bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of an experimental model for liver abscess induction in Holstein steers using an acidotic diet challenge and bacterial inoculation
Authors: McDaniel Zach S , Hales Kristin E , Salih Harith , Deters Alyssa , Shi Xiaorong , Nagaraja Tiruvoor G , Lawrence Ty E , Tennant Travis C , Amachawadi Raghavendra G , Carroll Jeff A , Burdick Sanchez Nicole C , Galyean Michael L , Smock Taylor M , Ballou Michael A , Machado Vinicius S , Davis Emily , Broadway Paul R
Published: March 2024

Holstein steers (n = 40; initial BW = 84.9 ± 7.1 kg) were used to study the genesis of liver abscesses (LA) using an acidotic diet challenge with or without intraruminal bacterial inoculation. Steers were housed in individual pens inside a barn and randomly assigned to one of three treatments: (1) low-starch control diet comprised primarily of dry-rolled corn and wet corn gluten feed (CON); (2) high-starch acidotic diet with steam-flaked corn (AD); or (3) acidotic diet plus intraruminal inoculation with Fusobacterium necrophorum subsp. necrophorum (9.8 × 108 colony forming units [CFU]/mL), Trueperella pyogenes (3.91 × 109 CFU/mL), and Salmonella enterica serovar Lubbock (3.07 × 108 CFU/mL), previously isolated from LA (ADB). Steers in AD and ADB were fed the acidotic diet for 3 d followed by 2 d of the CON diet, and this cycle was repeated four times. On day 23, ADB steers were intraruminally inoculated with the bacteria. At necropsy, gross pathology of livers, lungs, rumens, and colons was noted. Continuous data were analyzed via mixed models as repeated measures over time with individual steer as the experimental unit. Mixed models were also used to determine the difference in prevalence of necropsy scores among treatments. Ruminal pH decreased in AD and ADB steers during each acidotic diet cycle (P ≤ 0.05). LA prevalence was 42.9% (6 of 14) in ADB vs. 0% in AD or CON treatments (P < 0.01). Ruminal damage was 51.1% greater in ADB than in AD (P ≤ 0.04). Culture of LA determined that 100% of the abscesses contained F. necrophorum subsp. necrophorum, 0% contained T. pyogenes, 50% contained Salmonella, and 50% contained a combination of F. necrophorum subsp. necrophorum and Salmonella. The F. necrophorum subsp. necrophorum was clonally identical to the strain used for the bacterial inoculation based on phylogenetic analysis of the whole genome. This experimental model successfully induced rumenitis and LA in Holstein steers and confirms the central dogma of LA pathogenesis that acidosis and rumenitis lead to the entry of F. necrophorum into the liver to cause abscesses. Our findings suggest that an acidotic diet, in conjunction with intraruminal bacterial inoculation, is a viable model to induce LA. Further research is needed to determine the repeatability of this model, and a major application of the model will be in evaluations of novel interventions to prevent LA.
Five-dimensional facies-driven seismic inversion for igneous reservoirs based on rock-physics modelling
Authors: Gu Wen , Yin Xingyao , Wu Furong , Luo Ying , Liang Hong , Pei Song , Yang Yaming
Published: March 2024

The igneous reservoir has become an important exploration target for increasing reserves and production of oil and gas in the Junggar Basin. However, igneous reservoir exploration is restricted because the seismic exploration of high-quality igneous reservoirs is difficult and the anisotropy induced by high-angle fractures cannot be neglected. To implement the characterization of igneous reservoirs, we first study the correlation between anisotropy parameters and physical properties of igneous rock, and we propose a 5D facies-driven inversion method based on rock physics, which means we employ 3D seismic data at different incidence angles and azimuths to implement the estimation of a hydrocarbon reservoir constrained by the igneous rock facies. We also present an anisotropic igneous rock-physics model, in which micro-petrophysical characteristics, strong heterogeneity of skeleton minerals, and pore structures are considered. As a reasonable initial model is important for seismic inversion, we propose a facies-driven modelling seismic inversion method in which we use facies obtained on the basis of the difference between rock composition, reservoir physical parameters, and elastic parameters of different lithofacies igneous rocks to constrain the seismic inversion. Finally, we present a step seismic inversion method of using seismic data to estimate multi-parameters of horizontal transversely isotropic media. Therefore, the comprehensive processes of rock-physics modelling, inversion model establishment, and reservoir prediction of high-quality igneous rocks are proposed in this study, which demonstrates effective application for igneous reservoirs in China.
A complication of an axillary intra-aortic balloon pump
Authors: Kodack Eileen , Patel Riya , Bonner Carain , Pantin Enrique
Published: March 2024

Intra-aortic balloon pumps (IABPs) are used to mechanically temporize a failing heart by decreasing afterload while increasing coronary perfusion pressure of the heart while more definitive treatment is sought. We report a case of a 65-year-old male with nonischemic cardiomyopathy, atrial fibrillation, thyroiditis, and non-Hodgkin lymphoma who presented with worsening heart failure. He underwent a percutaneous placement of a left axillary IABP with seemingly no complications. Approximately 3 weeks post-placement, the patient was taken for a heart transplant when an intraoperative transesophageal echo showed that the IABP was in the aortic arch and ascending aorta, instead of its proper placement in the descending aorta. The patient’s arterial line showed waveforms appropriate for an IABP patient, and the patient showed no signs indicative of improper placement. This erroneous placement carried the potential to affect the aortic valve function, injure the aortic intima and/or occlude the aortic arch vessels. .
ACTION: a randomized phase 3 study of ONC201 (dordaviprone) in patients with newly diagnosed H3 K27M-mutant diffuse glioma
Authors: Arrillaga-Romany Isabel , Lassman Andrew , McGovern Susan L , Mueller Sabine , Nabors Burt , van den Bent Martin , Vogelbaum Michael A , Allen Joshua E , Melemed Allen S , Tarapore Rohinton S , Wen Patrick Y , Cloughesy Timothy
Published: March 2024

Background

H3 K27M-mutant diffuse glioma primarily affects children and young adults, is associated with a poor prognosis, and no effective systemic therapy is currently available. ONC201 (dordaviprone) has previously demonstrated efficacy in patients with recurrent disease. This phase 3 trial evaluates ONC201 in patients with newly diagnosed H3 K27M-mutant glioma.

