bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of suppressing inflammation by tofacitinib may simultaneously improve glycaemic parameters and inflammatory markers in rheumatoid arthritis patients with comorbid type 2 diabetes: a proof-of-concept, open, prospective, clinical study
Authors: Di Muzio Claudia , Di Cola Ilenia , Shariat Panahi Azadeh , Ursini Francesco , Iagnocco Annamaria , Giacomelli Roberto , Cipriani Paola , Ruscitti Piero
Published: January 2024

Background

A consistent connection has been increasingly reported between rheumatoid arthritis (RA), insulin resistance (IR), and type 2 diabetes (T2D). The β-cell apoptosis induced by pro-inflammatory cytokines, which could be exaggerated in the context of RA, is associated with increased expression pro-apoptotic proteins, which is dependent on JAnus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) activation. On these bases, we aimed to evaluate if the administration of tofacitinib, a potent and selective JAK inhibitor, could simultaneously improve glycaemic parameters and inflammatory markers in patients with RA and comorbid T2D.

Methods

The primary endpoint was the change in the 1998-updated homeostatic model assessment of IR (HOMA2-IR) after 6 months of treatment with tofacitinib in RA patients with T2D. Consecutive RA patients with T2D diagnosis were included in this proof-of-concept, open, prospective, clinical study, which was planned before the recent emergence of safety signals about tofacitinib. Additional endpoints were also assessed regarding RA disease activity and metabolic parameters.

Results

Forty consecutive RA patients with T2D were included (female sex 68.9%, mean age of 63.4 ± 9.9 years). During 6-month follow-up, a progressive reduction of HOMA2-IR was observed in RA patients with T2D treated with tofacitinib. Specifically, a significant effect of tofacitinib was shown on the overall reduction of HOMA2-IR (β =  − 1.1, p = 0.019, 95%CI − 1.5 to − 0.76). Also, HOMA2-β enhanced in these patients highlighting an improvement of insulin sensitivity. Furthermore, although a longer follow-up is required, a trend in glycated haemoglobin reduction was also recorded. The administration of tofacitinib induced an improvement in RA disease activity, and a significant reduction of DAS28-CRP and SDAI was observed; 76.8% of patients achieved a good clinical response. In this study, no major adverse events (AEs) were retrieved without the identification of new safety signals. Specifically, no life-threatening AEs and cardiovascular and/or thromboembolic events were recorded.

Conclusions

The administration of tofacitinib in RA with T2D led to a simultaneous improvement of IR and inflammatory disease activity, inducing a “bidirectional” benefit in these patients. However, further specific designed and powered studies are warranted to entirely evaluate the metabolic effects of tofacitinib in RA patients with T2D.
Manifestation and sociodemographic microdata of Brazil’s Unified Health System Ombudsman
Authors: de Freitas Saldanha Raphael , Kreischer Vinicius , Gritz Raquel , Miloski Matheus , Bonifácio Carmen Lúcia Corrêa , Cardoso Carlos Leonardo Souza , Alves Ariane Camilo Pinheiro , de Sá Domício Aurélio , Gurgel Junior Garibaldi Dantas , Moreira Rafael da Silveira , Fernandez Michelle Vieira , Lima Jefferson da Costa , Pedroso Marcel
Published: January 2024

Objectives

This article presents the process of extraction and treatment of two datasets from the General Ombudsman of the Brazilian Unified Health System (OUVSUS). The resulting datasets allow the analysis of manifestation characteristics and sociodemographic profile of the citizens that performed these manifestations.

Data description

The first dataset depicts the characteristics of the manifestations registered by the General Ombudsman. Each row represents an individual manifestation and contains information such as the registration date, classification, input channel, and subject, among others. The second dataset is constituted of sociodemographic information for each citizen that performed a manifestation, and characteristics such as sexual orientation, race, age, and geographic location of the citizen are presented, among others.
Consensus on relevant psychosocial interventions applied in health institutions to prevent psychological violence at work: Delphi method
Authors: Abregú-Tueros Luis Fidel , Bravo-Esquivel Cinthia Jannete , Abregú-Arroyo Sheyla Karol , Dos Santos-Rosa Roger , Galve-Manzano José Luis
Published: January 2024

Objective

Studies on psychological violence in the workplace (PVW) in Latin America have focused on incidence values. In contrast, studies on preventive interventions (PIs) in the health sector are very limited. Our objective was to determine to what extent there is consensus on the most relevant characteristics of the psychosocial interventions applied in the prevention of PVW in health institutions in Peru. To that end, health professionals with knowledge and experience in PVW at the national level were recruited, and the Delphi consensus technique was applied.

