bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of transplant recipients with pretransplant Nocardia colonization or infection
Authors: Yetmar Zachary A. , Chesdachai Supavit , Khodadadi Ryan B. , McHugh Jack W. , Challener Douglas W. , Wengenack Nancy L. , Bosch Wendelyn , Seville Maria Teresa , Beam Elena
Published: June 2023

Background

Specific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied.

Methods

We performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality.

Results

Nine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart‐kidney (N = 1), liver‐kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152–283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim‐sulfamethoxazole (TMP‐SMX) and all patients received TMP‐SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow‐up of 1.96 (IQR 0.90–6.33) years. Two patients died during follow‐up, both without evidence of nocardiosis.

Conclusions

This study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP‐SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis.

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Impact on canine neutrophil preservation with the addition of bovine serum albumin to K3‐EDTA whole blood samples
Authors: Reinhart Brodie , Gilroy Cornelia , Clancey Noel , Burton Shelley , Stull Jason W. , Bishop Nicole , Thakur Krishna
Published: June 2023

Background

Cellular deterioration occurs with blood sample aging, impacting white blood cell (WBC) identification and differential accuracy. This may be exacerbated in samples from patients experiencing inflammation. Previously, bovine serum albumin (BSA) has been shown to improve cellular preservation of blood and other samples, but the effect on cell preservation in canine blood has not been assessed.

Objectives

We aimed to determine the effects of BSA on neutrophil nuclear area when added to potassium ethylene diamine tetra‐acetic acid (K3‐EDTA)‐anticoagulated canine blood prior to blood smear preparation. We evaluated the impact of inflammatory leukograms, sample storage temperatures (4° and 20°C), and time on outcomes.

Materials and methods

Canine K3‐EDTA‐anticoagulated blood samples stored at 4° and 20°C were used from unique patients, 10 with and 10 without inflammatory leukograms. Blood smears were prepared from aliquots with or without the addition of 22% BSA at 0, 4, 8, 24, 48, and 72 h. The nuclear area was measured for 25 randomly selected neutrophils per slide using Fiji software. Mixed‐effect linear regression modeling was performed (significance: P < 0.05).

Results

Nuclear area increased over time with and without added BSA. Both sample storage temperatures and the presence or absence of an inflammatory leukogram significantly impacted neutrophil nuclear area. Samples with added BSA had slightly higher predicted nuclear areas than those without BSA, but this difference was not statistically significant.

Conclusions

BSA did not significantly impact neutrophil nuclear area and did not improve neutrophil preservation in canine blood samples.
Multimaterial Topology Optimization of Adhesive Backing Layers via J-Integral and Strain Energy Minimizations
Authors: Tong Zhiyuan , Benvidi Farid H. , Bacca Mattia
Published: June 2023

Strong adhesives often rely on reduced stress concentrations obtained via specific functional grading of material properties. This can be seen in many examples in nature and engineering. Basic design principles have been formulated based on parametric optimization, but a general design tool is still missing. We propose here the use of topology optimization to achieve optimal stiffness distribution in a multimaterial adhesive backing layer, reducing stress concentration at selected (crack tip) locations. The method involves the minimization of a linear combination of (i) the J-integral around the crack tip and (ii) the strain energy of the structure. This combination is due to the compromise between numerical stability and accuracy of the method, where (i) alone is numerically unstable and (ii) alone cannot eliminate the crack tip stress singularity. We analyze three cases in plane strain conditions, namely, (1) double-edged crack and (2) center crack, in tension, as well as (3) edge crack under shear. Each case evidences a different optimal topology with (1) and (2) providing similar results. The optimal topology allocates stiffness in regions that are far away from the crack tip, and the allocation of softer materials over stiffer ones produces a sophisticated structural hierarchy. To test our solutions, we plot the contact stress distribution across the interface. In all observed cases, we eliminate the stress singularity at the crack tip, albeit generating (mild) stress concentrations in other locations. The optimal topologies are tested to be independent of the crack size. Our method ultimately provides the robust design of flaw tolerant adhesives where the crack location is known.
A Computational Model of Human Proficiency in Engineering Configuration Design
Authors: Brownell Ethan , Cagan Jonathan , Kotovsky Kenneth
Published: June 2023

This work introduces the Proficient Simulated Annealing Design Agent Model (PSADA), a cognitively inspired, agent-based model of engineering configuration design. PSADA models different proficiency agents using move selection heuristics and problem space search strategies, both of which are identified and extracted from prior human subject studies. The model is validated with two design problems. Agents are compared to human designers and show the accurate simulation of the behaviors of the different proficiency designers. These behavior differences lead to significantly different performance levels, matching the human performance levels with just one exception. These validated heterogeneous agents are placed into teams and confirmed previous findings that the most proficient member of a configuration design team has the largest impact (positive or negative) on team performance. The PSADA model is introduced as a scalable platform to further explore configuration design proficiency’s role in design team performance and organizational behavior.
Four new Diptilomiopus mite species (Acari: Diptilomiopidae) from China
Authors: Gao Wei-Nan , Lotfollahi Parisa , Xue Xiao-Feng
Published: June 2023

