bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced biomanufacturing and evaluation of adeno-associated virus
Authors: Chen Kai , Kim Seulhee , Yang Siying , Varadkar Tanvi , Zhou Zhuoxin Zora , Zhang Jiashuai , Zhou Lufang , Liu Xiaoguang Margaret
Published: February 2024

Recombinant adeno-associated virus (rAAV) has been developed as a safe and effective gene delivery vehicle to treat rare genetic diseases. This study aimed to establish a novel biomanufacturing process to achieve high production and purification of various AAV serotypes (AAV2, 5, DJ, DJ8). First, a robust suspensive production process was developed and optimized using Gibco Viral Production Cell 2.0 in 30–60 mL shaker flask cultures by evaluating host cells, cell density at the time of transfection and plasmid amount, adapted to 60–100 mL spinner flask production, and scaled up to 1.2–2.0-L stirred-tank bioreactor production at 37 °C, pH 7.0, 210 rpm and DO 40%. The optimal process generated AAV titer of 7.52–8.14 × 1010 vg/mL. Second, a new AAV purification using liquid chromatography was developed and optimized to reach recovery rate of 85–95% of all four serotypes. Post-purification desalting and concentration procedures were also investigated. Then the generated AAVs were evaluated in vitro using Western blotting, transmission electron microscope, confocal microscope and bioluminescence detection. Finally, the in vivo infection and functional gene expression of AAV were confirmed in tumor xenografted mouse model. In conclusion, this study reported a robust, scalable, and universal biomanufacturing platform of AAV production, clarification and purification.
Identification of CD160-TM as a tumor target on triple negative breast cancers: possible therapeutic applications
Authors: Scheffges Claire , Devy Jérôme , Giustiniani Jérôme , Francois Stessy , Cartier Lucille , Merrouche Yacine , Foussat Arnaud , Potteaux Stéphane , Bensussan Armand , Marie-Cardine Anne
Published: February 2024

Background

Despite major therapeutic advances, triple-negative breast cancer (TNBC) still presents a worth prognosis than hormone receptors-positive breast cancers. One major issue relies in the molecular and mutational heterogeneity of TNBC subtypes that is reinforced by the absence of reliable tumor-antigen that could serve as a specific target to further promote efficient tumor cell recognition and depletion. CD160 is a receptor mainly expressed by NK lymphocytes and presenting two isoforms, namely the GPI-anchored form (CD160-GPI) and the transmembrane isoform (CD160-TM). While CD160-GPI is constitutively expressed on resting cells and involved in the generation of NK cells' cytotoxic activity, CD160-TM is neo-synthesized upon activation and promotes the amplification of NK cells' killing ability.

Methods

CD160 expression was assessed by immunohistochemistry (IHC) and flow cytometry on TNBC patient biopsies or cell lines, respectively. Antibody (Ab)-mediated tumor depletion was tested in vitro by performing antibody-dependent cell cytotoxicity (ADCC) and phagocytosis (ADCP) assays, and in vivo on a TNBC mouse model.

Results

Preliminary data obtained by IHC on TNBC patients' tumor biopsies revealed an unconventional expression of CD160 by TNBC tumor cells. By using a specific but conformation-dependent anti-CD160-TM Ab, we established that CD160-TM, but not CD160-GPI, was expressed by TNBC tumor cells. A conformation-independent anti-CD160-TM mAb (22B12; muIgG2a isotype) was generated and selected according to pre-defined specificity and functional criterions. In vitro functional assays demonstrated that ADCC and ADCP could be induced in the presence of 22B12, resulting in TNBC cell line apoptosis. The ability of 22B12 to exert an in vivo anti-tumor activity was also demonstrated on a TNBC murine model.

Conclusions

Our data identify CD160-TM as a tumor marker for TNBC and provide a rational for the use of anti-CD160-TM antibodies as therapeutic tools in this tumor context.
Continuous combined oral contraceptive use versus vitamin E in the treatment of menstrual migraine: rationale and protocol of a randomized controlled trial (WHAT!)
Authors: van der Arend Britt W. H. , van Casteren Daphne S. , Verhagen Iris E. , MaassenVanDenBrink Antoinette , Terwindt Gisela M.
Published: February 2024

Background

Currently, there is no evidence-based hormonal treatment for migraine in women. Several small studies suggest a beneficial effect of combined oral contraceptives, but no large randomized controlled trial has been performed. As proof of efficacy is lacking and usage may be accompanied by potentially severe side effects, there is a great need for clarity on this topic.

Methods

Women with menstrual migraine (n = 180) are randomly assigned (1:1) to ethinylestradiol/levonorgestrel 30/150 μg or vitamin E 400 IU. Participants start with a baseline period of 4 weeks, which is followed by a 12-week treatment period. During the study period, a E-headache diary will be used, which is time-locked and includes an automated algorithm differentiating headache and migraine days.

Results

The primary outcome will be change in monthly migraine days (MMD) from baseline (weeks − 4 to 0) to the last 4 weeks of treatment (weeks 9 to 12). Secondary outcomes will be change in monthly headache days (MHD) and 50% responder rates of MMD and MHD.

Conclusions

The WHAT! trial aims to investigate effectivity and safety of continuous combined oral contraceptive treatment for menstrual migraine. Immediate implementation of results in clinical practice is possible.

