bluuebunny/crossref_metadata_2025 huggingface dataset:
Suture-anchored cutaneous tension induces persistent hypertrophic scarring in a novel murine model
Authors: Li Yashu , Liu Anqi , Wang Jingyan , Yang Changsheng , Lv Kaiyang , He Weifeng , Wu Jun , Chen Wenbin
Published: October 2024

Background

Hypertrophic scars cause impaired skin appearance and function, seriously affecting physical and mental health. Due to medical ethics and clinical accessibility, the collection of human scar specimens is frequently restricted, and the establishment of scar experimental animal models for scientific research is urgently needed. The four most commonly used animal models of hypertrophic scars have the following drawbacks: the rabbit ear model takes a long time to construct; the immunodeficient mouse hypertrophic scar model necessitates careful feeding and experimental operations; female Duroc pigs are expensive to purchase and maintain, and their large size makes it difficult to produce a significant number of models; and mouse scar models that rely on tension require special skin stretch devices, which are often damaged and shed, resulting in unstable model establishment. Our group overcame the shortcomings of previous scar animal models and created a new mouse model of hypertrophic scarring induced by suture anchoring at the wound edge.

Methods

We utilized suture anchoring of incisional wounds to impose directional tension throughout the healing process, restrain wound contraction, and generate granulation tissue, thus inducing scar formation. Dorsal paired incisions were generated in mice, with wound edges on the upper back sutured to the rib cage and the wound edges on the lower back relaxed as a control. Macroscopic manifestation, microscopic histological analysis, mRNA sequencing, bioinformatics, and in vitro cell assays were also conducted to verify the reliability of this method.

Results

Compared with those in relaxed controls, the fibrotic changes in stretched wounds were more profound. Histologically, the stretched scars were hypercellular, hypervascular, and hyperproliferative with disorganized extracellular matrix deposition, and displayed molecular hallmarks of hypertrophic fibrosis. In addition, the stretched scars exhibited transcriptional overlap with mechanically stretched scars, and human hypertrophic and keloid scars. Phosphatidylinositol 3-kinase-serine/threonine-protein kinase B signaling was implicated as a profibrotic mediator of apoptosis resistance under suture-induced tension.

Conclusions

This straightforward murine model successfully induces cardinal molecular and histological features of pathological hypertrophic scarring through localized suture tension to inhibit wound contraction. The model enables us to interrogate the mechanisms of tension-induced fibrosis and evaluate anti-scarring therapies.
Linezolid Pharmacokinetic-Anemia Modeling in Children With Rifampicin-Resistant Tuberculosis
Authors: Brooks Jordan T , Solans Belén P , Béranger Agathe , Schaaf H Simon , van der Laan Louvina , Sharma Sangeeta , Furin Jennifer , Draper Heather R , Hesseling Anneke C , Garcia-Prats Anthony J , Savic Radojka M
Published: October 2024

Background

Linezolid, a component of rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) treatment, is associated with treatment-limiting toxicities, including anemia. Patient-level and linezolid pharmacokinetic risk factors for anemia have not been well described in children treated for RR/MDR-TB.

Methods

We evaluated the pharmacokinetics of linezolid and longitudinal hemoglobin data to validate an existing population linezolid pharmacokinetic model. We assessed the impact of linezolid pharmacokinetics and the risk of developing anemia in a prospectively enrolled cohort of children. A previously published population pharmacokinetic linezolid model was validated using nonlinear mixed effects modeling. A multivariable ordinal logistic regression model was built to predict the incidence of anemia.

Results

A total of 112 children, median age 7.2 years (interquartile range, 2.2–16.3), were included from South Africa (n = 87) and India (n = 25). Of these, 24 children contributed new linezolid pharmacokinetic data. The population pharmacokinetic model, which informs the currently recommended linezolid dosing in children (10–15 mg/kg), was validated with these additional new data. For every 1 g/dL lower baseline hemoglobin level, the odds of developing grade 3 or 4 anemia increased by 2.64 (95% confidence interval [CI], 1.98–3.62). For every 1 mg/L × h higher linezolid area under the concentration-time curve, the odds of developing grade 3 or 4 anemia increased by 1.012 (95% CI, 1.007–1.017).

Conclusions

Taken together, these data confirm currently recommended linezolid doses for children. The risk of anemia in children should be carefully considered and monitored. Initiating linezolid in children with low baseline hemoglobin increases the probability of experiencing grade 3 or 4 anemia.
Current Legal Fictions in Public Law
Authors: Allison John W F
Published: October 2024

