bluuebunny/crossref_metadata_2025 huggingface dataset:
The right to regulate and the interpretation of the WTO Agreement
Authors: Mitchell Andrew D
Published: July 2023

In contrast to international investment tribunals, World Trade Organization (WTO) adjudicators have been reluctant to acknowledge the inherent right to regulate under international law explicitly. Policy-based considerations arising from such a right have not been viewed as a standalone component under interpretive analyses in WTO dispute settlement. Instead, they have been integrated only to the extent they find expression in the treaty. This article explores how, on occasion, WTO adjudicators have departed from this orthodox approach by choosing to proactively interpret the WTO Covered Agreements in a way that presupposes a States’ right to regulate, even where this may seem contrary to, or unsupported by, the treaty text. In these cases, the question has not been whether such a right subsists within substantive WTO disciplines, but rather how such a right can be read into these disciplines in a manner that comports with the ordinary rules of treaty interpretation. While this unorthodox approach has resulted in interpretations that appear unclear and uncertain, these outcomes are ultimately explicable in terms of a general principle of regulatory autonomy that can form the basis for more principled interpretive choices.
Protecting vulnerable patient populations from climate hazards: the role of the nation’s cancer centers
Authors: Espinel Zelde , Shultz James M , Aubry Vanina Pavia , Abraham Omar Muñoz , Fan Qinjin , Crane Tracy E , Sahar Liora , Nogueira Leticia M
Published: July 2023

Individuals diagnosed with cancer are a vulnerable population during disasters. Emergency preparedness efforts are crucial for meeting the health and safety needs of patients, health-care professionals, health-care facilities, and communities before, during, and after a disaster. Recognizing the importance of advancing emergency preparedness expertise to cancer control efforts nationwide, especially in the era of climate change, we searched National Cancer Institute–designated cancer centers’ websites to examine emergency preparedness information sharing and evidence of research efforts focused on disaster preparedness. Of 71 centers, 56 (78.9%) presented some emergency preparedness information, and 36 (50.7%) presented information specific to individuals diagnosed with cancer. Only 17 (23.9%) centers provided emergency preparedness information for climate-driven disasters. Informed by these data, this commentary describes an opportunity for cancer centers to lead knowledge advancement on an important aspect of climate change adaptation: disaster preparedness.
Low-ionization structures in planetary nebulae – III. The statistical analysis of physico-chemical parameters and excitation mechanisms
Authors: Mari M Belén , Akras Stavros , Gonçalves Denise R
Published: July 2023

Nearly 30 yr after the first detailed studies of low-ionization structures (LISs) in planetary nebulae (PNe), we perform a statistical analysis of their physical, chemical, and excitation properties, by collecting published data in the literature. The analysis was made through the contrast between LISs and high-ionization structures – rims or shells – for a large sample of PNe, in order to highlight significant differences between these structures. Our motivation was to find robust results based on the largest sample of LISs gathered so far. (i) Indeed, LISs have lower electron densities (Ne[S ii]) than the rims/shells. (ii) The nitrogen electron temperatures (Te[N ii]) are similar between the two groups, while a bimodal distribution is observed for the Te based on [O iii] of the rims/shells, although the high- and low-ionization structures have Te[O iii] of similar median values. (iii) No significant variations are observed in total abundances of He, N, O, Ne, Ar, Cl, and S between the two groups. (iv) Through the analysis of several diagnostic diagrams, LISs are separated from rims/shells in terms of excitation. From two large grids of photoionization and shock models, we show that there is an important overlap between both mechanisms, particularly when low-ionization line ratios are concerned. We found a good tracer of high-velocity shocks, as well as an indicator of high- and low-velocity shocks that depends on temperature-sensitive line ratios. In conclusion, both excitation mechanisms could be present; however, shocks cannot be the main source of excitation for most of the LISs of PNe.
Reconciling the magnetic field in central disc galaxies with the dynamical mass using the cosmological simulations
Authors: Hosseinirad Mohammad , Tabatabaei Fatemeh , Raouf Mojtaba , Roshan Mahmood
Published: July 2023

The Universe is pervaded by magnetic fields in different scales, although for simplicity, they are ignored in most cosmological simulations. In this paper, we use the TNG50, which is a large cosmological galaxy formation simulation that incorporates magnetic fields with an unprecedented resolution. We study the correlation of the magnetic field with various galaxy properties such as the total, stellar, and gaseous mass, circular velocity, size, and star formation rate. We find a linear correlation between the average magnetic field pervading the disc of galaxies in relative isolation and their circular velocities. In addition, we observed that in this sample the average magnetic field in the disc is correlated with the total mass as $\overline{B}\sim M_{\mathrm{tot, R_{\star }}}^{0.2}$. We also find that the massive galaxies with active wind-driven black hole feedback, do not follow this trend, as their magnetic field is substantially affected by this feedback mode in the TNG50 simulation. We show that the correlation of the magnetic field with the star formation rate is a little weaker than the circular velocity. Moreover, we compare the magnetic field components of the above sample with a compiled observational sample of non-cluster non-interacting nearby galaxies. Similar to the observation, we find a coupling between the ordered magnetic field and the circular velocity of the flat part of the rotation curve in the simulation, although contrary to the observation, the ordered component is dominant in the simulation.
Genetically encoded RNA-based sensors with Pepper fluorogenic aptamer
Authors: Chen Zhenyin , Chen Wei , Reheman Zhayila , Jiang Haodong , Wu Jiahui , Li Xing
Published: July 2023

