bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of conventional diffusion-weighted imaging and intravoxel incoherent motion in differentiating between chromophobe renal cell carcinoma and renal oncocytoma: a preliminary study
Authors: Zhu Qingqiang , Sun Jun , Ye Jing , Zhu Wenrong , Chen Wenxin
Published: May 2024

Objective

Quantitative comparison of the diagnostic efficacy of conventional diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM) in differentiating between chromophobe renal cell carcinoma (ChRCC) from renal oncocytoma (RO).

Methods

A total of 48 patients with renal tumours who had undergone DWI and IVIM were divided into two groups—ChRCC (n = 28) and RO (n = 20) groups, and the apparent diffusion coefficient (ADC), true diffusivity (D), pseudo-diffusion coefficient (D*), perfusion fraction (f) and their diagnostic efficacy were compared between the two groups.

Results

The D* values were higher in the ChRCCs group compared to the RO groups (0.019 ± 0.003 mm2/s vs 0.008 ± 0.002 mm2/s, P < .05). Moreover, the ADC, D and f values were higher in ROs compared to ChRCCs (0.61 ± 0.08 × 10−3 mm2/s vs 0.51 ± 0.06 × 10−3 mm2/s, 1.02 ± 0.15 × 10−3 mm2/s vs 0.86 ± 0.07 × 10−3 mm2/s, 0.41 ± 0.05 vs 0.28 ± 0.02, P < .05). The areas of the ADC, D, D* and f values under the ROC curves in differentiating ChRCCs from ROs were 0.713, 0.839, 0.856 and 0.906, respectively. The cut-off values of ADC, D, D* and f were 0.54, 0.91, 0.013 and 0.31, respectively. The AUC, sensitivity, specificity and accuracy of the f values were 0.906, 89.3%, 80.0% and 89.6%, respectively. For pairwise comparisons of ROC curves and diagnostic efficacy, IVIM parameters, that is, D, D* and f offered better diagnostic accuracy than ADC in differentiating ChRCCs from ROs (P = .013, .016, and .008) with f having the highest diagnostic accuracy.

Conclusion

IVIM parameters presented better performance than ADC in differentiating ChRCCs from ROs.

Advances in knowledge

(1) D* values of ChRCCs were higher, while ADC, D and f values were lower than those of RO tumours. (2) f values had the highest diagnostic efficacy in differentiating ChRCC from RO. (3) IVIM parameters, that is, D, D* and f offered better diagnostic accuracy than ADC in differentiating ChRCC from RO (P=.013, .016, and .008).
The ketogenic diet does not improve cardiac function and blunts glucose oxidation in ischaemic heart failure
Authors: Ho Kim L , Karwi Qutuba G , Wang Faqi , Wagg Cory , Zhang Liyan , Panidarapu Sai , Chen Brandon , Pherwani Simran , Greenwell Amanda A , Oudit Gavin Y , Ussher John R , Lopaschuk Gary D
Published: May 2024

Aims

Cardiac energy metabolism is perturbed in ischaemic heart failure and is characterized by a shift from mitochondrial oxidative metabolism to glycolysis. Notably, the failing heart relies more on ketones for energy than a healthy heart, an adaptive mechanism that improves the energy-starved status of the failing heart. However, whether this can be implemented therapeutically remains unknown. Therefore, our aim was to determine if increasing ketone delivery to the heart via a ketogenic diet can improve the outcomes of heart failure.

Methods and results

C57BL/6J male mice underwent either a sham surgery or permanent left anterior descending coronary artery ligation surgery to induce heart failure. After 2 weeks, mice were then treated with either a control diet or a ketogenic diet for 3 weeks. Transthoracic echocardiography was then carried out to assess in vivo cardiac function and structure. Finally, isolated working hearts from these mice were perfused with appropriately 3H or 14C labelled glucose (5 mM), palmitate (0.8 mM), and β-hydroxybutyrate (β-OHB) (0.6 mM) to assess mitochondrial oxidative metabolism and glycolysis. Mice with heart failure exhibited a 56% drop in ejection fraction, which was not improved with a ketogenic diet feeding. Interestingly, mice fed a ketogenic diet had marked decreases in cardiac glucose oxidation rates. Despite increasing blood ketone levels, cardiac ketone oxidation rates did not increase, probably due to a decreased expression of key ketone oxidation enzymes. Furthermore, in mice on the ketogenic diet, no increase in overall cardiac energy production was observed, and instead, there was a shift to an increased reliance on fatty acid oxidation as a source of cardiac energy production. This resulted in a decrease in cardiac efficiency in heart failure mice fed a ketogenic diet.

Conclusion

We conclude that the ketogenic diet does not improve heart function in failing hearts, due to ketogenic diet-induced excessive fatty acid oxidation in the ischaemic heart and a decrease in insulin-stimulated glucose oxidation.
Spontaneous and double-strand break repair-associated quasipalindrome and frameshift mutagenesis in budding yeast: role of mismatch repair
Authors: Sugawara Neal , Towne Mason J , Lovett Susan T , Haber James E
Published: May 2024