The use of legal fiction in public law has shown no sign of abating, as demonstrated in the enactment of the Safety of Rwanda (Asylum and Immigration) Act 2024. Accompanying questions or concerns are about the degree to which they are problematic, useful, or detrimental, what is to be done about them, and whether their prevalence is specific to British or English legal culture. This article examines what has been done, or what has happened, to deal or to cope with them, in orthodox constitutional legal doctrine and administrative law liability. After adopting a working definition of legal fiction and showing Dicey’s own preoccupation with the constitution’s legal forms and fiction, it does so through two case studies. Both involve basic orthodox constitutional legal doctrines—parliamentary sovereignty and the rule of law—with which Dicey has long been associated. The one case study is of Parliament’s sovereignty, limitless in law, and limited in actuality. The other case study is of legal fiction in relation to developments in public authority liability under equality before the law, particularly for omissions, or non-conferrals of benefit. Through these studies, this article will argue that the fortunes of legal fiction in the British or English legal context have been not simply of all-or-nothing rejection or retention. They have been, because of the unease accompanying the use of legal fiction, also of their domestication, in analytical distinctions, and refinement of judicial language in common law reasoning. The extraordinary legal forms have been made more ordinary or so to appear, showing them as domesticated to have been and to remain of current, ongoing and present, relevance.
Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction
Authors: Airaksinen Juhani K E , Tuominen Tuulia , Paana Tuomas , Hellman Tapio , Vasankari Tuija , Salonen Selma , Junes Helea , Linko-Parvinen Anna , Pallari Hanna-Mari , Strandberg Marjatta , Teppo Konsta , Jaakkola Samuli , Wittfooth Saara
Published: October 2024

Aims

Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI.

Methods and results

The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. Troponin ratio was lower in TTS patients [0.13 (0.10–0.20) vs. 0.62 (0.29–0.96), P < 0.001]. In the receiver operating characteristic curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients {area under the curve [AUC] 0.869 [95% confidence interval (CI) 0.789–0.948] vs. 0.766 [95% CI 0.677–0.855], P = 0.047}. When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (95% CI 0.465–0.732) and 0.816 (95% CI 0.712–0.921) (P = 0.003). At a cut-off point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients.

Conclusion

In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS.

Clinical trial registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591
Remote workers’ life quality and stress during COVID-19: a systematic review
Authors: Elisabetta Carraro , Paola Rapisarda , Acquadro Maran Daniela , Filippetti Sofia , Marco Palella , Pellegrino Eliana , Ferrante Margherita , Giuseppe La Torre , Fiore Maria
Published: October 2024

COVID-19 pandemic led to the adoption of a different working approach: “The remote working.” Evidence about the association of remote working with stress outcomes and life quality is lacking. This systematic review provides an overview of the effects of COVID-19 pandemic on remote-workers’ stress and life quality. We conducted systematic literature searches in databases including Pubmed, Scopus and Web of science, from September 2020 to September 2023. Screening of titles, abstracts, and full texts were performed according to the Preferred Reporting Item for Systematic Review and Meta-analyses. The quality of the included studies was assessed using the Newcastle-Ottawa Scale. The review highlighted possible predictors (work-family conflict or a condition of social isolation) associated with improvement or worsening of quality of life and stress. The results highlighted the association between stress and family difficulties (β: −0.02, P-value <0.05), isolation during the first (β: −0.22, P-value <0.05) and second pandemic waves (β: −0.40, P-value <0.05) or due to the advancing age of workers (β:0.19, P-value <0.05) and (β: −0.05, P-value <0.05), furthermore some job categories presented greater stress such as teachers (16.94 ± 5.46). Conversely, remote working positively affected life quality, enhancing factors such as creativity (Average Variance Extracted, AVE: 0.41, R2: 0.17) and self-efficacy (AVE: 0.60, R2: 0.36). Future research should focus more on the relationship between work and family and on interventions that counteract social isolation.
Promoting physical activity among cancer survivors through general practice: a realist review
Authors: Sugiarto Matthew Patrio , Jabbour Victoria , Uebel Kerry , Agaliotis Maria , Clifford Briana , Chin Melvin , Harris Mark , Caperchione Cristina M , Vuong Kylie
Published: October 2024

Background

Multiple studies have shown that physical activity improves cancer survivorship, by decreasing risk of second primary cancers and chronic conditions. However, cancer survivor physical activity levels remain low. General practice presents more opportunities for lifestyle interventions, such as increasing physical activity. We conducted a realist review of physical activity interventions relevant to general practice.

Methods

A total of 9728 studies were obtained from a systematic search of the CINAHL, Embase, PsycINFO, PubMed, and SPORTDiscus databases from the inception of the electronic database to 21 June 2024. We focussed on intervention studies that improved physical activity among cancer survivors and were relevant to general practice. Data extraction focussed on: what makes physical activity interventions effective for cancer survivors (what works) and what factors promote physical activity for cancer survivors (for whom it works).

Results

Thirty-seven studies were used to generate themes on the components of physical activity interventions that are likely to work and for whom; these studies facilitated goal setting, action planning, self-monitoring, social support, and shaping of knowledge; through delivering tailored motivational support, evoking a teachable moment, and promoting the use of self-monitoring tools. Interventions that were cost-effective and easily implementable improved sustainability, deployability, and uptake by cancer survivors. Cancer survivor psychological and physical factors, such as baseline motivational levels and post-treatment symptoms, influenced the uptake of physical activity interventions.