Sensors to measure the abundance and signaling of intracellular molecules are crucial for understanding their physiological functions. Although conventional fluorescent protein-based sensors have been designed, RNA-based sensors are promising imaging tools. Numerous RNA-based sensors have been developed. These sensors typically contain RNA G-quadruplex (RG4) motifs and thus may be suboptimal in living cells. Here we describe RNA-based sensors based on Pepper, a fluorogenic RNA without an RG4 motif. With Pepper, we engineered various sensors for metabolites, synthetic compounds, proteins and metal ions in vitro and in living cells. In addition, these sensors show high activation and selectivity, demonstrating their universality and robustness. In the case of sensors responding to S-adenosylmethionine (SAM), a metabolite produced by methionine adenosyltransferase (MATase), we showed that our sensors exhibited positively correlated fluorescence responding to different SAM levels. Importantly, we revealed the SAM biosynthesis pathway and monitored MATase activity and gene expression spatiotemporally in living individual human cells. Additionally, we constructed a ratiometric SAM sensor to determine the inhibition efficacy of a MATase inhibitor in living cells. Together, these sensors comprising Pepper provide a useful platform for imaging diverse cellular targets and their signaling pathway.
Recovery of protein synthesis to assay DNA repair activity in transcribed genes in living cells and tissues
Authors: van der Woude Melanie , Davó-Martínez Carlota , Thijssen Karen L , Vermeulen Wim , Lans Hannes
Published: July 2023

Transcription-coupled nucleotide excision repair (TC-NER) is an important DNA repair mechanism that protects against the negative effects of transcription-blocking DNA lesions. Hereditary TC-NER deficiencies cause pleiotropic and often severe neurodegenerative and progeroid symptoms. While multiple assays have been developed to determine TC-NER activity for clinical and research purposes, monitoring TC-NER is hampered by the low frequency of repair events occurring in transcribed DNA. ’Recovery of RNA Synthesis’ is widely used as indirect TC-NER assay based on the notion that lesion-blocked transcription only resumes after successful TC-NER. Here, we show that measuring novel synthesis of a protein after its compound-induced degradation prior to DNA damage induction is an equally effective but more versatile manner to indirectly monitor DNA repair activity in transcribed genes. This ‘Recovery of Protein Synthesis’ (RPS) assay can be adapted to various degradable proteins and readouts, including imaging and immunoblotting. Moreover, RPS allows real-time monitoring of TC-NER activity in various living cells types and even in differentiated tissues of living organisms. To illustrate its utility, we show that DNA repair in transcribed genes declines in aging muscle tissue of C. elegans. Therefore, the RPS assay constitutes an important novel clinical and research tool to investigate transcription-coupled DNA repair.
A Small Compound, HYGIC, Promotes Hypocotyl Growth Through Ectopic Ethylene Response
Authors: Murao Mizuki , Kato Rika , Kusano Shuhei , Hisamatsu Rina , Endo Hitoshi , Kawabata Yasuki , Kimura Seisuke , Sato Ayato , Mori Hitoshi , Itami Kenichiro , Torii Keiko U , Hagihara Shinya , Uchida Naoyuki
Published: July 2023

Plant seedlings adjust the growth of the hypocotyl in response to surrounding environmental changes. Genetic studies have revealed key players and pathways in hypocotyl growth, such as phytohormones and light signaling. However, because of genetic redundancy in the genome, it is expected that not-yet-revealed mechanisms can be elucidated through approaches different from genetic ones. Here, we identified a small compound, HYGIC (HG), that simultaneously induces hypocotyl elongation and thickening, accompanied by increased nuclear size and enlargement of cortex cells. HG-induced hypocotyl growth required the ethylene signaling pathway activated by endogenous ethylene, involving CONSTITUTIVE PHOTOMORPHOGENIC 1, ETHYLENE INSENSITIVE 2 (EIN2) and redundant transcription factors for ethylene responses, ETHYLENE INSENSITIVE 3 (EIN3) and EIN3 LIKE 1. By using EBS:GUS, a transcriptional reporter of ethylene responses based on an EIN3-binding-cis-element, we found that HG treatment ectopically activates ethylene responses at the epidermis and cortex of the hypocotyl. RNA-seq and subsequent gene ontology analysis revealed that a significant number of HG-induced genes are related to responses to hypoxia. Indeed, submergence, a representative environment where the hypoxia response is induced in nature, promoted ethylene-signaling-dependent hypocotyl elongation and thickening accompanied by ethylene responses at the epidermis and cortex, which resembled the HG treatment. Collectively, the identification and analysis of HG revealed that ectopic responsiveness to ethylene promotes hypocotyl growth, and this mechanism is activated under submergence.
Putative NAD(P)-Binding Rossmann Fold Protein Is Involved in Chitosan-Induced Peroxidase Activity and Lipoxygenase Expression in Physcomitrium patens
Authors: Marttinen Eeva M. , Decker Eva L. , Heinonen Petra , Reski Ralf , Valkonen Jari P. T.
Published: July 2023