Although gene conversion (GC) in Saccharomyces cerevisiae is the most error-free way to repair double-strand breaks (DSBs), the mutation rate during homologous recombination is 1,000 times greater than during replication. Many mutations involve dissociating a partially copied strand from its repair template and re-aligning with the same or another template, leading to −1 frameshifts in homonucleotide runs, quasipalindrome (QP)-associated mutations and microhomology-mediated interchromosomal template switches. We studied GC induced by HO endonuclease cleavage at MATα, repaired by an HMR::KI-URA3 donor. We inserted into HMR::KI-URA3 an 18-bp inverted repeat where one arm had a 4-bp insertion. Most GCs yield MAT::KI-ura3::QP + 4 (Ura−) outcomes, but template-switching produces Ura+ colonies, losing the 4-bp insertion. If the QP arm without the insertion is first encountered by repair DNA polymerase and is then (mis)used as a template, the palindrome is perfected. When the QP + 4 arm is encountered first, Ura+ derivatives only occur after second-end capture and second-strand synthesis. QP + 4 mutations are suppressed by mismatch repair (MMR) proteins Msh2, Msh3, and Mlh1, but not Msh6. Deleting Rdh54 significantly reduces QP mutations only when events creating Ura+ occur in the context of a D-loop but not during second-strand synthesis. A similar bias is found with a proofreading-defective DNA polymerase mutation (poI3-01). DSB-induced mutations differed in several genetic requirements from spontaneous events. We also created a + 1 frameshift in the donor, expanding a run of 4 Cs to 5 Cs. Again, Ura+ recombinants markedly increased by disabling MMR, suggesting that MMR acts during GC but favors the unbroken, template strand.
Mechanisms and implications of bacterial–fungal competition for soil resources
Authors: Wang Chaoqun , Kuzyakov Yakov
Published: May 2024

Elucidating complex interactions between bacteria and fungi that determine microbial community structure, composition, and functions in soil, as well as regulate carbon (C) and nutrient fluxes, is crucial to understand biogeochemical cycles. Among the various interactions, competition for resources is the main factor determining the adaptation and niche differentiation between these two big microbial groups in soil. This is because C and energy limitations for microbial growth are a rule rather than an exception. Here, we review the C and energy demands of bacteria and fungi—the two major kingdoms in soil—the mechanisms of their competition for these and other resources, leading to niche differentiation, and the global change impacts on this competition. The normalized microbial utilization preference showed that bacteria are 1.4–5 times more efficient in the uptake of simple organic compounds as substrates, whereas fungi are 1.1–4.1 times more effective in utilizing complex compounds. Accordingly, bacteria strongly outcompete fungi for simple substrates, while fungi take advantage of complex compounds. Bacteria also compete with fungi for the products released during the degradation of complex substrates. Based on these specifics, we differentiated spatial, temporal, and chemical niches for these two groups in soil. The competition will increase under the main five global changes including elevated CO2, N deposition, soil acidification, global warming, and drought. Elevated CO2, N deposition, and warming increase bacterial dominance, whereas soil acidification and drought increase fungal competitiveness.
Canadian colorectal cancer screening programs: How do they measure up using the International Agency for Research on Cancer criteria for organized screening?
Authors: Law Cindy C Y , Zhang Li , Carvalho André L , Rabeneck Linda , Barkun Alan N , Nied-Kutterer Anja , Armstrong David , Wong Clarence K , Lamothe Diane , MacIntosh Donald , Dubé Catherine , Kilfoil Eileen , Telford Jennifer , Baxter Nancy N , Kumar Eshwar , Singh Harminder , McGrath Jerry , Coulter Laura , Sadowski Daniel , Efthimiou Karen , DuPlessis Hendrik , Bunzeluk Kelly , Gentile Laura , Guertin Marie-Hélène , McCurdy Bronwen R , Kohle Michael , Stewart Michael , Stimpson Ross , Antle Scott , Polos Shelley , Heitman Steven J , Zhu Tong , Ebenuwah Simbi , Kosloski Judy , Mok Melissa , Basu Partha , Tinmouth Jill
Published: May 2024

Background

Canada has one of the highest incidences of colorectal cancer (CRC) worldwide. CRC screening improves CRC outcomes and is cost-effective. This study compares Canadian CRC screening programs using essential elements of an organized screening program outlined by the International Agency for Research on Cancer (IARC).

Methods

We collaborated with the Cancer Screening in 5 continents (CanScreen5) program, an initiative of IARC. Standardized data collection forms were sent to representatives of provincial and territorial CRC screening programs. Twenty-five questions were selected to reflect IARC’s essential elements of an organized screening program. We performed a qualitative analysis of Canada’s CRC screening programs and compared programs within Canada and internationally.

Results

CRC screening programs exist in 10 provinces and 2 territories. None of the programs in Canada met all the essential criteria of an organized screening program outlined by IARC. Three programs do not send invitations to participate in screening. Among those that do, 4 programs do not include a stool test kit in the invitations. While all provinces met the essential elements for leadership, governance, finance, and access to essential services, there was more heterogeneity in the domains of service delivery as well as information systems and quality assurance.

Conclusions

There is considerable heterogeneity in the design of CRC screening programs in Canada and worldwide. Programs should strive to meet all the essential IARC criteria for organized screening if local resources allow, such as issuing invitations and implementing systems to track and compare outcomes to maximize screening program quality, effectiveness, and impact.
Taking the pulse of the outer Milky Way with the Halo Outskirts With Variable Stars (HOWVAST) survey: an RR Lyrae density profile out to >200 kpc
Authors: Medina Gustavo E , Muñoz Ricardo R , Carlin Jeffrey L , Vivas A Katherina , Grebel Eva K , Martínez-Vázquez Clara E , Hansen Camilla J
Published: May 2024