Methods

ACTION (NCT05580562) is a randomized, double-blind, placebo-controlled, parallel-group, international phase 3 study of ONC201 in newly diagnosed H3 K27M-mutant diffuse glioma. Patients who have completed standard frontline radiotherapy are randomized 1:1:1 to receive placebo, once-weekly dordaviprone, or twice-weekly dordaviprone on 2 consecutive days. Primary efficacy endpoints are overall survival (OS) and progression-free survival (PFS); PFS is assessed by response assessment in neuro-oncology high-grade glioma criteria (RANO-HGG) by blind independent central review. Secondary objectives include safety, additional efficacy endpoints, clinical benefit, and quality of life. Eligible patients have histologically confirmed H3 K27M-mutant diffuse glioma, a Karnofsky/Lansky performance status ≥70, and completed first-line radiotherapy. Eligibility is not restricted by age; however, patients must be ≥10 kg at time of randomization. Patients with a primary spinal tumor, diffuse intrinsic pontine glioma, leptomeningeal disease, or cerebrospinal fluid dissemination are not eligible. ACTION is currently enrolling in multiple international sites.
Control of defensive behavior by the nucleus of Darkschewitsch GABAergic neurons
Authors: Zhao Huiying , Liu Jinrong , Shao Yujin , Feng Xiang , Zhao Binhan , Sun Li , Liu Yijun , Zeng Linghui , Li Xiao-ming , Yang Hongbin , Duan Shumin , Yu Yan-qin
Published: March 2024

The nucleus of Darkschewitsch (ND), mainly composed of GABAergic neurons, is widely recognized as a component of the eye-movement controlling system. However, the functional contribution of ND GABAergic neurons (NDGABA) in animal behavior is largely unknown. Here, we show that NDGABA neurons were selectively activated by different types of fear stimuli, such as predator odor and foot shock. Optogenetic and chemogenetic manipulations revealed that NDGABA neurons mediate freezing behavior. Moreover, using circuit-based optogenetic and neuroanatomical tracing methods, we identified an excitatory pathway from the lateral periaqueductal gray (lPAG) to the ND that induces freezing by exciting ND inhibitory outputs to the motor-related gigantocellular reticular nucleus, ventral part (GiV). Together, these findings indicate the NDGABA population as a novel hub for controlling defensive response by relaying fearful information from the lPAG to GiV, a mechanism critical for understanding how the freezing behavior is encoded in the mammalian brain.
Energy spectrum theory of incommensurate systems
Authors: He Zhe , Guo Xin-Yu , Ma Zhen , Gao Jin-Hua
Published: March 2024

Because of the lack of translational symmetry, calculating the energy spectrum of an incommensurate system has always been a theoretical challenge. Here, we propose a natural approach to generalize energy band theory to incommensurate systems without reliance on the commensurate approximation, thus providing a comprehensive energy spectrum theory of incommensurate systems. Except for a truncation-dependent weighting factor, the formulae of this theory are formally almost identical to that of Bloch electrons, making it particularly suitable for complex incommensurate structures. To illustrate the application of this theory, we give three typical examples: one-dimensional bichromatic and trichromatic incommensurate potential models, as well as a moiré quasicrystal. Our theory establishes a fundamental framework for understanding incommensurate systems.
Characteristics of Patients With Initial Clostridioides difficile Infection (CDI) That Are Associated With Increased Risk of Multiple CDI Recurrences
Authors: Guh Alice Y , Li Rongxia , Korhonen Lauren , Winston Lisa G , Parker Erin , Czaja Christopher A , Johnston Helen , Basiliere Elizabeth , Meek James , Olson Danyel , Fridkin Scott K , Wilson Lucy E , Perlmutter Rebecca , Holzbauer Stacy M , D’Heilly Paige , Phipps Erin C , Flores Kristina G , Dumyati Ghinwa K , Pierce Rebecca , Ocampo Valerie L S , Wilson Christopher D , Watkins Jasmine J , Gerding Dale N , McDonald L Clifford
Published: March 2024

Background

Because interventions are available to prevent further recurrence in patients with recurrent Clostridioides difficile infection (rCDI), we identified predictors of multiple rCDI (mrCDI) in adults at the time of presentation with initial CDI (iCDI).

Methods

iCDI was defined as a positive C difficile test in any clinical setting during January 2018–August 2019 in a person aged ≥18 years with no known prior positive test. rCDI was defined as a positive test ≥14 days from the previous positive test within 180 days after iCDI; mrCDI was defined as ≥2 rCDI. We performed multivariable logistic regression analysis.