Conclusion

Our realist review has highlighted opportunities for general practices to promote physical activity among cancer survivors through collaborative goal setting, action planning, self-monitoring, social support, and shaping of knowledge.
LukProt: A Database of Eukaryotic Predicted Proteins Designed for Investigations of Animal Origins
Authors: Sobala Łukasz F
Published: October 2024

The origins and early evolution of animals are subjects with many outstanding questions. One problem faced by researchers trying to answer them is the absence of a comprehensive database with sequences from nonbilaterians. Publicly available data are plentiful but scattered and often not associated with proper metadata. A new database presented in this paper, LukProt, is an attempt at solving this issue. The database contains protein sequences obtained mostly from genomic, transcriptomic, and metagenomic studies and is an extension of EukProt (Richter DJ, Berney C, Strassert JFH, Poh Y-P, Herman EK, Muñoz-Gómez SA, Wideman JG, Burki F, de Vargas C. EukProt: a database of genome-scale predicted proteins across the diversity of eukaryotes. Peer Community J. 2022:2:e56. https://doi.org/10.24072/pcjournal.173). LukProt adopts the EukProt naming conventions and includes data from 216 additional animals. The database is associated with a taxonomic grouping (taxogroup) scheme suitable for studying early animal evolution. Minor updates to the database will contain species additions or metadata corrections, whereas major updates will synchronize LukProt to each new version of EukProt, and releases are permanently stored on Zenodo (https://doi.org/10.5281/zenodo.7089120). A BLAST server to search the database is available at: https://lukprot.hirszfeld.pl/. Users are invited to participate in maintaining and correcting LukProt. As it can be searched without downloading locally, the database aims to be a convenient resource not only for evolutionary biologists, but for the broader scientific community as well.
Neighborhood Stressors and Epigenetic Age Acceleration Among Older Americans
Authors: Choi Eun Young , Ailshire Jennifer A
Published: October 2024

Objectives

Exposure to stressful neighborhood environments is a well-established risk factor for health deterioration and premature death. However, the biological underpinnings are not fully understood. Epigenetic aging may function as a key molecular pathway to adverse health outcomes among residents of high-stress neighborhoods. This study examines the associations between neighborhood social stressors (socioeconomic deprivation, observed and perceived disorder, and low social cohesion) and epigenetic age (DunedinPACE and Principal component adjusted [PC] PCHorvath, PCHannum, PCPhenoAge, PCGrimAge). Further, we identify subpopulations most vulnerable to neighborhood stressors.

Methods

Respondent data are from the 2016 Health and Retirement Study (HRS) DNA methylation subsample. Neighborhood data come from respondent reports (2014/2016) and the census (2012–2016 ACS). The analytic sample included 3,146 adults ages 56 and older (mean age = 68.8), of whom 54.9% were women and 19.3% were non-White.

Results

In multilevel regression models adjusting for sociodemographic covariates, all neighborhood stressors were associated with faster DunedinPACE (B = 0.008 to 0.017). Neighborhood deprivation, perceived disorder, and low cohesion were associated with PCPhenoAge (B = 0.27 to 0.40) or PCGrimAge acceleration (B = 0.23). Health behaviors explained these associations to some degree. However, no significant associations were found with PCHorvath and PCHannum. In interaction analyses, adverse associations with deprivation, observed disorder, and low cohesion were more pronounced for women. No consistent interactions were found for race/ethnic and education groups.

Discussion

Our findings indicate that neighborhood stressors can accelerate epigenetic aging, with older women particularly vulnerable to their effects. These findings provide insights into the biological foundations of health disparities rooted in neighborhood environments.
Corticosteroid Use in Randomized Clinical Trials of Biologics and Small Molecules in Inflammatory Bowel Disease: A Systematic Review
Authors: da Silva Bruno César , Papasotiriou Sam , Hanauer Stephen B
Published: October 2024

Background and Aims

This systematic review aims to elucidate the use of corticosteroids in randomized clinical trials (RCTs) evaluating biologics and small molecules for inflammatory bowel disease (IBD). We analyzed corticosteroid use during both the induction and maintenance phases, highlighting areas needing standardization and improvement in clinical research.

Methods

We selected placebo-controlled phase 3 RCTs involving adults with moderate to severe IBD. These studies included detailed reports on corticosteroid use during induction and maintenance phases, with clinical remission and/or corticosteroid-free clinical remission (CSF-CR) as primary endpoints.

Results

Initially, 324 studies were identified and refined to 26 RCTs after screening. Analysis revealed variability in corticosteroid administration. Over time, corticosteroid use showed a decreasing trend (Spearman ρ = −0.42, P = .045). Studies allowing higher corticosteroid doses (up to 40 mg/day of prednisone or equivalent) reported a higher proportion of corticosteroid users (51.8%, range: 42.9%-61%) compared to those excluding patients on doses >20 mg/day (37.5%, range: 31.6%-51.8%; P = .007) or >30 mg/day (41.1%, range: 29.6%-53.7%; P = .023). Trials with mandatory tapering protocols showed a narrower gap between overall clinical remission and CSF-CR rates, with an average difference of 6% in the group without mandatory tapering and 1.2% in the group with forced tapering (T-test P = .038; Cohen’s d ≈ 1.1).