Trial registration

Clinical trials.gov NCT04007874. Registered 28 June 2019.
Lignin bioconversion based on genome mining for ligninolytic genes in Erwinia billingiae QL-Z3
Authors: Zhao Shuting , Deng Dongtao , Wan Tianzheng , Feng Jie , Deng Lei , Tian Qianyi , Wang Jiayu , Aiman Umm E. , Mukhaddi Balym , Hu Xiaofeng , Chen Shaolin , Qiu Ling , Huang Lili , Wei Yahong
Published: February 2024

Background

Bioconversion of plant biomass into biofuels and bio-products produces large amounts of lignin. The aromatic biopolymers need to be degraded before being converted into value-added bio-products. Microbes can be environment-friendly and efficiently degrade lignin. Compared to fungi, bacteria have some advantages in lignin degradation, including broad tolerance to pH, temperature, and oxygen and the toolkit for genetic manipulation.

Results

Our previous study isolated a novel ligninolytic bacterial strain Erwinia billingiae QL-Z3. Under optimized conditions, its rate of lignin degradation was 25.24% at 1.5 g/L lignin as the sole carbon source. Whole genome sequencing revealed 4556 genes in the genome of QL-Z3. Among 4428 protein-coding genes are 139 CAZyme genes, including 54 glycoside hydrolase (GH) and 16 auxiliary activity (AA) genes. In addition, 74 genes encoding extracellular enzymes are potentially involved in lignin degradation. Real-time PCR quantification demonstrated that the expression of potential ligninolytic genes were significantly induced by lignin. 8 knock-out mutants and complementary strains were constructed. Disruption of the gene for ELAC_205 (laccase) as well as EDYP_48 (Dyp-type peroxidase), ESOD_1236 (superoxide dismutase), EDIO_858 (dioxygenase), EMON_3330 (monooxygenase), or EMCAT_3587 (manganese catalase) significantly reduced the lignin-degrading activity of QL-Z3 by 47–69%. Heterologously expressed and purified enzymes further confirmed their role in lignin degradation. Fourier transform infrared spectroscopy (FTIR) results indicated that the lignin structure was damaged, the benzene ring structure and groups of macromolecules were opened, and the chemical bond was broken under the action of six enzymes encoded by genes. The abundant enzymatic metabolic products by EDYP_48, ELAC_205 and ESOD_1236 were systematically analyzed via liquid chromatography–mass spectrometry (LC–MS) analysis, and then provide a speculative pathway for lignin biodegradation. Finally, The activities of ligninolytic enzymes from fermentation supernatant, namely, LiP, MnP and Lac were 367.50 U/L, 839.50 U/L, and 219.00 U/L by orthogonal optimization.

Conclusions

Our findings provide that QL-Z3 and its enzymes have the potential for industrial application and hold great promise for the bioconversion of lignin into bioproducts in lignin valorization.
Stress-induced hyperglycemia is associated with the mortality of thrombotic thrombocytopenic purpura patients
Authors: Hu Lingling , Wang Jing , Jin Xiaxia , Lu Guoguang , Fang Meidan , Shen Jian , Tung Tao-Hsin , Shen Bo
Published: February 2024

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy with a rapid progression and high mortality rate. We aimed to explore early risk factors for mortality in patients with TTP.

Methods

We conducted a retrospective analysis of 42 TTP patients that were admitted to our hospital between 2000 and 2021, with a median age of 49 (29–63) years. Risk factors for mortality were evaluated using multivariate logistic regression. Receiver operating characteristic curve analysis was used to determine the cut-off value of glucose for predicting mortality in patients, which was validated by comparison to a similar cohort in the published literature.

Results

Elevated glucose level and reduced red blood cells (RBC) counts were risk factors for mortality in patients with TTP (glucose, odds ratio and 95% confidence interval: 2.476 [1.368–4.484]; RBC, odds ratio and 95% confidence interval: 0.095 [0.011–0.799]). The area under the curve of glucose was 0.827, and the cut-off value was 9.2 mmol/L, with a sensitivity of 75.0% and specificity of 95.8%. A total of 26 cases from the validation cohort had a sensitivity of 71.0% and a specificity of 84.0%. The change trends of the TTP-related laboratory indices differed during hospitalization.

Conclusion

Hyperglycemia at admission and unstable blood glucose levels during hospitalization may be potential predictors of mortality for TTP patients. The improved prognosis was associated with the recovery of platelet counts and a significant decrease in serum lactate dehydrogenase after five days of treatment.
Global trends and developments in mindfulness interventions for diabetes: a bibliometric study
Authors: Jiang Sijia , Pan Xiaoli , Li Hansen , Su Yuqin
Published: February 2024

Background

Diabetes is a metabolic disorder posing a global threat to health. Many scholars are dedicated to developing non-pharmacological therapies, and mindfulness intervention is among the potentially effective approaches. Due to the rapid increase in relevant research in recent years, along with the diverse focus and interventions used in studies, it has become challenging for practitioners to quickly comprehend the key features of this field and the directions worth paying attention to. Bibliometric analysis, in response, can help scholars understand this field and identify points of interest.