In order to constrain the evolutionary history of the Milky Way, we hunt for faint RR Lyrae stars (RRLs) using Dark Energy Camera data from the High cadence Transient Survey and the Halo Outskirts With Variable Stars survey. We report the detection of $\sim$500 RRLs, including previously identified stars and $\sim$90 RRLs not yet reported. We identify nine new RRLs beyond 100 kpc from the Sun, most of which are classified as fundamental-mode pulsators. The periods and amplitudes of the distant RRLs do not place them in either one of the two classical Oosterhoff groups, but in the Oosterhoff intermediate region. We detect two groups of clumped distant RRLs with similar distances and equatorial coordinates, which we interpret as an indication of their association with undiscovered bound or unbound satellites. We study the halo density profile using spheroidal and ellipsoidal ($q=0.7$) models, following a Markov chain Monte Carlo methodology. For a spheroidal halo, our derived radial profile is consistent with a broken power law with a break at $18.1^{+2.1}_{-1.1}$ kpc separating the inner and the outer halo, and an outer slope of $-4.47^{+0.11}_{-0.18}$. For an ellipsoidal halo, the break is located at $24.3^{+2.6}_{-3.2}$ kpc and the outer slope is $-4.57^{+0.17}_{-0.25}$. The break in the density profile is a feature visible in different directions of the halo. The similarity of these radial distributions with previous values reported in the literature seems to depend on the regions of the sky surveyed (direction and total area) and halo tracer used. Our findings are compatible with simulations and observations that predict that the outer regions of Milky Way-like galaxies are mainly composed of accreted material.
The GALAH survey: tracing the Milky Way’s formation and evolution through RR Lyrae stars
Authors: D’Orazi Valentina , Storm Nicholas , Casey Andrew R , Braga Vittorio F , Zocchi Alice , Bono Giuseppe , Fabrizio Michele , Sneden Christopher , Massari Davide , Giribaldi Riano E , Bergemann Maria , Campbell Simon W , Casagrande Luca , de Grijs Richard , De Silva Gayandhi , Lugaro Maria , Zucker Daniel B , Bragaglia Angela , Feuillet Diane , Fiorentino Giuliana , Chaboyer Brian , Dall’Ora Massimo , Marengo Massimo , Martínez-Vázquez Clara E , Matsunaga Noriyuki , Monelli Matteo , Mullen Joseph P , Nataf David , Tantalo Maria , Thevenin Frederic , Vitello Fabio R , Kudritzki Rolf-Peter , Bland-Hawthorn Joss , Buder Sven , Freeman Ken , Kos Janez , Lewis Geraint F , Lind Karin , Martell Sarah , Sharma Sanjib , Stello Dennis , Zwitter Tomaž
Published: May 2024

Stellar mergers and accretion events have been crucial in shaping the evolution of the Milky Way (MW). These events have been dynamically identified and chemically characterized using red giants and main-sequence stars. RR Lyrae (RRL) variables can play a crucial role in tracing the early formation of the MW since they are ubiquitous, old (t ≥ 10 Gyr) low-mass stars and accurate distance indicators. We exploited Data Release 3 of the GALAH survey to identify 78 field RRLs suitable for chemical analysis. Using synthetic spectra calculations, we determined atmospheric parameters and abundances of Fe, Mg, Ca, Y, and Ba. Most of our stars exhibit halo-like chemical compositions, with an iron peak around [Fe/H] ≈ −1.40, and enhanced Ca and Mg content. Notably, we discovered a metal-rich tail, with [Fe/H] values ranging from −1 to approximately solar metallicity. This sub-group includes almost 1/4 of the sample, it is characterized by thin disc kinematics and displays sub-solar α-element abundances, marginally consistent with the majority of the MW stars. Surprisingly, they differ distinctly from typical MW disc stars in terms of the s-process elements Y and Ba. We took advantage of similar data available in the literature and built a total sample of 535 field RRLs for which we estimated kinematical and dynamical properties. We found that metal-rich RRLs (1/3 of the sample) likely represent an old component of the MW thin disc. We also detected RRLs with retrograde orbits and provided preliminary associations with the Gaia–Sausage–Enceladus, Helmi, Sequoia, Sagittarius, and Thamnos stellar streams.
Redefining the concept of residual renal function with kidney sodium MRI: a pilot study
Authors: Lemoine Sandrine , Akbari Alireza , Brahm Gary , Dorie Justin , Tamasi Tanya , Penny Jarrin , McIntyre Christopher W
Published: May 2024

Background

The concept of residual kidney function (RKF) is exclusively based upon urine volume and small solute clearance, making RKF challenging to assess in clinical practice. The aim of this study was to test the technical feasibility of obtaining usable sodium magnetic resonance imaging (23Na-MRI) kidney images in hemodialysis (HD) participants.

Methods

We conducted an exploratory prospective study to quantify the cortico-medullary sodium gradient in 17 healthy volunteers and 21 HD participants. Participants fasted for 8 h prior to their study visit. Urine samples were collected to measure urinary osmolarity, before MRI. Proton and sodium pictures were merged; regions of interest were delineated for the medulla and cortex when feasible. In cases where cortex could not be identified, we considered the corticomedullary gradient (CMG) to be no longer present, resulting in a medulla-to-cortex ratio of 1.

Results

Median (interquartile range) fasting medulla-to-cortex ratio was significantly higher 1.56 (1.5–1.61) in healthy volunteers compared with HD patients 1.22 (1.13–1.3), P < .0001. Medulla to cortex ratio and median urinary osmolarity were correlated (r = 0.87, P < .0001) in the whole population. We found a significant association between HD vintage and medulla-to-cortex ratio, whereas we did not find any association with urine volume. Sodium signal intensity distribution within healthy kidney describes two different peaks relating to well defined cortex and medulla, whereas HD participants displays only a single peak indicative of the markedly lower sodium concentration.

Limitations

This study is only exploratory, with a modest number of patients.

Conclusions

The application of kidney 23Na-MRI to the study of RKF in patients receiving maintenance HD is practical and provides a previously unavailable ability to interrogate the function of remnant tubular function.

