bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing the efficacy of unilateral biportal endoscopic transforaminal lumbar interbody fusion and minimally invasive transforaminal lumbar interbody fusion in lumbar degenerative diseases: a systematic review and meta-analysis
Authors: Luan Haopeng , Peng Cong , Liu Kai , Song Xinghua
Published: November 2023

Objective

To compare the efficacy and safety of unilateral biportal endoscopic transforaminal lumbar interbody fusion (BE-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in lumbar degenerative diseases.

Methods

This study was registered on International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42023432460). We searched PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang Database, and Wei Pu Database by computer to collect controlled clinical studies on the efficacy and safety of unilateral BE-TLIF and MIS-TLIF in lumbar degenerative diseases from database establishment to May 2023. Two researchers screened the literature, extracted data and evaluated the risk of bias of the included studies, recorded the authors, and sample size, and extracted the intraoperative blood loss, operation time, postoperative drainage, Oswestry disability index, Visual analogue scale, lumbar lordosis, disk height, hospital length stay, fusion rate, and complications in each study. Meta-analysis was performed using Revman 5.4 software provided by Cochrane Library.

Results

A total of 14 cohort studies with a total of 1007 patients were included in this study, including 472 patients in the BE-TLIF group and 535 patients in the MIS-TLIF group. The BE-TLIF group had lower intraoperative blood loss than the MIS-TLIF group [mean difference (MD) = − 78.72, 95% CI (− 98.47, − 58.97), P < 0.00001] and significantly reduced postoperative drainage than the MIS-TLIF group [MD = − 43.20, 95% CI (− 56.57, − 29.83), P < 0.00001], and the operation time was longer than that of the MIS-TLIF group [MD = 22.68, 95% CI (12.03, 33.33), P < 0.0001]. Hospital length stay in BE-TLIF group was significantly less than that in MIS-TLIF group [MD = − 1.20, 95% CI (− 1.82, − 0.57), P = 0.0002].

Conclusion

Compared with MIS-TLIF, BE-TLIF for lumbar degenerative diseases has the advantages of less intraoperative blood loss, less early postoperative low back and leg pain, shorter postoperative hospital length stay, and faster early functional recovery.
Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC)
Authors: Lee Sang-Yun , Cho Hyeong Jun , Choi Jimin , Ku Bosung , Moon Seok Whan , Moon Mi Hyoung , Kim Kyung Soo , Hyun Kwanyong , Kim Tae-Jung , Sung Yeoun Eun , Hwang Yongki , Lee Eunyoung , Ahn Dong Hyuck , Choi Joon Young , Lim Jeong Uk , Park Chan Kwon , Kim Sung Won , Kim Seung Joon , Koo In-Seong , Jung Woo Seok , Lee Sang-Hyun , Yeo Chang Dong , Lee Dong Woo
Published: November 2023

Background

Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient‘s groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test.

Methods

On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides.

Results

The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response.

Conclusions

Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.
Detection of a novel Babesia sp. in Amblyomma javanense, an ectoparasite of Sunda pangolins
Authors: Chong Stacy Q. Y. , Yeo Darren , Aidil Nur Insyirah , Ong Jasmine L. Y. , Chan Amy H. J. , Fernandez Charlene Judith , Lim Bryan T. M. , Khoo Max D. Y. , Wong Anna M. S. , Chang Siow Foong , Yap Him Hoo
Published: November 2023

Background

Babesia is a protozoal, tick-borne parasite that can cause life-threatening disease in humans, wildlife and domestic animals worldwide. However, in Southeast Asia, little is known about the prevalence and diversity of Babesia species present in wildlife and the tick vectors responsible for its transmission. Recently, a novel Babesia species was reported in confiscated Sunda pangolins (Manis javanica) in Thailand. To investigate the presence of this parasite in Singapore, we conducted a molecular survey of Babesia spp. in free-roaming Sunda pangolins and their main ectoparasite, the Amblyomma javanense tick.

Methods

Ticks and tissue samples were opportunistically collected from live and dead Sunda pangolins and screened using a PCR assay targeting the 18S rRNA gene of Babesia spp. DNA barcoding of the cytochrome oxidase subunit I (COI) mitochondrial gene was used to confirm the species of ticks that were Babesia positive.

Results

A total of 296 ticks and 40 tissue samples were obtained from 21 Sunda pangolins throughout the 1-year study period. Babesia DNA was detected in five A. javanense ticks (minimum infection rate = 1.7%) and in nine different pangolins (52.9%) located across the country. Phylogenetic analysis revealed that the Babesia 18S sequences obtained from these samples grouped into a single monophyletic clade together with those derived from Sunda pangolins in Thailand and that this evolutionarily distinct species is basal to the Babesia sensu stricto clade, which encompasses a range of Babesia species that infect both domestic and wildlife vertebrate hosts.