Four new eriophyoid mite species of the genus Diptilomiopus Nalepa (Acari: Diptilomiopidae) from China are described and illustrated. They are D. cotoneastrus sp. nov. on Cotoneaster acutifolius Turcz. (Rosaceae), D. clidemioidus sp. nov. on Boehmeria clidemioides var. diffusa (Wedd.) Hand.-Mazz. (Urticaceae), D. quinatus sp. nov. on Vitex quinata (Lour.) F.N.Williams (Lamiaceae), and D. macropodus sp. nov. on Daphniphyllum macropodum Miq. (Daphniphyllaceae). All new species are distributed in the Oriental Region of China. They are vagrants on the leaves causing no apparent symptom to their host plants. We further provided mitochondrial cox1 gene sequences for the four new species.
Between-Seasons Variability of Cyclists’ Peak Performance: A Longitudinal Analysis of “Real-World” Power Output Data in Male Professional Cyclists
Authors: Valenzuela Pedro L. , Mateo-March Manuel , Muriel Xabier , Zabala Mikel , Lucia Alejandro , Barranco-Gil David , Pallares Jesús G.
Published: June 2023

Purpose: The record power profile (RPP) has gained popularity as a method of monitoring endurance cycling performance. However, the expected variation of cyclists’ performance between seasons remains unknown. We aimed to assess the between-seasons variability of peak performance (assessed through the RPP) in male professional cyclists. Methods: The study followed a longitudinal observational design. Sixty-one male professional cyclists (age 26 [5] y) with power output data from both training sessions and competitions were analyzed for a median of 4 consecutive seasons (range 2–12). The highest mean maximum power values attained for different durations (from 10 s to 30 min), as well as the resulting critical power, were determined for each season. Within-cyclist variability between seasons was assessed, and the upper threshold of expected changes (ie, twice the normal coefficient of variation) was determined. Results: All mean maximum power values showed an overall high agreement and low variability between seasons (intraclass correlation coefficient [ICC] = .76–.88 and coefficient of variation [CV] = 3.2%–5.9%), with the lowest variability observed for long efforts (>1 min). Critical power showed an ICC and CV of .79 (95% CI, .70–.85) and 3.3% (95% CI, 3.0%–3.7%), respectively. Upper thresholds of expected variation were <12% for short efforts (≤1 min) and <8% for long efforts. Conclusions: “Real-world” peak performance assessed through the RPP shows a low variability between seasons in male professional cyclists—especially for long efforts—with expected variation being around 6% and 3% for short (≤1 min) and long efforts, respectively, and with changes >12% and >8%, respectively, being infrequent for these effort durations.
Branched-chain actin dynamics polarizes vesicle trajectories and partitions apicobasal epithelial membrane domains
Authors: Jafari Gholamali , Khan Liakot A. , Zhang Hongjie , Membreno Edward , Yan Siyang , Dempsey Graham , Gobel Verena
Published: June 2023

In prevailing epithelial polarity models, membrane- and junction-based polarity cues such as the partitioning-defective PARs specify the positions of apicobasal membrane domains. Recent findings indicate, however, that intracellular vesicular trafficking can determine the position of the apical domain, upstream of membrane-based polarity cues. These findings raise the question of how vesicular trafficking becomes polarized independent of apicobasal target membrane domains. Here, we show that the apical directionality of vesicle trajectories depends on actin dynamics during de novo polarized membrane biogenesis in theC. elegansintestine. We find that actin, powered by branched-chain actin modulators, determines the polarized distribution of apical membrane components, PARs, and itself. Using photomodulation, we demonstrate that F-actin travels through the cytoplasm and along the cortex toward the future apical domain. Our findings support an alternative polarity model where actin-directed trafficking asymmetrically inserts the nascent apical domain into the growing epithelial membrane to partition apicobasal membrane domains.
Scale-free correlations and potential criticality in weakly ordered populations of brain cancer cells
Authors: Wood Kevin B. , Comba Andrea , Motsch Sebastien , Grigera Tomás S. , Lowenstein Pedro R.
Published: June 2023

Collective behavior spans several orders of magnitude of biological organization, from cell colonies to flocks of birds. We used time-resolved tracking of individual glioblastoma cells to investigate collective motion in an ex vivo model of glioblastoma. At the population level, glioblastoma cells display weakly polarized motion in the (directional) velocities of single cells. Unexpectedly, fluctuations in velocities are correlated over distances many times the size of a cell. Correlation lengths scale linearly with the maximum end-to-end length of the population, indicating that they are scale-free and lack a characteristic decay scale other than the size of the system. Last, a data-driven maximum entropy model captures statistical features of the experimental data with only two free parameters: the effective length scale (

n
c

) and strength (
J
) of local pairwise interactions between tumor cells. These results show that glioblastoma assemblies exhibit scale-free correlations in the absence of polarization, suggesting that they may be poised near a critical point.
Chasing iron bioavailability in the Southern Ocean: Insights from
Phaeocystis antarctica
and iron speciation
Authors: Fourquez Marion , Janssen David J. , Conway Tim M. , Cabanes Damien , Ellwood Michael J. , Sieber Matthias , Trimborn Scarlett , Hassler Christel
Published: June 2023

