 0.2% hyaluronic acid, or saline (16 in each group). Corneal epithelial thickness measurements were obtained along vertical and horizontal CASIA SS-1000 Optical Coherence Tomography scans at baseline and after 48 hours, 2 weeks, and 4 weeks. The Ocular Surface Disease Index questionnaire was administered at baseline, 2 weeks, and 4 weeks.

Results

Forty-eight participants (male-to-female ratio, 17:31) completed the study. Horizontal EIF was significantly lower at all follow-up visits compared with baseline (p=0.001), but there were no significant differences between study eye drops (p=0.34). No significant difference in vertical EIF was observed over time (p=0.32) or between eye drops (p=0.08). Ocular symptoms significantly improved after 2 and 4 weeks of treatment compared with baseline (p<0.001), but no differences were observed between eye drops (p=0.46).

Conclusions

All treatments were effective for reducing EIF along the horizontal meridian 48 hours after initiation of treatment, and improvements were maintained for 4 weeks. Improvements in ocular symptoms were observed with all study treatments.
Incidence of Bacteremia and Serious Bacterial Infections in Hyperpyrexic Infants Offered Universal Pneumococcal Conjugate Vaccine 13 and Haemophilus influenzae B Immunization
Authors: Be'er Moria , Rimon Ayelet , Segev Or , Huber Adi , Scolnik Dennis , Glatstein Miguel
Published: May 2024

Background

High fevers, especially in young children, often alarm clinicians and prompt extensive evaluation based on perceptions of increased risk of serious bacterial infection (SBI), and even brain damage or seizure disorders.

Objective

The aim of this study was to determine the prevalence of SBI in infants aged 3–36 months with fever ≥40.5°C in a population of infants offered universal pneumococcal conjugate vaccine 13 and Haemophilus influenzae B immunization.

Methods

This study is a retrospective review of all infants aged 3–36 months with temperature ≥40.5°C presenting to a tertiary care pediatric emergency department over a 30-month period in an era of universal pneumococcal conjugate 13 and H. influenzae B immunization.

Results

SBI was recorded in 54 (21.8%) of 247 study infants, most commonly pneumonia 30 patients (12.1%) and urinary tract infection 16 patients (6.5%). Two patients had positive blood cultures, yielding a bacteremia rate of 0.8%. Patients with SBI had a significantly higher WBC count (P < 0.0001) and C-reactive protein levels (P < 0.0001), and were significantly more likely to be hospitalized (P < 0.0001).

Discussion

Although SBI was common (21.8%) in our cohort of hyperpyrexic infants universally offered vaccination with pneumococcal conjugate 13 and H. influenzae B vaccines, bacteremia was a rare finding (0.8%).
Whole Spinal Cord FDG Uptake at PET/CT Caused by H3K27-Altered Diffuse Midline Glioma in an Adult Patient
Authors: Morin Léo , Godard François , Aubriot-Lorton Marie-Hélène , Drouet Clément
Published: May 2024

Diffuse midline glioma, H3K27-altered, is a relatively new entity, characterized by H3K27M histone mutation. This rare pediatric disease with severe prognosis has recently been identified as a new subtype of diffuse astrocytoma due to major breakthrough in histopathological and molecular characterization of gliomas. We report a case of H3K27-altered diffuse midline glioma in a 30-year-old woman.
Research Advances in Vascular Remodeling in Choke Vessels of Perforator Flap
Authors: Ji Jiahao , Chen Dondli , Ni Jiamin , Chang Fei
Published: May 2024

Background

As a significant bridge between perforasomes, choke vessels are the key structure of blood supply expansion, also a prerequisite for preventing distal ischemic necrosis of the multiterritory perforator flap, where the remodeling of choke vessels after flap elevation plays an essential role. This systematic review highlights the underlying mechanisms and clinical ways to promote remodeling of choke vessels, as well as experimental observation approaches to further guide researchers.