Clinical Trial Registration: NCT05014178
Efficacy and Safety of Switching to Dolutegravir/Lamivudine Versus Continuing a Tenofovir Alafenamide–Based Regimen in Virologically Suppressed Adults With Human Immunodeficiency Virus Type 1: Subgroup Analysis of Participants With Elvitegravir as Baseline Third Agent From the TANGO Study
Authors: Ait-Khaled Mounir , Oyee James , Ooi Adrian Yit Reen , Wynne Brian , Maldonado Andres , Jones Bryn , Wang Tao
Published: May 2024

TANGO results have established the durable efficacy of dolutegravir/lamivudine in virologically suppressed individuals who switched from 3- or 4-drug tenofovir alafenamide (TAF)–based regimens. In this post hoc subgroup analysis, 144-week efficacy and tolerability of dolutegravir/lamivudine in participants who switched from elvitegravir/cobicistat/emtricitabine/TAF were consistent with the overall switch population.

Clinical Trials Registration

NCT03446573.
Arabinosylation of cell wall extensin is required for the directional response to salinity in roots
Authors: Zou Yutao , Gigli-Bisceglia Nora , van Zelm Eva , Kokkinopoulou Pinelopi , Julkowska Magdalena M , Besten Maarten , Nguyen Thu-Phuong , Li Hongfei , Lamers Jasper , de Zeeuw Thijs , Dongus Joram A , Zeng Yuxiao , Cheng Yu , Koevoets Iko T , Jørgensen Bodil , Giesbers Marcel , Vroom Jelmer , Ketelaar Tijs , Petersen Bent Larsen , Engelsdorf Timo , Sprakel Joris , Zhang Yanxia , Testerink Christa
Published: May 2024

Soil salinity is a major contributor to crop yield losses. To improve our understanding of root responses to salinity, we developed and exploited a real-time salt-induced tilting assay. This assay follows root growth upon both gravitropic and salt challenges, revealing that root bending upon tilting is modulated by Na+ ions, but not by osmotic stress. Next, we measured this salt-specific response in 345 natural Arabidopsis (Arabidopsis thaliana) accessions and discovered a genetic locus, encoding the cell wall-modifying enzyme EXTENSIN ARABINOSE DEFICIENT TRANSFERASE (ExAD) that is associated with root bending in the presence of NaCl (hereafter salt). Extensins are a class of structural cell wall glycoproteins known as hydroxyproline (Hyp)-rich glycoproteins, which are posttranslationally modified by O-glycosylation, mostly involving Hyp-arabinosylation. We show that salt-induced ExAD-dependent Hyp-arabinosylation influences root bending responses and cell wall thickness. Roots of exad1 mutant seedlings, which lack Hyp-arabinosylation of extensin, displayed increased thickness of root epidermal cell walls and greater cell wall porosity. They also showed altered gravitropic root bending in salt conditions and a reduced salt-avoidance response. Our results suggest that extensin modification via Hyp-arabinosylation is a unique salt-specific cellular process required for the directional response of roots exposed to salinity.
Gamma ray spectrometric analysis and assessment of radiation hazards in soils of Mbeere North region, Kenya
Authors: Muya Joyce Wambui , Riara Martin , Kamweru Paul , Ngugi Fidelis
Published: May 2024

This study used gamma ray spectrometry to determine the radiological safety of construction soil sampled randomly from Mbeere North region, Kenya. The mean activity concentration of 232Th, 238U, and 40K was 149.7 ± 2.8 Bqkg−1, 88.3 ± 2.4 Bqkg−1, and 490 ± 35 Bqkg−1, respectively. These averages exceed the world average for all the radionuclides. The radionuclides were non-uniformly distributed, with higher concentrations along the slopes and on the feet of the hills. The mean absorbed dose rate, indoor and outdoor annual effective dose, radium equivalent, external hazard index, and internal hazard index were 157.9 ± 4.4 nGh−1, 0.58 ± 0.02 mSvy−1, 0.39 ± 0.01 mSvy−1, 340.7 ± 9.2 Bqkg−1, 0.92 ± 0.02 and 1.14 ± 0.03, respectively. Among the radiation safety indicators, only the average internal hazard index exceeded slightly the acceptable safe limit. Therefore, soils of Mbeere North region are radiologically safe for use in brick making and construction of human habitats.
Estimation of 241Am and 239Pu activity embedded in the tissue using portable planar HPGe detector
Authors: Murugan Manohari , Ponraj Sugumar , Ramasamy Mathiyarasu , Durairaj Ponraju , Balasubramanian Venkatraman
Published: May 2024

This paper describes a procedure for the estimation of 241Am and 239Pu activity present in the human tissue by measuring the depth of contaminant using a portable Planar High Purity Germanium detector (HPGe). The ratios of photopeak counts of X-rays or gammas obtained with the detector coupled to collimator are calculated for the estimation of depth of the contaminant and the optimum one is determined. Since Minimum Detectable Activities (MDA) for the detector coupled to a collimator are higher than that of bare detector, activity must be estimated using bare detector, after locating the contaminant. Two methods are described for the estimation of plutonium coexisting with 241Am: (i) Abundance and isotopic correction for 239Pu (ii) and 239Pu:241Am ratio. The procedure to estimate 239Pu when plutonium isotopes alone are present is also established. An optimum monitoring period to detect the minimum value of intake for both radionuclides corresponding to chelation therapy and excision is also derived.
Nitrogen-fixing and non-nitrogen-fixing legume plants differ in leaf nutrient concentrations and relationships between photosynthetic and hydraulic traits
Authors: Xiao Yan , Yang Da , Zhang Shu-Bin , Mo Yu-Xuan , Dong Yi-Yi , Wang Ke-Fei , He Ling-Yun , Dong Bing , Dossa Gbadamassi G O , Zhang Jiao-Lin
Published: May 2024