Conclusions

This is the first report documenting the detection of a Babesia species in A. javanense ticks, the main ectoparasite of Sunda pangolins. While our results showed that A. javanense can carry this novel Babesia sp., additional confirmatory studies are required to demonstrate vector competency. Further studies are also necessary to investigate the role of other transmission pathways given the low infection rate of ticks in relation to the high infection rate of Sunda pangolins. Although it appears that this novel Babesia sp. is of little to no pathogenicity to Sunda pangolins, its potential to cause disease in other animals or humans cannot be ruled out.

Graphical abstract
Assessing clusters of comorbidities in rheumatoid arthritis: a machine learning approach
Authors: Solomon Daniel H. , Guan Hongshu , Johansson Fredrik D. , Santacroce Leah , Malley Wendi , Guo Lin , Litman Heather
Published: November 2023

Background

Comorbid conditions are very common in rheumatoid arthritis (RA) and several prior studies have clustered them using machine learning (ML). We applied various ML algorithms to compare the clusters of comorbidities derived and to assess the value of the clusters for predicting future clinical outcomes.

Methods

A large US-based RA registry, CorEvitas, was used to identify patients for the analysis. We assessed the presence of 24 comorbidities, and ML was used to derive clusters of patients with given comorbidities. K-mode, K-mean, regression-based, and hierarchical clustering were used. To assess the value of these clusters, we compared clusters across different ML algorithms in clinical outcome models predicting clinical disease activity index (CDAI) and health assessment questionnaire (HAQ-DI). We used data from the first 3 years of the 6-year study period to derive clusters and assess time-averaged values for CDAI and HAQ-DI during the latter 3 years. Model fit was assessed via adjusted R2 and root mean square error for a series of models that included clusters from ML clustering and each of the 24 comorbidities separately.

Results

11,883 patients with RA were included who had longitudinal data over 6 years. At baseline, patients were on average 59 (SD 12) years of age, 77% were women, CDAI was 11.3 (SD 11.9, moderate disease activity), HAQ-DI was 0.32 (SD 0.42), and disease duration was 10.8 (SD 9.9) years. During the 6 years of follow-up, the percentage of patients with various comorbidities increased. Using five clusters produced by each of the ML algorithms, multivariable regression models with time-averaged CDAI as an outcome found that the ML-derived comorbidity clusters produced similarly strong models as models with each of the 24 separate comorbidities entered individually. The same patterns were observed for HAQ-DI.

Conclusions

Clustering comorbidities using ML algorithms is not computationally complex but often results in clusters that are difficult to interpret from a clinical standpoint. While ML clustering is useful for modeling multi-omics, using clusters to predict clinical outcomes produces models with a similar fit as those with individual comorbidities.
ProQ binding to small RNA RyfA promotes virulence and biofilm formation in avian pathogenic Escherichia coli
Authors: Wang Zhongxing , Chen Rui , Xia Fufang , Jiang Min , Zhu Dongyu , Zhang Yuting , Dai Jianjun , Zhuge Xiangkai
Published: November 2023

Avian pathogenic Escherichia coli (APEC) is a notable subpathotype of the nonhuman extraintestinal pathogenic E. coli (ExPEC). Recognized as an extraintestinal foodborne pathogen, the zoonotic potential of APEC/ExPEC allows for cross-host transmission via APEC-contaminated poultry meat and eggs. ProQ, an RNA binding protein, is evolutionarily conserved in E. coli. However, its regulatory roles in the biofilm formation and virulence of APEC/ExPEC have not been explored. In this study, proQ deletion in the APEC strain FY26 significantly compromised its biofilm-forming ability. Furthermore, animal tests and cellular infection experiments showed that ProQ depletion significantly attenuated APEC virulence, thereby diminishing its capacity for bloodstream infection and effective adherence to and persistence within host cells. Transcriptome analysis revealed a decrease in the transcription level of the small RNA (sRNA) RyfA in the mutant FY26ΔproQ, suggesting a direct interaction between the sRNA RyfA and ProQ. This interaction might indicate that sRNA RyfA is a novel ProQ-associated sRNA. Moreover, the direct binding of ProQ to the sRNA RyfA was crucial for APEC biofilm formation, pathogenicity, adhesion, and intracellular survival. In conclusion, our findings provide detailed insight into the interaction between ProQ and sRNA RyfA and deepen our understanding of the regulatory elements that dictate APEC virulence and biofilm development. Such insights are instrumental in developing strategies to counteract APEC colonization within hosts and impede APEC biofilm establishment on food surfaces.
Characterization of translocon proteins in the type III secretion system of Lawsonia intracellularis
Authors: Huang Beibei , Zhu Zihe , Dai Yimin , Yan Chengxian , Xu Jingyu , Sun Lingling , Zhang Qinghua , An Xuejiao , Lai Fenju
Published: November 2023