Methods

A systematic review was conducted from 1975 to 2023 through PubMed, EMBASE, Web of Science, and Cochrane database with the key words “choke vessels” and “perforator flap” to investigate the mechanisms and ways to promote remodeling of choke vessels as well as observation approaches. The inclusion criteria and exclusion criteria were set to screen the literature.

Results

A total of 94 literatures were obtained through database retrieval. After removing the duplicate literature, reading the title and abstract, and reviewing the full text finally, 33 articles were included in the final study.

Conclusions

The underlying remodeling of choke vessels may be related to fluid shear stress, hypoxia, and inflammation. The clinical ways to promote remodeling of choke vessels include surgical delay, arterial supercharge, venous superdrainage, drugs, and stem cells. Various experimental methods of observing microvascular morphology allow for a comprehensive research of choke vessels.
The difficult airway in trauma: What you need to know
Authors: Eugene Vadine , Hutzler Jason , Kempema James , Bradford James , Brown Carlos V.R.
Published: May 2024

Airway evaluation and management are generally the first priority for treatment of trauma patients from the prehospital setting throughout their hospital stay. Delay in recognition of an airway problem, or inability to oxygenate or ventilate because of an inadequate airway, will lead to rapid death. Therefore, all clinicians involved in the care of trauma patients should have adequate knowledge of current best practices for airway evaluation and management. In addition, trauma providers should develop and maintain the skills needed to perform various airway maneuvers to establish and maintain an adequate airway. While elective airway management has the luxury of time for thorough airway evaluation, the airway management in the trauma setting does not allow this same opportunity. For this reason, all trauma airways should be presumed to be a difficult airway, and teams should prepare accordingly. This review will summarize the best practices for airway evaluation and management for trauma patients from the prehospital setting through the emergency department.
Cherry on Top or Real Need? A Review of Explainable Machine Learning in Kidney Transplantation
Authors: Assis de Souza Alvaro , Stubbs Andrew P. , Hesselink Dennis A. , Baan Carla C. , Boer Karin
Published: May 2024

Research on solid organ transplantation has taken advantage of the substantial acquisition of medical data and the use of artificial intelligence (AI) and machine learning (ML) to answer diagnostic, prognostic, and therapeutic questions for many years. Nevertheless, despite the question of whether AI models add value to traditional modeling approaches, such as regression models, their “black box” nature is one of the factors that have hindered the translation from research to clinical practice. Several techniques that make such models understandable to humans were developed with the promise of increasing transparency in the support of medical decision-making. These techniques should help AI to close the gap between theory and practice by yielding trust in the model by doctors and patients, allowing model auditing, and facilitating compliance with emergent AI regulations. But is this also happening in the field of kidney transplantation? This review reports the use and explanation of “black box” models to diagnose and predict kidney allograft rejection, delayed graft function, graft failure, and other related outcomes after kidney transplantation. In particular, we emphasize the discussion on the need (or not) to explain ML models for biological discovery and clinical implementation in kidney transplantation. We also discuss promising future research paths for these computational tools.
Isavuconazole Versus Voriconazole as the First-line Therapy for Solid Organ Transplant Recipients With Invasive Aspergillosis: Comparative Analysis of 2 Multicenter Cohort Studies
Authors: Fernández-Ruiz Mario , Gioia Francesca , Bodro Marta , Gutiérrez Martín Isabel , Sabé Núria , Rodriguez-Álvarez Regino , Corbella Laura , López-Viñau Teresa , Valerio Maricela , Illaro Aitziber , Salto-Alejandre Sonsoles , Cordero Elisa , Arnaiz de Las Revillas Francisco , Fariñas María Carmen , Muñoz Patricia , Vidal Elisa , Carratalà Jordi , Goikoetxea Josune , Ramos-Martínez Antonio , Moreno Asunción , Martín-Dávila Pilar , Fortún Jesús , Aguado José María ,   For the SOTIS and DiasperSOT Study Groups
Published: May 2024

Background.