Methods

Publications related to mindfulness intervention in diabetes from the establishment of the Web of Science Core Collection (WOSCC) to September 2023 were searched. We employed four bibliometric techniques: General Analysis of Publications, Collaborative Network Analysis, Co-citation Analysis, and Keyword Analysis. The CiteSpace 6.1.R was used to analyze the literature with the strongest citation bursts, while VOSviewer 1.6.13 was used to provide visualizations of publicly available data by analyzing co-citations or co-authorship affiliations.

Results

We found a total of 387 articles. The results indicate that research on this topic has been steadily increasing over time. The United States is the top producer of relevant publications, with Tilburg University being the institution that publishes the most articles. The journal “Mindfulness” has the highest publication count. In the collaborative network analysis, the United States emerged as the main hub for global cooperation in this research field, contributing 182 articles with a total of 5872 citations. The journal “Diabetes Care” was frequently cited and played a central role. The keyword analysis revealed that researchers have shown a strong interest in how mindfulness interventions affect the mental health of diabetic individuals. Additionally, there is a focus on studying elderly diabetic groups and exploring how mindfulness interventions impact metabolic diseases. These areas are currently the main research priorities.

Conclusion

Our findings demonstrate the current trend and hotspots in mindfulness intervention and offer some directions for future research.
Relationship between a body shape index and muscle strength index in Chinese university students: a cross-sectional survey
Authors: Pi Qing , Xu Jiali , Sha Mian , Liu Xiangdong
Published: February 2024

Background

The problem of overweight obesity and decrease in muscle strength among university students has become an indisputable fact. In this study, a comprehensive index reflecting obesity degree a body shape index (ABSI) and a comprehensive index reflecting muscle strength muscle strength index (MSI) were studied to analyze the cross-sectional correlations existing between them.

Methods

This study began recruiting participants and conducting the test survey in April 2022 and closed in July 2022. Basic condition, height, weight, waist circumference, grip strength, pull-up (boys), bent-leg sit-up (girls), and standing long jump were tested on 12,046 (boys: 6011, 49.90%) university students aged 19–22 years in China, and ABSI and MSI were calculated separately. ABSI was categorized into 5 groups according to age and sex, namely ABSI < 5th percentile (A), 5th ≤ ABSI < 25th percentile (B), 25th ≤ ABSI < 75th percentile (C), 75th ≤ ABSI < 95th percentile (D) and ABSI ≥ 95th percentile (E). The comparison of MSI between different ABSI groups was performed using effect size, and the association between them was performed by curve estimation analysis.

Results

The association between ABSI and MSI of Chinese university students showed an inverted “U” curve. The effect of increased ABSI on MSI was greater in university girls compared to boys. The ABSI of boys was (0.080 ± 0.010) and MSI was (-0.005 ± 2.080); the ABSI of girls was (0.079 ± 0.008) and MSI was (-0.017 ± 1.867). Overall, university students ABSI was at a relatively high point for MSI between 0.050 and 0.100. The university students ABSI at 0.150 had an MSI of -1.229 for boys and − 2.779 for girls.

Conclusion

The ABSI of Chinese university students showed an inverted “U”-shaped curve relationship with MSI, and university students with low or high ABSI had lower MSI. The effect of increasing ABSI on the decrease of MSI was more obvious for girls than for boys.
Immune endotyping and gene expression profile of patients with chronic rhinosinusitis with nasal polyps in the aspirin-exacerbated respiratory disease (AERD) and the non-AERD subgroups
Authors: Nazari Javad , Shahba Faezeh , Jafariaghdam Negin , Mohebbi Saleh , Arshi Saba , Bemanian Mohammad Hassan , Fallahpour Morteza , Shokri Sima , Atashrazm Fatemeh , Amini Saeed , Roomiani Maryam , Jamee Mahnaz , Babaheidarian Pegah , Khoshmirsafa Majid , Nabavi Mohammad
Published: February 2024

Background

Chronic Rhinosinusitis (CRS) is a paranasal sinus inflammatory disease and is divided into two subgroups defined as CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). CRSwNP displays a T helper (Th)2 biased phenotype, and based on sensitivity or tolerance to aspirin or non-steroidal anti-inflammatory drugs (NSAID), is further subdivided into Aspirin-exacerbated respiratory disease (AERD) and non-AERD groups. Considering the challenge of diagnosis and treatment in patients with CRSwNP, particularly the AERD subtype, and the significance of endotyping in these patients, we examined the immune profile and endotyping based on gene expression analysis in the AERD and the non-AERD groups of patients with CRSwNP.

Material and method

In this study, 21 patients were enrolled and were categorized into AERD (N = 10) and non-AERD (N = 11) groups based on their sensitivity to aspirin. After the special washing period, nasal polyps were biopsied in both groups, and the infiltration of eosinophils, neutrophils, plasma cells, and lymphocytes was compared between the AERD and the non-AERD groups. Also, gene expression levels of transcription factors including Tbet, GATA3, RoRγt, and FoxP3 and inflammatory cytokines including interleukin (IL)1β, IL1RAP (IL1 receptor accessory protein), IL2, IL4, IL5, IL10, IL13, IL17, TNFα, and IFNγ were investigated by quantitative Real-time PCR (qRT-PCR). Statistical analyses were performed using analytical tests including Kolmogorov–Smirnov, Mann-Whitney, and T-test. A P value less than 0.05 was considered statistically significant.