Results

Of 18 829 patients with iCDI, 882 (4.7%) had mrCDI; 437 with mrCDI and 7484 without mrCDI had full chart reviews. A higher proportion of patients with mrCDI than without mrCDI were aged ≥65 years (57.2% vs 40.7%; P < .0001) and had healthcare (59.1% vs 46.9%; P < .0001) and antibiotic (77.3% vs 67.3%; P < .0001) exposures in the 12 weeks preceding iCDI. In multivariable analysis, age ≥65 years (adjusted odds ratio [aOR], 1.91; 95% confidence interval [CI], 1.55–2.35), chronic hemodialysis (aOR, 2.28; 95% CI, 1.48–3.51), hospitalization (aOR, 1.64; 95% CI, 1.33–2.01), and nitrofurantoin use (aOR, 1.95; 95% CI, 1.18–3.23) in the 12 weeks preceding iCDI were associated with mrCDI.

Conclusions

Patients with iCDI who are older, on hemodialysis, or had recent hospitalization or nitrofurantoin use had increased risk of mrCDI and may benefit from early use of adjunctive therapy to prevent mrCDI. If confirmed, these findings could aid in clinical decision making and interventional study designs.
ENHANCER OF SHOOT REGENERATION1 promotes de novo root organogenesis after wounding in Arabidopsis leaf explants
Authors: Lee Kyounghee , Yoon Hobin , Park Ok-Sun , Seo Pil Joon
Published: March 2024

Plants have an astonishing ability to regenerate new organs after wounding. Here, we report that the wound-inducible transcription factor ENHANCER OF SHOOT REGENERATION1 (ESR1) has a dual mode of action in activating ANTHRANILATE SYNTHASE ALPHA SUBUNIT1 (ASA1) expression to ensure auxin-dependent de novo root organogenesis locally at wound sites of Arabidopsis (Arabidopsis thaliana) leaf explants. In the first mode, ESR1 interacts with HISTONE DEACETYLASE6 (HDA6), and the ESR1–HDA6 complex directly binds to the JASMONATE-ZIM DOMAIN5 (JAZ5) locus, inhibiting JAZ5 expression through histone H3 deacetylation. As JAZ5 interferes with the action of ETHYLENE RESPONSE FACTOR109 (ERF109), the transcriptional repression of JAZ5 at the wound site allows ERF109 to activate ASA1 expression. In the second mode, the ESR1 transcriptional activator directly binds to the ASA1 promoter to enhance its expression. Overall, our findings indicate that the dual biochemical function of ESR1, which specifically occurs near wound sites of leaf explants, maximizes local auxin biosynthesis and de novo root organogenesis in Arabidopsis.
What is the problem represented to be in the Swedish police authority: A policy analysis
Authors: Danell Jenny-Ann Brodin , Jarl Josefina
Published: March 2024

In recent years, Sweden has witnessed a rise in criminal activity, notably in organized crime, gang violence, and incidents like shootings and explosions. This trend has sparked considerable political and media debates, in Sweden and internationally. This paper analyses how the Swedish police authority comprehend the situation discursively. How do they define their role and mission in society? What problems do they identify? What goals and strategies do they propose, and what values are attached to these? This is illustrated by policy documents and website materials from the police authority. The results show three main problematizations: crime and crime fighting, working within the police organization, and relations between the police and citizens. Key findings are that the police authority represents crimes and the role of the police in different ways depending on what type of crime discussed, and that they connect various aspects of police work to non-repressive values, such as trust and safety.
Virome release of an invasive exotic plant species in southern France
Authors: Moubset Oumaima , Filloux Denis , Fontes Hugo , Julian Charlotte , Fernandez Emmanuel , Galzi Serge , Blondin Laurence , Chehida Sélim Ben , Lett Jean-Michel , Mesléard François , Kraberger Simona , Custer Joy M , Salywon Andrew , Makings Elizabeth , Marais Armelle , Chiroleu Frédéric , Lefeuvre Pierre , Martin Darren P , Candresse Thierry , Varsani Arvind , Ravigné Virginie , Roumagnac Philippe
Published: March 2024

The increase in human-mediated introduction of plant species to new regions has resulted in a rise of invasive exotic plant species (IEPS) that has had significant effects on biodiversity and ecosystem processes. One commonly accepted mechanism of invasions is that proposed by the enemy release hypothesis (ERH), which states that IEPS free from their native herbivores and natural enemies in new environments can outcompete indigenous species and become invasive. We here propose the virome release hypothesis (VRH) as a virus-centered variant of the conventional ERH that is only focused on enemies. The VRH predicts that vertically transmitted plant-associated viruses (PAV, encompassing phytoviruses and mycoviruses) should be co-introduced during the dissemination of the IEPS, while horizontally transmitted PAV of IEPS should be left behind or should not be locally transmitted in the introduced area due to a maladaptation of local vectors. To document the VRH, virome richness and composition as well as PAV prevalence, co-infection, host range, and transmission modes were compared between indigenous plant species and an invasive grass, cane bluestem (Bothriochloa barbinodis), in both its introduced range (southern France) and one area of its native range (Sonoran Desert, Arizona, USA). Contrary to the VRH, we show that invasive populations of B. barbinodis in France were not associated with a lower PAV prevalence or richness than native populations of B. barbinodis from the USA. However, comparison of virome compositions and network analyses further revealed more diverse and complex plant–virus interactions in the French ecosystem, with a significant richness of mycoviruses. Setting mycoviruses apart, only one putatively vertically transmitted phytovirus (belonging to the Amalgaviridae family) and one putatively horizontally transmitted phytovirus (belonging to the Geminiviridae family) were identified from B. barbinodis plants in the introduced area. Collectively, these characteristics of the B. barbinodis-associated PAV community in southern France suggest that a virome release phase may have immediately followed the introduction of B. barbinodis to France in the 1960s or 1970s, and that, since then, the invasive populations of this IEPS have already transitioned out of this virome release phase, and have started interacting with several local mycoviruses and a few local plant viruses.
A Quantitative Examination of Illness Models Among People With Opioid Use Disorder Receiving Methadone Treatment
Authors: Gaeta Gazzola Marina , Carmichael Iain D. , Thompson Emma , Beitel Mark , Madden Lynn M. , Saeed Gul , Hoffman Kim , Hammouri Muhammad , Hsaio Connie , Barry Declan T.
Published: March 2024

Background

Few studies have examined illness models among people with addiction. We investigated illness models and their associations with demographics and treatment beliefs among patients receiving methadone treatment for opioid use disorder.

