bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiwavelength observation of an active M-dwarf star EV Lacertae and its stellar flare accompanied by a delayed prominence eruption
Authors: Inoue Shun , Enoto Teruaki , Namekata Kosuke , Notsu Yuta , Honda Satoshi , Maehara Hiroyuki , Zhang Jiale , Lu Hong-Peng , Uchida Hiroyuki , Tsuru Takeshi Go , Nogami Daisaku , Shibata Kazunari
Published: January 2024

We conducted four-night multiwavelength observations of an active M-dwarf star EV Lacertae on 2022 October 24–27 with simultaneous coverage of soft X-rays (NICER; 0.2–12 keV, Swift XRT; 0.2–10 keV), near-ultraviolet (Swift UVOT/UVW2; 1600–3500 Å), optical photometry (TESS; 6000–10000 Å), and optical spectroscopy (Nayuta/MALLS; 6350–6800 Å). During the campaign, we detected a flare starting at 12:28 UTC on October 25 with a white-light bolometric energy of 3.4 × 1032 erg. At about 1 h after this flare peak, our Hα spectrum showed a blueshifted excess component at a corresponding velocity of ∼100 km s−1. This may indicate that the prominence erupted with a 1 h delay of the flare peak. Furthermore, the simultaneous 20 s cadence near-ultraviolet (NUV) and white-light curves show gradual and rapid brightening behaviors during the rising phase at this flare. The ratio of flux in NUV to white light at the gradual brightening was ∼0.49, which may suggest that the temperature of the blackbody is low (<9000 K) or the maximum energy flux of a non-thermal electron beam is less than 5 × 1011 erg cm−2 s−1. Our simultaneous observations of the NUV and white-light flare raise the issue of a simple estimation of UV flux from optical continuum data by using a blackbody model.
The plant POLYMERASE-ASSOCIATED FACTOR1 complex links transcription and H2B monoubiquitination genome wide
Authors: Blanco-Touriñán Noel , Pérez-Alemany Jaime , Bourbousse Clara , Latrasse David , Ait-Mohamed Ouardia , Benhamed Moussa , Barneche Fredy , Blázquez Miguel A , Gallego-Bartolomé Javier , Alabadí David
Published: January 2024

The evolutionarily conserved POLYMERASE-ASSOCIATED FACTOR1 complex (Paf1C) participates in transcription, and research in animals and fungi suggests that it facilitates RNA POLYMERASE II (RNAPII) progression through chromatin. We examined the genomic distribution of the EARLY FLOWERING7 (ELF7) and VERNALIZATION INDEPENDENCE3 subunits of Paf1C in Arabidopsis (Arabidopsis thaliana). The occupancy of both subunits was confined to thousands of gene bodies and positively associated with RNAPII occupancy and the level of gene expression, supporting a role as a transcription elongation factor. We found that monoubiquitinated histone H2B, which marks most transcribed genes, was strongly reduced genome wide in elf7 seedlings. Genome-wide profiling of RNAPII revealed that in elf7 mutants, RNAPII occupancy was reduced throughout the gene body and at the transcription end site of Paf1C-targeted genes, suggesting a direct role for the complex in transcription elongation. Overall, our observations suggest a direct functional link between Paf1C activity, monoubiquitination of histone H2B, and the transition of RNAPII to productive elongation. However, for several genes, Paf1C may also act independently of H2Bub deposition or occupy these genes more stable than H2Bub marking, possibly reflecting the dynamic nature of Paf1C association and H2Bub turnover during transcription.
Rates of adverse events and related risk factors following e-cigarette use
Authors: Cuomo Raphael E , Purushothaman Vidya L , Mackey Tim K , Yang Joshua W
Published: January 2024

Background

E-cigarettes have emerged as popular products, especially for younger populations. However, concerns regarding health effects exist and there is a notable gap in understanding the prevalence and nature of adverse events. This study aims to examine the rate of adverse events in individuals who use e-cigarettes in a large sample.

Methods

A cross-sectional survey was conducted with a sample of 4695 current and former e-cigarette users with a median age of 34 years. The survey collected data on e-cigarette use, adverse events experienced, product characteristics, related behaviors, sociodemographic factors and presence of medical comorbidities. Statistical analyses were conducted using Pearson’s chi-squared tests and logistic regression.

Results

A total of 78.9% of respondents reported experiencing an adverse event within 6 h of using a vaping device, with the most common events being headache, anxiety and coughing. Product characteristics and related behaviors significantly influenced the risk of adverse events. There were also sociodemographic disparities, with Hispanic respondents and those with at least college-level education reporting higher rates of adverse events.