Results

The consensus study was developed in four stages that included three phases of Delphi consultation. In the third consultation phase, 428 experts participated in 25 analysis groups from 66 health institutions in the country. A total of 70.3% of the participants were women, and 27.6% of the participants worked in nursing and emergency services. After the Delphi consensus analysis, we obtained a list of 10 hierarchical psychosocial interventions to prevent PVW in the country. Most notable were interventions based on the prior resolution of interprofessional conflicts, on the visibility of incidents to generate an inverse effect and on experiential training to improve assertive and empathic communication skills.
A new pachypleurosaur (Reptilia: Sauropterygia) from the Middle Triassic of southwestern China and its phylogenetic and biogeographic implications
Authors: Hu Yi-Wei , Li Qiang , Liu Jun
Published: January 2024

After the devastating Permo-Triassic Mass Extinction, several new groups of large reptilian predators invaded the sea in the early part of the Triassic. Among these predators, sauropterygians, consisting of placodonts, pachypleurosaurs, nothosaurs and pistosaurs (including the iconic plesiosaurs), displayed the greatest diversity at both the generic and species levels, and persisted from the Early Triassic to the Late Cretaceous. Here, we report a new species of Pachypleurosauria, Dianmeisaurus mutaensis sp. nov., from a recently discovered Lagerstätte in the Upper Member of the Anisian Guanling Formation. The only known specimen of the new species was collected from a quarry near Muta village, Luxi County, Yunnan Province, South China. Our new phylogenetic analysis based on a novel data matrix recovered the new taxon as a sister group to Dianmeisaurus gracilis—a small pachypleurosaur from the Middle Triassic Luoping biota. The new phylogenetic analysis also collapsed the monophyly of the traditionally recognized Eusauropterygia. Pistosauroidea, Majiashanosaurus, and Hanosaurus comprise the consecutive sister groups to a new clade including Pachypleurosauria and Nothosauroidea. A monophyletic Pachypleurosauria, within which the clade consisting of Dianmeisaurus and Panzhousaurus occupies the basal-most position, is recovered by this study. The clade consisting of Dawazisaurus and Dianopachysaurus forms the sister group to the remaining pachypleurosaurs included in this study. Since Dianmeisaurus, Panzhousaurus, Dawazisaurus, and Dianopachysaurus are all exclusively known from South China, our study provides further evidence to the hypothesis that pachypleurosaurs had a palaeobiogeographic origin in the eastern Tethys.

ZooBank LSID: urn:lsid:zoobank.org:pub:83D12411-9189-4313-A8F0-27AF61BDA51E.
Effects of isoflurane anaesthesia depth and duration on renal function measured with [99mTc]Tc-mercaptoacetyltriglycine SPECT in mice
Authors: Schmitz-Peiffer Fabian , Lukas Mathias , Mohan Ajay-Mohan , Albrecht Jakob , Aschenbach Jörg R. , Brenner Winfried , Beindorff Nicola
Published: January 2024

Background

The influence of anaesthetic depth and the potential influence of different anaesthetic beds and thus different handling procedures were investigated in 86 severe combined immunodeficient (SCID) mice using semi-stationary dynamic single photon emission computed tomography (SPECT) for kidney scintigraphy. Therefore, isoflurane concentrations were adjusted using respiratory rate for low (80–90 breath/min) and deep anaesthesia (40–45 breath/min). At low anaesthesia, we additionally tested the influence of single bed versus 3-mouse bed hotel; the hotel mice were anaesthetized consecutively at ~ 30, 20, and 10 min before tracer injections for positions 1, 2, and 3, respectively. Intravenous [99mTc]Tc-MAG3 injection of ~ 28 MBq was performed after SPECT start. Time-activity curves were used to calculate time-to-peak (Tmax), T50 (50% clearance) and T25 (75% clearance).

Results

Low and deep anaesthesia corresponded to median isoflurane concentrations of 1.3% and 1.5%, respectively, with no significant differences in heart rate (p = 0.74). Low anaesthesia resulted in shorter aortic blood clearance half-life (p = 0.091) and increased relative renal tracer influx rate (p = 0.018). A tendency toward earlier Tmax occurred under low anaesthesia (p = 0.063) with no differences in T50 (p = 0.40) and T25 (p = 0.24). Variance increased with deep anaesthesia. Compared to single mouse scans, hotel mice in position 1 showed a delayed Tmax, T50, and T25 (p < 0.05 each). Furthermore, hotel mice in position 1 showed delayed Tmax versus position 3, and delayed T50 and T25 versus position 2 and 3 (p < 0.05 each). No difference occurred between single bed and positions 2 (p = 1.0) and 3 (p = 1.0).