Isavuconazole (ISA) and voriconazole (VORI) are recommended as the first-line treatment for invasive aspergillosis (IA). Despite theoretical advantages of ISA, both triazole agents have not been compared in solid organ transplant recipients.

Methods.

We performed a post hoc analysis of 2 retrospective multicenter cohorts of solid organ transplant recipients with invasive fungal disease (the SOTIS [Solid Organ Transplantation and ISavuconazole] and DiasperSOT [DIagnosis of ASPERgillosis in Solid Organ Transplantation] studies). We selected adult patients with proven/probable IA that were treated for ≥48 h with ISA (n = 57) or VORI (n = 77) as first-line therapy, either in monotherapy or combination regimen. The primary outcome was the rate of clinical response at 12 wk from the initiation of therapy. Secondary outcomes comprised 12-wk all-cause and IA-attributable mortality and the rates of treatment-emergent adverse events and premature treatment discontinuation.

Results.

Both groups were comparable in their demographics and major clinical and treatment-related variables. There were no differences in the rate of 12-wk clinical response between the ISA and VORI groups (59.6% versus 59.7%, respectively; odds ratio [OR], 0.99; 95% confidence interval [CI], 0.49-2.00). This result was confirmed after propensity score adjustment (OR, 0.81; 95% CI, 0.32-2.05) and matching (OR, 0.79; 95% CI, 0.31-2.04). All-cause and IA-attributable mortality were also similar. Patients in the ISA group were less likely to experience treatment-emergent adverse events (17.5% versus 37.7%; P = 0.011) and premature treatment discontinuation (8.8% versus 23.4%; P = 0.027).

Conclusions.

Front-line treatment with ISA for posttransplant IA led to similar clinical outcomes than VORI, with better tolerability and higher treatment completion.
Neuroinflammation in amyotrophic lateral sclerosis: pathogenic insights and therapeutic implications
Authors: Calma Aicee D. , Pavey Nathan , Menon Parvathi , Vucic Steve
Published: May 2024

Purpose of review

Neuroinflammation appears to be an important pathogenic process in amyotrophic lateral sclerosis (ALS). Dysfunction of central immune pathways, including activation of microglia and astrocytes, and peripherally derived immune cells, initiate noncell autonomous inflammatory mechanisms leading to degeneration. Cell autonomous pathways linked to ALS genetic mutations have been recently identified as contributing mechanism for neurodegeneration. The current review provides insights into the pathogenic importance of central and peripheral inflammatory processes in ALS pathogenesis and appraises their potential as therapeutic targets.

Recent findings

ALS is a multistep process mediated by a complex interaction of genetic, epigenetic, and environmental factors. Noncell autonomous inflammatory pathways contribute to neurodegeneration in ALS. Activation of microglia and astrocytes, along with central nervous system infiltration of peripherally derived pro-inflammatory innate (NK-cells/monocytes) and adaptive (cell-mediated/humoral) immune cells, are characteristic of ALS. Dysfunction of regulatory T-cells, elevation of pro-inflammatory cytokines and dysbiosis of gut microbiome towards a pro-inflammatory phenotype, have been reported as pathogenic mechanisms in ALS.

Dysregulation of adaptive and innate immunity is pathogenic in ALS, being associated with greater disease burden, more rapid disease course and reduced survival. Strategies aimed at modulating the pro-inflammatory immune components could be of therapeutic utility.
A failure criterion for genuinely orthotropic materials and integration of a series of criteria for materials of different degrees of anisotropy
Authors: Xu Mingming , Sitnikova Elena , Li Shuguang
Published: May 2024