Oxidative burst, the rapid production of high levels of reactive oxygen species in response to external stimuli, is an early defense reaction against pathogens. The fungal elicitor chitosan causes an oxidative burst in the moss Physcomitrium patens (formerly Physcomitrella patens), mainly due to the peroxidase enzyme Prx34. To better understand the chitosan responses in P. patens, we conducted a screen of part of a P. patens mutant collection to isolate plants with less peroxidase activity than wild-type (WT) plants after chitosan treatment. We isolated a P. patens mutant that affected the gene encoding NAD(P)-binding Rossmann fold protein (hereafter, Rossmann fold protein). Three Rossmann fold protein-knockout (KO) plants (named Rossmann fold KO lines) were generated and used to assess extracellular peroxidase activity and expression of defense-responsive genes, including alternative oxidase, lipoxygenase (LOX), NADPH oxidase, and peroxidase (Prx34) in response to chitosan treatment. Extracellular (apoplastic) peroxidase activity was significantly lower in Rossmann fold KO lines than in WT plants after chitosan treatments. Expression of the LOX gene in Rossmann fold KO plants was significantly lower before and after chitosan treatment when compared with WT. Peroxidase activity assays together with gene expression analyses suggest that the Rossmann fold protein might be an important component of the signaling pathway leading to oxidative burst and basal expression of the LOX gene in P. patens.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Fungal Microbiome Indicators Are Associated with Genotypic Variation in Pea Root Rot Susceptibility when Intercropped with Barley
Authors: Cadot Selma , Hohmann Pierre , Hsung Ming-Hui , Hartmann Martin , Haug Benedikt , Wille Lukas , Messmer Monika M. , Bodenhausen Natacha
Published: July 2023

Intercropping of legume and cereal crop species shows potential to reduce root disease pressures by changing root-associated microbiomes and improving nitrogen (N) use via soil N-dependent fixation of atmospheric N2by symbiotic rhizobia. A two-year field study was conducted to evaluate the effect of pea–barley association on crop performance and on the root fungal community. Five pea cultivars (Alvesta, Karpate, Mytic, Respect, and Vitra) were grown either in pure stands or mixed with one variety of barley (Atrika). We measured crop grain yield and root rot incidence and analyzed root fungal communities. In mixed stands, total grain yield was more stable compared with that in each pure stand, but pea root disease incidence was higher except for cultivars Vitra and Karpate. The effect of cropping system on fungal alpha diversity depended on the cultivar, with Vitra showing higher Shannon diversity and Alvesta showing lower richness in mixed compared with pure stands. All four operational taxonomic units (OTUs) belonging to the Didymellaceae family were positively associated with pea root rot, and another disease-associated OTU in pea, Neoascochyta exitialis, was found to be also part of the barley core microbiome. Eleven of twelve OTUs belonging to the Glomeraceae family were associated with healthy roots and abundant in cultivar Vitra. This study shows how the phenotype and fungal microbiome of different pea cultivars respond distinctly to intercropping. Furthermore, the identification of disease- and health-associated taxa in the pea root fungal community refines the characterization of different cultivar candidates for intercropping.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
A Metabolomics Assay to Diagnose Citrus Huanglongbing Disease and to Aid in Assessment of Treatments to Prevent or Cure Infection
Authors: McCartney Mitchell M. , Eze Michael O. , Borras Eva , Edenfield Michael , Batuman Ozgur , Manker Denise C. , da Graça John V. , Ebeler Susan E. , Davis Cristina E.
Published: July 2023

Citrus greening disease, or Huanglongbing (HLB), has devastated citrus crops globally in recent years. The causal bacterium, ‘ Candidatus Liberibacter asiaticus’, presents a sampling issue for qPCR diagnostics and results in a high false negative rate. In this work, we compared six metabolomics assays to identify HLB-infected citrus trees from leaf tissue extracted from 30 control and 30 HLB-infected trees. A liquid chromatography-mass spectrometry-based assay was most accurate. A final partial least squares-discriminant analysis (PLS-DA) model was trained and validated on 690 leaf samples with corresponding qPCR measures from three citrus varieties (Rio Red grapefruit, Hamlin sweet orange, and Valencia sweet orange) from orchards in Florida and Texas. Trees were naturally infected with HLB transmitted by the insect vector Diaphorina citri. In a randomized validation set, the assay was 99.9% accurate to classify diseased from nondiseased samples. This model was applied to samples from trees receiving plant defense-inducer compounds or biological treatments to prevent or cure HLB infection. From two trials, HLB-related metabolite abundances and PLS-DA scores were tracked longitudinally and compared with those of control trees. We demonstrate how our assay can assess tree health and the efficacy of HLB treatments and conclude that no trialed treatment was efficacious.
Evidence that an Unnamed Isometric Virus Associated with Potato Rugose Disease in Peru Is a New Species of Genus Torradovirus
Authors: Alvarez-Quinto Robert , Amao Melody , Muller Giovanna , Fuentes Segundo , Grinstead Samuel , Fuentes-Bueno Irazema , Roenhorst Annelien , Westenberg Marcel , Botermans Marleen , Kreuze Jan , Mollov Dimitre
Published: July 2023