Dissolved iron (dFe) availability limits the uptake of atmospheric CO
2
by the Southern Ocean (SO) biological pump. Hence, any change in bioavailable dFe in this region can directly influence climate. On the basis of Fe uptake experiments with
Phaeocystis antarctica
, we show that the range of dFe bioavailability in natural samples is wider (<1 to ~200% compared to free inorganic Fe′) than previously thought, with higher bioavailability found near glacial sources. The degree of bioavailability varied regardless of in situ dFe concentration and depth, challenging the consensus that sole dFe concentrations can be used to predict Fe uptake in modeling studies. Further, our data suggest a disproportionately major role of biologically mediated ligands and encourage revisiting the role of humic substances in influencing marine Fe biogeochemical cycling in the SO. Last, we describe a linkage between in situ dFe bioavailability and isotopic signatures that, we anticipate, will stimulate future research.
Deciphering the structural dynamics in molten salt–promoted MgO-based CO
2
sorbents and their role in the CO
2
uptake
Authors: Rekhtina Margarita , Krödel Maximilian , Wu Yi-Hsuan , Kierzkowska Agnieszka , Donat Felix , Abdala Paula M. , Müller Christoph R.
Published: June 2023

The development of effective CO
2
sorbents is vital to achieving net-zero CO
2
emission targets. MgO promoted with molten salts is an emerging class of CO
2
sorbents. However, the structural features that govern their performance remain elusive. Using in situ time-resolved powder x-ray diffraction, we follow the structural dynamics of a model NaNO
3
-promoted, MgO-based CO
2
sorbent. During the first few cycles of CO
2
capture and release, the sorbent deactivates owing to an increase in the sizes of the MgO crystallites, reducing in turn the abundance of available nucleation points, i.e., MgO surface defects, for MgCO
3
growth. After the third cycle, the sorbent shows a continuous reactivation, which is linked to the in situ formation of Na
2
Mg(CO
3
)
2
crystallites that act effectively as seeds for MgCO
3
nucleation and growth. Na
2
Mg(CO
3
)
2
forms due to the partial decomposition of NaNO
3
during regeneration at
T
≥ 450°C followed by carbonation in CO
2
.
Multidimensional definition of the interferonopathy of Down syndrome and its response to JAK inhibition
Authors: Galbraith Matthew D. , Rachubinski Angela L. , Smith Keith P. , Araya Paula , Waugh Katherine A. , Enriquez-Estrada Belinda , Worek Kayleigh , Granrath Ross E. , Kinning Kohl T. , Paul Eduthan Neetha , Ludwig Michael P. , Hsieh Elena W. Y. , Sullivan Kelly D. , Espinosa Joaquin M.
Published: June 2023

Individuals with Down syndrome (DS) display chronic hyperactivation of interferon signaling. However, the clinical impacts of interferon hyperactivity in DS are ill-defined. Here, we describe a multiomics investigation of interferon signaling in hundreds of individuals with DS. Using interferon scores derived from the whole blood transcriptome, we defined the proteomic, immune, metabolic, and clinical features associated with interferon hyperactivity in DS. Interferon hyperactivity associates with a distinct proinflammatory phenotype and dysregulation of major growth signaling and morphogenic pathways. Individuals with the highest interferon activity display the strongest remodeling of the peripheral immune system, including increased cytotoxic T cells, B cell depletion, and monocyte activation. Interferon hyperactivity accompanies key metabolic changes, most prominently dysregulated tryptophan catabolism. High interferon signaling stratifies a subpopulation with elevated rates of congenital heart disease and autoimmunity. Last, a longitudinal case study demonstrated that JAK inhibition normalizes interferon signatures with therapeutic benefit in DS. Together, these results justify the testing of immune-modulatory therapies in DS.
Chiral electroluminescence from thin-film perovskite metacavities
Authors: Kim Seongheon , An Soo-Chan , Kim Younggon , Shin Yun Seop , Antonov Alexander A. , Seo In Cheol , Woo Byung Hoon , Lim Yeonsoo , Gorkunov Maxim V. , Kivshar Yuri S. , Kim Jin Young , Jun Young Chul
Published: June 2023

Chiral light sources realized in ultracompact device platforms are highly desirable for various applications. Among active media used for thin-film emission devices, lead-halide perovskites have been extensively studied for photoluminescence due to their exceptional properties. However, up to date, there have been no demonstrations of chiral electroluminescence with a substantial degree of circular polarization (DCP) based on perovskite materials, being critical for the development of practical devices. Here, we propose a concept of chiral light sources based on a thin-film perovskite metacavity and experimentally demonstrate chiral electroluminescence with a peak DCP approaching 0.38. We design a metacavity created by a metal and a dielectric metasurface supporting photonic eigenstates with a close-to-maximum chiral response. Chiral cavity modes facilitate asymmetric electroluminescence of pairs of left and right circularly polarized waves propagating in the opposite oblique directions. The proposed ultracompact light sources are especially advantageous for many applications requiring chiral light beams of both helicities.
Jamming and depletion in extremely bidisperse mixtures of microscale emulsions and nanoemulsions
Authors: Xu Yixuan , Mason Thomas G.
Published: June 2023