Results

The mean ± SD age of the studied groups was 37 ± 8.7 years old (21–50) for the AERD, and 40.4 ± 7.7 years old (31–52) for the non-AERD. LMS/EPOS/SNOT scores and pulmonary function tests showed no difference between the two groups. Serum immunoglobulin E (IgE) levels were found to be higher in patients with AERD (p = 0.04), however, the peripheral blood counts of eosinophils were comparable in the two groups. In the histopathologic analysis, the AERD group showed higher percentages of eosinophils (p = 0.04), neutrophils (p = 0.04), and plasma cells (p = 0.04) than the non-AERD group. Additionally, the gene expression levels of GATA3 (p = 0.001), IL4 (p = 0.04), IL5 (p = 0.007), and IL17 (p = 0.03) were significantly higher in the AERD than the non-AERD groups.

Conclusion

Higher gene expression levels of GATA3, IL4, IL5, and IL17 were observed in the AERD group compared with the non-AERD group. These findings point to distinct patterns of inflammation in patients with AERD, with a predominance of Th2 inflammation.
Optimizing survival in Russell’s viper bite cases in low-resource setting: two case reports
Authors: Sharif Mohiuddin , Amin Mohammad Robed , Barshan Anindita Das , Hasan Mohammad Jahid , Faiz M. A.
Published: February 2024

Introduction

Snakebite envenomation poses a significant health risk, particularly in low-resource settings where access to proper treatment is limited.

Case presentation

This study reports two cases of Russell's viper bites in rural Bangladesh, involving 48 and 35-year-old Bangladesh males, respectively, and highlights the difficulties in providing adequate medical care and in treating any complications that may arise. Both cases involved delayed access to healthcare, initial visit to traditional healers, and the development of severe complications such as coagulopathy, renal failure. After the intervention both cases survived which is scarce in low resource settings.

Conclusion

The cases underscore the importance of early recognition, appropriate management, and improved healthcare infrastructure to optimize survival outcomes in snakebite cases in resource-limited settings. These cases will contribute valuable insights to the field of snakebite management and provide guidance for improving survival rates and outcomes among snakebite victims in Bangladesh.
A report on palaeontological excavations and sampling in mudrocks: some guidelines
Authors: Etter Walter
Published: February 2024

More than 60% of the world’s sedimentary rocks are mudrocks (Potter et al., 1980; Schieber, 1998; Potter, 2003; the term mudrock is favored here over mudstone because the latter term was used to characterize a limestone texture; Dunham, 1962). From a palaeontological perspective these are, compared to sandstones and limestones, heavily undersampled. The main reason for this is that mudrocks decay in surface exposures to small chips, which develop with sun/heat and rain into an awkward pulp. The decay of the mudstone concomitantly destroys all macrofossils which are not durable. This comprises fossils with an aragonitic or delicate calcitic shell unless they are preserved as pyritic or internal calcitic molds or preserved within calcareous concretions. Therefore, most of the fossils are not recorded in surface exposures. In addition, sedimentologic investigations of mudrocks are hampered because (i) compaction makes sedimentary structures hardly recognizableand (ii) good thin sections of mudrocks are exceedingly difficult to manufacture. For micropalaeontological investigations, mudrocks rich in organic material are especially difficult to process. Standard treatments with boiling water, sodium carbonate solution, or peroxide H2O2 generally fail to dissolve much of the sediment so that the fine fraction (and in mudrocks we usually need the 63μm-fraction) largely consists of clay particle aggregates. Yet there are methods to dissolve these aggregates. Otherwise, picking the microfossils would become extremely laborious. In this paper, some guidelines for successful palaeontological work in mudrocks are outlined. These are based on the author’s personal experience. Examples from Jurassic mudrocks of Switzerland/Europe show that such excavations can be very rewarding.
Phytocompounds as potential inhibitors of mycobacterial multidrug efflux pump Rv1258c: an in silico approach
Authors: Biswas Santasree Sarma , Roy Jayanti Datta
Published: February 2024

The number of infections and deaths caused by multidrug resistant (MDR) tuberculosis is increasing globally. One of the efflux pumps, that makesMycobacterium tuberculosisresistant to a number of antibiotics and results in unfavourable treatment results is Tap or Rv1258c. In our study, we tried to utilize a rational drug design technique using in silico approach to look for an efficient and secure efflux pump inhibitor (EPI) against Rv1258c. The structure of Rv1258c was built using the homology modeling tool MODELLER 9.24. 210 phytocompounds were used for blind and site-specific ligand docking against the modelled structure of Rv1258c using AutoDock Vina software. The best docked plant compounds were further analysed for druglikeness and toxicity. In addition to having excellent docking scores, two plant compounds—ellagic acid and baicalein—also exhibited highly desirable drug-like qualities. These substances outperform more well-known EPIs like piperine and verapamil in terms of effectiveness. This data shows that these two compounds might be further investigated for their potential as Rv1258c inhibitors.
Social connection measures for older adults living in long-term care homes: a systematic review protocol
Authors: Liougas Madalena P. , Sommerlad Andrew , O’Rourke Hannah M. , McGilton Katherine S. , Bethell Jennifer
Published: February 2024

Background

Various measures have assessed social connection in long-term care (LTC) home residents. However, they use inconsistent terminology, conceptualizations, and operationalizations of social connection. In this systematic review protocol, we propose a study that will characterize measures that assess aspects of LTC home residents’ social connection using a unified conceptual model. The objectives are to (1) describe and analyze the measures and (2) evaluate their measurement properties.