A previously uncharacterized torradovirus species infecting potatoes was detected by high-throughput sequencing from field samples from Peru and in customs intercepts in potato tubers that originated from South America in the United States of America and the Netherlands. This new potato torradovirus showed high nucleotide sequence identity to an unidentified isometric virus (SB26/29), which was associated with a disease named potato rugose stunting in southern Peru characterized over two decades ago. Thus, this virus is tentatively named potato rugose stunting virus (PotRSV). The genome of PotRSV isolates sequenced in this study were composed of two polyadenylated RNA segments. RNA1 ranges from 7,086 to 7,089 nt and RNA2 from 5,228 to 5,230 nt. RNA1 encodes a polyprotein containing the replication block (helicase-protease-polymerase), whereas RNA2 encodes a polyprotein cleaved into a movement protein and the three capsid proteins (CPs). Pairwise comparison among PotRSV isolates revealed amino acid identity values greater than 86% in the protease-polymerase (Pro-Pol) region and greater than 82% for the combined CPs. The closest torradovirus species, squash chlorotic leaf spot virus, shares amino acid identities of ∼58 and ∼41% in the Pro-Pol and the combined CPs, respectively.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Aortic carboxypeptidase‐like protein, a putative myokine, stimulates the differentiation and survival of bone‐forming osteoblasts
Authors: Kim Hanjun , Kim Min Ji , Moon Sung Ah , Cho Han Jin , Lee Young‐Sun , Park So Jeong , Kim Yewon , Baek In‐Jeoung , Kim Beom‐Jun , Lee Seung Hun , Koh Jung‐Min
Published: July 2023

A new target that stimulates bone formation is needed to overcome limitations of current anti‐osteoporotic drugs. Myokines, factors secreted from muscles, may modulate it. In this study, we investigated the role of aortic carboxypeptidase‐like protein (ACLP), which is highly expressed in skeletal muscles, on bone formation. MC3T3‐E1 cells and/or calvaria osteoblasts were treated with recombinant N‐terminal mouse ACLP containing a signal peptide [rmACLP (N)]. The expression and secretion of ACLP were higher in skeletal muscle and differentiated myotube than in other tissues and undifferentiated myoblasts, respectively. rmACLP (N) increased bone formation, ALP activity, and phosphorylated p38 mitogen‐activated protein (MAP) kinase in osteoblasts; reversal was achieved by pre‐treatment with a TGF‐β receptor inhibitor. Under H2O2 treatment, rmACLP (N) increased osteoblast survival, phosphorylated p38 MAP kinase, and the nuclear translocation of FoxO3a in osteoblasts. H2O2 treatment caused rmACLP (N) to suppress its apoptotic, oxidative, and caspase‐9 activities. rmACLP (N)‐stimulated osteoblast survival was reversed by pre‐treatment with a p38 inhibitor, a TGF‐β‐receptor II blocking antibody, and a FoxO3a shRNA. Conditioned media (CM) from muscle cells stimulated osteoblast survival under H2O2 treatment, in contrast to CM from ACLP knockdown muscle cells. rmACLP (N) increased the expressions of FoxO3a target anti‐oxidant genes such as Sod2, Trx2, and Prx5. In conclusion, ACLP stimulated the differentiation and survival of osteoblasts. This led to the stimulation of bone formation by the activation of p38 MAP kinase and/or FoxO3a via TGF‐β receptors. These findings suggest a novel role for ACLP in bone metabolism as a putative myokine.
GPCRs and fibroblast heterogeneity in fibroblast‐associated diseases
Authors: Dwivedi Nidhi V. , Datta Souvik , El‐Kersh Karim , Sadikot Ruxana T. , Ganti Apar K. , Batra Surinder K. , Jain Maneesh
Published: July 2023

G protein‐coupled receptors (GPCRs) are the largest and most diverse class of signaling receptors. GPCRs regulate many functions in the human body and have earned the title of “most targeted receptors”. About one‐third of the commercially available drugs for various diseases target the GPCRs. Fibroblasts lay the architectural skeleton of the body, and play a key role in supporting the growth, maintenance, and repair of almost all tissues by responding to the cellular cues via diverse and intricate GPCR signaling pathways. This review discusses the dynamic architecture of the GPCRs and their intertwined signaling in pathological conditions such as idiopathic pulmonary fibrosis, cardiac fibrosis, pancreatic fibrosis, hepatic fibrosis, and cancer as opposed to the GPCR signaling of fibroblasts in physiological conditions. Understanding the dynamics of GPCR signaling in fibroblasts with disease progression can help in the recognition of the complex interplay of different GPCR subtypes in fibroblast‐mediated diseases. This review highlights the importance of designing and adaptation of next‐generation strategies such as GPCR‐omics, focused target identification, polypharmacology, and effective personalized medicine approaches to achieve better therapeutic outcomes for fibrosis and fibrosis associated malignancies.
Evaluation and management of irritable bowel syndrome
Authors: Steinmetz Whitney Emerson
Published: July 2023

Irritable bowel syndrome (IBS) is a common diagnosis that providers encounter in primary and specialty care. IBS is characterized by chronic abdominal pain and altered bowel habits. The American College of Gastroenterology recently released an updated guideline for the evaluation and management of patients with IBS. According to the guideline, it remains important to confirm diagnosis based on criteria and lack of alarm signs; IBS should not be a diagnosis of exclusion. Management should be focused on addressing altered bowel habits and global symptoms using a multidisciplinary approach.
Opportunistic Use of Computed Tomography to Determine Muscle-Adipose Ratio Reliably Predicts Wound Complications after Kocher-Langenbeck Surgical Exposure of the Acetabulum
Authors: Avilucea Frank R. , Ferreira Rogerio , Shaath M. Kareem , Haidukewych George J.
Published: July 2023

Objectives:

To determine whether muscle-to-adipose ratio (MAR) along the course of a Kocher-Langenbeck (KL) incision is more accurate at predicting post-operative wound complications following acetabuluar fixation than waist-hip ratio (WHR) or body mass index (BMI).

Design:

Retrospective case series.

Setting:

Level-1 Trauma Center.

Patients/Participants: Patients who sustained an acetabular fracture and had fixation through a KL approach.