While much attention has been given to jamming of granular and colloidal particles having monomodal size distributions, jamming of systems having more complex size distributions remains an interesting direction. We create concentrated, disordered binary mixtures of size-fractionated nanoscale and microscale oil-in-water emulsions, which are stabilized by the same common ionic surfactant, and measure the optical transport properties, microscale droplet dynamics, and mechanical shear rheological properties of these mixtures over a wide range of relative and total droplet volume fractions. Simple effective medium theories do not explain all of our observations. Instead, we show that our measurements are consistent with more complex collective behavior in extremely bidisperse systems, involving an effective continuous phase that governs nanodroplet jamming, as well as depletion attractions between microscale droplets induced by nanoscale droplets.
Dynamics of molecular rotors in bulk superfluid helium
Authors: Milner Alexander A. , Apkarian V. A. , Milner Valery
Published: June 2023

Molecules immersed in liquid helium are excellent probes of superfluidity. Their electronic, vibrational, and rotational dynamics provide valuable clues about the superfluid at the nanoscale. Here we report on the experimental study of the laser-induced rotation of helium dimers inside the superfluid
4
He bath at variable temperature. The coherent rotational dynamics of

He

2
∗

is initiated in a controlled way by ultrashort laser pulses and tracked by means of time-resolved laser-induced fluorescence. We detect the decay of rotational coherence on the nanosecond time scale and investigate the effects of temperature on the decoherence rate. The observed temperature dependence suggests a nonequilibrium evolution of the quantum bath, accompanied by the emission of the wave of second sound. The method offers ways of studying superfluidity with molecular nanoprobes under variable thermodynamic conditions.
Technology matters, especially when deploying robots in the real world
Authors: Nelson Bradley J.
Published: June 2023

Making reliable robots that effectively operate in unstructured environments can be deceptively hard.
Notch signaling drives intestinal graft-versus-host disease in mice and nonhuman primates
Authors: Tkachev Victor , Vanderbeck Ashley , Perkey Eric , Furlan Scott N. , McGuckin Connor , Gómez Atria Daniela , Gerdemann Ulrike , Rui Xianliang , Lane Jennifer , Hunt Daniel J. , Zheng Hengqi , Colonna Lucrezia , Hoffman Michelle , Yu Alison , Outen Riley , Kelly Samantha , Allman Anneka , Koch Ute , Radtke Freddy , Ludewig Burkhard , Burbach Brandon , Shimizu Yoji , Panoskaltsis-Mortari Angela , Chen Guoying , Carpenter Stephen M. , Harari Olivier , Kuhnert Frank , Thurston Gavin , Blazar Bruce R. , Kean Leslie S. , Maillard Ivan
Published: June 2023

Notch signaling promotes T cell pathogenicity and graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) in mice, with a dominant role for the Delta-like Notch ligand DLL4. To assess whether Notch’s effects are evolutionarily conserved and to identify the mechanisms of Notch signaling inhibition, we studied antibody-mediated DLL4 blockade in a nonhuman primate (NHP) model similar to human allo-HCT. Short-term DLL4 blockade improved posttransplant survival with durable protection from gastrointestinal GVHD in particular. Unlike prior immunosuppressive strategies tested in the NHP GVHD model, anti-DLL4 interfered with a T cell transcriptional program associated with intestinal infiltration. In cross-species investigations, Notch inhibition decreased surface abundance of the gut-homing integrin α4β7 in conventional T cells while preserving α4β7 in regulatory T cells, with findings suggesting increased β1 competition for α4 binding in conventional T cells. Secondary lymphoid organ fibroblastic reticular cells emerged as the critical cellular source of Delta-like Notch ligands for Notch-mediated up-regulation of α4β7 integrin in T cells after allo-HCT. Together, DLL4-Notch blockade decreased effector T cell infiltration into the gut, with increased regulatory to conventional T cell ratios early after allo-HCT. Our results identify a conserved, biologically unique, and targetable role of DLL4-Notch signaling in intestinal GVHD.
Use and detection of a vitamin B1 degradation product yields new views of the marine B1 cycle and plankton metabolite exchange
Authors: Paerl Ryan W. , Curtis Nathaniel P. , Bittner Meriel J. , Cohn Melanie R. , Gifford Scott M. , Bannon Catherine C. , Rowland Elden , Bertrand Erin M.
Published: June 2023

Vitamin B1 (thiamin) is a vital nutrient for most cells in nature, including marine plankton. Early and recent experiments show that B1 degradation products instead of B1 can support the growth of marine bacterioplankton and phytoplankton. However, the use and occurrence of some degradation products remains uninvestigated, namely N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (FAMP), which has been a focus of plant oxidative stress research. We investigated the relevance of FAMP in the ocean. Experiments and global ocean meta-omic data indicate that eukaryotic phytoplankton, including picoeukaryotes and harmful algal bloom species, use FAMP while bacterioplankton appear more likely to use deformylated FAMP, 4-amino-5-aminomethyl-2-methylpyrimidine. Measurements of FAMP in seawater and biomass revealed that it occurs at picomolar concentrations in the surface ocean, heterotrophic bacterial cultures produce FAMP in the dark—indicating non-photodegradation of B1 by cells, and B1-requiring (auxotrophic) picoeukaryotic phytoplankton produce intracellular FAMP. Our results require an expansion of thinking about vitamin degradation in the sea, but also the marine B1 cycle where it is now crucial to consider a new B1-related compound pool (FAMP), as well as generation (dark degradation—likely via oxidation), turnover (plankton uptake), and exchange of the compound within the networks of plankton.