Conclusions

Deep anaesthesia and prolonged low anaesthesia should be avoided during renal scintigraphy because they result in prolonged blood clearance half-life, delayed renal influx and/or later Tmax. Vice versa, low anaesthesia with high respiratory rates of 80–90 rpm and short duration (≤ 20 min) should be preferred to obtain representative data with low variance.
Factors influencing HPV vaccine implementation in South Asia: a scoping review protocol
Authors: Rajkhowa Priyobrat , Pundir Prachi , Dsouza Sherize Merlin , Patil Divya Sussana , Narayanan Prakash , Brand Helmut
Published: January 2024

Introduction

The HPV vaccine is characterized by its significant effectiveness in preventing the occurrence of cervical cancer. However, the South Asian countries face multiple challenges in implementing the human papillomavirus vaccine (HPV) at scale. Implementation of human papillomavirus vaccination for eliminating cervical cancer necessitates investigating the factors that impact the health system of these nations. Hence, this review will map the evidence on factors influencing the scaling up of human papillomavirus vaccination in South Asia.

Methods

The proposed scoping review will follow the steps given by Arksey and O’Malley and Levac et al. The search approach will follow McGowan et al. (14) evidence-based manual for Peer Analysis of Electronic Search Strategies (PRESS 2015) for systematic searches. Using a comprehensive search, the literature from 2006 onward will be identified from PubMed, CINAHL, EMBASE, Web of Science, and Scopus. The search strategy will include terms relating to the HPV vaccine and implementation. A predefined criterion for the inclusion and exclusion of studies will be adopted by three review authors independently to determine the eligible studies. The results will be narratively synthesized and examined in addition to being quantitatively presented to provide an outline. The review will be presented per the “Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR)” guidelines.

Conclusions/discussion

The evaluation is anticipated to map the barriers and enablers influencing the rollout of the human papillomavirus vaccine. Lessons learned from the South Asian countries, where the vaccine has been implemented, may contribute to aiding the implementation of the vaccine in countries with similar health systems in an effective manner.

Systematic review registration

The protocol was prospectively registered on the “open science framework”. The registration DOI is https://doi.org/10.17605/OSF.IO/T5SW9.
The effects of apoptosis inhibitor of macrophage in kidney diseases
Authors: Cao Yixia , Hu Boyan , Fan Yunhe , Wang Wei , Chi Mingxuan , Nasser Moussa Ide , Ma Kuai , Liu Chi
Published: January 2024

Kidney disease is a progressive and irreversible condition in which immunity is a contributing factor that endangers human health. It is widely acknowledged that macrophages play a significant role in developing and causing numerous kidney diseases. The increasing focus on the mechanism by which macrophages express apoptosis inhibitor of macrophages (AIM) in renal diseases has been observed. AIM is an apoptosis inhibitor that stops different things that cause apoptosis from working. This keeps AIM-bound cell types alive. Notably, the maintenance of immune cell viability regulates immunity. As our investigation progressed, we concluded that AIM has two sides when it comes to renal diseases. AIM can modulate renal phagocytosis, expedite the elimination of renal tubular cell fragments, and mitigate tissue injury. AIM can additionally exacerbate the development of renal fibrosis and kidney disease by prolonging inflammation. IgA nephropathy (IgAN) may also worsen faster if more protein is in the urine. This is because IgA and immunoglobulin M are found together and expressed. In the review, we provide a comprehensive overview of prior research and concentrate on the impacts of AIM on diverse subcategories of nephropathies. We discovered that AIM is closely associated with renal diseases by playing a positive or negative role in the onset, progression, or cure of kidney disease. AIM is thus a potentially effective therapeutic target for kidney diseases.
Uncertainty about interest rates and crude oil prices
Authors: Qadan Mahmoud , Cohen Gil
Published: January 2024

The yield on the 10-year U.S. Treasury Note is among the most cited interest rates by investors, policymakers, and financial institutions. We show that the 10-year Treasury yield’s forward-looking volatility, a VIX-style measure that is a proxy for uncertainty about future interest rates, is a useful state variable capable of predicting the returns and volatility of crude oil prices over the near term. Using monthly data from 2003 to 2020, we document that higher implied volatility in the 10-year U.S. Treasury derivatives market predicts declining oil prices and higher forward-looking volatility in those prices. Our results are robust to different subsamples and various empirical designs.
The Tardive Dyskinesia Impact Scale (TDIS), a novel patient-reported outcome measure in tardive dyskinesia: development and psychometric validation
Authors: Farber Robert H. , Stull Donald E. , Witherspoon Brooke , Evans Christopher J. , Yonan Charles , Bron Morgan , Dhanda Rahul , Jen Eric , Brien Christopher O.’
Published: January 2024

Background

Tardive dyskinesia (TD), a movement disorder in which patients experience abnormal involuntary movements, can have profound negative impacts on physical, cognitive, and psychosocial functioning. The Abnormal Involuntary Movement Scale (AIMS), a clinician-rated outcome, is considered the gold standard for evaluating treatment efficacy in TD clinical trials. However, it provides little information about the impacts of uncontrolled movements from a patient perspective and can be cumbersome to administer in clinical settings. The Tardive Dyskinesia Impact Scale (TDIS) was developed as a patient-reported outcome measure to fulfill the need for a disease-specific impact assessment in TD. The objective of the present study was to develop and evaluate the psychometric properties of the TDIS to determine whether it is fit-for-purpose to measure TD impact.