Intervention:

The calculation of the MAR.

Main Outcome Measurements:

Presence of a surgical site infection or a wound healing complication.

Results:

193 patients were included in the study and mean follow-up was 17.4 months. Thirty (15.5%) patients developed a wound complication. Seventeen (8.8%) patients developed a superficial infection and thirteen (6.7%) developed a deep infection. Mean BMI for those who developed a wound complication was 35.9. The mean MAR was 0.67 for patients who developed a wound complication versus 0.75 for those who did not. ROC analysis showed an area under curve (AUC) for BMI to be .717 (95% CI, .577-.857, p = .006) and for MAR to be .680 (inverted, 95% CI .507-.854, p = .022). The AUC for WHR was not statistically significant.

Conclusion:

MAR is a significant predictor of post-operative wound complication in obese patients undergoing treatment of posterior wall acetabular fractures. The higher rate of wound complications in patients with a low MAR should be considered in the treatment of these patients and may be used to guide discussion regarding the risks of surgery, as well as the potential use of adjuncts to reduce wound healing complications.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Changes in Spinopelvic Parameters Between Standing and Sitting Postures
Authors: Tan Tuan Hao , Tan Jun-Hao , Hey Hwee Weng Dennis
Published: July 2023

Study Design:

Systematic review and meta-analysis.

Objective:

To report the ratio-of-differences between standing and sitting. To understand how sex and age influence these differences.

Summary of Background Data:

Currently, spinal deformity surgery aims to realign the sagittal profile of the spine with-reference-to the standing posture resulting in overcorrection. New studies report significant disparities between standing and sitting spinal alignment.

Methods:

A comprehensive search and review of the published literature was performed on 4 platforms in accordance with the PRISMA 2009 checklist by 2 authors independently.

Results:

From 753 abstracts extracted from the databases, 38 papers involving 5423 patients were identified. sagittal vertical axis was more positive in sitting, with a pooled mean difference of 29.5 mm (95% CI: 17.9–41.0). Pelvic tilt (PT) was larger in sitting, with a pooled mean difference of 16.7 degrees (95% CI: 12.5–20.9), and a pooled odds ratio of 1.2(95% CI:1.1–1.3. P=0.001). Sacral Slope (SS) was smaller and lumbar lordosis (LL) was less lordotic in sitting, with a pooled mean difference of 15.0 degrees (95% CI: 11.918.1) and 21.1 degrees (95% CI:14.5–27.8), respectively, and a pooled odds ratio of 0.7 (95% CI: 0.6–0.8. P<0.001) and 0.7 (95% CI:0.6–0.7, P<0.001), respectively. Pelvic incidence and thoracic kyphosis was similar in sitting. Subgroup meta-analysis comparing odd ratio of standing to sitting showed: Among younger patients (age younger than 50), the PT and LL pooled odds-ratios were 1.4 and 0.7, respectively. Among older patients (age older than or equal to 50), the PT and LL pooled odds-ratios were 1.1 and 0.8, respectively. Among female patients, the SS pooled odds ratio was 0.6. Among male patients, the SS pooled odds ratio was 0.7.

Conclusion:

When comparing sitting to standing, it gives a more positive sagittal vertical axis, a smaller SS and LL, and a larger PT. pelvic incidence and thoracic kyphosis remained similar. Younger and female patients have pronounced differences in SS, PT, and LL, suggesting the existence of age and sex variations, and its role to be considered when planning for spinal realignment surgeries. Clinical outcome studies are required to ascertain the impact of these findings.
Treatment of Cancer Pain
Authors: Rosenscheg Marcelen , Pedron Julia , Pedroso Lorena
Published: July 2023

Contextualization:

One of the biggest problems regarding the treatment of cancer patients is pain, whether due to the cancer or the treatment itself. Therefore, there is a search for treatments that aims to promote an effective treatment in this sense.

Purpose:

This article aims to verify which are the recent methods used to treat pain in cancer patients in a multidisciplinary sense, and to evaluate their effectiveness.

Methodology:

Systematic reviews, meta-analyses and randomized clinical trials utilizing the LILACS, NCBI, and MEDLINE platforms of the last 5 years were included. The descriptors were pain treatment in oncology, pain management, complementary therapies, and other synonyms, in Portuguese, English and Spanish. This included any technique that was effective in the treatment of cancer pain.

Results:

The initial search found 2246 articles, of which 22 were included in the systematic review. Most of these are acupuncture treatments, opioids versus anti-inflammatories versus analgesics, radiotherapy, behavioral therapies, among others. Most articles suggest benefits with these therapies, improved quality of life for patients and tolerable side effects.

Conclusion:

This study demonstrates the effectiveness of the current methods used in the treatment of pain in cancer patients so that professionals in the area can have more options for treating cancer pain. Despite the important limitations, the guideline for further research and the situations in which treatments have shown effectiveness are present in it.
Impact of an advanced image based monoenergetic reconstruction algorithm on coronary artery stent visualization by dual source dual energy computed tomography: A primary study
Authors: Xie Lixiang , Yang Xiaoying , Xu Zhihan , Liu Zhongxiao , Wang Hao , Li Ke , Zhao Mingming , Meng Yankai , Hu Chunfeng , Xu Kai
Published: July 2023

Background:

The aim of this study was to investigate the qualities of advanced image based virtual monoenergetic (Mono+) images using a noise optimized algorithm at different kiloelectron volts (keV) compared with linear blended 120 kilovoltage (kV) images in patients with coronary stents.