Legumes account for a significant proportion of plants in the terrestrial ecosystems. Nitrogen (N)-fixing capability of certain legumes is a pivotal trait that contributes to their ecological dominance. Yet, the functional traits and trait relationships between N-fixer and non-N-fixer legumes are poorly understood. Here, we investigated 27 functional traits associated with morphology, nutrients, hydraulic conductance and photosynthesis in 42 woody legumes (19 N-fixers and 23 non-N-fixers) in a common garden. Our results showed that N-fixers had higher specific leaf area, photosynthetic phosphorus (P)-use efficiency, leaf N, and iron concentrations on both area and mass basis, N/P ratio, and carbon (C) to P ratio, but lower wood density, area-based maximum photosynthetic rate (Aa), photosynthetic N-use efficiency, leaf mass- and area-based P and molybdenum and area-based boron concentrations, and C/N ratio, compared with non-N-fixers. The mass-based maximum photosynthetic rate (Am), stomatal conductance (gs), intrinsic water-use efficiency (WUEi), mass- and area-based leaf potassium and mass-based boron concentrations, leaf hydraulic conductance (Kleaf), and whole-shoot hydraulic conductance (Kshoot) showed no difference between N-fixers and non-N-fixers. Significant positive associations between all hydraulic and photosynthetic trait pairs were found in N-fixers, but only one pair (Kshoot–Aa) in non-N-fixers, suggesting that hydraulic conductance plays a more important role in mediating photosynthetic capacity in N-fixers compared with non-N-fixers. Higher mass-based leaf N was linked to lower time-integrated gs and higher WUEi among non-N-fixer legumes or all legumes pooled after phylogeny was considered. Moreover, mass-based P concentration was positively related to Am and gs in N-fixers, but not in non-N-fixers, indicating that the photosynthetic capacity and stomatal conductance in N-fixers were more dependent on leaf P status than in non-N-fixers. These findings expand our understanding of the trait-based ecology within and across N-fixer and non-N-fixer legumes in tropics.
MicroRNA‐181 in cardiovascular disease: Emerging biomarkers and therapeutic targets
Authors: Lv Bingjie , He Shaolin , Li Peixin , Jiang Shijiu , Li Dazhu , Lin Jibin , Feinberg Mark W.
Published: May 2024

Cardiovascular disease (CVD) is the leading cause of death worldwide. MicroRNAs (MiRNAs) have attracted considerable attention for their roles in several cardiovascular disease states, including both the physiological and pathological processes. In this review, we will briefly describe microRNA‐181 (miR‐181) transcription and regulation and summarize recent findings on the roles of miR‐181 family members as biomarkers or therapeutic targets in different cardiovascular‐related conditions, including atherosclerosis, myocardial infarction, hypertension, and heart failure. Lessons learned from these studies may provide new theoretical foundations for CVD.
Navigating the complexity of pain in psoriatic arthritis and axial spondyloarthritis
Authors: Mease Philip J.
Published: May 2024

Purpose of review

Pain is the most common and often most troublesome feature of chronic autoimmune diseases such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). A predominant concept is that the main source of pain is from disease-induced tissue inflammation and structural damage, activating peripheral nerve fibers which relay to the central nervous system. This mechanism is nociceptive pain and the presumption has been that controlling inflammation will be sufficient to reduce this form of pain. However, despite control of inflammation, patients may still have significant residual pain.

Recent findings

We are learning that there are additional pain mechanisms, neuropathic and nociplastic, that are often operative in patients with rheumatologic conditions, that can significantly influence pain experience, quantitation of disease activity, and may benefit from therapeutic approaches distinct from immunotherapy. Neuropathic pain arises from diseased or damaged nerve tissue and nociplastic pain reflects sensitization of the central nervous system due to multiple genetic, neurobiologic, neural network dysregulation, and psychosocial factors. Pain arising from these mechanisms influence assessment of disease activity and thus needs to be factored into decision-making about immunotherapy efficacy.

This review addresses the importance of accurately assessing the complex mechanisms of pain experience in patients with PsA and AxSpA to more appropriately manage immunomodulatory, neuromodulatory, and nonpharmacologic therapies.
Effectiveness of the Bilateral and Bilevel Erector Spinae Plane Block (ESPB) in Pediatric Idiopathic Scoliosis Surgery: A Randomized, Double-Blinded, Controlled Trial
Authors: Domagalska Małgorzata , Ciftsi Bahadir , Janusz Piotr , Reysner Tomasz , Daroszewski Przemysław , Kowalski Grzegorz , Wieczorowska-Tobis Katarzyna , Kotwicki Tomasz
Published: May 2024

Background:

This study aimed to compare the effect of the ultrasound-guided bilateral and bilevel erector spinae plane block (ESPB) on pain scores, opioid requirement, intraoperative motor-evoked potentials (MEPs), and stress response to surgery expressed by the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) versus standard analgesia methods following idiopathic scoliosis surgery.

Methods:

This was a prospective, double-blinded, randomized controlled trial. Sixty patients aged 10 to 18 years and physical status ASA 1 or 2 were randomized into 2 equal groups, each receiving an ESPB or sham block. The primary outcome was the pain scores (Numerical Rating Scale, NRS) within 48 hours after spinal correction and fusion surgery for idiopathic thoracic scoliosis. The secondary outcomes were total opioid consumption, NLR, and PLR levels at 12 and 24 hours postoperatively and intraoperative MEPs.

Results:

ESPB patients presented lower NRS scores, signifying less pain, at all time points (30, 60, 90, 120 min; and 6, 12, 24, and 48 h after surgery), all P<0.0001. The total opioid consumption, the incidence of nausea or vomiting, and the need for remifentanil and propofol during surgery were significantly lower in the ESPB group. The surgery-induced stress response expressed by NLR and PLR was considerably lower in the ESPB group. ESPB did not affect the intraoperative MEP’s amplitude.