Conclusions

This review highlights the variability in corticosteroid use across RCTs and its impact on evaluating new IBD therapies. Standardizing tapering protocols and defining CSF-CR are essential for accurate outcomes.
Extracting social support and social isolation information from clinical psychiatry notes: comparing a rule-based natural language processing system and a large language model
Authors: Patra Braja Gopal , Lepow Lauren A , Kasi Reddy Jagadeesh Kumar Praneet , Vekaria Veer , Sharma Mohit Manoj , Adekkanattu Prakash , Fennessy Brian , Hynes Gavin , Landi Isotta , Sanchez-Ruiz Jorge A , Ryu Euijung , Biernacka Joanna M , Nadkarni Girish N , Talati Ardesheer , Weissman Myrna , Olfson Mark , Mann J John , Zhang Yiye , Charney Alexander W , Pathak Jyotishman
Published: October 2024

Objectives

Social support (SS) and social isolation (SI) are social determinants of health (SDOH) associated with psychiatric outcomes. In electronic health records (EHRs), individual-level SS/SI is typically documented in narrative clinical notes rather than as structured coded data. Natural language processing (NLP) algorithms can automate the otherwise labor-intensive process of extraction of such information.

Materials and Methods

Psychiatric encounter notes from Mount Sinai Health System (MSHS, n = 300) and Weill Cornell Medicine (WCM, n = 225) were annotated to create a gold-standard corpus. A rule-based system (RBS) involving lexicons and a large language model (LLM) using FLAN-T5-XL were developed to identify mentions of SS and SI and their subcategories (eg, social network, instrumental support, and loneliness).

Results

For extracting SS/SI, the RBS obtained higher macroaveraged F1-scores than the LLM at both MSHS (0.89 versus 0.65) and WCM (0.85 versus 0.82). For extracting the subcategories, the RBS also outperformed the LLM at both MSHS (0.90 versus 0.62) and WCM (0.82 versus 0.81).

Discussion and Conclusion

Unexpectedly, the RBS outperformed the LLMs across all metrics. An intensive review demonstrates that this finding is due to the divergent approach taken by the RBS and LLM. The RBS was designed and refined to follow the same specific rules as the gold-standard annotations. Conversely, the LLM was more inclusive with categorization and conformed to common English-language understanding. Both approaches offer advantages, although additional replication studies are warranted.
Acceptability of linking individual credit, financial, and public records data to healthcare records for suicide risk machine learning models
Authors: Penfold Robert B , Yoo Hong Il , Richards Julie E , Crossnohere Norah L , Johnson Eric , Pabiniak Chester J , Renz Anne D , Campoamor Nicola B , Simon Gregory E , Bridges John F P
Published: October 2024

Objectives

Individual-level information about negative life events (NLE) such as bankruptcy, foreclosure, divorce, and criminal arrest might improve the accuracy of machine learning models for suicide risk prediction. Individual-level NLE data is routinely collected by vendors such as Equifax. However, little is known about the acceptability of linking this NLE data to healthcare data. Our objective was to assess preferences for linking external NLE data to healthcare records for suicide prevention.

Materials and Methods

We conducted a discrete choice experiment (DCE) among Kaiser Permanente Washington (KPWA) members. Patient partners assisted in the design and pretesting of the DCE survey. The DCE included 12 choice tasks involving 4 data linking program attributes and 3 levels within each attribute. We estimated latent class conditional logit models to derive preference weights.

Results

There were 743 participants. Willingness to link data varied by type of information to be linked, demographic characteristics, and experience with NLE. Overall, 65.1% of people were willing to link data and 34.9% were more private. Trust in KPWA to safeguard data was the strongest predictor of willingness to link data.

Discussion

Most respondents supported linking NLE data for suicide prevention. Contrary to expectations, People of Color and people who reported experience with NLEs were more likely to be willing to link their data.

Conclusions

A majority of participants were willing to have their credit and public records data linked to healthcare records provided that conditions are in place to protect privacy and autonomy.
Digital platforms and the reconfiguration of global production networks
Authors: Verfürth Philip , Helwing-Hentschel Veronique
Published: October 2024

Digital business-to-business (B2B) platforms have become essential components of today's economy. However, the impact of digital B2B platforms on global production networks has not yet been sufficiently conceptualized and empirically examined. This article proposes an analytical framework to theorize platform-based reconfigurations of global production networks. By using the case of digital logistics platforms, the article illustrates that service-centred platforms, in particular, have a major impact on global production networks, as they are able to position themselves as lead firms and to utilize data to shape the organizational and spatial composition of global production networks.
The Vicious Circle of Securitization Processes in the Former Indian State of Jammu and Kashmir
Authors: Constantin Sergiu , Carlà Andrea
Published: October 2024