Materials and Methods:

Thirty two patients who had undergone coronary computed tomography angiography were retrospectively enrolled in the study. Linear blended 120 kV image and 16 Mono+ images were reconstructed. Quantitative assessments included luminal attenuation difference, in stent image noise, in stent signal to noise ratio (SNR) and contrast to noise ratio (CNR). Double blinded and independent qualitative evaluation of image quality was performed by two readers using a five point scale.

Results:

The luminal attenuation difference value in the 190 keV group was the lowest. The in stent image noise in the 190 keV group was the lowest, in comparison with that in the 90–180 keV groups; however, it showed no significant difference. The 40 keV group had the highest in stent SNR, and there were no differences between the 40 keV group and the 50–100 keV groups. The 60 keV group had the highest in stent CNR, although no significant difference was found between the 60 keV group and the 40–120 keV groups. The highest subjective score was observed in the 80 keV group, with significant differences from the other groups (P < 0.05), except for the 90 keV group.

Conclusion:

In comparison with computed tomography image with conventional reconstruction, Mono+ reconstructions at 90 keV can significantly reduce the in stent noise and provide better image quality of coronary stents.
Hepatocytes reprogram liver macrophages involving control of TGF-β activation, influencing liver regeneration and injury
Authors: Wolf Stephanie D. , Ehlting Christian , Müller-Dott Sophia , Poschmann Gereon , Petzsch Patrick , Lautwein Tobias , Wang Sai , Helm Barbara , Schilling Marcel , Saez-Rodriguez Julio , Vucur Mihael , Stühler Kai , Köhrer Karl , Tacke Frank , Dooley Steven , Klingmüller Ursula , Luedde Tom , Bode Johannes G.
Published: July 2023

Background:

Macrophages play an important role in maintaining liver homeostasis and regeneration. However, it is not clear to what extent the different macrophage populations of the liver differ in terms of their activation state and which other liver cell populations may play a role in regulating the same.

Methods:

Reverse transcription PCR, flow cytometry, transcriptome, proteome, secretome, single cell analysis, and immunohistochemical methods were used to study changes in gene expression as well as the activation state of macrophages in vitro and in vivo under homeostatic conditions and after partial hepatectomy.

Results:

We show that F4/80+/CD11bhi/CD14hi macrophages of the liver are recruited in a C-C motif chemokine receptor (CCR2)–dependent manner and exhibit an activation state that differs substantially from that of the other liver macrophage populations, which can be distinguished on the basis of CD11b and CD14 expressions. Thereby, primary hepatocytes are capable of creating an environment in vitro that elicits the same specific activation state in bone marrow–derived macrophages as observed in F4/80+/CD11bhi/CD14hi liver macrophages in vivo. Subsequent analyses, including studies in mice with a myeloid cell–specific deletion of the TGF-β type II receptor, suggest that the availability of activated TGF-β and its downregulation by a hepatocyte-conditioned milieu are critical. Reduction of TGF-βRII-mediated signal transduction in myeloid cells leads to upregulation of IL-6, IL-10, and SIGLEC1 expression, a hallmark of the activation state of F4/80+/CD11bhi/CD14hi macrophages, and enhances liver regeneration.

Conclusions:

The availability of activated TGF-β determines the activation state of specific macrophage populations in the liver, and the observed rapid transient activation of TGF-β may represent an important regulatory mechanism in the early phase of liver regeneration in this context.
Clinical Features of Sjögren Syndrome–Related Dry Eye Disease in Anterior Segment Photographs
Authors: Shimizu Eisuke , Sato Shinri , Asai Kazuki , Ogawa Yoko , Shimmura Shigeto , Negishi Kazuno
Published: July 2023

Purpose:

Dry eye disease (DED) is a major complication of autoimmune disorders, including Sjögren syndrome (SS), ocular graft-versus-host disease, and other rheumatic diseases. DED often affects patients’ quality of life, necessitating early detection and treatment. However, no simple screening method for DED has yet been established in ophthalmologic practice. This retrospective study aimed to identify the characteristic features of SS-related DED from anterior segment images.

Methods:

Five hundred two cases (SS, 68 cases; ocular graft-versus-host disease, 50 cases; other conditions, 27 cases; simple DED, 72 cases; and no DED, 97 cases) were enrolled.

Results:

The inferior corneal fluorescein staining score (CFS_I) was significantly higher in the SS group (P < 0.001). Moreover, the nasal lissamine green staining score (LG_N) was high in the SS group (P < 0.001). The sensitivity, specificity, and area under the curve of the receiver operating characteristic curve were calculated for the CFS_I plus LG_N in relation to the SS-positive and SS-negative statuses; the sensitivity and specificity were 80.6% and 91.1%, respectively, with an area under the curve of 0.926.