Methods

Data from qualitative studies and phase 3 trials of a VMAT2 inhibitor for the treatment of TD (KINECT3 and KINECT4) were used to determine the psychometric properties of the TDIS. Qualitative research included concept elicitation and cognitive debriefing interviews with TD patients and their caregivers in order to assess how well the TDIS captured key domains of TD impact. Quantitative analyses to examine the psychometric properties of the TDIS included assessing construct validity (factor structure, known groups, and predictive validity) and responsiveness to change.

Results

Qualitative results showed that the TDIS captures the key TD impacts reported by patients and caregivers and that the TDIS was interpreted as intended and relevant to patients’ experiences. Quantitative results found evidence of 2 underlying domains of the TDIS: physical and socioemotional (Comparative Fit Index > 0.9). Known groups and predictive validity indicated that, compared with the AIMS, the TDIS captures unique content (correlation between AIMS and TDIS = 0.2–0.28). The TDIS showed responsiveness to change in treatment, with TDIS scores improving over 48 weeks in the 2 phase 3 trials.

Conclusions

The TDIS captures relevant information about the impact of TD and is easily administered in a clinician’s office or patient’s home. It may be used longitudinally to show changes in TD burden over time. The TDIS complements the AIMS; using these assessments together provides a more holistic assessment of TD.
Influence of fall armyworm Spodoptera frugiperda egg mass scales and layers on the performance of three species of egg parasitoid Trichogramma with different ovipositor lengths
Authors: Navik Omprakash , Dsilva Lerissa Sweety , Patil Jagadeesh , Sushil S. N.
Published: January 2024

Background

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is a highly polyphagous and destructive pest of maize and other cereal crops. Biological control is a potential alternative to chemical insecticides used for the management of FAW in maize. Egg parasitoids are promising biocontrol agents as they kill the insect pest at their egg stage before it hatches, thus preventing the damaging larval stage. Trichogramma is widely used in augmentative biological control of FAW in native and invaded regions. However, FAW lay egg masses in layer by layer and eggs are covered with egg scales, this may affect the performance of Trichogramma parasitoids. Therefore, the parasitism potential of three Trichogramma species was studied on eggs with or without scales and layered eggs of FAW, further the impact of parasitoids ovipositor length on parasitism was also determined. This helps to understand the parasitism potential of parasitoids on different egg type for better implementation of biological control programs against FAW.

Results

The effect of FAW egg mass with or without scales and layered eggs on the performance of Trichogramma chilonis, T. pretiosum and T. mwanzai was studied and results indicated that egg mass scales and the layered eggs were significantly affected the parasitism potential of Trichogramma species, but did not affect the parasitoid emergence. In general, T. chilonis parasitized a higher percentage of eggs with or without scales and layered eggs of FAW than the other two species. T. chilonis and T. mwanzai had a greater ovipositor length than T. pretiosum.

Conclusion

The performance of evaluated Trichogramma species on FAW eggs with or without scales and layered eggs affected the parasitism success. The parasitism success of T. chilonis was comparably higher than other tested species. Hence, the scales on egg masses and layered eggs of FAW should be taken into account while selecting the Trichogramma species in the biological control of FAW.
Nutritional composition and mineral profile of leaves of Moringa oleifera provenances grown in Gaborone, Botswana
Authors: Masitlha Eng P. , Seifu Eyassu , Teketay Demel
Published: January 2024

Although Moringa is an important vegetable crop elsewhere, its nutritional and non-food uses are not widely known in Botswana community. This study was conducted to determine the chemical composition and mineral contents of leaves of Moringa oleifera trees grown in Gaborone, Botswana. The leaf samples were collected from Moringa trees grown in the backyards of six different households in Gaborone city. They were dried separately at 55 ºC for 24 h and then ground to obtain a powder for analysis. The data on the proximate composition of the Moringa samples were subjected to Analysis of Variance to determine statistical differences among the mean values. The overall mean values of moisture, fat, protein, ash, fiber and total available carbohydrates of the leaves were 6.93 ± 0.16, 7.78 ± 0.13, 27.1 ± 0.43, 7.34 ± 0.31, 9.1 ± 1 and 46.5 ± 3%, respectively. The Moringa leaves contained average values of 520 ± 96.0, 7.7 ± 1.3, 30.1 ± 15.5, 0.8 ± 0.1, 82.6 ± 6.4, 1.7 ± 0.2, 1.6 ± 0.2 and 0.02 ± 0.00 mg/100g of Calcium, Iron, Sodium, Zinc, Magnesium, Aluminum, Manganese and Chromium, respectively. Significant differences were observed for moisture, fat, protein and ash contents among the six Moringa samples. The results showed that the leaves are rich in nutrients, particularly with high amounts of protein and ash. This suggests that Moringa leaf could serve as an important protein and mineral supplement in the diet and can be consumed as a vegetable in Botswana. The difference in composition observed between the Moringa leaf samples suggests a possible genotypic difference between the Moringa trees used in this experiment. Thus, there is a need for further study to verify this.