Lawsonia intracellularis, the etiologic agent of proliferative enteropathy (PE), is an obligate intracellular Gram-negative bacterium possessing a type III secretion system (T3SS), which enables the pathogen to translocate effector proteins into targeted host cells to modulate their functions. T3SS is a syringe-like apparatus consisting of a base, an extracellular needle, a tip, and a translocon. The translocon proteins assembled by two hydrophobic membrane proteins can form pores in the host-cell membrane, and therefore play an essential role in the function of T3SS. To date, little is known about the T3SS and translocon proteins of L. intracellularis. In this study, we first analyzed the conservation of the T3S apparatus between L. intracellularis and Yersinia, and characterized the putative T3S hydrophobic major translocon protein LI1158 and minor translocon protein LI1159 in the L. intracellularis genome. Then, by using Yersinia pseudotuberculosis as a surrogate system, we found that the full-length LI1158 and LI1159 proteins, but not the putative class II chaperone LI1157, were secreted in a − Ca2+ and T3SS-dependent manner and the secretion signal was located at the N terminus (aa 1–40). Furthermore, yeast-two hybrid experiments revealed that LI1158 and LI1159 could self-interact, and LI1159 could interact with LI1157. However, unlike CPn0809 and YopB, which are the major hydrophobic translocon proteins of the T3SS of C. pneumoniae and Yersinia, respectively, full-length LI1158 was non-toxic to both yeast and Escherichia coli cells, but full-length LI1159 showed certain toxicity to E. coli cells. Taken together, despite some differences from the findings in other bacteria, our results demonstrate that LI1158 and LI1159 may be the translocon proteins of L. intracellularis T3SS, and probably play important roles in the translocation of effector proteins at the early pathogen infection stage.
Resuscitation-associated endotheliopathy (RAsE): a conceptual framework based on a systematic review and meta-analysis
Authors: Obonyo Nchafatso G. , Sela Declan P. , Raman Sainath , Rachakonda Reema , Schneider Bailey , Hoe Louise E. See , Fanning Jonathon P. , Bassi Gianluigi Li , Maitland Kathryn , Suen Jacky Y. , Fraser John F.
Published: November 2023

Introduction

Shock-induced endotheliopathy (SHINE), defined as a profound sympathoadrenal hyperactivation in shock states leading to endothelial activation, glycocalyx damage, and eventual compromise of end-organ perfusion, was first described in 2017. The aggressive resuscitation therapies utilised in treating shock states could potentially lead to further worsening endothelial activation and end-organ dysfunction.

Objective

This study aimed to systematically review the literature on resuscitation-associated and resuscitation-induced endotheliopathy.

Methods

A predetermined structured search of literature published over an 11-year and 6-month period (1 January 2011 to 31 July 2023) was performed in two indexed databases (PubMed/MEDLINE and Embase) per PRISMA guidelines. Inclusion was restricted to original studies published in English (or with English translation) reporting on endothelial dysfunction in critically ill human subjects undergoing resuscitation interventions. Reviews or studies conducted in animals were excluded. Qualitative synthesis of studies meeting the inclusion criteria was performed. Studies reporting comparable biomarkers of endothelial dysfunction post-resuscitation were included in the quantitative meta-analysis.

Results

Thirty-two studies met the inclusion criteria and were included in the final qualitative synthesis. Most of these studies (47%) reported on a combination of mediators released from endothelial cells and biomarkers of glycocalyx breakdown, while only 22% reported on microvascular flow changes. Only ten individual studies were included in the quantitative meta-analysis based on the comparability of the parameters assessed. Eight studies measured syndecan-1, with a heterogeneity index, I2 = 75.85% (pooled effect size, mean = 0.27; 95% CI − 0.07 to 0.60; p = 0.12). Thrombomodulin was measured in four comparable studies (I2 = 78.93%; mean = 0.41; 95% CI − 0.10 to 0.92; p = 0.12). Three studies measured E-selectin (I2 = 50.29%; mean =  − 0.15; 95% CI − 0.64 to 0.33; p = 0.53), and only two were comparable for the microvascular flow index, MFI (I2 = 0%; mean =  − 0.80; 95% CI − 1.35 to − 0.26; p < 0.01).

Conclusion

Resuscitation-associated endotheliopathy (RAsE) refers to worsening endothelial dysfunction resulting from acute resuscitative therapies administered in shock states. In the included studies, syndecan-1 had the highest frequency of assessment in the post-resuscitation period, and changes in concentrations showed a statistically significant effect of the resuscitation. There are inadequate data available in this area, and further research and standardisation of the ideal assessment and panel of biomarkers are urgently needed.
Interprofessional diagnostic management teams: a scoping review protocol
Authors: Hansen Nicoline Lykke , Precht Helle , Larsen Palle , Noehr-Jensen Lene
Published: November 2023

Background

Diagnostic errors are a major problem in healthcare. In 2015, the report “Improving Diagnosis in Health Care” by the National Academies of Sciences, Engineering, and Medicine (NASEM) stated that it is likely that most people will experience at least one diagnostic error in their lifetime. The report suggests implementing diagnostic management teams, including patients and their relatives, diagnosticians, and healthcare professionals who support the diagnostic process, to limit diagnostic error and improve patient safety. Implementing interprofessional diagnostic management teams (IDMT), however, is not an easy task due to the complexity of the diagnostic processes and the traditional organization of healthcare with divided departments and healthcare professional who operate in different geographic locations. As this topic is still emerging, a scoping review is ideal to determine the scope of the body of literature on IDMT, indicate the volume of literature and studies available and identify any gaps in knowledge. In a long-term perspective, this scoping review will contribute to prevent diagnostic errors and improve patient safety, for adults and children with physical health issues.