Conclusions:

A positive CFS_I combined with a positive LG_N correlates with a high risk for SS. A positive CFS_I and a positive LG_N are important signs for an immune-related DED, especially SS, and may be useful in the early detection of SS-related DED.
COVID-19–Related Insomnia Populations Research and Management Strategies: A Review
Authors: Liu Fei-Xiang , Dong Zi-Bei , Zhao Min , Gao Ya-Hui , Li Xiang , Jiang Ya-Nan , Li Yi-Ming , Zheng Yu-Xin , Wang Zhen , Feng Yan-Chen , Liu Ya-Li
Published: July 2023

Coronavirus disease 2019 (COVID-19) has affected the quality of sleep for various populations, causing anxiety and depression worldwide. COVID-19–related insomnia (COVIDRI) appears to be more common in certain populations, including females, urban residents and other individuals who reside in high-risk COVID-19–related areas, lack higher socioeconomic and educational levels, have a history of underlying mental illness, have no access to social support and work, or have been mandated for isolation. Among vulnerable populations, pregnant women, adolescents and children are more likely to suffer from anxiety and depression, which leads to irregular sleep-wake cycles and significantly poor sleep quality. Insomnia in COVID-19 patients is associated with decreased immune levels, excessive psychological stress and severe anxiety. The COVIDRI incidence and severity among frontline healthcare workers is high, especially among females and those working in isolation wards and intensive care units. The factors related to COVIDRI for college students during home study are stress from upcoming graduation, disharmonious family relationships and inadaptability to online education. For military personnel, anxiety and depression are the main causes of poor sleep quality. Based on the characteristics of different populations, active Chinese and Western medications, non-drug therapy, psychological counseling and suitable sleep management are vital measures to strengthen immunity, alleviate insomnia and limit recurrence.
TAK1 Deficiency in Macrophages Increases Host Susceptibility to Leishmania Infection
Authors: Cao Xiankai , Kokou Kossiwa C. , Yu Shi , Chen Mengdan , Niu Junling , Lecoeur Hervé , Prina Eric , Späth Gerald F. , Meng Guangxun
Published: July 2023

Leishmania parasites mainly infect macrophages and may cause severe immunopathologies in their host, which are called leishmaniases. In the current work, we infected human and mouse macrophages in vitro with Leishmania major, an etiological agent of cutaneous leishmaniasis, and found that inhibition or deletion of the transforming growth factor β–activated kinase 1 (TAK1) gene resulted in increased parasite loads. In vivo, following a challenge with L. major, mice with a macrophage-specific deletion of TAK1 showed increased clinical signs and higher parasite loads compared with wild-type controls. TAK1 deficiency in mouse macrophages led to biased Th2 cell responses during the acute stage of infection, characterized by a decrease in interferon-γ expression, and increased expression of IL-4, IL-5 and IL-10. Finally, we found that, in the late stage of L. major infection, excessive Th2-related cytokines led to high arginase 1 expression in mouse tissues and a significant reduction of NO production both locally and systemically, resulting in compromised control of Leishmania. These findings suggest that TAK1 plays a vital role in host resistance to Leishmania infection.
Qualitative Assessment of Perceived Organizational Support for Employed Breast Cancer Survivors
Authors: Dugan Alicia G. , Decker Ragan E. , Austin Hannah L. , Namazi Sara , Bellizzi Keith M. , Blank Thomas O. , Shaw William S. , Swede Helen , Cherniack Martin G. , Tannenbaum Susan H. , Cavallari Jennifer M.
Published: July 2023

Objective

A more detailed understanding of unmet organizational support needs and workplace-based best practices for supporting cancer survivors is needed.

Methods

Ninety-four working breast cancer survivors responded to an open-ended survey question regarding the desired types of organizational support that were and were not received during early survivorship. We performed content-analysis of qualitative data.

Results

Major themes included instrumental support, emotional support, and time-based support. The need for flexible arrangements and reduced workloads was mostly met. Unmet needs included navigation/coordination, understanding/empathy, and time off for treatment and recovery.

Conclusions

Organizational support can help cancer survivors manage their health and work roles, diminishing work-health conflict and turnover intent. Study findings can be used to design targeted interventions to fulfill cancer survivors’ unmet organizational support needs, which may also apply to workers with other chronic health conditions.
Experiences of Homeless Recipients of Social Model Hospice Care
Authors: Jensen Francine Bench , Supiano Katherine P. , Towsley Gail L. , Ellington Lee , Cloyes Kristin G.
Published: July 2023

Homelessness and caregiver insecurity are barriers to accessing hospice for end-of-life care. Some communities have implemented a community-based social model of hospice care, and reports of its characteristics and outcomes are growing in hospice and homeless literature. This case report explored the experiences of social model hospice recipients using photovoice, a community-based participatory method to photograph meaningful aspects of care. Participants (n = 3) took photos (n = 93), journaled, and participated in semistructured interviews as co-analyzers. Through deductive codes from the literature and inductive analysis of data, 6 themes were identified: having a physical location to receive care, involving the community, having spiritual needs attended to, acknowledging family/family of choice, connecting with animals, and feeling cared for. Participants offered few suggestions to improve care. Social model hospice provided a location for care, funding, and social support to address housing and caregiver insecurity. Results corroborated the social model hospice concept (antecedents, attributes, consequences). Findings add to the growing literature with implications for communities and leaders looking to start or improve care. Results suggest that photovoice may be a feasible method for eliciting firsthand experiences of residents. Findings may guide discussions about patient-reported aspects of care for a more accurate understanding of meaningful social model hospice care.
Predictors of nonunion for transverse femoral shaft fractures treated with intramedullary nailing: a SIGN database study
Authors: Jones Brett , Cohoe Blake , Brown Kelsey , Flores Michael , Peurrung Kevin , Smith Terry , Shearer David , Zirkle Lewis
Published: July 2023

Introduction:

Nonunion is a common postfracture complication resulting in decreased quality of life for patients in resource-limited settings. This study aims to determine how age, sex, injury mechanism, and surgical intervention affect the rate of nonunion in transverse femur fractures treated with a SIGN intramedullary nail (IMN).