Conclusions

Our study found a high rate of adverse events among e-cigarette users. We identified that certain e-cigarette product characteristics, behaviors and medical comorbidities significantly increased the risk of these events.
Bayesian Phylogenetic Analysis on Multi-Core Compute Architectures: Implementation and Evaluation of BEAGLE in RevBayes With MPI
Authors: Smith Killian , Ayres Daniel , Neumaier René , Wörheide Gert , Höhna Sebastian
Published: January 2024

Phylogenies are central to many research areas in biology and commonly estimated using likelihood-based methods. Unfortunately, any likelihood-based method, including Bayesian inference, can be restrictively slow for large datasets—with many taxa and/or many sites in the sequence alignment—or complex substitutions models. The primary limiting factor when using large datasets and/or complex models in probabilistic phylogenetic analyses is the likelihood calculation, which dominates the total computation time. To address this bottleneck, we incorporated the high-performance phylogenetic library BEAGLE into RevBayes, which enables multi-threading on multi-core CPUs and GPUs, as well as hardware specific vectorized instructions for faster likelihood calculations. Our new implementation of RevBayes+BEAGLE retains the flexibility and dynamic nature that users expect from vanilla RevBayes. In addition, we implemented native parallelization within RevBayes without an external library using the message passing interface (MPI); RevBayes+MPI. We evaluated our new implementation of RevBayes+BEAGLE using multi-threading on CPUs and 2 different powerful GPUs (NVidia Titan V and NVIDIA A100) against our native implementation of RevBayes+MPI. We found good improvements in speedup when multiple cores were used, with up to 20-fold speedup when using multiple CPU cores and over 90-fold speedup when using multiple GPU cores. The improvement depended on the data type used, DNA or amino acids, and the size of the alignment, but less on the size of the tree. We additionally investigated the cost of rescaling partial likelihoods to avoid numerical underflow and showed that unnecessarily frequent and inefficient rescaling can increase runtimes up to 4-fold. Finally, we presented and compared a new approach to store partial likelihoods on branches instead of nodes that can speed up computations up to 1.7 times but comes at twice the memory requirements.
Occurrence of the Reniform Nematode Rotylenchulus reniformis Parasitizing Cucumber and Eggplant in Mexico
Authors: Valdez-Morales Maria T. , Carrillo-Fasio José A. , García-Estrada Raymundo S. , Correia Kamila C. , Cruz-Lachica Isabel , Marquez-Zequera Isidro , Tovar-Pedraza Juan M.
Published: January 2024

Cucumber and eggplant exhibiting symptoms of root necrosis and yellowing foliage were observed in two shade houses in Culiacán, Sinaloa, Mexico. Through morphological characterization and molecular analysis of the coxI sequences, Rotylenchulus reniformis was identified as the causal agent. This identification was further confirmed by the infection and reisolation of the nematodes. This is the first report of R. reniformis causing diseases in cucumber and eggplant in Mexico.
Patient-centered precision care in anaesthesia – the PC-square (PC)2 approach
Authors: Berger-Estilita Joana , Marcolino Isabel , Radtke Finn M.
Published: January 2024

Purpose of review

This review navigates the landscape of precision anaesthesia, emphasising tailored and individualized approaches to anaesthetic administration. The aim is to elucidate precision medicine principles, applications, and potential advancements in anaesthesia. The review focuses on the current state, challenges, and transformative opportunities in precision anaesthesia.

Recent findings

The review explores evidence supporting precision anaesthesia, drawing insights from neuroscientific fields. It probes the correlation between high-dose intraoperative opioids and increased postoperative consumption, highlighting how precision anaesthesia, especially through initiatives like Safe Brain Initiative (SBI), could address these issues. The SBI represents multidisciplinary collaboration in perioperative care. SBI fosters effective communication among surgical teams, anaesthesiologists, and other medical professionals.

Precision anaesthesia tailors care to individual patients, incorporating genomic insights, personalised drug regimens, and advanced monitoring techniques. From EEG to cerebral/somatic oximetry, these methods enhance precision. Standardised reporting, patient-reported outcomes, and continuous quality improvement, alongside initiatives like SBI, contribute to improved patient outcomes. Precision anaesthesia, underpinned by collaborative programs, emerges as a promising avenue for enhancing perioperative care.
Risk Factors for Stiffness After Surgical Treatment of Pediatric Humeral Lateral Condyle Fractures: Results of a Multicenter Study
Authors: Tippabhatla Abhishek , Torres-Izquierdo Beltran , Pereira Daniel E. , Goldstein Rachel , Sanders Julia , Neal Kevin , Bellaire Laura , Denning Jaime , Hosseinzadeh Pooya
Published: January 2024

Introduction:

Pediatric humeral lateral condyle fractures are the second most common elbow fractures. Their treatment presents challenges due to physeal and intra-articular involvement. Postoperative stiffness is a common concern that can limit limb functionality. This study aims to identify risk factors for postoperative stiffness in a large cohort of these fractures across multiple institutions.

Methods:

A large, multicenter retrospective review of medical records from 6 level I trauma centers was conducted. Data from children aged 1 to 12 years with lateral condyle fractures treated between 2005 and 2019 were collected. Elbow stiffness was defined in the present study as having a limited elbow ROM that led to requiring a physical or occupational therapy referral or needing surgical treatment to address stiffness. Relevant patient demographics, fracture characteristics, treatment approaches, and complications were analyzed.