Methods

We will conduct this scoping review in accordance with the JBI methodology and report it based on the PRISMA-ScR. We will systematically search six databases (EMBASE, PubMed, CINAHL, Academic Search Premier, SCOPUS and Web of Science) for papers published between 1985 and 2023 that describe the use of interprofessional diagnostic management teams. The participants included will be adults and children seeking diagnostic care for physical health issues. The concept studied will be interprofessional diagnostic management teams, and the context will be the diagnostic process in the healthcare system. Studies examining the diagnostic process in psychiatry, odontology or complementary medicine will be excluded. Data extraction, including key study characteristics and findings, will be done by two reviewers independently. Any disagreement will be resolved by discussion and eventually by including the two remainder reviewers.

Discussion

To our knowledge, this will be the first scoping review regarding IDMT and the derived effects on diagnostic safety and can therefore be a very important contribution to improve patient safety significantly during the diagnostic process.

Protocol registration

The project is registered at Open Science Framework (OSF) with ID: osf.io/kv2n6.
Existence and multiplicity of periodic solutions for a nonlinear resonance equation with singularities
Authors: Xing Xiumei , Wang Lingling , Lai Shaoyong
Published: November 2023

We investigate a second-order periodic system with singular potential and resonance. Utilizing the main integral method and fixed point theorems, we establish the existence and multiplicity of periodic solutions with respect to time under certain assumptions on the unbounded or oscillatory term.
A generalized Darbo’s fixed point theorem and its applications to different types of hybrid differential equations
Authors: Das Anupam , Deb Sudip , Goswami Rupanjali , Ahmed Tazuddin , Izadi Zeynab , Parvaneh Vahid
Published: November 2023

In this article, a generalization of Darbo’s fixed point theorem using a new contraction operator is obtained to solve our proposed hybrid differential and fractional hybrid differential equations in a Banach space. The applicability of our results with the help of a suitable example has also been shown.
Exploring the health literacy status of people with hearing impairment: a systematic review
Authors: Piao Zhaoyan , Lee Hanbin , Mun Yeongrok , Lee Hankil , Han Euna
Published: November 2023

Background

People with hearing impairment have many problems with healthcare use, which is associated with health literacy. Research on health literacy is less focused on people with hearing impairments. This research aimed to explore the levels of health literacy in people with hearing impairment, find the barriers to health literacy, and summarize methods for improving health literacy.

Methods

A systematic review was conducted using three databases (PubMed, Cochrane, and Embase) to search the relevant articles and analyze them. The studies were selected using pre-defined inclusion/exclusion criteria in two steps: first, selection by examining the title and abstract; and second, after reading the study in full. The Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) was used to assess the quality of the articles.

Results

Twenty-nine studies were synthesized qualitatively. Individuals with hearing impairment were found to have lower health literacy, when compared to those without impairment, which can lead to a higher medical cost. Most of the people with hearing impairment faced barriers to obtaining health-related information and found it difficult to communicate with healthcare providers. To improve their health literacy, it is essential to explore new ways of accessing health information and improving the relationship between patients and healthcare providers.

Conclusions

Our findings show that people with hearing impairment have lower health literacy than those without. This suggests that developing new technology and policies for people with hearing impairment is necessary not to mention promoting provision of information via sign language.

Trial registration

OSF: https://doi.org/10.17605/OSF.IO/V6UGW. PROSPERO ID: CRD42023395556.
Social protection as a right of people affected by tuberculosis: a scoping review and conceptual framework
Authors: Ferreira Melisane Regina Lima , Bonfim Rafaele Oliveira , Bossonario Pedro Augusto , Maurin Venisse Paschoalin , Valença Ana Beatriz Marques , Abreu Paula Daniella de , Andrade Rubia Laine de Paula , Fronteira Inês , Monroe Aline Aparecida
Published: November 2023

Background

Tuberculosis is an infectious disease strongly influenced by social determinants closely associated with cycles of poverty and social exclusion. Within this context, providing social protection for people affected by the disease constitutes a powerful instrument for reducing inequalities and enhancing inclusion and social justice. This study aimed to identify and synthesize strategies and measures aimed at ensuring social protection as a right of people affected by tuberculosis.

Methods

This is a scoping review, with searches conducted in six databases in February 2023. We included publications from 2015 onwards that elucidate strategies and measures of social protection aimed at safeguarding the rights to health, nutrition, employment, income, housing, social assistance, and social security for people affected by tuberculosis. These strategies could be implemented through policies, programs, and/or governmental agreements in any given context. The data extracted from the articles underwent descriptive analysis and a narrative synthesis of findings based on the dimensions of social protection. Additionally, we developed a conceptual framework illustrating the organizational and operational aspects of measures and strategies related to each dimension of social protection identified in this review.