IMPORTANCE

Results of this collaborative study newly show that a vitamin B1 degradation product, N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (FAMP), can be used by diverse marine microbes (bacteria and phytoplankton) to meet their vitamin B1 demands instead of B1 and that FAMP occurs in the surface ocean. FAMP has not yet been accounted for in the ocean and its use likely enables cells to avoid B1 growth deficiency. Additionally, we show FAMP is formed in and out of cells without solar irradiance—a commonly considered route of vitamin degradation in the sea and nature. Altogether, the results expand thinking about oceanic vitamin degradation, but also the marine B1 cycle where it is now crucial to consider a new B1-related compound pool (FAMP), as well as its generation (dark degradation—likely via oxidation), turnover (plankton uptake), and exchange within networks of plankton.
A New Algivorous Heterolobosean Amoeba, Euplaesiobystra perlucida sp. nov. (Tetramitia, Discoba), Isolated from Pilot-Scale Cultures of Phaeodactylum tricornutum
Authors: Zhang Hanwen , He Qing , Jiang Xiaoying , Wang Hongxia , Wang Yulu , Ma Mingyang , Hu Qiang , Gong Yingchun
Published: June 2023

Heteroloboseans have garnered considerable interest because of their extraordinary ecological, morphological, and physiological diversity. Many heteroloboseans have adapted to various extensive habitats, including halophilic, acidophilic, thermophilic, psychrophilic, and anaerobic habitats.
Revealing the link between A-type granites and hottest melts from residual metasedimentary crust
Authors: Carvalho B.B. , Bartoli O. , Cesare B. , Satish-Kumar M. , Petrelli M. , Kawakami T. , Hokada T. , Gilio M.
Published: June 2023

Among S-, I-, and A-type granites, the latter are the most debated in terms of origin, and metasedimentary crust is usually discarded as a potential source. Here we tackle this issue by adopting an in-source perspective, rather than focusing on the final product (granite), documenting the occurrence of pristine melt inclusions (MIs) in garnet from residual metapelitic ultrahigh-temperature (UHT) granulite from East Antarctica. Coexistence of sapphirine + quartz, phase equilibria calculations, and Zr-in-rutile thermometry indicate that MIs trapped UHT melts formed at peak conditions (930–1000 °C) from a residual metapelitic source. MIs are granitic with weakly peraluminous to weakly peralkaline affinity, ferroan character, high alkali contents, high K/Na and Ga/Al, and low Ca, Ba, Sr, and H2O concentrations. These features and geochemical modeling indicate that MIs represent primary melts for high-SiO2 A-type granites. Therefore, MIs reveal the missing link between A-type granites and the hottest metasedimentary crust. Voluminous amounts of slightly peraluminous, high-SiO2 A-type granites can be produced in large, residual UHT terranes such as those of eastern Gondwana. Our results provide a wider view of processes responsible for granite formation and show that a larger variety of granites must be considered in models of the effects of UHT anatexis on crustal differentiation.
Association between chronic cerebrospinal venous insufficiency and multiple sclerosis: a systematic review and meta-analysis
Authors: Yang Jun , Zhang Na , Ding Cong , He Xiuying , Li Meihua , Meng Wei , Ouyang Taohui
Published: June 2023

Objectives

Numerous studies have indicated that chronic cerebrospinal venous insufficiency is a potential factor in causing multiple sclerosis in recent years, but this conclusion remains unconfirmed. This meta-analysis examined the correlation between multiple sclerosis and chronic cerebrospinal venous insufficiency.

Methods

We searched Embase and Medline (Ovid) for publications published from 1 January 2006 to 1 May 2022. The meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Results

Eligible studies (n=20) included 3069 participants from seven countries. Pooled analysis indicated that chronic cerebrospinal venous insufficiency was more frequent in patients with multiple sclerosis than in healthy controls (OR 3.36; 95% CI 1.92 to 5.85; p<0.001) with remarkable heterogeneity among studies (I2=79%). Results were more strongly correlated in subsequent sensitivity analyses, but heterogeneity was also more substantial. We removed studies that initially proposed a chronic cerebrospinal venous insufficiency team as well as studies by authors involved in or advocating endovascular therapies.

Conclusions

Chronic cerebrospinal venous insufficiency is significantly associated with multiple sclerosis and it is more prevalent in patients with multiple sclerosis than in healthy individuals, but considerable heterogeneity of results is still observed.
Transcatheter closure of atrial septal defect in the elderly: a systematic review and meta-analysis
Authors: Baroutidou Amalia , Arvanitaki Alexandra , Farmakis Ioannis T , Patsiou Vasiliki , Giannopoulos Andreas , Efthimiadis Georgios , Ziakas Antonios , Giannakoulas George
Published: June 2023

Objective

Despite the establishment of transcatheter closure as the treatment of choice in adults with secundum atrial septal defects (ASDs), the effectiveness of this approach in the elderly is disputed. This systematic review and meta-analysis aims to explore the impact of transcatheter ASD closure in patients ≥60 years old.