Methods

A literature search was conducted in MEDLINE ALL (Ovid), Embase Classic and Embase (Ovid), Emcare Nursing (Ovid), APA PsycInfo (Ovid), Scopus, CINAHL Complete (EBSCOhost), AgeLine (EBSCOhost), and Sociological Abstracts (ProQuest). We will include primary research papers with no language limit, published from database inception. We will include studies of a measure of any aspect of social connection in LTC home residents that report at least one measurement property. Independently, two reviewers will screen titles and abstracts, review full-text articles against eligibility criteria, and extract data from included studies. In objective 1, we will analyze identified tools using an adapted framework method. In objective 2, we will evaluate each measure’s measurement properties using COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. We will engage experts and stakeholders to assist with interpreting results and translating knowledge.

Discussion

Our findings will inform the social connection in long-term care home residents (SONNET) study’s development of a novel, person-centered measure for social connection in LTC home settings. We will present our findings in academic and non-academic forums, including conferences, peer-reviewed journals, and other publications.

Systemic review registration

Prospero—“Systematic review of measures of social connection used in long-term care home research.” CRD42022303526.
A secure and efficient electronic medical record data sharing scheme based on blockchain and proxy re-encryption
Authors: Liu Guijiang , Xie Haibo , Wang Wenming , Huang Haiping
Published: February 2024

With the rapid development of the Internet of Medical Things (IoMT) and the increasing concern for personal health, sharing Electronic Medical Record (EMR) data is widely recognized as a crucial method for enhancing the quality of care and reducing healthcare expenses. EMRs are often shared to ensure accurate diagnosis, predict prognosis, and provide health advice. However, the process of sharing EMRs always raises significant concerns about potential security issues and breaches of privacy. Previous research has demonstrated that centralized cloud-based EMR systems are at high risk, e.g., single points of failure, denial of service (DoS) attacks, and insider attacks. With this motivation, we propose an EMR sharing scheme based on a consortium blockchain that is designed to prioritize both security and privacy. The interplanetary file system (IPFS) is used to store the encrypted EMR while the returned hash addresses are recorded on the blockchain. Then, the user can authorize other users to decrypt the EMR ciphertext via the proxy re-encryption algorithm, ensuring that only authorized personnel may access the files. Moreover, the scheme attains personalized access control and guarantees privacy protection by employing attribute-based access control. The safety analysis shows that the designed scheme meets the expected design goals. Security analysis and performance evaluation show that the scheme outperforms the comparison schemes in terms of computation and communication costs.
Large-scale genotypic identification reveals density-dependent natal dispersal patterns in an elusive bird of prey
Authors: Penttinen Ida , Nebel Carina , Stjernberg Torsten , Kvist Laura , Ponnikas Suvi , Laaksonen Toni
Published: February 2024

Background

Natal dispersal, the distance between site of birth and site of first breeding, has a fundamental role in population dynamics and species’ responses to environmental changes. Population density is considered a key driver of natal dispersal. However, few studies have been able to examine densities at both the natal and the settlement site, which is critical for understanding the role of density in dispersal. Additionally, the role of density on natal dispersal remains poorly understood in long-lived and slowly reproducing species, due to their prolonged dispersal periods and often elusive nature. We studied the natal dispersal of the white-tailed eagle (Haliaeetus albicilla) in response to local breeder densities. We investigated the effects of the number of active territories around the natal site on (a) natal dispersal distance and (b) the difference between natal and settlement site breeder density. We were interested in whether eagles showed tendencies of conspecific attraction (positive density-dependence) or intraspecific competition (negative density-dependence) and how this related to settlement site breeder density.

Methods

We used a combination of long-term visual and genotypic identification to match individuals from their breeding site to their natal nest. We identified natal dispersal events for 355 individuals hatched between 1984 and 2015 in the Baltic Sea coast and Arctic areas of Finland. Of those, 251 were identified by their genotype.

Results

Individuals born in high-density areas dispersed shorter distances than those born in low-density areas, but settled at lower density breeding sites in comparison to their natal site. Eagles born in low natal area densities dispersed farther but settled in higher density breeding sites compared to their natal site.

Conclusions

We show that eagles might be attracted by conspecifics (positive density-dependence) to identify high-quality habitats or find mates, but do not settle in the most densely populated areas. This indicates that natal dispersal is affected by an interplay of conspecific attraction and intraspecific competition, which has implications for population dynamics of white-tailed eagles, but also other top predators. Furthermore, our study demonstrates the value of long-term collection of both nestling and (non-invasive) adult DNA samples, and thereafter using genotype matching to identify individuals in long-lived and elusive species.
Deep structure and geothermal resource effects of the Gonghe basin revealed by 3D magnetotelluric
Authors: Yang Yi , Zhang Jie , Wang Xingchun , Liang Mingxing , Li Dewei , Liang Meng , Ou Yang , Jia Dingyu , Tang Xianchun , Li Xufeng
Published: February 2024