This article analyzes processes of securitization in India’s former State of Jammu and Kashmir (SJK), a disputed borderland characterized by a three-dimensional conflict: the international conflict over Jammu and Kashmir, the inter-governmental conflict between the autonomous SJK and the Indian government, and the inter-communal conflict within the SJK. Applying the concept of securitization beyond its traditional Eurocentric perspective, we explore the securitization of transborder kinship in a case study outside the Global North. We examine the perceived threats vis-à-vis the SJK and the Kashmiri Muslim in light of ontological insecurities rooted in the main Indian national narratives and show how dysfunctional diversity governance in a complex geopolitical context intersects with processes of securitization, affecting inter-communal, inter-governmental, and inter-state relations. The article shows that ontological insecurities, combined with fear of separatism and short-sighted political strategies, led Indian political elites to erode the autonomy of the SJK, and undermine its democratic political processes. This, in turn, led to an increasing dissatisfaction among various communities and, in time, to civil unrest, strong religious polarization, communal and state violence, human rights abuses, insurgency, and the rise of separatist Islamic militant groups. This vicious circle turned New Delhi’s fears into a self-fulfilling prophecy. We highlight the continuum of securitization processes and argue that the former SJK could escape the vicious circle of securitization only through a combination of self-governance, good governance, and international governance.
DST regulates cisplatin resistance in colorectal cancer via PI3K/Akt pathway
Authors: Yu Jianwei , Deng Xueqiong , Lin Xueqin , Xie Li , Guo Sisi , Lin Xiaoliang , Lin Dong
Published: October 2024

Objectives

Dystonin (DST), a potential tumor suppressor gene, plays a crucial role in regulating cancer cell proliferation and resistance to chemotherapy. However, DST’s specific role in colorectal cancer (CRC) has not been thoroughly investigated, and this study aims to elucidate its molecular role in modulating cisplatin (DDP) resistance in CRC.

Methods

DST expression was analyzed in CRC tumors, DDP-resistant CRC tissues, paracancer tissues, and normal tissues. Lentiviral overexpression and shRNA knockdown were conducted in advanced CRC and DDP-resistant cell lines to assess cell viability, apoptosis, invasion, migration, proliferation, and angiogenesis. Xenograft mouse models studied DST’s impact on CRC tumor growth and DDP resistance in vivo.

Results

DST expression was significantly reduced in CRC tumor and DDP-resistant CRC tissues compared to paracancer and normal tissues (P < .001). Upregulating DST inhibited CRC and DDP-resistant cell viability, proliferation, invasion, and migration while promoting apoptosis. DST overexpression also reduced angiogenesis and attenuated DDP-induced cytotoxicity in CRC cells. Mechanistically, DST upregulation suppressed DDP resistance in CRC cells via the PI3K/Akt signaling pathway. DST upregulation reduced CRC tumor growth and mitigated DDP resistance, in vivo.

Conclusion

DST plays a crucial role in limiting CRC progression and overcoming DDP resistance, suggesting potential for targeted CRC therapies.
On the nature of the eccentric eclipsing binary star SY Phe with a pulsating γ Dor component
Authors: Erdem Ahmet , Sürgit Derya , Engelbrecht Chris A , Zasche Petr , Bakış Volkan , Marang Fred
Published: October 2024

Spectroscopic observations of the eccentric binary system SY Phe were made at the South African Astronomical Observatory in 2019, 2020, and 2021, and its mid-resolution spectra were obtained. The radial velocities of the component stars were measured using the cross-correlation method and Fourier disentangling of the spectra. The spectral type (hence the effective temperature) of the primary star was determined from a model-atmosphere analysis. The radial velocity and Transiting Exoplanet Survey Satellite (TESS) light curves of the system were analysed, and its absolute parameters were derived. A strong (5.2 mmag) periodic signal with a frequency typical of $\gamma$ Dor stars (1.169 cycles per day) dominates the Fourier spectrum of the light curve between the eclipses. Apsidal motion parameters of SY Phe were calculated by studying eclipse timing variations. The Geneva evolution models indicate an evolutionary age of 2 Gyr and solar metallicity for the primary component; however, although the position of the secondary component in the H–R diagram matches the isochrone of 2 Gyr, it appears to have a larger radius and higher effective temperature than expected for its determined mass. Here, the secondary component has too large a radius, which is in accordance with the radius discrepancy problem that has been encountered in other studies, especially in late-type dwarfs, and has not been solved for half a century.
MeerKAT observations of pair-plasma induced birefringence in the double pulsar eclipses
Authors: Lower M E , Kramer M , Johnston S , Breton R P , Wex N , Bailes M , Buchner S , Camilo F , Oswald L S , Reardon D J , Shannon R M , Serylak M , Krishnan V Venkatraman
Published: October 2024

PSR J0737−3039A/B is unique among double neutron star systems. Its near-perfect edge-on orbit causes the fast spinning pulsar A to be eclipsed by the magnetic field of the slow spinning pulsar B. Using high-sensitivity MeerKAT radio observations combined with updated constraints on the system geometry, we studied the impact of these eclipses on the incident polarization properties of pulsar A. Averaging light curves together after correcting for the rotation of pulsar B revealed enormous amounts of circular polarization and rapid changes in the linear polarization position angle, which occur at phases where emission from pulsar A is partially transmitted through the magnetosphere of pulsar B. These behaviours confirm that the eclipse mechanism is the result of synchrotron absorption in a relativistic pair-plasma confined to the closed-field region of pulsar B’s truncated dipolar magnetic field. We demonstrate that changes in circular polarization handedness throughout the eclipses are directly tied to the average line of sight magnetic field direction of pulsar B, from which we unambiguously determine the complete magnetic and viewing geometry of the pulsar.
Interleukin-22 improves ovulation in polycystic ovary syndrome via STAT3 signaling
Authors: Liao Baoying , Chen Weixuan , Qi Xinyu , Yun Chuyu , Pang Yanli
Published: October 2024