Existing failure criteria for orthotropic materials are subject to an underlying assumption which cause contradictions when applied to genuinely orthotropic materials that are significantly anisotropic in elasticity as well as in strengths. For such materials, there is lack of consistent failure criteria to support their applications in engineering structures. A general quadratic failure criterion tends to leave undetermined coefficients for interactive terms. A rational approach is adopted in this paper based on mathematical and logical considerations to determine these coefficients as the objective of this paper. Considerations are based on the intrinsic characteristics of the quadric surfaces introduced by the quadratic failure criterion. These coefficients must take the values as obtained, leaving no alternatives if logic prevails. The obtained criterion integrates for the first time a range of criteria separately formulated for materials of different degrees of anisotropy, from genuinely orthotropic, through transversely isotropic, cubically symmetric, to completely isotropic ones with different or identical tensile and compression strengths.
A tensor density measure of topological charge in three-dimensional nematic phases
Authors: Schimming Cody D. , Vinals Jorge
Published: May 2024

A path-independent measure in order parameter space is introduced such that, when integrated along any closed contour in a three-dimensional nematic phase, it yields the topological charge of any line defects encircled by the contour. A related measure, when integrated over either closed or open surfaces, reduces to known results for the charge associated with point defects (hedgehogs) or Skyrmions. We further define a tensor density, the disclination density tensor

D

, from which the location of a disclination line can be determined. This tensor density has a dyadic decomposition near the line into its tangent and its rotation vector, allowing a convenient determination of both. The tensor

D

may be non-zero in special configurations in which there are no defects (double-splay or double-twist configurations), and its behaviour there is provided. The special cases of Skyrmions and hedgehog defects are also examined, including the computation of their topological charge from

D

.
Fear of the human ‘super predator’ in native marsupials and introduced deer in Australia
Authors: McGann Katherine , Johnson Christopher N. , Clinchy Michael , Zanette Liana Y. , Cunningham Calum X.
Published: May 2024

Recent experiments have demonstrated that carnivores and ungulates in Africa, Asia, Europe and North America fear the human ‘super predator’ far more than other predators. Australian mammals have been a focus of research on predator naiveté because it is suspected they show atypical antipredator responses. To experimentally test if mammals in Australia also most fear humans, we quantified the responses of four native marsupials (eastern grey kangaroo, Bennett’s wallaby, Tasmanian pademelon, common brushtail possum) and introduced fallow deer to playbacks of predator (human, dog, Tasmanian devil, wolf) or non-predator control (sheep) vocalizations. Native marsupials most feared the human ‘super predator’, fleeing humans 2.4 times more often than the next most frightening predator (dogs), and being most, and significantly, vigilant to humans. These results demonstrate that native marsupials are not naïve to the peril humans pose, substantially expanding the taxonomic and geographic scope of the growing experimental evidence that wildlife worldwide generally perceive humans as the planet’s most frightening predator. Introduced fallow deer fled humans, but not more than other predators, which we suggest may result from their being introduced. Our results point to both challenges concerning marsupial conservation and opportunities for exploiting fear of humans as a wildlife management tool.
Topological Structures in the Space of Treatment-Naïve Patients With Chronic Lymphocytic Leukemia
Authors: McGee Reginald L. , Reed Jake , Coombes Caitlin E. , Herling Carmen D. , Keating Michael J. , Abruzzo Lynne V. , Coombes Kevin R.
Published: May 2024

Patients are complex and heterogeneous; clinical data sets are complicated by noise, missing data, and the presence of mixed-type data. Using such data sets requires understanding the high-dimensional “space of patients”, composed of all measurements that define all relevant phenotypes. The current state-of-the-art merely defines spatial groupings of patients using cluster analyses. Our goal is to apply topological data analysis (TDA), a new unsupervised technique, to obtain a more complete understanding of patient space. We applied TDA to a space of 266 previously untreated patients with Chronic Lymphocytic Leukemia (CLL), using the “daisy” metric to compute distances between clinical records. We found clear evidence for both loops and voids in the CLL data. To interpret these structures, we developed novel computational and graphical methods. The most persistent loop and the most persistent void can be explained using three dichotomized, prognostically important factors in CLL:IGHVsomatic mutation status, beta-2 microglobulin, and Rai stage. In conclusion, patient space turns out to be richer and more complex than current models suggest. TDA could become a powerful tool in a researchers arsenal for interpreting high-dimensional data by providing novel insights into biological processes and improving our understanding of clinical and biological data sets.