Methods

From January 2019 to February 2020, patients receiving methadone treatment at outpatient opioid treatment programs provided demographics and rated using 1 to 7 Likert-type scales agreement with addiction illness models (brain disease model, chronic medical condition model [CMCM], and no explanation [NEM]) and treatment beliefs. Pairwise comparisons and multivariate regressions were used to examine associations between illness models, demographics, and treatment beliefs. Statistical significance was set at P < 0.05.

Results

A total of 450 patients participated in the study. Forty percent self-identified as female, 13% as Hispanic, and 78% as White; mean age was 38.5 years. Brain disease model was the most frequently endorsed illness model (46.2%), followed by CMCM (41.7%) and NEM (21.9%). In multivariate analyses, agreement with brain disease model was significantly positively associated with beliefs that methadone treatment would be effective, counseling is important, and methadone is lifesaving, whereas agreement with CMCM was significantly positively associated with beliefs that methadone treatment would be effective, counseling is important, 12-step is the best treatment, taking methadone daily is important, and methadone is lifesaving. In multivariate analyses, agreement with NEM was negatively significantly associated with beliefs that methadone would be effective, counseling is important, taking methadone daily is important, and methadone is lifesaving.

Discussion

Many patients in methadone treatment endorsed medicalized addiction models. Agreement with addiction illness models appear to be related to treatment beliefs.
Trends in Pediatric Anterior Cruciate Ligament Reconstruction in Australia: An Analysis of Australian Medicare Benefits Schedule Database From 2001 to 2020
Authors: Campbell Ryan J. , An Vincent , Molnar Robert , St George Justine , Sivakumar Brahman S. , Symes Michael
Published: March 2024

Background:

Anterior cruciate ligament (ACL) injuries are common and increasingly prevalent in the pediatric population. However, there remain sparse epidemiological data on the surgical treatment of these injuries. The objective of this study is to assess the trends in the rate of pediatric ACL reconstruction in Australia over the past 2 decades.

Methods:

The incidence of ACL reconstruction from 2001 to 2020 in patients 5 to 14 years of age was analyzed using the Australian Medicare Benefits Schedule (MBS) database. Data were stratified by sex and year. An offset term was introduced using population data from the Australian Bureau of Statistics to account for population changes over the study period.

Results:

A total of 3719 reconstructions for the management of pediatric ACL injuries were performed in Australia under the MBS in the 20-year period from 2001 to 2020. There was a statistically significant annual increase in the total volume and per capita volume of pediatric ACL reconstructions performed across the study period (P<0.0001). There was a significant increase in the rate of both male and female reconstructions (P<0.0001), with a greater proportion of reconstructions performed on males (n=2073, 56%) than females (n=1646, 44%). In 2020, the rate of pediatric ACL reconstructions decreased to a level last seen in 2015, likely due to the effects of COVID-19.

Conclusions:

The incidence of ACL reconstruction in skeletally immature patients has increased in Australia over the 20-year study period. This increase is in keeping with evidence suggesting poor outcomes with nonoperative or delayed operative management.
Evaluation of ChatGPT in Predicting 6-Month Outcomes After Traumatic Brain Injury
Authors: Gakuba Clement , Le Barbey Charlene , Sar Alexandre , Bonnet Gregory , Cerasuolo Damiano , Giabicani Mikhael , Moyer Jean-Denis
Published: March 2024

Objectives:

To evaluate the capacity of ChatGPT, a widely accessible and uniquely popular artificial intelligence-based chatbot, in predicting the 6-month outcome following moderate-to-severe traumatic brain injury (TBI).

Design:

Single-center observational retrospective study.

Setting:

Data are from a neuro-ICU from a level 1 trauma center.

Patients:

All TBI patients admitted to ICU between September 2021 and October 2022 were included in a prospective database.

Interventions:

None.

Measurements and Main Results:

Based on anonymized clinical, imaging, and biological information available at the patients’ hospital admission and extracted from the database, clinical vignettes were retrospectively submitted to ChatGPT for prediction of patients’ outcomes. The predictions of two intensivists (one neurointensivist and one non-neurointensivist) both from another level 1 trauma center (Beaujon Hospital), were also collected as was the International Mission on Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) scoring. Each intensivist, as well as ChatGPT, made their prognostic evaluations independently, without knowledge of the others’ predictions and of the patients’ actual management and outcome. Both the intensivists and ChatGPT were given access to the exact same set of information. The main outcome was a 6-month-functional status dichotomized into favorable (Glasgow Outcome Scale Extended [GOSE] ≥ 5) versus poor (GOSE < 5). Prediction of intracranial hypertension management, pulmonary infectious risk, and removal of life-sustaining therapies was also investigated as secondary outcomes. Eighty consecutive moderate-to-severe TBI patients were included. For the 6-month outcome prognosis, area under the receiver operating characteristic curve (AUC-ROC) for ChatGPT, the neurointensivist, the non-neurointensivist, and IMPACT were, respectively, 0.62 (0.50–0.74), 0.70 (0.59–0.82), 0.71 (0.59–0.82), and 0.81 (0.72–0.91). ChatGPT had the highest sensitivity (100%), but the lowest specificity (26%). For secondary outcomes, ChatGPT’s prognoses were generally less accurate than clinicians’ prognoses, with lower AUC values for most outcomes.