Conclusions:

ESPB is effective for postoperative analgesia, can reduce opioid consumption in patients undergoing scoliosis surgery, and reduces the stress response to surgery. ESPB does not interfere with neuromonitoring.

Level of Evidence:

Level I.
Tocilizumab in the treatment of steroid refractory immune-related hepatotoxicity: a case series and review of the literature
Authors: Ozluk Ahmet Anil , Gunenc Damla , Yildirim Saadet Sim , Karaca Burcak
Published: May 2024

With the widespread use of immune checkpoint inhibitors, management of immune-related adverse effects specific to these treatments became an important research era in patient management. Among these, immune-related hepatotoxicity (IRH) is an adverse event that can be fatal. While the first-line treatment of IRH is well established, there is still no consensus regarding the management approach for steroid-refractory, severe IRH. Here, we report four patients with metastatic melanoma who developed IRH during antiprogrammed cell death protein-1 plus anticytotoxic T-lymphocyte-associated protein-4 combination therapy and review of the literature. All of our patients were steroid-refractory and were successfully treated with tocilizumab. Given the rapid improvement in liver enzymes and patient’s clinical status with tocilizumab, this treatment should be prioritized in steroid-refractory IRH.
Background and Self-selected Music Listening in Pulmonary and Cardiac Rehabilitation Programs
Authors: Frank Hannah E. , Munro Prue E. , Clark Imogen N. , Lee Annemarie L.
Published: May 2024

Purpose:

Music is recognized as a useful distractor from unpleasant symptoms during exercise and provides motivation; however, little is known about its application during pulmonary or cardiac rehabilitation programs, including its use, genres, and influences on genre selection. This study aimed to determine the current practice of background and self-selected music listening during exercise training in pulmonary and cardiac rehabilitation programs in Australia.

Methods:

This was a cross-sectional study, using 2 anonymous, electronic surveys. Participants were program contacts (clinicians) listed on national databases.

Results:

There were 17 of 100 (17%) and 31 of 250 (12%) respondents for pulmonary and cardiac rehabilitation programs, respectively. A total of 15 respondents (88%) reported using background music for pulmonary rehabilitation, whereas 29 respondents (94%) reported using background music for cardiac rehabilitation. Clinicians and participants had input into the selection of background music genres. Background music was preferentially upbeat and energizing, selected to motivate participants. Use of self-selected music listening by participants for individual use was uncommon in pulmonary (24%) and cardiac rehabilitation (32%).

Conclusions:

Background music is played during exercise training sessions within a limited proportion of pulmonary and cardiac rehabilitation programs surveyed in Australia. A wide range of genres were applied in background music listening, with selections predominantly based on their potential to motivate participants to exercise. There is little use of self-selected, individualized music listening among participants in these environments.
Gut-liver axis: Recent concepts in pathophysiology in alcohol-associated liver disease
Authors: Raya Tonetti Fernanda , Eguileor Alvaro , Mrdjen Marko , Pathak Vai , Travers Jared , Nagy Laura E. , Llorente Cristina
Published: May 2024

The growing recognition of the role of the gut microbiome’s impact on alcohol-associated diseases, especially in alcohol-associated liver disease, emphasizes the need to understand molecular mechanisms involved in governing organ-organ communication to identify novel avenues to combat alcohol-associated diseases. The gut-liver axis refers to the bidirectional communication and interaction between the gut and the liver. Intestinal microbiota plays a pivotal role in maintaining homeostasis within the gut-liver axis, and this axis plays a significant role in alcohol-associated liver disease. The intricate communication between intestine and liver involves communication between multiple cellular components in each organ that enable them to carry out their physiological functions. In this review, we focus on novel approaches to understanding how chronic alcohol exposure impacts the microbiome and individual cells within the liver and intestine, as well as the impact of ethanol on the molecular machinery required for intraorgan and interorgan communication.
Protein disulfide isomerase-mediated transcriptional upregulation of Nox1 contributes to vascular dysfunction in hypertension
Authors: Camargo Livia De Lucca , Trevelin Silvia Cellone , da Silva Guilherme Henrique Gatti , dos Santos Dias Ana Alice , Oliveira Maria Aparecida , Mikhaylichenko Olga , Androwiki Aline C.D. , dos Santos Celio Xavier , Holbrook Lisa-Marie , Ceravolo Graziela Scalianti , Denadai-Souza Alexandre , Ribeiro Izabela Martina Ramos , Sartoretto Simone , Laurindo Francisco Rafael Martins , Coltri Patricia Pereira , Antunes Vagner Roberto , Touyz Rhian , Miller Francis J. , Shah Ajay M. , Lopes Lucia Rossetti
Published: May 2024

Nox1 signaling is a causal key element in arterial hypertension. Recently, we identified protein disulfide isomerase A1 (PDI) as a novel regulatory protein that regulates Nox1 signaling in VSMCs. Spontaneously hypertensive rats (SHR) have increased levels of PDI in mesenteric resistance arteries compared with Wistar controls; however, its consequences remain unclear. Herein, we investigated the role of PDI in mediating Nox1 transcriptional upregulation and its effects on vascular dysfunction in hypertension. We demonstrate that PDI contributes to the development of hypertension via enhanced transcriptional upregulation of Nox1 in vascular smooth muscle cells (VSMCs). We show for the first time that PDI sulfenylation by hydrogen peroxide contributes to EGFR activation in hypertension via increased shedding of epidermal growth factor-like ligands. PDI also increases intracellular calcium levels, and contractile responses induced by ANG II. PDI silencing or pharmacological inhibition in VSMCs significantly decreases EGFR activation and Nox1 transcription. Overexpression of PDI in VSMCs enhances ANG II-induced EGFR activation and ATF1 translocation to the nucleus. Mechanistically, PDI increases ATF1-induced Nox1 transcription and enhances the contractile responses to ANG II. Herein we show that ATF1 binding to Nox1 transcription putative regulatory regions is augmented by PDI. Altogether, we provide evidence that HB-EGF in SHR resistance vessels promotes the nuclear translocation of ATF1, under the control of PDI, and thereby induces Nox1 gene expression and increases vascular reactivity. Thus, PDI acts as a thiol redox-dependent enhancer of vascular dysfunction in hypertension and could represent a novel therapeutic target for the treatment of this disease.
Altered gut microbiota and metabolite profiles provide clues in understanding resistant hypertension
Authors: Guo Jiuqi , Jia Pengyu , Gu Zhilin , Tang Wenyi , Wang Ai , Sun Yingxian , Li Zhao
Published: May 2024