In order to better understand the crustal shortening and orogenic uplift in the northeastern margin of the Tibetan Plateau, as well as the geothermal resource effects formed during this process, we used ModEM software to perform 3D MT imaging on broadband magnetotelluric survey points deployed at 710 points in the Gonghe Basin and its surrounding areas. The resistivity model suggests that the Gonghe Basin exhibits a low–high–low overall electrical structure, with high conductivity widely distributed in the middle and lower crust. The resistivity model also reveals a significant discontinuity between high and low resistivity blocks at various depths in the upper and middle crust. These discontinuities are align with the faults observed on the surface related to strong crustal fluctuations, which are connected to high conductors in the middle and upper crust. Using empirical formulas for high-temperature and high-pressure testing of granite, it is estimated that the melting volume of these high conductors ranges from 3 to 43%, demonstrating good "plasticity". These high conductors can act as detachment layers for crustal shortening and deformation during the expansion of the Tibetan Plateau towards the northeast edge and can continuously conduct heat energy upwards, creating a high thermal background in the Gonghe Basin.
Transcriptome analysis reveals the potential mechanism of altering viability, yield, and isoquinoline alkaloids in Coptis chinensis through Cunninghamia lanceolata understory cultivation
Authors: Duan Yuanyuan , You Jingmao , Wang Jintao , Tang Tao , Guo Xiaoliang , Wang Fanfan , Wang Xiaoyue , Mu Sen , Wang Qingfang , Niu Xiaofeng , Guo Jie
Published: February 2024

The dried rhizomes of Coptis chinensis hold significance in Chinese medicine. Monocropping C. chinensis under the shade of a manmade scaffold, the primary planting mode, poses a threat to the ecological balance. In recent years, the practice of C. chinensis–Cunninghamia lanceolata understory cultivation has gained prevalence in southwest China. However, there is no evidence to suggest that understory cultivation enhances the viability, yield, or isoquinoline alkaloid content of C. chinensis. This study examined the physiological properties, yield indicators, and isoquinoline alkaloid content to investigate variations in C. chinensis in response to understory cultivation. Transcriptome analysis was conducted to elucidate potential mechanisms driving these alterations. The results indicate that understory cultivation significantly enhances the viability, yield, and levels of epiberberine, palmatine, and berberine in C. chinensis while reducing coptisine content. Transcriptomic analyses identified 2062 upregulated and 1853 downregulated genes in the understory cultivation system. Pathways such as “phenylpropanoid biosynthesis,” “zeatin biosynthesis,” “photosynthesis,” “tyrosine metabolism,” “isoquinoline alkaloid biosynthesis,” and “starch and sucrose metabolism” exhibited significant enrichment of differentially expressed genes (DEGs). DEGs involved in these pathways were thoroughly analyzed. INV, BGL-2, BGL-4, SPS-2, AMY-3, Psb B, Psb R, Psb S, Psa D, Psa E, Psa H, Psa O, Pet C, Pet H, deta, and b exhibited significant positive correlations with plant fresh weight, aboveground fresh weight, and underground fresh weight. 6-OMT-2 and COMT1-3 displayed significant positive correlations with coptisine content, but negative correlations with epiberberine, palmatine, and berberine content. ZOG-1, ZOG-3, TAT, PPO, POD-13 and UGT 73C5-1 showed noteworthy positive correlations with berberine content. Conversely, MIFH, POD-4, POD-5, and POD-8 displayed significant positive correlations with epiberberine, palmatine, and berberine content. POD-5, and POD-7 were significantly negatively correlated with coptisine content. Furthermore, gene expression levels determined by qRT–PCR aligned with the transcriptomic sequencing results, confirming the reliability of the transcriptomic findings. The results of this study contribute evidence elucidating potential mechanisms through which C. chinensis responds to understory cultivation.

Graphical Abstract
External validation of the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 pneumonia managed on high-flow nasal cannula therapy: a multicenter retrospective observational study in Japan
Authors: Okano Hiromu , Yamamoto Ryohei , Iwasaki Yudai , Irimada Daisuke , Konno Daisuke , Tanaka Taku , Oishi Takatoshi , Nawa Hiroki , Yano Akihiko , Taniguchi Hiroaki , Otawara Masayuki , Matsuoka Ayaka , Yamauchi Masanori
Published: February 2024

Background

The HACOR score for predicting treatment failure includes vital signs and acid–base balance factors, whereas the ROX index only considers the respiratory rate, oxygen saturation, and fraction of inspired oxygen (FiO2). We aimed to externally validate the HACOR score and ROX index for predicting treatment failure in patients with coronavirus disease 2019 (COVID-19) on high-flow nasal cannula (HFNC) therapy in Japan.

Methods

This retrospective, observational, multicenter study included patients, aged ≥ 18 years, diagnosed with COVID-19 and treated with HFNC therapy between January 16, 2020, and March 31, 2022. The HACOR score and ROX index were calculated at 2, 6, 12, 24, and 48 h after stating HFNC therapy. The primary outcome was treatment failure (requirement for intubation or occurrence of death within 7 days). We calculated the area under the receiver operating characteristic curve (AUROC) and assessed the diagnostic performance of these indicators. The 2-h time-point prediction was considered the primary analysis and that of other time-points as the secondary analysis. We also assessed 2-h time-point sensitivity and specificity using previously reported cutoff values (HACOR score > 5, ROX index < 2.85).