Graphical Abstract
Machine learning-driven optimization of enterprise resource planning (ERP) systems: a comprehensive review
Authors: Jawad Zainab Nadhim , Balázs Villányi
Published: January 2024

In the dynamic and changing realm of technology and business operations, staying abreast of recent trends is paramount. This review evaluates the progress in the development of the integration of machine learning (ML) with enterprise resource planning (ERP) systems, revealing the impact of these trends on the ERP optimization. In recent years, there has been a significant advancement in the integration of ML technology within ERP environments. ML algorithms characterized by their ability to extract intricate patterns from vast datasets are being harnessed to enable ERP systems to make more accurate predictions and data-driven decisions. Therefore, ML enables ERP systems to adapt dynamically based on real-time insights, resulting in enhanced efficiency and adaptability. Furthermore, organizations are increasingly looking for artificial intelligence (AI) solutions as they actually try to make ML models within ERP clear and comprehensible for stakeholders. These solutions enable ERP systems to process and act on data as it flows in, due to the utilization of ML models, which enables enterprises to react effectively to changing circumstances. The rapid insights and useful intelligence offered by this trend have had a significant impact across industries. IoT (Internet of Things) and ML integration with ERP are continuously gaining significance. These algorithms allow for the creation of adaptable strategies supported by ongoing learning and data-driven optimization, which has a number of benefits for ERP system optimization. In addition, the Industrial Internet of Things (IIoT) was investigated in this review to provide the state-of-the-art and emerging challenges due to ML integration. This review provides a comprehensive analysis of the integration of machine learning algorithms across several ERP applications by conducting an extensive literature assessment of recent publications. By synthesizing the latest research findings, this comprehensive review provides an in-depth analysis of the cutting-edge techniques and recent advancements in the context of machine learning (ML)-driven optimization of enterprise resource planning (ERP) systems. It not only provides an insight into the methodology and impact of the state-of-the-art but also offers valuable insights into where the future of ML in ERP may lead, propelling ERP systems into a new era of intelligence, efficiency, and innovation.
Nanocrystals: an emerging paradigm for cancer therapeutics
Authors: Patel Ayush , Patel Krishi , Patel Viral , Rajput Mithun Singh , Patel Ravish , Rajput Amarjitsing
Published: January 2024

Background

Medical fraternity are continuously pitching toward the development of novel mechanisms to combat the menace of cancer and to enhance the efficacy of prevailing molecules. During the drug development phase, majority of new molecular entity pose a threat due to hydrophobic nature, that compromises its bioavailability upon administration. These suboptimal accumulation and low drug loading hampers the clinical translation in cancer therapy.

Main body of abstract

Nanotechnology with valuable advantages create possibilities to accelerate the efficacy of treatment. Compared to matrix-based formulations, drug nanocrystals (NCs) with smaller size, high drug loading, high active targeting, extended circulation, great structural stability, tailored dissolution, and being carrier free have sparked a lot of interest in drug delivery. Many hydrophobic drugs were explored as drug NCs such as—doxorubicin, paclitaxel, campothecin and so on. However, premature leakage and clearance by mononuclear phagocytosis system lead to some great obstacles in the clinical applications of drug NCs.

Conclusion

In the recent years, strategies leading to surface modification are applied to improve uncontrolled drug release and targeting efficiency to tumor cells. The current review sheds light on various properties of drug nanocrystals, brief insights on its fabricating techniques, approaches for tumor targeting with NCs, and their applications in cancer imaging and therapeutics.
Wavefield simulation and reverse time migration for acoustic TTI media
Authors: Zhang Yi , Stovas Alexey , De Siena Luca
Published: January 2024