Background:

Resistant hypertension is a severe phenotype in hypertension that may be driven by interactions between genetic and environmental factors. Specific changes in gut microbiota and metabolites have been shown to influence cardiovascular disease progression. However, microbial and metabolomic changes associated with resistant hypertension remain elusive.

Methods:

In this study, the gut microbiome of 30 participants with resistant hypertension, 30 with controlled hypertension, and 30 nonhypertension was characterized using 16S rRNA amplicon sequencing. In addition, the serum metabolome of the same population was assessed by untargeted metabolomics.

Results:

The alpha diversity of microbiome in the resistant hypertension decreased, and changes were also observed in the composition of the gut microbiota. The resistant hypertension group was characterized by elevated levels of Actinobacteitia and Proteobacteria. Twenty-three genera were found to have significantly different abundances between resistant hypertension and controlled hypertension, as well as 55 genera with significantly different abundances between resistant hypertension and nonhypertension. Compared with the controlled hypertension group, the genera Rothia and Sharpea in resistant hypertension were more abundant. Compared with the nonhypertension group, the genera Escherichia–Shigella, Lactobacillus, Enterococcus were more abundant. Untargeted metabolomics provided distinctly different serum metabolic profiles for the three groups and identified a range of differential metabolites. These metabolites were mainly associated with the pathway of glycerophospholipid metabolism. Furthermore, correlation analysis provided evidence of new interactions between gut microbiota and metabolites in the resistant hypertension.

Conclusion:

In conclusion, our study provides a comprehensive understanding of the resistant hypertension gut microbiota and metabolites, suggesting that treatment resistance in resistant hypertension patients may be related to the gut microbiota and serum metabolites.
Evaluation of the oscillometric method for noninvasive blood pressure measurement during cuff deflation and cuff inflation with reference to intra-arterial blood pressure
Authors: Celler Branko G. , Yong Andy , Rubenis Imants , Butlin Mark , Argha Ahmadreza , Rehan Rajan , Avolio Alberto
Published: May 2024

There is little quantitative clinical data available to support blood pressure measurement accuracy during cuff inflation. In this study of 35 male and 5 female lightly anaesthetized subjects aged 64.1 ± 9.6 years, we evaluate and compare the performance of both the oscillometric ratio and gradient methods during cuff deflation and cuff inflation with reference to intra-arterial measurements. We show that the oscillometric waveform envelopes (OWE), which are key to both methods, exhibit significant variability in both shape and smoothness leading to at least 15% error in the determination of mean pressure (MP). We confirm the observation from our previous studies that K1 Korotkoff sounds underestimate systolic blood pressure (SBP) and note that this underestimation is increased during cuff inflation. The estimation of diastolic blood pressure (DBP) is generally accurate for both the ratio and the gradient method, with the latter showing a significant increase during inflation. Since the gradient method estimates SBP and DBP from points of maximum gradient on each OWE recorded, it may offer significant benefits over the ratio method. However, we have shown that the ratio method can be optimized for any data set to achieve either a minimum mean error (ME) of close to 0 mmHg or minimum root mean square error (RMSE) with standard deviation (SD) of <5.0 mmHg. We conclude that whilst cuff inflation may offer some advantages, these are neither significant nor substantial, leaving as the only benefit, the potential for more rapid measurement and less patient discomfort.
Circulating angiotensin-(1–7) is decreased in patients with isolated nocturnal hypertension
Authors: Minetto Julián , Cuello María B. , Dominici Fernando P. , Caniffi Carolina , Brizzio Ana M. , Cerri Gustavo , Salazar Martin R. , Espeche Walter G. , Gironacci Mariela M.
Published: May 2024

Isolated nocturnal hypertension (INHT), defined as nighttime elevated blood pressure (BP) with normal daytime BP assessed by ambulatory BP monitoring, is associated with higher cardiovascular morbidity and mortality. We hypothesized that an alteration in the circulating renin-angiotensin system (RAS) contributes to INHT development. We examined circulating levels of angiotensin (Ang) (1–7) and Ang II and ACE2 activity in 26 patients that met the INHT criteria, out of 50 that were referred for BP evaluation (62% women, 45 ± 16 years old). Those with INHT were older, had a higher BMI, lower circulating Ang-(1–7) (P = 0.002) and Ang II levels (P = 0.02) and no change in ACE2 activity compared to those normotensives. Nighttime DBP was significantly correlated with Ang-(1–7) and Ang II levels. Logistic regression showed significant association in Ang-(1–7) and Ang II levels with INHT. Our study reveals differences in circulating RAS in individuals with INHT.
Management of hypertensive disorders in pregnancy: a Position Statement of the European Society of Hypertension Working Group ‘Hypertension in Women’
Authors: Thomopoulos Costas , Hitij Jana Brguljan , De Backer Tine , Gkaliagkousi Eugenia , Kreutz Reinhold , Lopez-Sublet Marilucy , Marketou Maria , Mihailidou Anastasia S. , Olszanecka Agnieszka , Pechère-Bertschi Antoinette , Pérez Mariana Paula , Persu Alexandre , Piani Federica , Socrates Thenral , Stolarz-Skrzypek Katarzyna , Cífková Renata
Published: May 2024