Results:

Six hundred sixty-five fractures were analyzed. The average patient age was 8.8 years with 21% experiencing stiffness. The stiffness group had older patients, a higher incidence of elbow dislocations, a higher rate of open reduction, and more severe fracture patterns. Multivariate regression analysis identified open reduction, increased age, and concurrent elbow dislocation as significant risk factors for stiffness. Patients with stiffness commonly utilized only physical or occupational therapy (96%), while a small percentage (4%) required surgical interventions.

Conclusions:

This study highlights the risk factors for postoperative stiffness in pediatric humeral lateral condyle fractures, namely increased age, concomitant elbow dislocation, and treatment with open reduction. Families of older patients or severe fracture patterns requiring open reduction and those with concurrent elbow instability should be counseled about their increased risk of stiffness. The authors recommend initially attempting a closed reduction in high-risk patients to help mitigate the risk of postoperative stiffness. Early initiation of range of motion exercises may also be beneficial for at-risk patients.

Level of Evidence:

Level III: Therapeutic studies—Investigating the results of treatment
Lumbar Total Disc Replacement Device Removals and Revisions Performed During a 20 Year Experience with 2,141 Patients
Authors: Guyer Richard D. , Blumenthal Scott L. , Shellock Jessica L. , Zigler Jack E. , Ohnmeiss Donna D.
Published: January 2024

Study Design:

This was a retrospective study with prospective patient contact attempted to collect current data.

Objective:

The purpose was to investigate the incidence and reasons for lumbar total disc replacement (TDR) removal or revision.

Summary of Background Data:

A concern regarding lumbar TDR was safety, particularly the need for device removal or revision. This may be particularly important considering removal/revision requires repeat anterior exposure with increased risk of vascular injury.

Methods:

Data were collected for a series of 2,141 lumbar TDR patients beginning with the first case experience in 2000. Mean follow-up was 78.6 months. For each case of device removal/revision, the reason, duration from index surgery, and procedure performed were recorded.

Results:

Of 2,141 patients, 27 (1.26%) underwent TDR removal or revision. Device removal was performed in 24 patients (1.12%) while 3 patients underwent revision (0.14%). Of the 24 removals: 12 were due to migration and/or loosening, 3 developed problems post-trauma, 2 developed lymphocytic reaction to device materials, 2 had ongoing pain, and there was one case of each: TDR was too large, vertebral body fracture (osteoporosis), lytic lesion, device subsidence and facet arthrosis, and infection seeded from a chest infection 146 months post-TDR. The 3 revisions were for: Core repositioning (technique error), device repositioning after displacement, and core replacement due to wear/failure. With respect to timing, 37.0% of removals/revisions occurred within one month post-implantation. Of note, 40.7% of removals/revisions occurred in the first 25 TDR cases performed by individual surgeons. There was one significant vascular complication, occurring in a patient whose TDR was removed due to trauma. This was also the only patient among 258 with >15-year follow-up who underwent removal/revision.

Conclusion:

In this large consecutive series, 1.26% of TDRs were removed/revised. The low rate over a 20 year period supports the safety of these devices.
New Oral PCSK9 Inhibitor: “MK-0616”
Authors: Siddiqui Zoya , Frishman William
Published: January 2024

MK-0616, a novel oral macrocyclic peptide inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), represents a significant advancement in the treatment of hypercholesterolemia. Unlike current PCSK9 inhibitors, which are injectable monoclonal antibodies and siRNA molecules, MK-0616 offers a patient-friendly alternative. The development of MK-0616 involved innovative synthetic chemistry and in vitro mRNA display technology. This cutting-edge approach led to the creation of an orally administered peptide with the ability to cover a larger portion of PCSK9 compared to smaller, linear peptides. Phase 1 and 2b clinical trials have demonstrated MK-0616’s safety, efficacy, and pharmacokinetics. These trials indicate the drug’s dose-dependent systemic absorption and long half-life. Notably, MK-0616 has exhibited comparable low-density lipoprotein cholesterol-lowering effects to currently available PCSK9 inhibitors, all while maintaining good tolerability in diverse patient populations, including those concurrently on statin therapy. As MK-0616 advances to Phase 3 trials, its lipid-lowering potential for heterozygous familial hypercholesterolemia and its impact on reducing the time to adverse cardiac events will be evaluated in a broad and diverse population, including underrepresented groups. The results achieved so far are promising for individuals with hypercholesterolemia, as they offer a potential solution for effectively lowering low-density lipoprotein cholesterol in patients on statin therapy and mitigating the risk of cardiovascular events. Ongoing research and monitoring will be critical to establish its long-term safety and efficacy, but MK-0616 may emerge as a valuable addition to the array of lipid-lowering therapies available to patients.
Heterogeneity of treatment response to beta-blockers in the treatment of portal hypertension: A systematic review
Authors: Alsaeid Mohammad , Sung Shuen , Bai Wayne , Tam Matthew , Wong Yu Jun , Cortes Jordi , Cobo Erik , Gonzalez Jose Antonio , Abraldes Juan G.
Published: January 2024

Background:

It has been suggested that a relevant proportion of patients do not respond to nonselective beta-blockers (NSBB)s, which raises questions regarding the need for individualized therapy. The existence of potential heterogeneity in the treatment response can be assessed using the variability ratio (VR) of the outcome measurement (in this case, HVPG) between the treated and placebo groups. We conducted a systematic review and meta-analysis of randomized controlled trials to assess the potential heterogeneity in the portal pressure response to NSBBs.