Results

A total of 9317 publications were retrieved from the databases, of which sixty-three publications were included. The study’s results highlighted measures and strategies concerning the social protection of people affected by tuberculosis. These measures and strategies revolved around the rights to proper nutrition and nourishment, income, housing, and health insurance, as well as expanded rights encompassing social assistance and social welfare. It was reported that ensuring these rights contributes to improving nutritional status and the quality of life for individuals with tuberculosis, along with reducing catastrophic costs, expanding access to healthcare interventions and services, and fostering TB treatment adherence, thereby leading to higher rates of TB cure.

Conclusions

Our findings identify social protection measures as a right for people affected by tuberculosis and have the potential to guide the development of evidence-based social and health policies through collaboration between tuberculosis control programs and governmental entities.
Biostimulants promoting growth of Vicia faba L. seedlings: inulin coated ZnO nanoparticles
Authors: Carbone Marilena , De Rossi Silvia , Donia Domenica Tommasa , Di Marco Gabriele , Gustavino Bianca , Roselli Ludovica , Tagliatesta Pietro , Canini Antonella , Gismondi Angelo
Published: November 2023

In the present contribution, inulin coated ZnO nanoparticles (ZnO@inu NPs) were investigated for their potential application on crop production systems, by appraisal of their biostimulating effects on Vicia faba L (faba bean). Naked and coated ZnO NPs were synthesized according to purposely implemented eco-friendly protocols and characterized with multiple techniques to determine their crystallographic phase, average particle size, and degree of coating. Faba beans were grown in culture medium supplemented with NPs at 50 or 100 mg kg−1, using ZnO NPs alone, inulin alone, a mixture of the two, or ZnO@inu NPs. Seed germination rate and biometric evaluations on seedlings were carried out, together with Zn localization in the plant tissues. Cellular and molecular effects were ascertained by analyses of photosynthetic pigments, cytotoxicity, genotoxicity, viability, induction of oxidative stress and tissue damage, antioxidant response, and modulation of gene expression. These combined studies indicated a potential role of ZnO@inu NPs in promoting growth and development of V. faba seedlings, acting at a post-germinative phase, probably by stimulating the stem cell mitosis. Finally, inulin as a coating agent for the ZnO NPs favored the bioavailability and adsorption of the nanomaterials into the plant tissues, without altering their bioactivity but mitigating any adverse side effect.

Graphical Abstract
Comparison of postoperative isokinetic quadriceps and gluteal muscular strength after primary THA: is there an early benefit through enhanced recovery programs?
Authors: Reinhard Jan , Schreiner Annika , Dullien Silvia , Götz Julia Sabrina , Leiss Franziska , Maderbacher Günther , Grifka Joachim , Greimel Felix
Published: November 2023

Purpose

Although total hip arthroplasty (THA) is expected to result in a postoperative loss of muscular strength, no study investigated the benefit of an enhanced‐recovery‐after‐surgery (ERAS) concept on the hip muscles in detail. We evaluated if (1) an ERAS‐concept for primary THA results in reduced loss of muscular strength five days and four weeks postoperative. We (2) compared the two groups regarding Patient‐Related‐Outcome‐Measures (PROMs), WOMAC‐index (Western‐Ontario‐and‐McMaster‐Universities‐Osteoarthritis‐Index), HHS (Harris‐Hip‐Score) and EQ‐5d‐3L‐score.

Methods

In a prospective, single‐blinded, randomized controlled trial, we compared isokinetic muscular strength of 24 patients receiving primary THA with an enhanced recovery concept with early mobilization (n = 12, ERAS‐group) and such receiving conventional THA (n = 12, non‐ERAS). Isokinetic muscular strength was measured with a Biodex‐Dynamometer before, as well as five days and four weeks after surgery (peak‐torque, total‐work, power). Furthermore, WOMAC, HHS, PROMs and EQ‐5d‐3L were imposed.

Results

The ERAS group revealed significant higher isokinetic strength (peak‐torque, total‐work, power) at both time points. Both groups showed a significant pain decrease at both time points meeting very high rates of patient satisfaction resembled by good results in PROMs, WOMAC, HHS, EQ‐5d. There was no significant difference in any of the scores between both groups.

Conclusion

We proved a significant reduced loss of muscular strength five days and four weeks after primary THA in combination with an ERAS concept. However, the reduced loss of muscular strength is not reflected by patient’s functional outcome and quality of life, showing no significant differences in WOMAC, HHS, EQ‐5d‐3L, PROMs and NRS. Therefore, this study supports the implementation of an ERAS concept for primary THA in terms of isokinetic strength. Further studies are needed to evaluate the development of muscular strength over a long period.
Achieving safe and high-performance gastrointestinal tract spectral CT imaging with small-molecule lanthanide complex
Authors: Che Xiaoling , Yang Chunmei , Pan Liping , Gu Didi , Dai Guidong , Shu Jian , Yang Lu
Published: November 2023

Background

Non-intrusive imaging of gastrointestinal (GI) tract using computed tomography (CT) contrast agents is of the most significant issues in the diagnosis and treatment of GI diseases. Moreover, spectral CT, which can generate monochromatic images to display the X-ray attenuation characteristics of contrast agents, provides a better imaging sensitivity for diagnose inflammatory bowel disease (IBD) than convention CT imaging.