Conclusions:

This study does not support the use of ChatGPT for prediction of outcomes after TBI.
Unveiling the Silent Intruder: H. pylori’s Hidden Link to Ischemic Heart Disease
Authors: Aggarwal Kanishk , Singh Sandeep , Singla Ankur , Kanagala Sai Gautham , Anamika Fnu , Singh Bhupinder , Aggarwal Priyanka , Jain Rohit
Published: March 2024

Cardiovascular disease is the leading cause of death. In addition to the well-known risk factors associated with cardiovascular disease, such as age, diabetes mellitus, smoking, hypertension, and obesity, there has been a growing concern regarding cardiac complications stemming from the Gram-negative bacteria Helicobacter pylori. While H. pylori is most commonly associated with chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and gastric lymphoma, it has also been implicated in extra gastric manifestations, encompassing cardiac, neurologic, ocular, and dermatologic issues. Key virulent factors for coronary artery disease include the vacuolating cytotoxin gene A and the cytotoxin-associated gene A. The most likely pathogenic mechanism of the relationship between H. pylori and coronary artery disease is initiating a chronic inflammatory process associated with infection and the modifications of classic risk factors. These alterations lead to the creation of prothrombotic and procoagulant environments. Here, we review the cardiac manifestations of H. pylori and the underlying pathophysiological mechanisms.
In-Vivo Evaluation of a Novel Integrated Pediatric Pump Lung in a 30-Day Ovine Animal Model
Authors: Leibowitz Joshua L. , Awad Morcos A. , Han Dong , Shah Aakash , Sun Wenji , Zhang Jiafeng , Griffith Bartley P. , Wu Zhongjun J.
Published: March 2024

Recently there has been increased use of mechanical circulatory support in pediatric patients as a bridge to cardiopulmonary recovery or transplantation. However, there are few devices that are optimized and approved for use in pediatric patients. We designed and prototyped a novel integrated pediatric pump lung (PPL) that underwent 30 day in-vivo testing in seven juvenile Dorset Hybrid sheep. Devices were implanted in a right atrial to pulmonary artery configuration. Six of seven sheep survived with a device functioning for 25–35 days. The device flow rate was maintained at 2.08 ± 0.34 to 2.54 ± 0.16 L/min with oxygen transfer of 109.8 ± 24.8 to 151.2 ± 26.2 ml/min over the study duration. Aside from a postoperative drop in hematocrit, all hematologic and blood chemistry test values returned to normal ranges after 1–2 weeks postoperatively. Similarly, lactate dehydrogenase increased postoperatively and returned to baseline. In two sheep, there were early device failures due to oxygenator thrombosis on postoperative days zero and five; they then had oxygenator exchanges with subsequent devices performing stably for 30 days. This study demonstrated that the integrated PPL device exhibited stable performance and acceptable biocompatibility in a 30 day ovine model.
The Impact of Pre-Heart Transplantation Blood Transfusion Varies Based on Recipient MELD-XI Score
Authors: Nordan Taylor , Lee Hansuh H. , Chen Frederick Y. , Couper Gregory S. , Kawabori Masashi
Published: March 2024

Prior studies reveal adverse effects of transfusion on cardiac surgery, but little is known of transfusion impact on heart transplantation. First-time, single-organ adult heart transplant recipients between January 1, 2010, and December 31, 2020, were included, stratified above or below a model for end-stage liver disease excluding international normalized ratio (MELD-XI) score of 9.4, and propensity score matched to their nearest neighbor. A 90 day landmark analysis within each cohort was also performed. Unadjusted analysis showed transfusion recipients, MELD-XI ≥9.4, were more likely to experience post-heart transplantation mortality (Hazard Ratio (HR), 1.352 [95% Confidence Interval (CI), 1.239–1.477], p < 0.001), persisting after adjustment for potential confounders (adjusted HR, 1.211 [95% CI, 1.100–1.335], p < 0.001) and after propensity-score matching (HR, 1.174 [95% CI, 1.045–1.319], p = 0.007). Post-transplant length of stay was longer (25.9 vs. 23.2 days, p < 0.001). Post-transplant dialysis was more common (18.7 vs. 15.9%, p = 0.009). There was no survival difference on 90 day landmarked analysis (p = 0.108). With MELD-XI <9.4, there was slight survival detriment among transfusion recipients on univariable analysis (HR, 1.111 [95% CI, 1.001–1.234], p = 0.049) but not on multivariable analysis (adjusted HR, 1.061 [95% CI, 0.952–1.181], p = 0.285). There was similar survival after propensity-score matching (HR, 1.032 [95% CI, 0.903–1.180], p = 0.642) and on landmark analysis (p = 0.581). Ultimately, transfusion was associated with worse post-heart transplantation outcomes among recipients with a MELD-XI ≥9.4.
Does Size Matter? The Effect of Size of Distal Perfusion Catheter on Acute Limb Ischemia: A Meta-Analysis
Authors: Gouchoe Doug A. , Chaurasia Sameer , Henn Matthew C. , Whitson Bryan A. , Mokadam Nahush A. , Mast David , Satyapriya Sree , Vallakati Ajay , Ganapathi Asvin M.
Published: March 2024