Methods:

After a systematic search, we quantified the heterogeneity of treatment response with the VR between the treatment and control groups, with VR > 1 indicating potential heterogeneity. We used a similar approach to compare carvedilol with propranolol and statins with placebo.

Results:

We identified 18 studies that included 965 patients. A comparison between beta-blockers and placebo showed a pooled VR of 0.99 (95% CI:0.87–1.14), which suggests a homogeneous HVPG response to NSBB at the individual patient level (ie, no evidence to support that some patients responded to beta-blockers and others did not). For the comparison between carvedilol and propranolol, pooled VR was 0.97 (95% CI 0.82–1.14), suggesting that carvedilol achieves a greater average response (rather than an increase in the proportion of responders). There was no evidence of a heterogeneous response to statins.

Conclusion:

Our analysis did not support the existence of a heterogeneous patient-by-patient response to NSBBs in cirrhosis. These findings challenge the concept of personalized therapy based on portal pressure response and indicate that routine portal pressure measurement may not be necessary to guide NSBB therapy.
African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis
Authors: Yazdanfar Maryam , Zepeda Joseph , Dean Richard , Wu Jialin , Levy Cynthia , Goldberg David , Lammert Craig , Prenner Stacey , Reddy K. Rajender , Pratt Daniel , Forman Lisa , Assis David N. , Lytvyak Ellina , Montano-Loza Aldo J. , Gordon Stuart C. , Carey Elizabeth J. , Ahn Joseph , Schlansky Barry , Korzenik Joshua , Karagozian Raffi , Hameed Bilal , Chandna Shaun , Yu Lei , Bowlus Christopher L.
Published: January 2024

Background:

The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood.

Methods:

Transplant-free survival and hepatic decompensation–free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code.

Results:

Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p=0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4–15.2 vs. 15.1, 14.1–15.7, p=0.002), but Mayo risk score (0.03, −0.8 to 1.1 vs. 0.02, −0.7 to 1.0, p=0.83), Model for End-stage Liver Disease (5.9, 2.8–10.7 vs. 6.4, 2.6–10.4, p=0.95), and cirrhosis (27.4% vs. 27.1%, p=0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02–1.06, p<0.0001), total bilirubin (1.06, 1.04–1.08, p<0.0001), and albumin (0.44, 0.33–0.61, p<0.0001). AA race did not affect the performance of prognostic models.

Conclusions:

AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.
Cellular origin and molecular mechanisms of lung metastases in patients with aggressive hepatoblastoma
Authors: Gulati Ruhi , Lutz Maggie , Hanlon Margaret , Cast Ashley , Karns Rebekah , Geller James , Bondoc Alex , Tiao Gregory , Timchenko Lubov , Timchenko Nikolai A.
Published: January 2024

Background and Aims:

Lung metastases are the most threatening signs for patients with aggressive hepatoblastoma (HBL). Despite intensive studies, the cellular origin and molecular mechanisms of lung metastases in patients with aggressive HBL are not known. The aims of these studies were to identify metastasis-initiating cells in primary liver tumors and to determine if these cells are secreted in the blood, reach the lung, and form lung metastases.

Approach:

We have examined mechanisms of activation of key oncogenes in primary liver tumors and lung metastases and the role of these mechanisms in the appearance of metastasis-initiating cells in patients with aggressive HBL by RNA-Seq, immunostaining, chromatin immunoprecipitation, Real-Time Quantitative Reverse Transcription PCR and western blot approaches. Using a protocol that mimics the exit of metastasis-initiating cells from tumors, we generated 16 cell lines from liver tumors and 2 lines from lung metastases of patients with HBL.

Results:

We found that primary HBL liver tumors have a dramatic elevation of neuron-like cells and cancer-associated fibroblasts and that these cells are released into the bloodstream of patients with HBL and found in lung metastases. In the primary liver tumors, the ph-S675-β-catenin pathway activates the expression of markers of cancer-associated fibroblasts; while the ZBTB3-SRCAP pathway activates the expression of markers of neurons via cancer-enhancing genomic regions/aggressive liver cancer domains leading to a dramatic increase of cancer-associated fibroblasts and neuron-like cells. Studies of generated metastasis-initiating cells showed that these cells proliferate rapidly, engage in intense cell-cell interactions, and form tumor clusters. The inhibition of β-catenin in HBL/lung metastases–released cells suppresses the formation of tumor clusters.