Simple Summary

Clinical data sets incorporate continuous data like blood pressure or sodium levels, categorical data like cancer grade or stage, and binary data like sex or marital status. Measurements on an individual patient define a point in a high-dimensional space; data from many patients defines a “point cloud”. The “shape” of the point cloud influences experimental design by describing patient variability. Topological data analysis (TDA) is a mathematical technique for understanding the shape of point clouds by finding “holes” that correspond to combinations of patient characteristics that are never observed. TDA results are stratified by dimension. Zero-dimensional features define patient subtypes. One-dimensional features (“loops”) are analogs of the inside of a circle or a donut hole. Two-dimensional features (“voids”) are analogs of the inside of a balloon. Here, we apply TDA to a clinical data set of previously untreated patients with Chronic Lymphocytic Leukemia to find loops and voids.
Prognostic Factors for Mortality in Patients Infected with Hantavirus: A Systematic Review with GRADE Certainty Assessment
Authors: Tortosa Fernando , Perré Fernando , Neumann Ignacio , Ragusa Martín Alberto , Lossetti Lucia , Guaresti Germán , Izcovich Ariel
Published: May 2024

Introduction

One of the challenges in managing patients with hantavirus infection is accurately identifying individuals who are at risk of developing severe disease. Prompt identification of these patients can facilitate critical decisions, such as early referral to an intensive care unit. The identified prognostic factors could be incorporated into predictive models to enhance the management of hantavirus infection.

Objective

To identify and evaluate prognostic factors associated with mortality in hantavirus infection, providing a basis for a risk assessment model for hantavirus mortality

Methods

We conducted a systematic review following the ‘Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ (PRISMA) guidelines. We conducted a comprehensive search in PubMed/MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase from their inception to January 2024. Furthermore, we included studies evaluating individual prognostic factors or risk assessment models of hantavirus infections, with no restrictions on study design, publication status, or language. When feasible, we conducted meta-analyses for prognostic factors using the inverse variance-based method with random effect model. We assessed the certainty of the evidence using the GRADE approach,

Results

We included 30 studies with a total of 92,183 participants. We identified the following key prognostic factors which predicted and increased mortality and disease severity: over 15 years, female gender, elevated creatinine levels (>1.4 mg/dL), increased hematocrit (>42%), and presence of infiltrates on chest radiographs.

Discussion

Our systematic review not only sheds light on the pivotal prognostic factors for hantavirus infection but also sets the stage for the development of comprehensive management strategies that are informed by robust empirical evidence. These strategies, underpinned by predictive modeling and regional customization, can significantly enhance outcomes for individuals at risk of severe hantavirus disease, aligning with global health objectives aimed at zoonotic disease control and prevention.

PROSPERO Registration Number

CRD42021225823
The impact of chronic pain on brain gene expression
Authors: Collier Lily , Seah Carina , Hicks Emily M. ,   Traumatic Stress Brain Research Group, Holtzheimer Paul E. , Krystal John H. , Girgenti Matthew J. , Huckins Laura M. , Johnston Keira J.A.
Published: May 2024

Background

Chronic pain affects one fifth of American adults, contributing significant public health burden. Chronic pain mechanisms can be further understood through investigating brain gene expression.

Methods

We tested differentially expressed genes (DEGs) in chronic pain, migraine, lifetime fentanyl and oxymorphone use, and with chronic pain genetic risk in four brain regions (dACC, DLPFC, MeA, BLA) and imputed cell type expression data from 304 postmortem donors. We compared findings across traits and with independent transcriptomics resources, and performed gene-set enrichment.

Results

We identified two chronic pain DEGs: B4GALT and VEGFB in bulk dACC. We found over 2000 (primarily BLA microglia) chronic pain cell type DEGs. Findings were enriched for mouse microglia pain genes, and for hypoxia and immune response. Cross-trait DEG overlap was minimal.