Prevention of limb ischemia in patients with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is primarily achieved through the use of distal perfusion catheters (DPC). Our objective was to assess the role of DPC, and specifically the size of the catheter, in reducing the incidence of acute limb ischemia (ALI) through a meta-analysis. Seventeen studies met criteria for analysis. Pooled analysis included a total of 2,040 patients, of which 904 patients received ECMO with DPC and 1,136 patients underwent ECMO without DPC. Compared with ECMO alone, ECMO with DPC, regardless of size, significantly decreased ALI (relative risk [RR]: 0.49, 95% confidence interval [CI]: 0.31–0.77; p = 0.002). When comparing reactive versus prophylactic placement of DPC, prophylactic DPC was associated with significantly decreased ALI (RR: 0.41, 95% CI: 0.24–0.71; p = 0.02). No differences in mortality (RR: 0.89, 95% CI: 0.76–1.03; p = 0.12) and bleeding events (RR: 1.43, 95% CI: 0.41–4.96; p = 0.58) were observed between the two groups. This analysis demonstrates that the placement of DPC, if done prophylactically and regardless of size, is associated with a reduced risk of ALI versus the absence of DPC placement, but is not associated with differences in mortality or bleeding events.
Association of Continuity of Care With Health Care Utilization and Expenditures Among Patients Discharged Home After Stroke or Transient Ischemic Attack
Authors: Hou Yucheng , Trogdon Justin G. , Freburger Janet K. , Bushnell Cheryl D. , Halladay Jacqueline R. , Duncan Pamela W. , Kucharska-Newton Anna M.
Published: March 2024

Objectives:

To examine the association of prestroke continuity of care (COC) with postdischarge health care utilization and expenditures.

Study Population:

The study population included 2233 patients with a diagnosis of stroke or a transient ischemic attack hospitalized in one of 41 hospitals in North Carolina between March 2016 and July 2019 and discharged directly home from acute care.

Methods:

COC was assessed from linked Centers for Medicare and Medicaid Services Medicare claims using the Modified, Modified Continuity Index. Logistic regressions and 2-part models were used to examine the association of prestroke primary care COC with postdischarge health care utilization and expenditures.

Results:

Relative to patients in the first (lowest) COC quartile, patients in the second and third COC quartiles were more likely [21% (95% CI: 8.5%, 33.5%) and 33% (95% CI: 20.5%, 46.1%), respectively] to have an ambulatory care visit within 14 days. Patients in the highest COC quartile were more likely to visit a primary care provider but less likely to see a stroke specialist. Highest as compared with lowest primary care COC quartile was associated with $45 lower (95% CI: $14, $76) average expenditure for ambulatory care visits within 30 days postdischarge. Patients in the highest, as compared with the lowest, primary care COC quartile were 36% less likely (95% CI: 8%, 64%) to be readmitted within 30 days postdischarge and spent $340 less (95% CI: $2, $678) on unplanned readmissions.

Conclusions:

These findings underscore the importance of primary care COC received before stroke hospitalization to postdischarge care and expenditures.
Caring for screenagers (part 2): a pediatrician's primer on popular games and educational tools
Authors: Margolis Alex , Barile Joseph , Cason Grace , Milanaik Ruth
Published: March 2024

Purpose of review

The internet has changed the way children can work and play. With the preferences of the youth population constantly evolving, it is important that parents and pediatricians continue to be informed of the ways children spend their time on the internet. Online gaming continues to soar in popularity, as does school usage of educational platforms.

Recent findings

Roblox, Fortnite, and Minecraft are three examples of games that have widespread popularity among youth populations. Though none of the game are designed to display graphic violence, sexual content, or other features that could be considered off-limits for children, there still ways for children to exposed to inappropriate material or engage with strangers. The rise in popularity of eSports also reflects changing attitudes about the value of gaming. On the educational side, school-student platforms and powerful artificial intelligence (AI) tools are becoming more and more prevalent.

Parents should not simply know which games or educational tools their children are using, but understand them. This article seeks to provide some insight into popular games and platforms so that parents and pediatricians can make better decisions about what children access.
“Prehabilitation” for Pediatric Patients With Cancer Before Undergoing Hematopoietic Stem Cell Transplantation
Authors: Sandblom Lily , Keole Maya , Winsten Corinne , Stanford Ray
Published: March 2024

Hematopoietic stem cell transplantation (HSCT) is associated with significant physical debility. Studies have suggested that physical activity can improve endurance and strength. However, studies have not yet investigated “prehabilitation,” exercise before HSCT, to improve functional outcomes. We describe the impact of exercise therapy on physical debility in children undergoing HSCT to inform the implementation of prehabilitation. This review was conducted through a search of the electronic database PubMed. Articles included were those with original research, including randomized control trials, prospective studies, case controls, and retrospective studies. Eleven of the 191 resulting studies met our review criteria. None focused on prehabilitation, but instead on interventions during HSCT. Ten studies showed improvement or maintenance of strength, endurance, stretching, or aerobic fitness. This review shows that exercise therapy can positively affect outcomes in patients undergoing HSCT. Further investigations are needed to determine whether prehabilitation has better results than concurrent exercise.
High Symptom Burden Predicts Poorer Quality of Life Among Children and Adolescents Receiving Hematopoietic Stem Cell Transplantation or Chimeric Antigen Receptor T-Cell Therapy
Authors: Montgomery Kathleen E. , Raybin Jennifer L. , Powers Kimberly , Hellsten Melody , Murray Paula , Ward Jessica
Published: March 2024

Background

Children with cancer and other serious illnesses experience symptom burden during hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy, yet limited research has characterized how these symptoms interact with overall quality of life over time.