Conclusions:

The inhibition of the β-catenin-cancer-enhancing genomic regions/aggressive liver cancer domains axis could be considered as a therapeutic approach to treat/prevent lung metastases in patients with HBL.
Sirtuin3 promotes the degradation of hepatic Z alpha-1 antitrypsin through lipophagy
Authors: Poole Brittney , Oshins Regina , Huo Zhiguang , Aranyos Alek , West Jesse , Duarte Sergio , Clark Virginia C. , Beduschi Thiago , Zarrinpar Ali , Brantly Mark , Khodayari Nazli
Published: January 2024

Background:

Alpha-1 antitrypsin deficiency (AATD) is a genetic disease caused by misfolding and accumulation of mutant alpha-1 antitrypsin (ZAAT) in the endoplasmic reticulum of hepatocytes. Hepatic ZAAT aggregates acquire a toxic gain-of-function that impacts the endoplasmic reticulum which is theorized to cause liver disease in individuals with AATD who present asymptomatic until late-stage cirrhosis. Currently, there is no treatment for AATD-mediated liver disease except liver transplantation. In our study of mitochondrial RNA, we identified that Sirtuin3 (SIRT3) plays a role in the hepatic phenotype of AATD.

Methods:

Utilizing RNA and protein analysis in an in vitro AATD model, we investigated the role of SIRT3 in the pathophysiology of AATD-mediated liver disease while also characterizing our novel, transgenic AATD mouse model.

Results:

We show lower expression of SIRT3 in ZAAT-expressing hepatocytes. In contrast, the overexpression of SIRT3 increases hepatic ZAAT degradation. ZAAT degradation mediated by SIRT3 appeared independent of proteasomal degradation and regular autophagy pathways. We observed that ZAAT-expressing hepatocytes have aberrant accumulation of lipid droplets, with ZAAT polymers localizing on the lipid droplet surface in a direct interaction with Perilipin2, which coats intracellular lipid droplets. SIRT3 overexpression also induced the degradation of lipid droplets in ZAAT-expressing hepatocytes. We observed that SIRT3 overexpression induces lipophagy by enhancing the interaction of Perilipin2 with HSC70. ZAAT polymers then degrade as a consequence of the mobilization of lipids through this process.

Conclusions:

In this context, SIRT3 activation may eliminate the hepatic toxic gain-of-function associated with the polymerization of ZAAT, providing a rationale for a potential novel therapeutic approach to the treatment of AATD-mediated liver disease.
Targeting G9a/DNMT1 methyltransferase activity impedes IGF2-mediated survival in hepatoblastoma
Authors: Demir Salih , Razizadeh Negin , Indersie Emilie , Branchereau Sophie , Cairo Stefano , Kappler Roland
Published: January 2024

Background:

As the variable clinical outcome of patients with hepatoblastoma (HB) cannot be explained by genetics alone, the identification of drugs with the potential to effectively reverse epigenetic alterations is a promising approach to overcome poor therapy response. The gene ubiquitin like with PHD and ring finger domains 1 (UHRF1) represents an encouraging epigenetic target due to its regulatory function in both DNA methylation and histone modifications and its clinical relevance in HB.

Methods:

Patient-derived xenograft in vitro and in vivo models were used to study drug response. The mechanistic basis of CM-272 treatment was elucidated using RNA sequencing and western blot experiments.

Results:

We validated in comprehensive data sets that UHRF1 is highly expressed in HB and associated with poor outcomes. The simultaneous pharmacological targeting of UHRF1-dependent DNA methylation and histone H3 methylation by the dual inhibitor CM-272 identified a selective impact on HB patient-derived xenograft cell viability while leaving healthy fibroblasts unaffected. RNA sequencing revealed downregulation of the IGF2-activated survival pathway as the main mode of action of CM-272 treatment, subsequently leading to loss of proliferation, hindered colony formation capability, reduced spheroid growth, decreased migration potential, and ultimately, induction of apoptosis in HB cells. Importantly, drug response depended on the level of IGF2 expression, and combination assays showed a strong synergistic effect of CM-272 with cisplatin. Preclinical testing of CM-272 in a transplanted patient-derived xenograft model proved its efficacy but also uncovered side effects presumably caused by its strong antitumor effect in IGF2-driven tumors.

Conclusions:

The inhibition of UHRF1-associated epigenetic traces, such as IGF2-mediated survival, is an attractive approach to treat high-risk HB, especially when combined with the standard-of-care therapeutic cisplatin.
Influential Signs of Dry Eye–Related Ocular Symptoms in Participants With Unstable Tear Film
Authors: Shen Jiahui , Xu Zhiqiang , Wang Yuzhou , Ye Jingjian , Wei Linzhi , Xia Jiahui , Sun Yiran , Lu Fan , Hu Liang
Published: January 2024

Purpose:

The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT).

Methods:

This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included.

Results:

Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA (P < 0.001) and NIBUTave (P = 0.010). OSDI was negatively associated with upper RMGA (r = −0.450, P < 0.001) and NIBUTave (r = −0.414, P = 0.001), and positively associated with upper MG grade (r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = −41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave.