Methods

We systematically searched four major electronic databases (PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus and Web of Science),ClinicalTrials.gov, article references and grey literature. Primary outcomes were the right ventricular end-diastolic diameter (RVEDD) and the New York Heart Association functional class change, whereas secondary outcomes included systolic pulmonary arterial pressure (sPAP), left ventricular end-diastolic diameter (LVEDD), brain natriuretic peptide (BNP), tricuspid valve regurgitation (TR) change, as well as the rate of atrial arrhythmias and all-cause mortality.

Results

In total, 18 single-arm cohorts comprising 1184 patients were included. RVEDD was reduced after ASD closure (standardised mean difference (SMD) −0.9, 95% CI −1.2 to −0.7). Elderly patients had 9.5 times higher odds of being asymptomatic after ASD closure (95% CI 5.06 to 17.79). Furthermore, ASD closure improved sPAP (mean difference (MD) −10.8, 95% CI −14.6 to −7), LVEDD (SMD 0.8, 95% CI 0.7 to 1.0), TR severity (OR 0.39, 95% CI 0.25 to 0.60) and BNP (MD −68.3, 95% CI −114.4 to −22.1). There was a neutral effect of ASD closure on atrial arrhythmias.

Conclusions

Transcatheter ASD closure is beneficial for the elderly population since it improves functional capacity, biventricular dimensions, pulmonary pressures, TR severity and BNP. However, the incidence of atrial arrhythmias did not change significantly after the intervention.

PROSPERO registration number

CRD42022378574.
PRMT5 reduces immunotherapy efficacy in triple-negative breast cancer by methylating KEAP1 and inhibiting ferroptosis
Authors: Wang Zhe , Li Ruolei , Hou Niuniu , Zhang Juliang , Wang Ting , Fan Pengyu , Ji Cheng , Zhang Bo , Liu Liuyin , Wang Yaping , Kong Jing , Yao Qing , Duan Jie , Zhao Ge , Ling Rui , Zhang Jian
Published: June 2023

Background

As an emerging treatment strategy for triple-negative breast cancer (TNBC), immunotherapy acts in part by inducing ferroptosis. Recent studies have shown that protein arginine methyltransferase 5 (PRMT5) has distinct roles in immunotherapy among multiple cancers by modulating the tumor microenvironment. However, the role of PRMT5 during ferroptosis, especially for TNBC immunotherapy, is unclear.

Methods

PRMT5 expression in TNBC was measured by IHC (immunohistochemistry) staining. To explore the function of PRMT5 in ferroptosis inducers and immunotherapy, functional experiments were conducted. A panel of biochemical assays was used to discover potential mechanisms.

Results

PRMT5 promoted ferroptosis resistance in TNBC but impaired ferroptosis resistance in non-TNBC. Mechanistically, PRMT5 selectively methylated KEAP1 and thereby downregulated NRF2 and its downstream targets which can be divided into two groups: pro-ferroptosis and anti-ferroptosis. We found that the cellular ferrous level might be a critical factor in determining cell fate as NRF2 changes. In the context of higher ferrous concentrations in TNBC cells, PRMT5 inhibited the NRF2/HMOX1 pathway and slowed the import of ferrous. In addition, a high PRMT5 protein level indicated strong resistance of TNBC to immunotherapy, and PRMT5 inhibitors potentiated the therapeutic efficacy of immunotherapy.

Conclusions

Our results reveal that the activation of PRMT5 can modulate iron metabolism and drive resistance to ferroptosis inducers and immunotherapy. Accordingly, PRMT5 can be used as a target to change the immune resistance of TNBC.
Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies
Authors: Godinho Rita , Noto Alessandra , Fenwick Craig , Stravodimou Athina , Hugelshofer Sarah , Peters Solange , Hullin Roger , Obeid Michel
Published: June 2023

Cytokine storm induced by anti-human epidermal growth factor receptor-2 (HER2) therapies has not been reported. We report a patient with breast cancer treated with trastuzumab/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1β, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this FcγR-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2 months of initial presentation, together with a resolution of the myocardial inflammation on MRI.
Impairing the impairment argument
Authors: van Oosterum Kyle , Curran Emma J
Published: June 2023

Blackshaw and Hendricks have recently developed and defended the impairment argument against abortion, arguing that the immorality of giving a child fetal alcohol syndrome (FAS) provides us with reason to believe that abortion is immoral. In this paper, we forward two criticisms of the impairment argument. First, we highlight that, as it currently stands, the argument is very weak and accomplishes very little. Second, we argue that Blackshaw and Hendricks are fundamentally mistaken about what makes giving a child FAS immoral. Once we acknowledge this, it is clear that our intuitions about giving a child FAS provide no support for the supposed immorality of abortion.
Peer-to-peer counselling and emotional guidance on infertility in Britain and Belgium (1970s–1980s)
Authors: Hilevych Yuliya , Claes Tinne
Published: June 2023