Hypertensive disorders in pregnancy (HDP), remain the leading cause of adverse maternal, fetal, and neonatal outcomes. Epidemiological factors, comorbidities, assisted reproduction techniques, placental disorders, and genetic predisposition determine the burden of the disease. The pathophysiological substrate and the clinical presentation of HDP are multifarious. The latter and the lack of well designed clinical trials in the field explain the absence of consensus on disease management among relevant international societies. Thus, the usual clinical management of HDP is largely empirical. The current position statement of the Working Group ‘Hypertension in Women’ of the European Society of Hypertension (ESH) aims to employ the current evidence for the management of HDP, discuss the recommendations made in the 2023 ESH guidelines for the management of hypertension, and shed light on controversial issues in the field to stimulate future research.
Accuracy of new intraocular lens power calculation formula for short and long eyes using segmental refractive indices
Authors: Kato Yukihito , Ayaki Masahiko , Tamaoki Akeno , Tanaka Yoshiki , Ichikawa Kei , Ichikawa Kazuo
Published: May 2024

Purpose:

To evaluate the accuracy of a new intraocular lens power calculation formula using segmental refractive index-based axial length (AL).

Setting:

Chukyo Eye Clinic, Nagoya, Japan.

Design:

Retrospective observational study.

Methods:

This study included patients undergoing preoperative examination for cataract surgery with the new Barrett True AL (BTAL) and Emmetropia Verifying Optical (EVO) formulas using segmental refractive index, and conventional Barrett Universal II (BU II) formula using equivalent refractive index. The predicted refractive error of each formula was compared with the postoperative subjective spherical equivalent.

Results:

The mean prediction error (MPE) in the short AL group (≤22 mm; 44 eyes) was 0.32 ± 0.40 diopter (D) for BU II, 0.22 ± 0.37 D for BTAL, and 0.10 ± 0.37 D for EVO (P< .0001). MPE in the long AL group (≥26 mm; 92 eyes) was 0.01 ± 0.32 D for BU II, 0.04 ± 0.32 D for BTAL, and 0.09 ± 0.32 D for EVO (P< .0001). In patients with an AL ≥ 28 mm, BU II showed a myopic trend in 57.1% of cases, while BTAL and EVO showed a hyperopic trend in 71.4%. The MPE for patients with an AL ≥ 28 mm was −0.16 ± 0.34 D for BU II, 0.18 ± 0.33 D for BTAL, and 0.16 ± 0.32 D for EVO (P< .0001).

Conclusions:

The new EVO and BTAL formulas showed higher accuracy than BU II in short eyes, whereas there was no difference in long eyes.
Wearable wireless continuous vital signs monitoring on the general ward
Authors: Leenen Jobbe PL. , Schoonhoven Lisette , Patijn Gijs A.
Published: May 2024

Purpose of review

Wearable wireless sensors for continuous vital signs monitoring (CVSM) offer the potential for early identification of patient deterioration, especially in low-intensity care settings like general wards. This study aims to review advances in wearable CVSM – with a focus on the general ward – highlighting the technological characteristics of CVSM systems, user perspectives and impact on patient outcomes by exploring recent evidence.

Recent findings

The accuracy of wearable sensors measuring vital signs exhibits variability, especially notable in ambulatory patients within hospital settings, and standard validation protocols are lacking. Usability of CMVS systems is critical for nurses and patients, highlighting the need for easy-to-use wearable sensors, and expansion of the number of measured vital signs. Current software systems lack integration with hospital IT infrastructures and workflow automation. Imperative enhancements involve nurse-friendly, less intrusive alarm strategies, and advanced decision support systems. Despite observed reductions in ICU admissions and Rapid Response Team calls, the impact on patient outcomes lacks robust statistical significance.

Widespread implementation of CVSM systems on the general ward and potentially outside the hospital seems inevitable. Despite the theoretical benefits of CVSM systems in improving clinical outcomes, and supporting nursing care by optimizing clinical workflow efficiency, the demonstrated effects in clinical practice are mixed. This review highlights the existing challenges related to data quality, usability, implementation, integration, interpretation, and user perspectives, as well as the need for robust evidence to support their impact on patient outcomes, workflow and cost-effectiveness.
New insights into renal calcium-sensing receptor activation
Authors: Dimke Henrik
Published: May 2024

Purpose of review

Activation of the calcium-sensing receptor (CASR) in the parathyroid gland suppresses the release of parathyroid hormone (PTH). Furthermore, activation of the renal CASR directly increases the urinary excretion of calcium, by inhibiting transepithelial calcium transport in the nephron. Gain-of-function mutations in the CASR gene lead to autosomal dominant hypocalcemia 1 (ADH1), with inappropriately low PTH levels and hypocalcemia, indicative of excessive activation of the parathyroid CASR. However, hypercalciuria is not always observed. The reason why the manifestation of hypercalciuria is not uniform among ADH1 patients is not well understood.

Recent findings

Direct activation of the CASR in the kidney has been cumbersome to study, and an indirect measure to effectively estimate the degree of CASR activation following chronic hypercalcemia or genetic gain-of-function CASR activation has been lacking. Studies have shown that expression of the pore-blocking claudin-14 is strongly stimulated by the CASR in a dose-dependent manner. This stimulatory effect is abolished after renal Casr ablation in hypercalcemic mice, suggesting that claudin-14 abundance may gauge renal CASR activation. Using this marker has led to unexpected discoveries regarding renal CASR activation.

These new studies have informed on renal CASR activation thresholds and the downstream CASR-regulated calcium transport mechanisms.