Conclusions:

The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED.
Risk Factors for Poor Outcomes in Children Hospitalized With Virus-associated Acute Lower Respiratory Infections: A Systematic Review and Meta-analysis
Authors: Trusinska Daira , Zin Si Thu , Sandoval Emmanuel , Homaira Nusrat , Shi Ting
Published: January 2024

Background:

Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify risk factors for poor outcomes in children <5 years old hospitalized with ALRI caused by respiratory syncytial virus (RSV), influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods:

We searched Embase, Medline and Global Health databases and included observational studies reporting risk factors for poor outcomes (defined as use of supplemental oxygen, mechanical ventilation, intensive care unit admission, prolonged hospital stay and mortality) published between January 2011 and January 2023. Two authors independently extracted data on study characteristics, outcomes and risk factors. Due to limited data, meta-analyses were only conducted for RSV-ALRI poor outcome risk factors using random effects model when there were at least 3 studies.

Results:

We included 30 studies. For RSV-related ALRI, significant risk factors based on meta-analysis were: neurological disease [odds ratio (OR): 6.14; 95% confidence intervals (CIs): 2.39–15.77], Down’s syndrome (5.43; 3.02–9.76), chronic lung disease (3.64; 1.31–10.09), immunocompromised status (3.41; 1.85–6.29), prematurity (2.98; 1.93–4.59), congenital heart disease (2.80; 1.84–4.24), underlying disease (2.45; 1.94–3.09), age <2 months (2.29; 1.78–2.94), age <6 months (2.08; 1.81–2.39), viral coinfection (2.01; 1.27–3.19), low birth weight (1.88; 1.19–2.95) and being underweight (1.80; 1.38–2.35). For influenza-related ALRI, chronic conditions and age 6–24 months were identified as risk factors for poor outcomes. Cardiovascular disease, immunosuppression, chronic kidney disease, diabetes and high blood pressure were reported as risk factors for mortality due to SARS-CoV-2 associated ALRI.

Conclusions:

These findings might contribute to the development of guidelines for prophylaxis and management of ALRI caused by RSV, influenza and SARS-CoV-2.
Prevalence, Clinical and Imaging Characteristics of Superior Ophthalmic Vein Periphlebitis in Thyroid Eye Disease
Authors: Goodyear Kendall , Ghiam Sean , Strawbridge Jason , Oh Angela J. , Singh Pallavi , Roelofs Kelsey A. , Rootman Daniel B.
Published: January 2024

Purpose:

To determine the prevalence, clinical features, and radiographic findings of superior ophthalmic vein periphlebitis (SOVP) in thyroid eye disease (TED).

Methods:

Patients with a clinical diagnosis of thyroid eye disease and contrast-enhanced imaging were included. Imaging was reviewed for the presence of SOVP, and patients with SOVP were compared to those without. A random eye was determined to be the affected eye in patients without SOVP.

Results:

A total of 212 patients met the inclusion criteria. Unilateral SOVP was identified in 4.7% of cases. There was no significant difference in age (p = 0.22), gender (p = 0.09), or disease duration (p = 0.14) between patients with and without SOVP. There was a significant (p < 0.05) difference in stage classification and clinical activity core between the groups. The affected eye in patients with SOVP had significantly (p < 0.05) greater margin reflex distance 1, degree of relative proptosis, horizontal motility restriction, and vertical motility restriction than in patients without SOVP. There was no significant difference in horizontal strabismus (p = 1.0), vertical strabismus (p = 0.87), or relative intraocular pressure (p = 0.77). On imaging, the maximal diameter of the SR and IR were found to be significantly (p < 0.05) larger in the affected eye of patients with periphlebitis; however, there was no difference in measured diameter of the medial rectus and (p = 0.30) or lateral rectus (p = 0.78).

Conclusions:

SOVP is an under-reported imaging finding of thyroid eye disease. It is associated with significantly greater margin reflex distance 1, relative proptosis, and motility restriction on exam as well as larger superior rectus and inferior rectus diameter on imaging. These patients tend to present in the active stage of disease with greater clinical activity score.
Interindividual variability in cold-pressor pain sensitivity is not explained by peripheral vascular responding and generalizes to a C-nociceptor–specific pain phenotype
Authors: Martel Richard D. , Papafragou Georgios , Weigand Sylvia , Rolke Roman , Prawitt Dirk , Birklein Frank , Treede Rolf-Detlef , Magerl Walter
Published: January 2024

Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor–sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex–mediated microcirculatory responses. Cold-pressor–sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor–mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber–mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water–exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.
Improving risk models for patients having emergency bowel cancer surgery using linked electronic health records: a national cohort study
Authors: Blake Helen A. , Sharples Linda D. , Boyle Jemma M. , Kuryba Angela , Moonesinghe Suneetha R. , Murray Dave , Hill James , Fearnhead Nicola S. , van der Meulen Jan H. , Walker Kate
Published: January 2024

Background:

Life-saving emergency major resection of colorectal cancer (CRC) is a high-risk procedure. Accurate prediction of postoperative mortality for patients undergoing this procedure is essential for both healthcare performance monitoring and preoperative risk assessment. Risk-adjustment models for CRC patients often include patient and tumour characteristics, widely available in cancer registries and audits. The authors investigated to what extent inclusion of additional physiological and surgical measures, available through linkage or additional data collection, improves accuracy of risk models.