In the wake of sexual and reproductive health counselling in postwar Western Europe, emotional guidance on infertility was as yet neither readily recognised nor available. In this article, we show that in Britain and Belgium, infertile couples themselves identified the need for systematic emotional guidance on their infertility experiences. They set up self-help support groups to provide counselling on infertility in their respective countries. Originally formed by heterosexual, white, middle-class couples, who were childless due to infertility, these support groups were cautious—rather than affirmative—of reproductive technologies to aid conception. In their view, these technologies were not readily available and did not work for everyone. In this social climate, systematic interactions with peers sought to provide emotional guidance to destigmatise infertility and accept childlessness. This emotional guidance was grounded in the contemporary psychological literature—on grief, mourning and other emotions—that the support groups applied to infertility experiences.

We suggest that these groups could be seen as among the first—in their respective countries and arguably within Europe—to offer infertility counselling through a peer-to-peer format, which is today recognised as a crucial part of professional infertility counselling provision. In this light, our findings uncover previously unseen connections between grassroots support groups, infertility counselling and emotional guidance in the period before infertility counselling was professionalised in Britain and Belgium. Our analysis is based on various archival and published sources as well as oral history accounts, many of which have not been analysed before. Our findings contribute to the history of sexual and reproductive health, history of self-help, history of counselling, and history of emotions.
Cohort study of new off-label gabapentin prescribing in chronic opioid users
Authors: Billig Jessica I , Bicket Mark C , Yazdanfar Maryam , Gunaseelan Vidhya , Sears Erika D , Brummett Chad M , Waljee Jennifer F
Published: June 2023

Introduction

Gabapentin is commonly prescribed as an off-label adjunct to opioids because of its safer risk profile. Recent evidence has shown an increased risk of mortality when coprescribed with opioids. Therefore, we aimed to evaluate whether the addition of off-label gabapentin in patients with chronic opioid use is associated with a reduction in opioid dosage.

Methods

We performed a retrospective cohort study of patients with chronic opioid use with a new off-label gabapentin prescription (2010–2019). Our primary outcome of interest was a reduction in opioid dosage measured via oral morphine equivalents (OME) per day after the addition of a new off-label gabapentin prescription.

Results

In our cohort of 172,607 patients, a new off-label gabapentin prescription was associated with a decrease in opioid dosage in 67,016 patients (38.8%) (median OME/day reduction:13.8), with no change in opioid dosage in 24,468 patients (14.2%), and an increase in opioid dosage in 81,123 patients (47.0%) (median OME/day increase: 14.3). A history of substance/alcohol use disorders was associated with a decrease in opioid dosage after the addition of a new off-label gabapentin (aOR 1.20, 95% CI 1.16 to 1.23). A history of pain disorders was associated with a decrease in opioid dosage after the initiation of a new gabapentin prescription including arthritis (aOR 1.12, 95% CI 1.09 to 1.15), back pain (aOR 1.10, 95% CI 1.07 to 1.12), and other pain conditions (aOR 1.08, 95% CI 1.06 to 1.10).

Conclusions

In this study of patients with chronic opioid use, an off-label gabapentin prescription did not reduce opioid dosage in the majority of patients. The coprescribing of these medications should be critically evaluated to ensure optimal patient safety.
Are trauma surgeons prepared? A survey of trauma surgeons’ disaster preparedness before and during the COVID-19 pandemic
Authors: Doucet Jay , Shatz David V , Kaplan Lewis J , Bulger Eileen M , Capella Jeannette , Kuhls Deborah A , Fallat Mary , Remick Kyle N. , Newton Christopher , Fox Adam , Jawa Randeep , Harvin John A , Blake David P , Bukur Marko , Gates Jonathan , Ficke James , Gestring Mark L
Published: June 2023

Objective

US trauma centers (TCs) must remain prepared for mass casualty incidents (MCIs). However, trauma surgeons may lack formal MCI training. The recent COVID-19 pandemic drove multiple patient surges, overloaded Emergency Medical Services (EMS) agencies, and stressed TCs. This survey assessed trauma surgeons’ MCI training, experience, and system and personal preparedness before the pandemic compared with the pandemic’s third year.

Methods

Survey invitations were emailed to all 1544 members of the American Association for the Surgery of Trauma in 2019, and then resent in 2022 to 1575 members with additional questions regarding the pandemic. Questions assessed practice type, TC characteristics, training, experience, beliefs about personal and hospital preparedness, likelihood of MCI scenarios, interventions desired from membership organizations, and pandemic experiences.

Results

The response rate was 16.7% in 2019 and 12% in 2022. In 2022, surgeons felt better prepared than their hospitals for pandemic care, mass shootings, and active shooters, but remained feeling less well prepared for cyberattack and hazardous material events, compared with 2019. Only 35% of the respondents had unintentional MCI response experience in 2019 or 2022, and even fewer had experience with intentional MCI. 78% had completed a Stop the Bleed (STB) course and 63% own an STB kit. 57% had engaged in family preparedness activities; less than 40% had a family action plan if they could not come home during an MCI. 100% of the respondents witnessed pandemic-related adverse events, including colleague and coworker illness, patient surges, and resource limitations, and 17% faced colleague or coworker death.