Seismic imaging necessitates precisely separating P and S waves to mitigate undesirable crosstalk between them. Failure to properly handle this crosstalk can lead to distorted or misinterpreted images. In an elastic anisotropic medium, the polarization of a P wave is not necessarily parallel to its propagating direction, making the separation of P and S waves more difficult than in the case of an elastic isotropic medium. A pure acoustic transversely isotropic (TI) wave equation involves a mixed-domain problem. This usually means the space dependencies and wavenumbers are coupled in the wavefield extrapolator. An efficient solution to the wavefield requires a separation between the space dependencies and wavenumbers in the extrapolator. There are two primary approaches: (1) an analytical separation of the mixed-domain term; and (2) a numerical solution to the mixed-domain term, such as low-rank and Poynting vector methods. In this study, the acoustic approximation is derived by setting the S-wave phase velocity to zero in all phase directions. An analytical separation is developed in this study by employing a Taylor series to linearize the anellipticity term, thereby decoupling the space-dependent and wavenumber-dependent variables within the wavefield extrapolator. The kinematics analysis demonstrates that our method has competitive phase velocity accuracy compared with existing methods. Moreover, the corresponding TI acoustic wave equation can be efficiently solved by the hybrid finite-difference/pseudospectral method. In a 2D case, it only requires one fast Fourier transform, two inverse Fourier transforms, and a few additional spatial differentiations at each time step. Remarkably, our wavefield solution remains independent of the wavefield heterogeneity (as observed in the low-rank approach) and is immune to wavefield interference (as encountered in the Poynting vector method). The developed acoustic approximation ensures the absence of any S-wave artifacts with relatively cheap computation. Numerical examples indicate our acoustic tilted transversely isotropic wave equation is reliable for accurate wavefield modeling and reverse time migration.
An exploratory study of psychosis risk factors in individuals who are referred but do not meet criteria for an early intervention in psychosis service
Authors: Naughton Sean , Brady Aoife , Geary Eoin , Counihan Eimear , Clarke Mary
Published: January 2024

Background

The ‘at-risk mental state’ (ARMS) for psychosis has been critiqued for its limited prognostic ability and identification of a limited proportion of those who will develop a first episode of psychosis (FEP). Broadening the search for high-risk groups is key to improving population-level ascertainment of psychosis risk.

Aims

To explore risk enrichment in diagnostic, demographic and socio-functional domains among individuals referred to an early intervention in psychosis (EIP) service not meeting ARMS or FEP criteria.

Method

A retrospective file review of 16 years of referrals to a tertiary EIP service in Ireland was undertaken. Diagnostic outcomes from standardised assessments (Structured Clinical Interview for DSM), demographic (age, gender, family history, nationality) and socio-occupational (relationship status, living status, working status) variables were compiled for those not meeting criteria. These were compared with individuals diagnosed with an FEP in the same period.

Results

From 2005 to 2021 inclusive, of 2025 index assessments, 27.6% (n = 558) did not meet either FEP or ARMS criteria, which is notably higher than the 5.4% (n = 110) meeting ARMS criteria. This group had high psychiatric morbidity, with 65.4% meeting criteria for at least one DSM Axis I disorder. Depressive, anxiety and substance use disorders predominated. Their functional markers were poor, and comparable to the FEP cohort.

Conclusions

This group is enriched for psychosis risk factors. They are a larger group than those meeting ARMS criteria, a finding that may reflect EIP service configuration. They may be an important focus for further study in the search for at-risk populations beyond the current ARMS model.
The role of cognitive reserve and clinical symptoms in the association between genetic liability for educational attainment and functioning in first-episode psychosis: A mediation analysis
Authors: Clougher Derek , Segura Àlex G. , Forte Maria F. , Mezquida Gisela , Cuesta Manuel J. , Vieta Eduard , Amoretti Silvia , Lobo Antonio , González-Pinto Ana , Díaz-Caneja Covadonga M. , Roldán Alexandra , Fico Giovanna , de la Serna Elena , Bergé Daniel , Gassó Patricia , Rodriguez Natalia , Verdolini Norma , Tortorella Alfonso , Menculini Giulia , Ribasés Marta , Bernardo Miguel , Mas Sergi ,   PEPs Group
Published: January 2024

Background

Polygenic risk scores for educational attainment (PRSEA), cognitive reserve (CR), and clinical symptoms are associated with functioning in first-episode psychosis (FEP). Nevertheless, the mechanisms underlying their complex interaction are yet to be explored. This study assessed the mediating role of CR and clinical symptoms, both negative (NS) and positive (PS), on the interrelationship between PRSEA and functionality, one year after a FEP.

Methods

A total of 162 FEP patients underwent clinical, functional, and genetic assessments. Using genome-wide association study summary results, PRSEA were constructed for each individual. Two mediation models were performed. The parallel mediation model explored the relationship of PRSEA with functionality through CR and clinical symptoms. The serial mediation model tested a causal chain of the three mediators: CR, NS, and PS. Mediation analysis was performed using the PROCESS function V.4.1 in SPSS V.22.

Results

A serial mediation model revealed a causal chain for PRSEA > CR > NS > Functionality (β = −0.35, 95%CI [−0.85, −0.04], p < 0.05). The model fit the data satisfactorily (CFI = 1.00; RMSEA = 0.00; SRMR = 7.2 × 10−7). Conversely, no parallel mediation was found between the three mediators, PRSEA and functionality and the model poorly fit the data (CFI = 0.30; RMSEA = 0.25; SRMR = 0.11).