Conclusions

Chronic pain-associated gene expression is heterogeneous across cell type, largely distinct from that in pain-related traits, and shows BLA microglia are a key cell type.
Automated quantitative analysis of peri-articular bone microarchitecture in HR-pQCT knee images
Authors: Neeteson Nathan J. , Hasick Sasha M. , Souza Roberto , Boyd Steven K.
Published: May 2024

There is growing interest in applying HR-pQCT to image the knee, particularly in the study of osteoarthritis, which necessitates the development and validation of novel image analysis workflows. In this work, we present and validate the first fully automated workflow forin vivoquantitative assessment of peri-articular bone density and microarchitecture in the human knee. Bone segmentation models were trained by transfer learning with a large dataset of radius and tibia images (N=2,598) and fine-tuned on a knee image dataset (N=131), atlas-based registration was used to identify medial and lateral contact surfaces, and morphological operations combined these intermediate outputs to generate peri-articular regions of interest (ROIs) for morphological analysis. Accuracy was assessed with an external validation dataset (N=131), where predicted and reference morphological parameters showed excellent correspondence (0.86≤R2≤0.99), with moderate bias present in predictions of subchondral bone plate density (-80 mg HA/cm3) and thickness (+0.15 mm). Precision was assessed with a triple-repeat measures dataset (N=29), where the short-term precision RMS%CV estimates ranged from 0.7% to 3.5% when rigid registration was used to synchronize ROI generation across images.
When two communication differences intersect: Comparing inpatient rehabilitation care and outcomes for people with post-stroke aphasia who do and do not require an interpreter
Authors: Mellahn Kathleen , Kilkenny Monique , Siyambalapitiya Samantha , Lakhani Ali , Burns Catherine , Cadilhac Dominique A. , Rose Miranda L.
Published: May 2024

Background

Communicative ability after stroke influences patient outcomes. Limited research has explored the impact of aphasia when it intersects with cultural or linguistic differences on receiving stroke care and patient outcomes. We investigated associations between requiring an interpreter and the provision of evidence-based stroke care and outcomes for people with aphasia in the inpatient rehabilitation setting.

Methods

Patient-level data from people with aphasia were aggregated from the Australian Stroke Foundation National Stroke Audit - Rehabilitation Services (2016-2020). Multivariable regression models compared adherence to processes of care (e.g. home assessment complete, type of aphasia management) and in-hospital outcomes (e.g. length of stay, discharge destination) by requirement of an interpreter. Outcome models were adjusted for sex, stroke type, hospital size, year, and stroke severity factors.

Results

Among 3160 people with aphasia (median age 76, 56% male), 208 (7%) required an interpreter (median age 77, 52% male). The interpreter group had more severe disability on admission, reflected by reduced cognitive (6% vs 12%, p<0.0000) and motor FIM scores (6% vs 12%, p<0.009). The interpreter group were less likely to have phonological and semantic interventions for their aphasia (OR 0.56, 95% CI 0.40, 0.78) compared to people not requiring an interpreter. They more often had a carer (OR 2.03, 95% CI 1.41, 2.96) and were less likely to have a home assessment prior to discharge (OR 0.34, 95% CI 0.12, 0.95) despite increased likelihood of discharging home with supports (OR 1.49, 95% CI 1.08, 2.05). The interpreter group had longer lengths of stay (median 31 vs 26 days, p=0.005).

Conclusion

Some processes of care and outcomes differed in inpatient rehabilitation for people with post-stroke aphasia who required an interpreter compared with those who did not. Equitable access to therapy is imperative and greater support for cultural/linguistic minorities during rehabilitation is indicated.
Prevalence and Clinical Outcomes of Acute Noncardiac Organ Failure among Non-Acute Myocardial Infarction Cardiogenic Shock: A Nationwide Cohort Analysis
Authors: Majmundar Monil , Faisaluddin Mohammed , Alarfaj Mohammad , Ahmed Asmaa , Patel Kunal N , Majmundar Vidit , Doshi Rajkumar , Shah Hirak , Gupta Kamal , Shah Zubair , Dalia Tarun
Published: May 2024

Background

Noncardiac organ failure often complicates cardiogenic shock (CS). The results of cardiogenic shock caused by noncardiac organ failures in patients without acute myocardial infarction (AMI) are not well documented.