Conclusions

Trauma surgeons thought that they became better at pandemic care and rated themselves as better prepared than their hospitals for MCI care, which is an opportunity for them to take greater leadership roles. Opportunities remain to improve surgeons’ family and personal MCI preparedness. Surgeons’ most desired professional organization interventions include advocacy, national standards for TC preparedness, and online training.

Level of evidence

VII, survey of expert opinion.
Differential digestive and metabolic profile of juveniles and adults of the estuarine-dependent marine fish Mugil liza (Mugilidae) cohabiting inside a southwestern Atlantic coastal lagoon
Authors: Albanesi C. , González-Castro M. , López-Mañanes A.
Published: June 2023

Integrative studies on intraspecific differences of digestive enzymes, energy reserves, and morphological/somatic traits in juveniles and adults of estuarine-dependent marine fish while inhabiting inside a coastal lagoon are lacking. This study was carried on juveniles and adults of Mugil liza Valenciennes, 1836 inhabiting inside Mar Chiquita Coastal Lagoon (Argentina). Both stages exhibited amylase, maltase, sucrase, lipase, trypsin, and aminopeptidase-N activities in the intestine, which were active over a wide range of pH and temperatures and exhibited Michaelis–Menten kinetics. Adults exhibited higher intestinal coefficient (31%), higher amylase (32%), and lower maltase (82%) and lipase activities (38%). Glycogen concentration in liver and muscle was similar, while free glucose concentration was higher in adults (772% and 400%, respectively). In adults, retroperitoneal fat (absent in juveniles) constituted the main triglycerides (TAG) storage site, while TAG concentration in liver and muscle was lower (86% and 80%, respectively) than that in juveniles. No differences were found in protein concentration in any storage organ. The results show that juveniles and adults exhibit a digestive and metabolic profile at the biochemical level and intraspecific differences in key components of carbohydrate and lipid metabolism that could support preparation for reproductive migration of adults outside the coastal lagoon.
Growth, Inequality, and Poverty: An Introduction
Authors: Kakwani Nanak , Prakash Brahm , Son Hyun
Published: June 2023

The paper provides a summary of all the papers in this special volume. It also gives a brief theoretical introduction to the subject of growth, inequality, and poverty, including the neoclassical growth and new growth theories. It discusses the relationship between growth and inequality, and presents empirical evidence that argues that growth does not lead to inequality. The reverse causation from inequality to growth is also examined. The Dollar and Kraay methodology, which concludes that growth is good for the poor, is also reviewed. Finally, the paper argues that the emphasis on pro-poor growth policies will reduce poverty more rapidly than simple reliance on the trickle down effect. However, poverty reduction with growth also depends on initial inequalities and assets.
How Good is Growth?
Authors: Foster James , Székely Miguel
Published: June 2023

This paper argues that the use of different methodologies for characterizing the well-being of the poor can lead to totally different views about the relationship between economic growth and poverty. The paper focuses on “general means”, which are well-known income standards that place greater weight on lower incomes. In contrast to results obtained using the “mean income of the bottom 20 percent of the distribution”, the paper finds that growth is good for the poor, but not necessarily as good as for other sectors of the population.
The European Social Model: Lessons for Developing Countries
Authors: Lindbeck Assar
Published: June 2023

Developing countries, in particular the least developed ones, probably have more to learn from social policies in Europe during the early 20th century than from the elaborate welfare-state arrangements after World War II. In addition to macroeconomic growth and stability, the main ambitions must be to fight human deprivation, including illiteracy, malnutrition, and poor access to water and sanitation; in some cases, also weak, incompetent, and/or corrupt governments. It is also important that informal systems in the fields of transfers and social services are not destroyed when developing countries embark on more formal systems in these fields in the future. The European experience also warns against the creation of social systems that are so generous that disincentives, moral hazard, and receding social norms seriously distort the national economy, including the labor market.
Family Farms and Plantations in Tropical Development
Authors: Hayami Yujiro
Published: June 2023

Small family farms and plantations are the two contrasting systems of agricultural production in the tropics. While the family farm is an old institution, which has existed since time immemorial, the plantation is a new institution brought by the West for extracting tropical cash crops for export to home countries. Large-scale operation of the plantation was necessary for internalizing gains from investment in infrastructure needed for opening vast tracts of unused lands. However, where the communities of indigenous smallholders had already been established, family farms proved to be equally or more efficient producers of tropical export crops with their family labor characterized by low supervision costs, relative to plantations based on hired labor. This advantage of family farms rose as population density increased and rural infrastructure improved, while not only economic but also social drawbacks of the plantation system loomed. Reorganization of the plantation is desired. However, breaking down plantations for operation by smallholders through government coercive measures will likely prove to be disruptive and inefficient A better approach will be to support private sector initiative to reorganize the plantation system into a contract farming system in which an agribusiness enterprise manages the processing/marketing process and contracts with small growers for an assured supply of farm-produced raw materials.