Objective

The aim of this study was to examine the longitudinal relationship between symptoms and quality of life in children receiving hematopoietic stem cell transplantation or chimeric antigen receptor T-cell therapy.

Methods

A multisite study design was used to collect symptom and quality of life information at pre–cell infusion and days +30, +60, and +90 from children (N = 140) receiving hematopoietic stem cell transplantation and chimeric antigen receptor T-cell therapy. A longitudinal parallel process model was used to characterize the relationship between symptoms and quality of life.

Results

Children (mean age, 8.4 years) received allogeneic transplant (57.9%), autologous transplant (25.7%), or chimeric antigen receptor T-cell therapy (16.4%). Symptom prevalence was highest at baseline (>50%) for pain, fatigue, nausea, vomiting, and low appetite. Quality of life scores were worse at baseline (mean [SD], 69.5 [15.8]) and improved by 10 points by day +90. The longitudinal model indicated high symptom prevalence at baseline predicted worse quality of life at both baseline and day +90.

Conclusions

Children felt worse early in the treatment trajectory and improved by day +90. The level of symptom burden predicted the overall quality of life at all time points.

Implications for Practice

Children experiencing high symptom burden should receive frequent assessment and enhanced symptom management throughout the treatment trajectory to mitigate negative impacts on quality of life.
Dimethyl sulfoxide as a novel therapy in a murine model of acute lung injury
Authors: Taghavi Sharven , Engelhardt David , Campbell Alexandra , Goldvarg-Abud Inna , Duchesne Juan , Shaheen Farhana , Pociask Derek , Kolls Jay , Jackson-Weaver Olan
Published: March 2024

INTRODUCTION

The endothelial glycocalyx on the luminal surface of endothelial cells contributes to the permeability barrier of the pulmonary vasculature. Dimethyl sulfoxide (DMSO) has a disordering effect on plasma membranes, which prevents the formation of ordered membrane domains important in the shedding of the endothelial glycocalyx. We hypothesized that DMSO would protect against protein leak by preserving the endothelial glycocalyx in a murine model of acute respiratory distress syndrome (ARDS).

METHODS

C57BL/6 mice were given ARDS via intratracheally administered lipopolysaccharide (LPS). Dimethyl sulfoxide (220 mg/kg) was administered intravenously for 4 days. Animals were sacrificed postinjury day 4 after bronchoalveolar lavage (BAL). Bronchoalveolar lavage cell counts and protein content were quantified. Lung sections were stained with fluorescein isothiocyanate-labeled wheat germ agglutinin to quantify the endothelial glycocalyx. Human umbilical vein endothelial cells (HUVECs) were exposed to LPS. Endothelial glycocalyx was measured using fluorescein isothiocyanate-labeled wheat germ agglutinin, and co-immunoprecipitation was performed to measure interaction between sheddases and syndecan-1.

RESULTS

Dimethyl sulfoxide treatment resulted in greater endothelial glycocalyx staining intensity in the lung when compared with sham (9,641 vs. 36,659 arbitrary units,p< 0.001). Total BAL cell counts were less for animals receiving DMSO (6.93 × 106vs. 2.49 × 106cells,p= 0.04). The treated group had less BAL macrophages (189.2 vs. 76.9 cells,p= 0.02) and lymphocytes (527.7 vs. 200.0 cells,p= 0.02). Interleukin-6 levels were lower in DMSO treated. Animals that received DMSO had less protein leak in BAL (1.48 vs. 1.08 μg/μL,p= 0.02). Dimethyl sulfoxide prevented LPS-induced endothelial glycocalyx loss in HUVECs and reduced the interaction between matrix metalloproteinase 16 and syndecan-1.

CONCLUSION

Systemically administered DMSO protects the endothelial glycocalyx in the pulmonary vasculature, mitigating pulmonary capillary leak after acute lung injury. Dimethyl sulfoxide also results in decreased inflammatory response. Dimethyl sulfoxide reduced the interaction between matrix metalloproteinase 16 and syndecan-1 and prevented LPS-induced glycocalyx damage in HUVECs. Dimethyl sulfoxide may be a novel therapeutic for ARDS.
Effects of leaf silicon on drought performance of tropical tree seedlings
Authors: Klotz Marius , Schaller Jörg , Knauft Alicia Madleen , Contreras Blexein , Engelbrecht Bettina M. J.
Published: March 2024

Elevated leaf silicon (Si) concentrations improve drought resistance in cultivated plants, suggesting Si might also improve drought performance of wild species. Tropical tree species, for instance, take up substantial amounts of Si, and leaf Si varies markedly at local and regional scales, suggesting consequences for seedling drought resistance. Yet, whether elevated leaf Si improves seedling drought performance in tropical forests is unknown. To manipulate leaf Si concentrations, seedlings of seven tropical tree species were grown in Si-rich and -poor soil, before exposing them to drought in the forest understorey. Survival, growth and wilting were monitored. Elevated leaf Si did not improve drought survival and growth in any of the species. In one species, drought survival was reduced in seedlings previously grown in Si-rich soil, contrary to our expectation. Our results suggest that elevated leaf Si does not improve drought resistance of wild tropical tree species. Elevated leaf Si may even reduce drought performance, suggesting differences in soil conditions influencing leaf Si may contribute to soil-related variation of tropical seedling performance. Furthermore, our results are at odds with most studies on cultivated species and show that alleviative effects of Si in crops cannot be generalized to wild plants in natural systems.
Understanding the impact of numerical solvers on inference for differential equation models
Authors: Creswell Richard , Shepherd Katherine M. , Lambert Ben , Mirams Gary R. , Lei Chon Lok , Tavener Simon , Robinson Martin , Gavaghan David J.
Published: March 2024