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease, which leads to serious impairment of reproductive health in women of child-bearing age. Anovulation or oligo-ovulation is a common clinical manifestation of PCOS patients. A disturbance of the ovarian immune microenvironment contributes to the disorders of follicle development and ovulation; however, the underlying mechanism remains unclear. Here we demonstrated the protective effect of immune factor interleukin-22 (IL-22) on PCOS follicle development and ovulation. Follicular IL-22 levels were significantly lower in PCOS patients than in the control group and were positively correlated with oocyte fertilization rate and high-quality embryo rate. Additionally, IL-22 evidently improved follicle development in vitro and promoted ovulation-related gene expression, which was disrupted by the depletion of interleukin-22 receptor 1 (IL-22R1) or inhibition of STAT3 in granulosa cells. This indicates that IL-22 acts through IL-22R1 and the STAT3 signaling pathway to promote follicle development and ovulation in PCOS. In summary, this study has elucidated the vital role of the ovarian immune microenvironment in follicle development and ovulation. Application of IL-22 may provide new insights into the treatment of PCOS patients.
Do Personalized Nutrition Interventions Improve Dietary Intake and Risk Factors in Adults With Elevated Cardiovascular Disease Risk Factors? A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Cross Victoria , Stanford Jordan , Gómez-Martín María , Collins Clare E , Robertson Seaton , Clarke Erin D
Published: October 2024

Context

Dietary modifications can improve cardiovascular disease (CVD) risk factors. Personalized nutrition (PN) refers to individualized nutrition care based on genetic, phenotypic, medical, behavioral, and/or lifestyle characteristics. PN may be beneficial in improving CVD risk factors, including diet. However, this has not been reviewed previously.

Objective

The aim was to evaluate the effectiveness of PN interventions on CVD risk factors and diet in adults at elevated CVD risk.

Data Sources

Six databases were searched for randomized controlled trials published between 2000 and 2023 that tested the impact of PN interventions on CVD risk factors in people at elevated risk.

Data Extraction

Risk of bias was assessed using the Academy of Nutrition and Dietetics Quality Criteria checklist. Data synthesis of eligible articles included participant characteristics, intervention details, and change in primary CVD risk factor outcomes, including blood pressure (BP), plasma lipids, and CVD risk score, and secondary risk factors, including anthropometric outcomes and diet quality. Random-effects meta-analyses were conducted to explore weighted mean differences (WMDs) in change or final mean values for studies with comparable data (studies with dietary counseling interventions) for outcomes including BP, blood lipids, and anthropometric measurements.

Data Analysis

Of 7676 identified articles, 16 articles representing 15 studies met the inclusion criteria. Studies included between 40 and 563 participants and reported outcomes for CVD risk factors, including hyperlipidemia (n = 5), elevated BP (n = 3), overweight/obesity (n = 1), and multiple risk factors (n = 6). Risk of bias was low. Results suggested potential benefit of PN on systolic BP (WMD: −1.91; 95% CI: −3.51, −0.31 mmHg) and diastolic BP (WMD: −1.49; 95% CI: −2.39, −0.58 mmHg) and dietary intake in individuals at high CVD risk. Results were inconsistent for plasma lipid and anthropometric outcomes.

Conclusion

Results were promising for PN interventions that used dietary counseling on CVD risk factors in at-risk individuals. However, further evidence for other personalization methods is required, including improving methodological quality and longer study duration in future PN interventions.

Systematic Review Registration

OpenScience Framework (https://doi.org/10.17605/OSF.IO/SHVWP).
Validation of Cefiderocol Package Insert Dosing Recommendation for Patients Receiving Continuous Renal Replacement Therapy: A Prospective Multicenter Pharmacokinetic Study
Authors: Fouad Aliaa , Kobic Emir , Nicolasora Nelson P , Bastin Melissa L Thompson , Adams Paul M , Shen Yuwei , Fratoni Andrew J , Ye Xiaoyi , Kuti Joseph L , Nicolau David P , Asempa Tomefa E
Published: October 2024

Background

Cefiderocol is the first antibiotic with effluent flow rate–based dosing recommendations outlined in the product label for patients receiving continuous renal replacement therapy (CRRT). We aimed to investigate the population pharmacokinetics of cefiderocol among patients receiving CRRT and validate these dosing recommendations.

Methods

A multicenter, prospective cefiderocol pharmacokinetic study among intensive care unit patients receiving CRRT was conducted (2022–2023). Blood sampling was performed at steady-state and cefiderocol concentrations were assayed by validated liquid chromatography–tandem mass spectrometry. Population pharmacokinetic analyses were conducted in Pmetrics using R software. The free time above the minimum inhibitory concentration (f T > MIC) and total daily area under the concentration time curve (AUCdaily) were calculated.