Results

We analyzed 300 patients from 9 institutions (median age, 60 years; median SpO2/FiO2 ratio at the start of HFNC therapy, 121). Within 7 days of HFNC therapy, treatment failure occurred in 127 (42%) patients. The HACOR score and ROX index at the 2-h time-point exhibited AUROC discrimination values of 0.63 and 0.57 (P = 0.24), respectively. These values varied with temporal changes—0.58 and 0.62 at 6 h, 0.70 and 0.68 at 12 h, 0.68 and 0.69 at 24 h, and 0.75 and 0.75 at 48 h, respectively. The 2-h time-point sensitivity and specificity were 18% and 91% for the HACOR score, respectively, and 3% and 100% for the ROX index, respectively. Visual calibration assessment revealed well calibrated HACOR score, but not ROX index.

Conclusions

In COVID-19 patients receiving HFNC therapy in Japan, the predictive performance of the HACOR score and ROX index at the 2-h time-point may be inadequate. Furthermore, clinicians should be mindful of time-point scores owing to the variation of the models’ predictive performance with the time-point.

Trial registration UMIN (registration number: UMIN000050024, January 13, 2023)
Strong culture, healthy lifestyles: a mixed methods feasibility study for a co-created afterschool cultural programme for Australian Aboriginal children
Authors: Stanley Rebecca M. , McKnight Anthony , Probst Yasmine , O’Flynn Gabrielle , Tillott Sarah ,   Cullunghutti Aboriginal Child and Family Centre
Published: February 2024

Background

Having a strong connection to culture and Country is fundamental to the health and wellbeing of Australian Aboriginal children. The aim of the research was to evaluate the feasibility of study methods and programme implementation of a co-created afterschool cultural programme, and identify areas for improvement.

Methods

Aboriginal Relational Research Methodology and mixed methods were applied to evaluate the feasibility of the implementation of the programme and study methods using a non-randomised single-group study design. Australian Aboriginal children and their siblings aged 5–13 years were recruited within regional New South Wales, Australia. The primary outcomes for feasibility included recruitment rates of children and Aboriginal programme mentors, compliance rates of outcome data collection and of the planned programme activities, programme attendance, retention rates and mean enjoyment scores. Follow-up yarning circles were conducted with the children, their parents/caregivers, programme mentors and teachers to explore aspects of feasibility, and areas for improvement.

Results

A total of 90 caregivers consented to their children (n = 111) being part of the research. Sixteen Aboriginal mentors were recruited to deliver the programmes across the communities. Overall, 74.4% of all health outcome measures were completed across baseline (86.5%) and follow-up (55.9%). Only 61.0% of the programme activities were delivered as originally planned. The average programme attendance rate was 70.0% with a 92.0% retention rate. Eighty-nine percent of children reported a high level of enjoyment with the programmes. Follow-up yarning identified the importance of relational methodologies and flexibility within the programme design and implementation to ensure programmes were adapted to the local community, conditions and differing age groups. Considerations for future programmes included the timing of the programme and identifying health outcome assessment tools and methods that acknowledge cultural protocols and experiences.

Conclusions

Engaging the communities in the development, implementation and evaluation of the programmes were key to community support of the programme and conducting the feasibility study. Future programmes and evaluations need to be built on strong partnerships and embrace flexible and culturally embedded methodologies in order to be adaptive and responsive to research approaches, communities and to Country.

Trial registration

ACTRN12619001224112. Retrospectively registered on 05 September 2019.
Opioid reduction and enhanced recovery in orthopaedic surgery (OREOS): a protocol for a feasibility randomised controlled trial in patients undergoing total knee arthroplasty
Authors: Madden Kim , Pallapothu Sushmitha , Young Shing Darren , Adili Anthony , Bhandari Mohit , Carlesso Lisa , Khan Moin , Kleinlugtenbelt Ydo V. , Krsmanovic Adrijana , Nowakowski Matilda , Packham Tara , Romeril Eric , Tarride Jean-Eric , Thabane Lehana , Tushinski Daniel M. , Wallace Christine , Winemaker Mitchell , Shanthanna Harsha
Published: February 2024

Background

Knee arthritis is a leading cause of limited function and long-term disability in older adults. Despite a technically successful total knee arthroplasty (TKA), around 20% of patients continue to have persisting pain with reduced function, and low quality of life. Many of them continue using opioids for pain control, which puts them at risk for potential long-term adverse effects such as dependence, overdose and risk of falls. Although persisting pain and opioid use after TKA have been recognised to be important issues, individual strategies to decrease their burden have limitations and multi-component interventions, despite their potential, have not been well studied. In this study, we propose a multi-component pathway including personalized pain management, facilitated by a pain management coordinator. The objectives of this pilot trial are to evaluate feasibility (recruitment, retention, and adherence), along with opioid-free pain control at 8 weeks after TKA.