Conclusions

Both CR and NS mediate the relationship between PRSEA and functionality at one-year follow-up, using serial mediation analysis. This may be relevant for prevention and personalized early intervention to reduce illness impact and improve functional outcomes in FEP patients.
Radiographic Progression-Free Survival and Clinical Progression-Free Survival as Potential Surrogates for Overall Survival in Men With Metastatic Hormone-Sensitive Prostate Cancer
Authors: Halabi Susan , Roy Akash , Rydzewska Larysa , Guo Siyuan , Godolphin Peter , Hussain Maha , Tangen Catherine , Thompson Ian , Xie Wanling , Carducci Michael A. , Smith Matthew R. , Morris Michael J. , Gravis Gwenaelle , Dearnaley David P. , Verhagen Paul , Goto Takayuki , James Nick , Buyse Marc E. , Tierney Jayne F. , Sweeney Christopher ,   on behalf of the STOPCAP/ICECaP Collaboration
Published: January 2024

PURPOSE

Despite major increases in the longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC), most men still die of prostate cancer. Phase III trials assessing new therapies in mHSPC with overall survival (OS) as the primary end point will take approximately a decade to complete. We investigated whether radiographic progression-free survival (rPFS) and clinical PFS (cPFS) are valid surrogates for OS in men with mHSPC and could potentially be used to expedite future phase III clinical trials.

METHODS

We obtained individual patient data (IPD) from 9 eligible randomized trials comparing treatment regimens (different androgen deprivation therapy [ADT] strategies or ADT plus docetaxel in the control or research arms) in mHSPC. rPFS was defined as the time from random assignment to radiographic progression or death from any cause whichever occurred first; cPFS was defined as the time from random assignment to the date of radiographic progression, symptoms, initiation of new treatment, or death, whichever occurred first. We implemented a two-stage meta-analytic validation model where conditions of patient-level and trial-level surrogacy had to be met. We then computed the surrogate threshold effect (STE).

RESULTS

IPD from 6,390 patients randomly assigned from 1994 to 2012 from 13 units were pooled for a stratified analysis. The median OS, rPFS, and cPFS were 4.3 (95% CI, 4.2 to 4.5), 2.4 (95% CI, 2.3 to 2.5), and 2.3 years (95% CI, 2.2 to 2.4), respectively. The STEs were 0.80 and 0.81 for rPFS and cPFS end points, respectively.

CONCLUSION

Both rPFS and cPFS appear to be promising surrogate end points for OS. The STE of 0.80 or higher makes it viable for either rPFS or cPFS to be used as the primary end point that is surrogate for OS in phase III mHSPC trials with testosterone suppression alone as the backbone therapy and would expedite trial conduct.
Access to Financial Assistance Programs and Their Impact on Overall Spending on Oral Anticancer Medications at an Integrated Specialty Pharmacy
Authors: Ragavan Meera V. , Swartz Scott , Clark Mackenzie , Lo Mimi , Gupta Arjun , Chino Fumiko , Lin Tracy Kuo
Published: January 2024

PURPOSE

Financial assistance (FA) programs are increasingly used to help patients afford oral anticancer medications (OAMs), but access to such programs and their impact on out-of-pocket (OOP) spending has not been well explored. This study aimed to (1) characterize the impact of receipt of FA on both OOP spending and likelihood of catastrophic spending on OAMs and (2) evaluate racial/ethnic disparities in access to FA programs.

METHODS

Patients with a cancer diagnosis prescribed an OAM anytime between January 1, 2021, and December 31, 2021 were included in this retrospective, single-center study at an integrated specialty pharmacy affiliated with a tertiary academic cancer center. Fixed-effect regression models were used to characterize the impact of receipt of FA on overall spending and likelihood of catastrophic spending on OAMs, as well as explore the association of race/ethnicity with receipt of FA.

RESULTS

Across 1,186 patients prescribed an OAM, 37% received FA. Receipt of FA was associated with lower annual spending on OAMs (β = –$1,236 US dollars [USD; 95% CI, –$1,841 to –$658], P < .001) but not reduced risk of catastrophic spending (odds ratio [OR], 0.442 [95% CI, 0.755 to 3.199], P = .23). Non-White patients (OR, 0.60 [95% CI, 0.43 to 0.85], P = .004) and patients who spoke English as a second language (OR, 0.46 [95% CI, 0.23 to 0.90], P = .02) were less likely to receive FA compared with White and English-speaking patients, respectively.