Methods

Herein, a convenient and one-pot synthesis method is provided for the fabrication of small-molecule lanthanide complex Holmium-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (Ho-DOTA) as a biosafe and high-performance spectral CT contrast agent for GI imaging with IBD. In vivo CT imaging was administered with both healthy mice and colitis mice induced by dextran sodium sulfate.

Results

We found that Ho-DOTA accumulated in inflammation sites of large intestines and produced high CT contrast compared with healthy mice. Both in vitro and in vivo experimental results also showed that Ho-DOTA provided much more diagnostic sensitivity and accuracy due to the excellent X-ray attenuation characteristics of Ho-DOTA compared with clinical iodinate agent. Furthermore, the proposed contrast media could be timely excreted from the body via the urinary and digestive system, keeping away from the potential side effects due to long-term retention in vivo.

Conclusion

Accordingly, Ho-DOTA with excellent biocompatibility can be useful as a potential high-performance spectral CT contrast agent for further clinical imaging of gastrointestinal tract and diagnosis of intestinal system diseases.

Graphical Abstract
Detection of in vivo mutagenicity in rat liver samples using error-corrected sequencing techniques
Authors: Izawa Kazuki , Tsuda Masataka , Suzuki Takayoshi , Honma Masamitsu , Sugiyama Kei-ichi
Published: November 2023

Background

Mutagenicity, the ability of chemical agents to cause mutations and potentially lead to cancer, is a critical aspect of substance safety assessment for protecting human health and the environment. Metabolic enzymes activate multiple mutagens in living organisms, thus in vivo animal models provide highly important information for evaluating mutagenicity in human. Rats are considered suitable models as they share a similar metabolic pathway with humans for processing toxic chemical and exhibit higher responsiveness to chemical carcinogens than mice. To assess mutagenicity in rats, transgenic rodents (TGRs) are widely used for in vivo gene mutation assays. However, such assays are labor-intensive and could only detect transgene mutations inserted into the genome. Therefore, introducing a technology to directly detect in vivo mutagenicity in rats would be necessary. The next-generation sequencing (NGS) based error-corrected sequencing technique is a promising approach for such purposes.

Results

We investigated the applicability of paired-end and complementary consensus sequencing (PECC-Seq), an error-corrected sequencing technique, for detecting in vivo mutagenicity in the rat liver samples. PECC-Seq allows for the direct detection of ultra-rare somatic mutations in the genomic DNA without being constrained by the genomic locus, tissue, or organism. We tested PECC-Seq feasibility in rats treated with diethylnitrosamine (DEN), a mutagenic compound. Interestingly, the mutation and mutant frequencies between PECC-Seq and the TGR assay displayed a promising correlation. Our results also demonstrated that PECC-Seq could successfully detect the A:T > T:A mutation in rat liver samples, consistent with the TGR assay. Furthermore, we calculated the trinucleotide mutation frequency and proved that PECC-Seq accurately identified the DEN treatment-induced mutational signatures.

Conclusions

Our study provides the first evidence of using PECC-Seq for in vivo mutagenicity detection in rat liver samples. This approach could provide a valuable alternative to conventional TGR assays as it is labor- and time-efficient and eliminates the need for transgenic rodents. Error-corrected sequencing techniques, such as PECC-Seq, represent promising approaches for enhancing mutagenicity assessment and advancing regulatory science.
Optimized, automated and cGMP-compliant synthesis of the HER2 targeting [68Ga]Ga-ABY-025 tracer
Authors: Jussing Emma , Ferrat Mélodie , Moein Mohammad M. , Alfredéen Henrik , Tegnebratt Tetyana , Bratteby Klas , Samén Erik , Feldwisch Joachim , Altena Renske , Axelsson Rimma , Tran Thuy A.
Published: November 2023

Background

The Affibody molecule, ABY-025, has demonstrated utility to detect human epidermal growth factor receptor 2 (HER2) in vivo, either radiolabelled with indium-111 (111In) or gallium-68 (68Ga). Using the latter, 68Ga, is preferred due to its use in positron emission tomography with superior resolution and quantifying capabilities in the clinical setting compared to 111In. For an ongoing phase II study (NCT05619016) evaluating ABY-025 for detecting HER2-low lesions and selection of patients for HER2-targeted treatment, the aim was to optimize an automated and cGMP-compliant radiosynthesis of [68Ga]Ga-ABY-025.