Methods:

A retrospective study was conducted using the SIGN online surgical database. All patients older than 16 years with simple transverse (<30 degrees), open or closed, femur fractures treated using a SIGN IMN between 2007 and 2021 were included. Our primary outcome of nonunion was measured with the modified Radiographic Union Scale for Tibial fractures (mRUST); scores ≤9 of 16 defined nonunion. The secondary outcome was squat depth. Outcomes were evaluated at follow-up appointments between 240 and 365 days postoperatively. Univariate and multivariate analysis were used for statistical comparison.

Results:

Inclusion criteria were met for 182 patients. The overall radiographic union rate was 61.0%, and a high proportion (84.4%) of patients could squat with their hips at or below the level of their knees. Older age, retrograde approach, and fracture distraction were associated with nonunion, but sex, injury mechanism, and other surgical variables were not.

Conclusion:

Poor reduction with fracture distraction was associated with a higher rate of nonunion. Loss of follow-up may have contributed to our overall union rate; however, we observed high rates of functional healing using the SIGN IMN.

Level of evidence:

IV.
Evaluating time-limited and persistent symptoms of adjustment disorder in cancer patients after a colorectal cancer diagnosis: a longitudinal observational study
Authors: Wijnhoven Lonneke M.A. , Kwakkenbos Linda , Verdonck-de Leeuw Irma M. , Prins Judith B. , Custers José A.E.
Published: July 2023

Background:

Patients with colorectal cancer (CRC) may experience symptoms of adjustment disorder (AD) after cancer diagnosis and treatment. Time-limited symptoms of AD may become persistent if the stressor or its consequences have not disappeared after 6 months, but evidence on the course of AD symptoms is scarce. This longitudinal observational study investigates the proportion of patients with CRC with time-limited and persistent AD symptoms within the first year after diagnosis, in relation to demographic, clinical, and psychological factors and health-related quality of life (HRQoL).

Methods:

Informed consent was retrieved from 232 participants, and 194 participants completed questionnaires at baseline, 3, 6, and 12 months postdiagnosis. Hospital Anxiety and Depression Scale total scores (HADS-T) were categorized as indication for no symptoms of a mental disorder (MD) (HADS-T ≤10), AD symptoms (HADS-T 11–14), and other MD symptoms (HADS-T ≥15). Symptom subgroups over time were a priori defined: no MD, time-limited AD, persistent AD, other MD, and fluctuating symptoms.

Results:

Complete data were available for 81 participants (41.4%). Over time, 38.3% had no MD symptoms, 8.6% had time-limited AD symptoms, 1.2% had persistent AD symptoms, 4.9% had other MD symptoms, and 46.9% had fluctuating symptoms. Participants with AD and fluctuating symptoms reported higher fear of cancer recurrence, lower HRQoL, and higher cancer-specific distress than participants without MD symptoms (P < .5).

Conclusions:

During the first year after CRC diagnosis, only a small proportion of the patients showed time-limited and persistent AD symptoms and most showed fluctuating symptoms. More prospective research is needed to determine how repeated assessments for elevated AD symptoms relate to an AD diagnosis established with a diagnostic interview.
Examining Soft and Hard Attributes of Health Care Service Quality and Their Impacts on Patient Satisfaction and Loyalty
Authors: Chen Li-Hsin , Chen Chun-Hung , Loverio Jennifer Pasion , Wang Mei-Jung (Sebrina) , Lee Ling-Hui , Hou Ya-Pin
Published: July 2023

Background and Objectives:

Many studies have confirmed the influences of various service quality dimensions on patient satisfaction and loyalty, but no existing theoretical model accounts for variation in how different types of patients evaluate service quality's soft and hard attributes. This research gap may cause problems for administrators needing to decide how to distribute resources appropriately across multiple departments. Therefore, this study establishes a theoretical model of the differences between inpatients' and outpatients' evaluations of hard and soft qualities and compares such evaluations' influences on patient satisfaction and loyalty. Also, to supplement statistical analysis and respond to scholars' calls for more mixed-methods studies of health care quality, this research incorporates analysis of online reviews to provide a holistic, close to real-time picture of patients' service experience perceptions.

Methods:

This study's survey sample comprised 292 inpatients and 137 outpatients from a Taiwanese hospital. We used partial least squares structural equation modeling to test the hypothetical model and importance-performance map analysis to identify factors that were significant to the service process but performed poorly. Finally, we used a text-mining technique to scrape 536 reviews posted on Google Maps, and Leximancer Portal to perform automated content and sentiment analyses on those data, as a means of mapping the critical concepts and themes that influenced patient experiences.

Results:

This study's analyses support the ideas that both hard and soft qualities are critical dimensions of service quality, and that each has different influences on inpatients' and outpatients' satisfaction and loyalty. Specifically, the sampled inpatients strongly valued the hard qualities of the hospital but were not satisfied with it. On the other hand, soft qualities attracted outpatients' attention and influenced their satisfaction and loyalty. In addition, content analysis revealed that soft qualities were the main reason patients left comments, whether positive or negative. Waiting time emerged as another critical element in triggering patients' unfavorable reviews.

Conclusions:

Patient population type, whether inpatient or outpatient, has been found to impact perceptions of service quality within health care institutions. As such, health care administrators should be cognizant of this phenomenon and make informed and tailored decisions when addressing quality within their respective services. Emphasis on the development of both interpersonal and professional skills among health care personnel may prove beneficial in enhancing the patient experience and ultimately fostering positive online reviews.