Methods

This is a protocol for a multicentre pilot randomised controlled trial using a 2-arm parallel group design. Adult participants undergoing unilateral total knee arthroplasty will be considered for inclusion and randomised to control and intervention groups. Participants in the intervention group will receive support from a pain management coordinator who will facilitate a multicomponent pain management pathway including (1) preoperative education on pain and opioid use, (2) preoperative risk identification and mitigation, (3) personalized post-discharge analgesic prescriptions and (4) continued support for pain control and recovery up to 8 weeks post-op. Participants in the control group will undergo usual care. The primary outcomes of this pilot trial are to assess the feasibility of participant recruitment, retention, and adherence to the interventions, and key secondary outcomes are persisting pain and opioid use.

Discussion

The results of this trial will determine the feasibility of conducting a definitive trial for the implementation of a multicomponent pain pathway to improve pain control and reduce harms using a coordinated approach, while keeping an emphasis on patient centred care and shared decision making.

Trial registration

Prospectively registered in Clinicaltrials.gov (NCT04968132).
Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy
Authors: Shah Stavan V. , Singh Sumit Randhir , Selvam Amrish , Harihar Sanjana , Parmar Yash , Mangla Rubble , Arora Supriya , Vupparaboina Kiran K. , Venkatesh Ramesh , Chhablani Jay
Published: February 2024

Purpose

To compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months.

Methods

This was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F).

Results

A total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = − 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = − 0.53; p < 0.001 and PCV, r = − 0.09; p = 0.58).

Conclusion

PEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.
Rapid and high-purity differentiation of human medium spiny neurons reveals LMNB1 hypofunction and subtype necessity in modeling Huntington’s disease
Authors: Wu Junjiao , Ren Jie , Cui Hongfei , Xie Yali , Tang Yu
Published: February 2024

Background

Different neural subtypes are selectively lost in diverse neurodegenerative diseases. Huntington’s disease (HD) is an inherited neurodegenerative disease characterized by motor abnormalities that primarily affect the striatum. The Huntingtin (HTT) mutation involves an expanded CAG repeat, leading to insoluble polyQ, which renders GABA+ medium spiny neurons (MSN) more venerable to cell death. Human pluripotent stem cells (hPSCs) technology allows for the construction of disease-specific models, providing valuable cellular models for studying pathogenesis, drug screening, and high-throughput analysis.

Methods

In this study, we established a method that allows for rapid and efficient generation of MSNs (> 90%) within 21 days from hPSC-derived neural progenitor cells, by introducing a specific combination of transcription factors.

Results

We efficiently induced several neural subtypes, in parallel, based on the same cell source, and revealed that, compared to other neural subtypes, MSNs exhibited higher polyQ aggregation propensity and overexpression toxicity, more severe dysfunction in BDNF/TrkB signaling, greater susceptibility to BDNF withdrawal, and more severe disturbances in nucleocytoplasmic transport (NCT). We further found that the nuclear lamina protein LMNB1 was greatly reduced in HD neurons and mislocalized to the cytoplasm and axons. Knockdown of HTT or treatment with KPT335, an orally selective inhibitor of nuclear export (SINE), effectively attenuated the pathological phenotypes and alleviated neuronal death caused by BDNF withdrawal.

Conclusions

This study thus establishes an effective method for obtaining MSNs and underscores the necessity of using high-purity MSNs to study HD pathogenesis, especially the MSN-selective vulnerability.
Creative thinking and cognitive estimation in Parkinson’s disease
Authors: Heldmann Marcus , Rinckens Celia , Brüggemann Norbert , Al-Khaled Mohamed , Münte Thomas F.
Published: February 2024

Background

Patients with Parkinson’s disease (PD) have been reported to exhibit unusual bouts of creativity (e.g., painting, writing), in particular in the context of treatment with dopaminergic agents. Here we investigated divergent and convergent thinking thought to underlie creativity. In addition we assessed cognitive estimation.

Method

Twenty PD patients and 20 matched healthy control participants were subjected to the Guilford Alternate Uses task (divergent thinking), the remote associates task (convergent thinking) and two tests of cognitive estimation.

Results

No group differences were found for the convergent thinking task, while the Guilford Alternate Uses task revealed a decreased number of correct responses and a reduced originality for PD patients. Originality in PD was correlated to total daily dose of dopaminergic medication. Moreover, both tasks of cognitive estimation showed an impairment in PD.

Conclusion

Only minor effects were found for psychometric indices of subprocesses of creative thinking, while estimation, relying on executive functioning, is impaired in PD. We suggest to take a product oriented view of creativity in further research on altered creative processes in PD.
Factors affecting land value of urban voids in western part of India
Authors: Pareek Sanjeev , Kumar Manoj
Published: February 2024

Urban voids are the key determining factors to utilize efficient manner for sustainable development. These areas need to be understood through their land potentials. Land valuation determines the value of urban voids based solely on their natural characteristics. The research papers present a papered examination of land value modeling and its influencing factors. The study concentrates on Jaipur, the capital city of Rajasthan, selected as the research area. The land value modeling process consists of three stages. Initially, various approaches and issues have been identified for land valuation. In the second stage, factors have been identified for land valuation. Lastly, land valuation methods such as the ordinary least squares (OLS) regression have been used. The primary factors influencing land value in the research area include distance to major highways, proximity to schools, railway lines, specific communities, availability of infrastructure, etc. Interestingly, variables such as slum area, landfill, rail line, and proximity to specific communities exhibit an inverse relationship. This research provides valuable insights into the localized variations in land prices within an Indian city.