Methods:

Linked, routinely-collected data on patients undergoing emergency CRC surgery in England between December 2016 and November 2019 were used to develop a risk model for 90-day mortality. Backwards selection identified a ‘selected model’ of physiological and surgical measures in addition to patient and tumour characteristics. Model performance was assessed compared to a ‘basic model’ including only patient and tumour characteristics. Missing data was multiply imputed.

Results:

Eight hundred forty-six of 10 578 (8.0%) patients died within 90 days of surgery. The selected model included seven preoperative physiological and surgical measures (pulse rate, systolic blood pressure, breathlessness, sodium, urea, albumin, and predicted peritoneal soiling), in addition to the 10 patient and tumour characteristics in the basic model (calendar year of surgery, age, sex, ASA grade, TNM T stage, TNM N stage, TNM M stage, cancer site, number of comorbidities, and emergency admission). The selected model had considerably better discrimination compared to the basic model (C-statistic: 0.824 versus 0.783, respectively).

Conclusion:

Linkage of disease-specific and treatment-specific datasets allowed the inclusion of physiological and surgical measures in a risk model alongside patient and tumour characteristics, which improves the accuracy of the prediction of the mortality risk for CRC patients having emergency surgery. This improvement will allow more accurate performance monitoring of healthcare providers and enhance clinical care planning.
Role of the revised Baux score in predicting mortality among burn patients in an African low-income country: a multicentre prospective cohort
Authors: Baraka Samuel Mandro , Kiswezi Ahmed , Olasinde Anthony Ayotunde , Edyedu Isaac , Molen Selamo Fabrice , Muhumuza Joshua , Zawadi Gift Vulwaghe , Okedi Francis Xaviour
Published: January 2024

Introduction:

Burn injury is a major cause of mortality. Majority of the burns occur in low and middle-income countries like Uganda. Uganda has a limited number of burn centres and medical resources, making a predictor of mortality necessary in allocation of the limited resources. Although the revised Baux (r-Baux) score has been validated and used in many high income countries, no study has assessed its role in an African low-income country; the reason this study was done.

Methods:

This was a prospective multicentre cohort that enroled 101 burn patients with moderate and severe burns admitted in three tertiary hospitals in western Uganda. Follow-up was done until discharge, documenting mortality. A receiver operator characteristic curve was used to determine the role of r-Baux score in predicting mortality.

Results:

This study included 101 patients, with a mean age of 21.3 (SD=16.8) years. The majority of the participants were male (69.3%). The area under the curved for r-Baux score’s prediction of mortality was 0.943 (P<0.001). The most appropriate cut-off was determined to be 74.5. At this cut-off, r-Baux score predicted mortality with a sensitivity of 100% and specificity of 83.5%. After controlling for burn severity using Poisson regression, a patient with r-Baux score greater than 74.5 was 1.358 times more likely to die (adjusted risk ratio=1.358, 95% CI=1.195–1.543, P<0.001).

Conclusion:

The r-Baux score was found to be excellent at predicting mortality among burn patients in Uganda and therefore should be done for all patients at admission, in order to predict mortality and do proper planning.
Artificial Dermis and Human Recombinant Epidermal Growth Factor Application for the Management of Critical Size Calvarial Defect
Authors: Çiçek Çağla , Filinte Gaye , Başak Kayhan , Kayiş Ahmet F.
Published: January 2024

Restoration of the 3-dimensional structure of the facial and calvarial skeleton after trauma or ablative oncologic surgeries serves as a framework for soft tissue reconstruction. In the present study, the authors aimed to evaluate the osteogenic effect of artificial dermis and epidermal growth factor treatment in critical-sized calvarial defects, which cannot be healed spontaneously. 8 mm calvarial defects were created in 28 male rats and filled with the artificial dermis, the artificial dermis and growth factor, growth factor or left untreated. Atomic absorption spectrometry was used to determine the amount of calcium, scanning electron microscopy was used to show the bone tissue in 3 dimensions, and immunohistochemistry was used to assess the bone formation and cell density. Histologic evaluation at 6 weeks showed incomplete bone regeneration in all groups. No statistical differences were found between the groups with regard to their scores for the following: inflammation, new bone formation, osteocyte density, resorption of bone at the edges of the defect, or fibrous tissue formation in the defect area. In conclusion, the predictability of bone formation in critical-size defects is not clear. Contrary to popular belief, the combined use of epidermal growth factor with artificial dermis or alone did not enhance the potential for osseous healing.
Combining contextuality and causality: a game semantics approach
Authors: Abramsky Samson , Barbosa Rui Soares , Searle Amy
Published: January 2024

We develop an approach to combining contextuality with causality, which is general enough to cover causal background structure, adaptive measurement-based quantum computation and causal networks. The key idea is to view contextuality as arising from a game played between Experimenter and Nature, allowing for causal dependencies in the actions of both the Experimenter (choice of measurements) and Nature (choice of outcomes).