Methods

We examined the National Inpatient Sample (NIS) data from 2016 to 2020 to identify cases of CS and non-AMI CS-related hospitalizations. We divided both cohorts based on the number of acute noncardiac organ failures and evaluated the influence of organ failure on the primary outcome, which was in-hospital mortality.

Results

A total of 599,210 (100%) cardiogenic shock and 366,905 (61.2%) non-AMI CS hospitalizations were identified. Among those with non-AMI CS, 58,965 (16.07%) had no organ failure, 121,845 (33.21%) had a single organ failure, and 186,095 (50.72%) had a multiorgan failure. Acute Kidney Injury (AKI) was the most common non-cardiac organ failure (38.1%). Multiorgan failure was associated with an increased risk of in-hospital mortality (aOR: 4.91, 95% CI: 4.72-5.06, p <0.001) compared to no organ failure. A notable increase in mortality rates was observed in correlation with the number of organ involvement. The highest mortality rates were seen in cases where five or more organs were affected. Neurological failure exhibited a significant association with mortality when compared to other organ failures. Similar trends were seen among the CS cohort.

Conclusions

In non-acute myocardial infarction and all cardiogenic shock patients, AKI is the most common type of organ failure, and neurological failure was associated with the highest mortality rate. The presence of noncardiac multiorgan failure was found to be strongly associated with a higher mortality rate. This risk increased as more organs were affected.

Clinical Perspective

What Is New?

● Non-AMI patients bear a considerable load of non-cardiac organ failure, where AKI is the most prevalent form of organ failure. Additionally, neurological failure has the highest in-hospital mortality rate.

● A predictor model for calculating the probability of in-hospital mortality in all CS patients.

● Non-AMI cardiogenic shock and all cardiogenic shock patients are associated with higher morbidity, mortality, and resource utilization, as well as advanced circulatory support therapies, which increase as the number of affected organs increases.

What are the Clinical Implications?

● Multi-organ failure in non-AMI CS can have worse cardiovascular outcomes.

● A multidisciplinary team’s involvement in managing these complex CS patients should be considered.
Elucidating the Epigenetic Landscape of Type 2 Diabetes: A Multi-Omics Analysis Revealing Novel CpG Sites and Their Association with Cardiometabolic Traits
Authors: Chung Ren-Hua , Wang Chun-Chao , Onthoni Djeane Debora , Liao Ben-Yang , Hsu Tzu-Sheng , Martin Eden R. , Hsiung Chao A. , Sheu Wayne Huey-Herng , Chiou Hung-Yi
Published: May 2024

Type 2 Diabetes (T2D) is a complex, multifactorial disease with a significant global health burden. Genome-Wide Association Studies (GWAS) have identified numerous genetic variants associated with T2D, yet understanding their functional mechanisms remains challenging due to the polygenic nature of the disease and the prevalence of non-coding region variants. This study leverages a multi-omics approach integrating methylome-wide association studies (MWAS), Mendelian Randomization (MR), and functional analyses in human pancreatic cells and mouse models to elucidate the functional consequences of genetic variants on T2D. Using summary statistics calculated from large-scale GWAS for T2D and a DNA methylation (DNAm) prediction model, our MWAS tested the association of DNAm at CpGs in whole blood with T2D across the genome. We identified 87 significant and independent CpG sites associated with T2D risk in Europeans, including 13 novel CpG sites located in or near genes not previously associated with T2D, with these results being replicated in an additional dataset. Our analyses also revealed a significant overlap of these CpGs with cardiometabolic traits, underscoring the interconnectedness of metabolic diseases. Additionally, we demonstrated trans-ethnic effects of significant CpGs in East Asians, highlighting their global relevance. Functional analyses in human pancreatic alpha and beta cells identified potential regulatory roles of these CpGs in gene expression, particularly in genes involved in glucose metabolism. Notably, differential expression of the PPP1R3B gene, regulated by a significant CpG, between T2D cases and normal controls was observed in both alpha and beta cells, with mouse models confirming its role in glucose homeostasis. Our findings provide new insights into the epigenetic architecture of T2D, revealing novel genetic susceptibilities and highlighting potential targets for therapeutic intervention.
Conserving steppe-land birds under climate change: a gap analysis for the Eurasian Stone-curlew (Burhinus oedicnemus) in the Western Palearctic
Authors: Simoncini Andrea , Ramellini Samuele , Falaschi Mattia , Brambilla Mattia , Martineau Alexis , Massolo Alessandro , Giunchi Dimitri
Published: May 2024