[68Ga]Ga-ABY-025 was produced on a synthesis module, Modular-Lab PharmTracer (Eckert & Ziegler), commonly used for 68Ga-labelings. The radiotracer has previously been radiolabeled on this module, but to streamline the production, the method was optimized. Steps requiring manual interactions to the radiolabeling procedure were minimized including a convenient and automated pre-concentration of the 68Ga-eluate and a simplified automated final formulation procedure. Every part of the radiopharmaceutical production was carefully developed to gain robustness and to avoid any operator bound variations to the manufacturing. The optimized production method was successfully applied for 68Ga-labeling of another radiotracer, verifying its versatility as a universal and robust method for radiosynthesis of Affibody-based peptides.

Results

A simplified and optimized automated cGMP-compliant radiosynthesis method of [68Ga]Ga-ABY-025 was developed. With a decay corrected radiochemical yield of 44 ± 2%, a radiochemical purity (RCP) of 98 ± 1%, and with an RCP stability of 98 ± 1% at 2 h after production, the method was found highly reproducible. The production method also showed comparable results when implemented for radiolabeling another similar peptide.

Conclusion

The improvements made for the radiosynthesis of [68Ga]Ga-ABY-025, including introducing a pre-concentration of the 68Ga-eluate, aimed to utilize the full potential of the 68Ge/68Ga generator radioactivity output, thereby reducing radioactivity wastage. Furthermore, reducing the number of manually performed preparative steps prior to the radiosynthesis, not only minimized the risk of potential human/operator errors but also enhanced the process’ robustness. The successful application of this optimized radiosynthesis method to another similar peptide underscores its versatility, suggesting that our method can be adopted for 68Ga-labeling radiotracers based on Affibody molecules in general.

Trial registration: NCT, NCT05619016, Registered 7 November 2022, https://clinicaltrials.gov/study/NCT05619016?term=HER2&cond=ABY025&rank=1
To see or not to see: the parallel processing of self-relevance and facial expressions
Authors: Liu Tuo , Sui Jie , Hildebrandt Andrea
Published: November 2023

The self, like the concept of central "gravity", facilitates the processing of information that is directly relevant to the self. This phenomenon is known as the self-prioritization effect. However, it remains unclear whether the self-prioritization effect extends to the processing of emotional facial expressions. To fill this gap, we used a self-association paradigm to investigate the impact of self-relevance on the recognition of emotional facial expressions while controlling for confounding factors such as familiarity and overlearning. Using a large and diverse sample, we replicated the effect of self-relevance on face processing but found no evidence for a modulation of self-relevance on facial emotion recognition. We propose two potential theoretical explanations to account for these findings and emphasize that further research with different experimental designs and a multitasks measurement approach is needed to understand this mechanism fully. Overall, our study contributes to the literature on the parallel cognitive processing of self-relevance and facial emotion recognition, with implications for both social and cognitive psychology.
Mapping fruit tree dynamics using phenological metrics from optimal Sentinel-2 data and Deep Neural Network
Authors: Chabalala Yingisani , Adam Elhadi , Kganyago Mahlatse
Published: November 2023

Accurate and up-to-date crop-type maps are essential for efficient management and well-informed decision-making, allowing accurate planning and execution of agricultural operations in the horticultural sector. The assessment of crop-related traits, such as the spatiotemporal variability of phenology, can improve decision-making. The study aimed to extract phenological information from Sentinel-2 data to identify and distinguish between fruit trees and co-existing land use types on subtropical farms in Levubu, South Africa. However, the heterogeneity and complexity of the study area—composed of smallholder mixed cropping systems with overlapping spectra—constituted an obstacle to the application of optical pixel-based classification using machine learning (ML) classifiers. Given the socio-economic importance of fruit tree crops, the research sought to map the phenological dynamics of these crops using deep neural network (DNN) and optical Sentinel-2 data. The models were optimized to determine the best hyperparameters to achieve the best classification results. The classification results showed the maximum overall accuracies of 86.96%, 88.64%, 86.76%, and 87.25% for the April, May, June, and July images, respectively. The results demonstrate the potential of temporal phenological optical-based data in mapping fruit tree crops under different management systems. The availability of remotely sensed data with high spatial and spectral resolutions makes it possible to use deep learning models to support decision-making in agriculture. This creates new possibilities for deep learning to revolutionize and facilitate innovation within smart horticulture.
Evaluating the effectiveness of the MicroPlastic Sediment Separator (MPSS)
Authors: Prume Julia A. , Laermanns Hannes , Löder Martin G. J. , Laforsch Christian , Bogner Christina , Koch Martin
Published: November 2023