This article is part of the theme issue ‘Quantum contextuality, causality and freedom of choice’.
Agreement and disagreement in a non-classical world
Authors: Brandenburger Adam , Contreras-Tejada Patricia , La Mura Pierfrancesco , Scarpa Giannicola , Steverson Kai
Published: January 2024

The Agreement Theorem Aumann (1976
Ann. Stat.
4
, 1236–1239. (
doi:10.1214/aos/1176343654
)) states that if two Bayesian agents start with a common prior, then they cannot have common knowledge that they hold different posterior probabilities of some underlying event of interest. In short, the two agents cannot ‘agree to disagree’. This result applies in the classical domain where classical probability theory applies. But in non-classical domains, such as the quantum world, classical probability theory does not apply. Inspired principally by their use in quantum mechanics, we employ signed probabilities to investigate the epistemics of the non-classical world. We find that here, too, it cannot be common knowledge that two agents assign different probabilities to an event of interest. However, in a non-classical domain, unlike the classical case, it can be common certainty that two agents assign different probabilities to an event of interest. Finally, in a non-classical domain, it cannot be common certainty that two agents assign different probabilities, if communication of their common certainty is possible—even if communication does not take place.

This article is part of the theme issue ‘Quantum contextuality, causality and freedom of choice’.
Comparing the cost of violating causal assumptions in Bell experiments: locality, free choice and arrow-of-time
Authors: Blasiak Pawel , Gallus Christoph
Published: January 2024

The causal modelling of Bell experiments relies on three fundamental assumptions: locality, freedom of choice and arrow-of-time. It turns out that nature violates Bell inequalities, which implies the failure of at least one of those assumptions. Since rejecting any of them, even partially, is sufficient to explain the observed correlations, it is natural to inquire about the cost in each case. This paper builds upon the findings in Blasiak
et al.
2021
Proc. Natl Acad. Sci. USA
118
, e2020569118 (
doi:10.1073/pnas.2020569118
) showing the equivalence between the locality and free choice assumptions. Here, we include retrocausal models to complete the picture of causal explanations of the observed correlations. Furthermore, we refine the discussion by considering more challenging causal scenarios which allow only single-arrow type violations of a given assumption. The figure of merit chosen for the comparison of the causal cost is defined as the minimal frequency of violation of the respective assumption required for a simulation of the observed experimental statistics.

This article is part of the theme issue ‘Quantum contextuality, causality and freedom of choice’.
Measures of contextuality in cyclic systems and the negative probabilities measure CNT
3
Authors: Camillo Giulio , Cervantes Víctor H.
Published: January 2024

Several principled measures of contextuality have been proposed for general systems of random variables (i.e. inconsistently connected systems). One such measure is based on quasi-couplings using negative probabilities (here denoted by

CNT

3

, Dzhafarov & Kujala, 2016
Quantum interaction
). Dzhafarov & Kujala (Dzhafarov & Kujala 2019
Phil. Trans. R. Soc. A
377
, 20190149. (
doi:10.1098/rsta.2019.0149
)) introduced a measure of contextuality,

CNT

2

, that naturally generalizes to a measure of non-contextuality. Dzhafarov & Kujala (Dzhafarov & Kujala 2019
Phil. Trans. R. Soc. A
377
, 20190149. (
doi:10.1098/rsta.2019.0149
)) additionally conjectured that in the class of cyclic systems these two measures are proportional. Here we prove that conjecture is correct. Recently, Cervantes (Cervantes 2023
J. Math. Psychol
.
112
, 102726. (
doi:10.1016/j.jmp.2022.102726
)) showed the proportionality of

CNT

2

and the Contextual Fraction measure introduced by Abramsky & Brandenburger (Abramsky & Brandenburger 2011
New J. Phys
.
13
, 113036. (
doi:10.1088/1367-2630/13/11/113036
)). The present proof completes the description of the interrelations of all contextuality measures proposed within or translated into the Contextuality-by-Default framework so far as they pertain to cyclic systems.

This article is part of the theme issue ‘Quantum contextuality, causality and freedom of choice’.
On geometrical aspects of the graph approach to contextuality
Authors: Amaral Barbara , Terra Cunha Marcelo
Published: January 2024

The connection between contextuality and graph theory has paved the way for numerous advancements in the field. One notable development is the realization that sets of probability distributions in many contextuality scenarios can be effectively described using well-established convex sets from graph theory. This geometric approach allows for a beautiful characterization of these sets. The application of geometry is not limited to the description of contextuality sets alone; it also plays a crucial role in defining contextuality quantifiers based on geometric distances. These quantifiers are particularly significant in the context of the resource theory of contextuality, which emerged following the recognition of contextuality as a valuable resource for quantum computation. In this paper, we provide a comprehensive review of the geometric aspects of contextuality. Additionally, we use this geometry to define several quantifiers, offering the advantage of applicability to other approaches to contextuality where previously defined quantifiers may not be suitable.

This article is part of the theme issue ‘Quantum contextuality, causality and freedom of choice’.