Climate change is having dramatic impacts on the distribution of animals. Birds, and especially steppe-land birds, are particularly sensitive to climate change and identifying areas that are critical for their conservation is pivotal, as well as estimating the expected impact on these areas under different climate and land use change scenarios. In-situ climate refugia (areas suitable under both current and future climates) are especially valuable for the conservation of climate-sensitive species, and is therefore important to identify them and evaluate their coverage by protected areas. Via species distribution modelling, we aimed to identify in-situ climate refugia in the Western Palearctic for the Eurasian Stone-curlewBurhinus oedicnemus, an umbrella steppic species of conservation concern. We used a comprehensive dataset of occurrences in the breeding period to fine-tune a Maxent species distribution model and project it under three carbon emission scenarios of increasing severity for the year 2050. We then identified in-situ climate refugia and performed a gap analysis estimating the percentage of refugia falling within the network of currently protected areas. In all modelled future scenarios a northward expansion of suitable breeding habitats was predicted, and suitable areas had similar extents, with a slight increase of the overall suitability under more severe scenarios. According to our results, the Eurasian Stone-curlew has the potential to maintain viable populations in the Western Palearctic, even though dispersal limitations might hinder the colonization of newly suitable breeding areas. In-situ climate refugia were mainly identified outside protected areas, particularly in Northern Africa and the Middle East. Therefore, we advocate targeted actions in climate refugia to promote the conservation of this and other steppe-land species under global environmental change.
Plasmacytoid dendritic cells are dispensable or detrimental in murine systemic or respiratory viral infections
Authors: Ngo Clemence , Rahmani Khalissa , Valente Michael , Collinet Nils , Bessou Gilles , Fabregue Manon , Sharkaoui Sarah , Mazzoli Sophie , Pierini-Malosse Camille , Sansoni Amandine , Fiore Frederic , Laprie Caroline , Gaya Mauro , Gregoire Claude , Broggi Achille , Milpied Pierre , Escalière Bertrand , Vu Manh Thien Phong , Fallet Mathieu , Chasson Lionel , Tran Hien , Le Bert Marc , Malissen Bernard , Zarubica Ana , Dalod Marc , Tomasello Elena
Published: May 2024

Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As these cytokines are crucial for antiviral defense, it is assumed to be also the case for pDCs. However, robust evidence supporting this dogma is scarce. Genetic mutations or pharmacological manipulations causing pDC loss or disrupting their interferon production affect other immune cells, which could confound interpretation. To overcome this bottleneck, we engineered pDC-less mice, specifically and constitutively devoid of pDCs as expressing diphtheria toxin under coordinated control of theSiglechandPacsin1genes co-expressed uniquely in pDCs. pDC-less mice mounted protective intrinsic and innate immune responses against systemic infection with mouse Cytomegalovirus, and were more resistant to intranasal infection with influenza virus and SARS-CoV2. Thus, contrary to dogma, pDCs and their interferon production proved dispensable or deleterious during systemic or respiratory viral infections, respectively. pDC-less mice will enable rigorously revisiting the roles of pDCs in health and disease.