Results

Fourteen patients with effluent flow rates ranging from 2.1 to 5.1 L/h were enrolled. Cefiderocol concentrations best fitted a 2-compartment model. Mean ± standard deviation (SD) parameter estimates for clearance, central compartment volume, and intercompartment transfer constants (k12 and k21) were 3.5 ± 1.5 L/hour, 10.7 ± 8.4 L, 3.9 ± 1.8 hours−1, and 2.2 ± 2.2 hours−1, respectively. With simulations based on product label dosing recommendations, all patients achieved 100% fT > MIC up to MIC 8 mg/L with an AUCdaily (mean ± SD) of 1444 ± 423 mg × hour/L. Cefiderocol was well tolerated among the 14 patients.

Conclusions

The current package insert dosing recommendations resulted in pharmacodynamically optimized cefiderocol exposures. Cefiderocol concentrations exceeded relevant MIC breakpoints in all patients at each effluent flow rate, and AUCdaily was within the range observed in patients in the phase 3 clinical trials, suggestive of a safe and therapeutic drug profile.
A world of evidence: the global spread and silent politics of evidence cultures
Authors: Straßheim Holger
Published: October 2024

How can we explain the worldwide spread of evidence-based policymaking despite continuous criticism? What are the underlying mechanisms of its persistence on a global scale? This article aims at answering these questions by focusing on the cultural constellations in which evidence is imbued with political as well as epistemic authority. Evidence cultures are discursive and institutional forces (re-)producing both the scientific validation of knowledge and its relevance in policymaking. They need to be understood as self-propagating constellations of interlinking science and policy through practices, discourses and institutionally sedimented regulations. Evidence is the product of chains of practices in which the initial knowledge struggles are gradually made publicly invisible and often inaccessible. The article reconstructs the immunization of evidence cultures from criticism and their silent politics by looking at quantifications, benchmarking and randomized controlled trials as typical cases. To overcome the circularities and closures so characteristic of the evidence culture of evidence-based policymaking, politico-epistemic diversity should be actively promoted.
Thermophysical Properties and Mass Spectra of Meson Systems via the Nikiforov–Uvarov Method
Authors: Horchani Ridha , Al Kharusi Omama , Ikot Akpan N , Ahmed Faizuddin
Published: October 2024

In this study, we analyze the mass spectra of meson systems within an N-dimensional space using the Killingbeck potential combined with an inversely quadratic potential. We employ the Nikiforov–Uvarov method along with the Pekeris approximation scheme to account for the centrifugal barrier. This approach enables us to compute numerical energy eigenvalues, normalized eigenfunctions, and mass spectra for both heavy and heavy–light meson systems. We explore various scenarios of the potential and find that the resulting energy eigenvalues are consistent with those obtained through previous analytical methods and experimental data. Additionally, we compute the thermodynamic properties of quarkonium particles, including mean energy, specific heat, free energy, and entropy. Furthermore, we investigate the effects of temperature and the dimensional number on meson masses and thermodynamic properties, providing valuable insights into the behavior of meson systems under different conditions.
Determinants of Longitudinal Changes in Exercise Capacity in Patients With Independent Functioning on Hemodialysis
Authors: Usui Naoto , Nakata Junichiro , Uehata Akimi , Kojima Sho , Hisadome Hideki , Inatsu Akihito , Tsubaki Atsuhiro , Saitoh Masakazu , Ando Shuji , Kitayama Tatsuro , Maikusa Kenta , Nishiyama Yuki , Suzuki Yusuke
Published: October 2024

Objective

Patients with chronic kidney disease reportedly have decreased muscle oxygen utilization, which most substantially decreases exercise capacity, followed by cardiac reserve. However, determinants of longitudinal changes in exercise capacity in patients on hemodialysis (HD) and the effects of long-term exercise interventions (EI) are unknown. This study was conducted to clarify these concerns.

Methods

This was a prospective cohort study. Patients on HD that were not hospitalized were followed from baseline up to 2 years, and cardiopulmonary exercise testing results, including peak oxygen uptake, peak work rate, heart rate reserve, and ventilatory equivalent for carbon dioxide slope, as well as implementation of EI were assessed. Based on the 2-year change in peak oxygen uptake, they were divided into improvement or declined groups.

Results

Forty-five patients who were not hospitalized completed the follow-up were analyzed. In the improvement group, the variation was determined by an increase in peak work rate, which is a peripheral factor (partial regression coefficient 0.08 [95% CI = 0.01 to 0.16]), while in the decline group, the variation was determined by a decrease in the ventilatory equivalent for carbon dioxide slope, which is a cardiac factor (partial regression coefficient = −0.12; 95% CI = −0.21 to −0.03). Moreover, exercise intervention was associated with the change in peak oxygen uptake (partial regression coefficient = 3.09; 95% CI = 1.45 to 4.72).

Conclusion

Exercise intolerance even in patients on HD that were not hospitalized and stable progressed over time with deterioration of cardiac reserve, whereas EI were associated with improved exercise capacity through enhanced peripheral function.