Most ordinary differential equation (ODE) models used to describe biological or physical systems must be solved approximately using numerical methods. Perniciously, even those solvers that seem sufficiently accurate for the
forward problem
, i.e. for obtaining an accurate simulation, might not be sufficiently accurate for the
inverse problem
, i.e. for inferring the model parameters from data. We show that for both fixed step and adaptive step ODE solvers, solving the forward problem with insufficient accuracy can distort likelihood surfaces, which might become jagged, causing inference algorithms to get stuck in local ‘phantom’ optima. We demonstrate that biases in inference arising from numerical approximation of ODEs are potentially most severe in systems involving low noise and rapid nonlinear dynamics. We reanalyse an ODE change point model previously fit to the COVID-19 outbreak in Germany and show the effect of the step size on simulation and inference results. We then fit a more complicated rainfall run-off model to hydrological data and illustrate the importance of tuning solver tolerances to avoid distorted likelihood surfaces. Our results indicate that, when performing inference for ODE model parameters, adaptive step size solver tolerances must be set cautiously and likelihood surfaces should be inspected for characteristic signs of numerical issues.
A Bayesian approach to identifying the role of hospital structure and staff interactions in nosocomial transmission of SARS-CoV-2
Authors: Bridgen Jessica R. E. , Lewis Joseph M. , Todd Stacy , Taegtmeyer Miriam , Read Jonathan M. , Jewell Chris P.
Published: March 2024

Nosocomial infections threaten patient safety, and were widely reported during the COVID-19 pandemic. Effective hospital infection control requires a detailed understanding of the role of different transmission pathways, yet these are poorly quantified. Using patient and staff data from a large UK hospital, we demonstrate a method to infer unobserved epidemiological event times efficiently and disentangle the infectious pressure dynamics by ward. A stochastic individual-level, continuous-time state-transition model was constructed to model transmission of SARS-CoV-2, incorporating a dynamic staff–patient contact network as time-varying parameters. A Metropolis–Hastings Markov chain Monte Carlo (MCMC) algorithm was used to estimate transmission rate parameters associated with each possible source of infection, and the unobserved infection and recovery times. We found that the total infectious pressure exerted on an individual in a ward varied over time, as did the primary source of transmission. There was marked heterogeneity between wards; each ward experienced unique infectious pressure over time. Hospital infection control should consider the role of between-ward movement of staff as a key infectious source of nosocomial infection for SARS-CoV-2. With further development, this method could be implemented routinely for real-time monitoring of nosocomial transmission and to evaluate interventions.
Optimal control of ribosome population for gene expression under periodic nutrient intake
Authors: Soubrier Clément , Foxall Eric , Ciandrini Luca , Dao Duc Khanh
Published: March 2024

Translation of proteins is a fundamental part of gene expression that is mediated by ribosomes. As ribosomes significantly contribute to both cellular mass and energy consumption, achieving efficient management of the ribosome population is also crucial to metabolism and growth. Inspired by biological evidence for nutrient-dependent mechanisms that control both ribosome-active degradation and genesis, we introduce a dynamical model of protein production, that includes the dynamics of resources and control over the ribosome population. Under the hypothesis that active degradation and biogenesis are optimal for maximizing and maintaining protein production, we aim to qualitatively reproduce empirical observations of the ribosome population dynamics. Upon formulating the associated optimization problem, we first analytically study the stability and global behaviour of solutions under constant resource input, and characterize the extent of oscillations and convergence rate to a global equilibrium. We further use these results to simplify and solve the problem under a quasi-static approximation. Using biophysical parameter values, we find that optimal control solutions lead to both control mechanisms and the ribosome population switching between periods of feeding and fasting, suggesting that the intense regulation of ribosome population observed in experiments allows to maximize and maintain protein production. Finally, we find some range for the control values over which such a regime can be observed, depending on the intensity of fasting.
Synthesis of pyrimido[4,5-
b
]quinolindiones and formylation: ultrasonically assisted reactions
Authors: Trilleras Jorge , Charris-Molina Andrés , Pérez-Gamboa Alfredo , Acosta-Guzman Paola , Quiroga Jairo
Published: March 2024

Ultrasound-assisted synthesis of pyrimido‌quinolindione derivatives via a multicomponent reaction and subsequent formylation with Vilsmeier–Haack reagent were performed. Compounds were prepared by a one-pot method from aminopyrimidinones, dimedone and aromatic aldehydes through a Mannich-type reaction sequence, and then functionalized under ultrasound irradiation and Vilsmeier–Haack conditions to give β-chlorovinylaldehyde products. Ultrasonically assisted reactions, experimental simplicity, good yields without using metallic catalysts and the control of hazardous material release are features of this simple procedure.
Multichannel scattering for the Schrödinger equation on a line with different thresholds at both infinities
Authors: Kazinski Peter O. , Korolev Petr S.
Published: March 2024

The multichannel scattering problem for the stationary Schrödinger equation on a line with different thresholds at both infinities is investigated. The analytical structure of the Jost solutions and of the transition matrix relating the Jost solutions as functions of the spectral parameter is described. Unitarity of the scattering matrix is proved in the general case when some of the scattering channels can be closed and the thresholds can be different at left and right infinities on the line. The symmetry relations of the

S

-matrix are established. The condition determining the bound states is obtained. The asymptotics of the Jost functions and of the transition matrix are derived for a large spectral parameter.