Effective laboratory methods are a requirement to obtain accurate data on the contamination of the environment with microplastics. However, current methods often lack specification and validation of performance. The aim of this work was to provide the first evaluation of the effectiveness of the commercially available MicroPlastic Sediment Separator (MPSS) operated with sodium chloride. We performed density separation experiments with pristine plastic particles spiked into both commercial sand (experiment I) and natural river sediments (experiment II) and with environmental microplastics contained in natural river sediments (experiment III). The natural sediments were taken from the Lahn River in Germany, a medium-scale central European tributary. The pristine test particles were ground polypropylene fragments, sieved in three different size classes: larger than 1 mm, 0.5–1 mm, and 0.3–0.5 mm. In experiment I, the mean recovery rate was 97 % for particles of the largest size class (standard deviation $$s=6~\%$$

s
=
6

%

; $$n=30$$

n
=
30

per size class), but dropped to 75.33 % ($$s=21.29~\%$$

s
=
21.29

%

) in the medium and to 54 % ($$s=25~\%$$

s
=
25

%

) in the smallest size class. After density separation, 87 % of all unsuccessfully separated test particles were found at the inner walls of the MPSS. In experiment II, the recovery rate was not correlated with the particle size distribution of the natural river sediments. In experiment III, a subsequent second density separation step contributed on average 38 % ($$s=18~\%$$

s
=
18

%

; $$n=5$$

n
=
5

) to the total number of extracted environmental microplastics. This study illuminates central aspects of a density separation and aims to contribute to quality improvements of recovery rate experiments and field studies for the generation of reliable data on microplastics in the environment.
Fluctuation relations at large scales in three-dimensional hydrodynamic turbulence
Authors: Alexakis Alexandros , Chibbaro Sergio , Michel Guillaume
Published: November 2023

It has long been conjectured that, in three-dimensional turbulence, velocity modes at scales larger than the forcing scale follow equilibrium dynamics. Recent numerical and experimental evidence shows that such modes share the same mean energy and therefore support this claim, but equilibrium dynamics does not reduce to equipartition of energy. In this work, a large set of direct numerical simulations is carried out to investigate if fluctuation-dissipation relations and the fluctuation theorem also apply at these scales. These two results link out-of-equilibrium properties of a forced system with its behavior at equilibrium. Both relations are verified quantitatively by the results of our simulations, further supporting that large-scale modes display equilibrium dynamics. They provide new tools to characterize both the mean value and the fluctuations of the injected energy by a large-scale force acting on turbulence driven by small scale random noise.
Development of a New Model of Insulin Sensitivity in Patients With Type 2 Diabetes and Association With Mortality
Authors: Ciardullo Stefano , Dodesini Alessandro Roberto , Lepore Giuseppe , Corsi Anna , Scaranna Cristiana , Perseghin Gianluca , Trevisan Roberto
Published: November 2023

Context

Despite being one of the major drivers of diabetes incidence, the degree of insulin resistance in patients with type 2 diabetes (T2D) is not usually evaluated in clinical practice or in large epidemiologic studies.

Objective

To identify a model of insulin sensitivity using widely available clinical and laboratory parameters in patients with T2D and evaluate its association with all-cause and cardiovascular mortality.

Methods

One hundred forty patients with T2D underwent a euglycemic hyperinsulinemic clamp to measure total body glucose disposal rate (mg kg−1 minute−1). We used demographic, clinical, and common laboratory parameters to estimate insulin sensitivity (IS) via stepwise linear regression on 85 patients (training cohort) and validated it in the remaining 55 (validation cohort). The identified equation was then applied to 3553 patients with T2D from the 1999-2010 cycles of the National Health and Nutrition Examination Survey (NHANES) to evaluate its association with all-cause and cardiovascular mortality up to December 2015.

Results

The best model included triglycerides, gamma glutamyl transpeptidase, albumin excretion rate, and body mass index. The identified IS score correlated well with the clamp-derived glucose disposal rate in both the training (r = 0.77, P < .001) and the validation (r = 0.74, P < .001) cohorts. In the NHANES cohort, after a median follow-up of 8.3 years, 1054 patients died, 265 of cardiovascular causes. In a multivariable Cox proportional hazard model adjusted for age, sex, race-ethnicity, education, cigarette smoke, total cholesterol, chronic kidney disease, blood pressure, prevalent cardiovascular disease, and alcohol consumption, a higher estimated IS was associated with a lower risk of both all-cause and cardiovascular mortality.

Conclusion

We propose a new model of IS in patients with T2D based on readily available clinical and laboratory data. Its potential applications are in both diagnosis as well as prognostication.
A framework to unlock marine bird energetics
Authors: Dunn Ruth E. , Duckworth James , Green Jonathan A.
Published: November 2023

Energetics can provide novel insights into the roles of animals, but employing an energetics approach has traditionally required extensive empirical physiological data on the focal species, something that can be challenging for those that inhabit marine environments. There is therefore a demand for a framework through which to estimate energy expenditure from readily available data. We present the energetic costs associated with important time- and energy-intensive behaviours across nine families of marine bird (including seabirds, ducks, divers and grebes) and nine ecological guilds. We demonstrate a worked example, calculating the year-round energetic expenditure of the great auk, Pinguinus impennis, under three migration scenarios, thereby illustrating the capacity of this approach to make predictions for data-deficient species. We provide a comprehensive framework through which to model marine bird energetics and demonstrate the power of this approach to provide novel, quantitative insights into the influence of marine birds within their ecosystems.