Impact

The results support the early measurement of cardiopulmonary or skeletal muscle reserve through cardiopulmonary exercise testing and the implementation of long-term EI based on the measurement results to address the potential deterioration in exercise capacity associated with reduced cardiac reserve, even in patients on HD that are asymptomatic and stable.
Deucravacitinib, a selective, TYK2 inhibitor, in psoriatic arthritis: achievement of minimal disease activity components in a phase 2 trial
Authors: Kavanaugh Arthur , Coates Laura C , Mease Philip J , Nowak Miroslawa , Hippeli Lauren , Lehman Thomas , Banerjee Subhashis , Merola Joseph F
Published: October 2024

Objectives

Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor belonging to a distinct class of enzyme inhibitors. In a phase 2 trial in psoriatic arthritis (NCT03881059), deucravacitinib was significantly more efficacious than placebo across multiple endpoints, including achieving minimal disease activity (MDA). This post hoc analysis further evaluated the achievement of individual components of the MDA criteria with deucravacitinib treatment and the time course of responses in the phase 2 trial.

Methods

Patients (N = 203) were randomized 1:1:1 to once daily treatment with placebo, deucravacitinib 6 mg or deucravacitinib 12 mg. The proportions of patients achieving MDA and each of the seven individual MDA components through week 16 were assessed.

Results

At baseline, although some patients met criteria for individual MDA components, none of the patients met the composite MDA criterion, and all components were balanced overall across treatment arms. Treatment with deucravacitinib was associated with a numerically greater mean reduction from baseline in all MDA components vs placebo over 16 weeks of treatment. At week 16, a greater percentage of patients treated with either dose of deucravacitinib vs placebo achieved the threshold criteria for meeting MDA in each of the components.

Conclusions

More patients treated with deucravacitinib met each of the MDA components vs placebo, along with a higher rate of MDA response, after 16 weeks of treatment.
Rationale and Challenges for a New Instrument for Remote Measurement of Negative Symptoms
Authors: Daniel David Gordon , Cohen Alex S , Harvey Philip D , Velligan Dawn I , Potter William Z , Horan William P , Moore Raeanne C , Marder Stephen R
Published: October 2024

There is a broad consensus that the commonly used clinician-administered rating scales for assessment of negative symptoms share significant limitations, including (1) reliance upon accurate self-report and recall from the patient and caregiver; (2) potential for sampling bias and thus being unrepresentative of daily-life experiences; (3) subjectivity of the symptom scoring process and limited sensitivity to change. These limitations led a work group from the International Society of CNS Clinical Trials and Methodology (ISCTM) to initiate the development of a multimodal negative symptom instrument. Experts from academia and industry reviewed the current methods of assessing the domains of negative symptoms including diminished (1) affect; (2) sociality; (3) verbal communication; (4) goal-directed behavior; and (5) Hedonic drives. For each domain, they documented the limitations of the current methods and recommended new approaches that could potentially be included in a multimodal instrument. The recommended methods for assessing negative symptoms included ecological momentary assessment (EMA), in which the patient self-reports their condition upon receipt of periodic prompts from a smartphone or other device during their daily routine; and direct inference of negative symptoms through detection and analysis of the patient’s voice, appearance or activity from audio/visual or sensor-based (eg, global positioning systems, actigraphy) recordings captured by the patient’s smartphone or other device. The process for developing an instrument could resemble the NIMH MATRICS process that was used to develop a battery for measuring cognition in schizophrenia. Although the EMA and other digital measures for negative symptoms are at relatively early stages of development/maturity and development of such an instrument faces substantial challenges, none of them are insurmountable.
Donor country official development assistance in health R&D: domestic economic burden vs. medical disseminative capacity
Authors: Williams Christopher
Published: October 2024

This study examines domestic determinants of donor country official development assistance (ODA) in health research and development (R&D). It argues that health R&D ODA is negatively related to domestic economic burden, i.e. pressures that donor governments face because of economic issues in their own country, while also positively influenced by long-standing capabilities in medicine and medical research that are projected globally. Using panel data on forty-four donor countries over a 6-year period, the study finds support for a negative relationship between domestic economic burden and donor country health R&D ODA. It also finds a positive relationship between medical disseminative capacity (MDC) and donor country health R&D ODA, as well as with the ratio of health R&D ODA to overall ODA. While domestic economic burden dampens the overall appetite for health R&D ODA, MDC helps to reverse this and ensures that the proportion of ODA that goes to health R&D in developing countries is increased.
Gender Equality Policies “Confined”: Adopted Frames in the Prison System in Spain
Authors: Ballesteros-Pena Ana , Bustelo María
Published: October 2024

The literature on gender and politics has consistently neglected the study of gender inequalities in penal institutions. Our article contributes to filling this gap by examining how gender inequality is represented and framed as a policy problem in the Spanish “Action Program for Gender Equality between Women and Men in the Prison System.” Using critical frame analysis, our findings reveal that gender equality policies in prisons reinforce maternal and caregiving roles, emphasize personal dependency and low self-esteem, and characterize women prisoners as “defective subjects” and “victims,” without adopting an intersectional approach. Our main argument is that the prison system’s failure to embrace the exchange of ideas, involve diverse actors, and engage with civil society, particularly feminist and women’s movements, constrains the formulation process of gender equality policies in this area, and also influences understandings of the issues and the proposed solutions.