CONCLUSION

FA programs can mitigate high OOP spending but not for patients who spend at catastrophic levels. There are racial/ethnic and language disparities in access to such programs. Future studies should evaluate access to FA programs across diverse delivery settings.
Handling Incomplete or Late-Onset Toxicities in Early-Phase Dose-Finding Clinical Trials: Current Practice and Future Prospects
Authors: Yin Zhulin , Mander Adrian P. , de Bono Johann S. , Zheng Haiyan , Yap Christina
Published: January 2024

PURPOSE

The way late-onset toxicities are managed can affect trial outcomes and participant safety. Specifically, participants often might not have completed their entire follow-up period to observe any toxicities before new participants would be recruited. We conducted a methodological review of published early-phase dose-finding clinical trials that used designs accounting for partial and complete toxicity information, aiming to understand (1) how such designs were implemented and reported and (2) if sufficient information was provided to enable the replicability of trial results.

METHODS

Until March 26, 2023, we identified 141 trials using the rolling 6 design, the time-to-event continuous reassessment method (TITE-CRM), the TITE-CRM with cycle information, the TITE Bayesian optimal interval design, the TITE cumulative cohort design, and the rapid enrollment design. Clinical settings, design parameters, practical considerations, and dose-limiting toxicity (DLT) information were extracted from these published trials.

RESULTS

The TITE-CRM (61, 43.3%) and the rolling 6 design (76, 53.9%) were most frequently implemented in practice. Trials using the TITE-CRM had longer DLT assessment windows beyond the first cycle compared with the rolling 6 design (52.5% v 6.6%). Most trials implementing the TITE-CRM (91.8%, 56 of 61) failed to describe essential parameters in the protocols or the study result papers. Only five TITE-CRM trials (8.2%, 5 of 61) reported sufficient information to enable replication of the final analysis.

CONCLUSION

When compared with trials using the rolling 6 design, those implementing the TITE-CRM design exhibited notable deficiencies in reporting essential details necessary for reproducibility. Inadequate reporting quality of advanced model-based trial designs hinders their credibility. We provide recommendations that can improve transparency, reproducibility, and accurate interpretation of the results for such designs.
Force model in the penetration by impact into confined granular media
Authors: Seguin A.
Published: January 2024

We study analytically the influence of lateral confinement on the penetration depth of a sphere into a granular medium by impact. The granular medium is contained in a cylindrical tank of diameter D and a sphere of diameter d plunges along its axis. The presence of side walls, parametrized by the distance

between the walls and the sphere, influences the penetration depth. Here, we deploy a continuous analytical model to account for the presence of side walls. After solving and calibrating this model for an infinite medium

, we show that it is possible to extend this model without any additional parameters to account for lateral confinement. The influence of side walls is modelled by an exponential effect, which modifies the sphere's penetration dynamics. The solution of the model is shown to be in agreement with experimental results.
Salivary Cortisol and Cortisone Can Circumvent Confounding Effects of Oral Contraceptives in the Short Synacthen Test
Authors: Bäcklund Nils , Lundstedt Staffan , Tornevi Andreas , Wihlbäck Anna-Carin , Olsson Tommy , Dahlqvist Per , Brattsand Göran
Published: January 2024

Context

Adrenal insufficiency (AI) is usually diagnosed by low plasma cortisol levels following a short Synacthen test (SST). Most plasma cortisol is bound to corticosteroid-binding globulin, which is increased by estrogen in combined estrogen-progestin oral contraceptives (COCs). Women with AI using COCs are therefore at risk of having an apparently normal plasma cortisol level during SST, which would not adequately reflect AI.

Objective

This work aimed to test whether salivary cortisol or cortisone during SST is more robust against the COC effect and to calculate the lower reference limits (LRLs) for these to be used as tentative diagnostic cutoffs to exclude AI.

Methods

Forty-one healthy women on COCs and 46 healthy women without exogenous estrogens underwent an SST with collection of plasma and salivary samples at 0, 30, and 60 minutes after Synacthen injection. The groups were compared using regression analysis with age as covariate and the LRLs were calculated parametrically.

Results

SST-stimulated plasma cortisol levels were significantly higher in the COC group vs controls, while mean salivary cortisol and cortisone levels were slightly lower in the COC group. Importantly, COC use did not significantly alter LRLs for salivary cortisol or cortisone. The smallest LRL difference between groups was seen for salivary cortisone.

Conclusion

Salivary cortisol and especially salivary cortisone are considerably less affected by COC use than plasma cortisol during SST. Due to similar LRLs, a common cutoff for salivary cortisol and cortisone during SST can be used to exclude AI in premenopausal women irrespective of COC use.
Preconception Stress and Pregnancy Serum Glucose Levels Among Women Attending a Fertility Center
Authors: Mínguez-Alarcón Lidia , Chagnon Olivia , Tanaka Aya , Williams Paige L , James-Todd Tamarra , Ford Jennifer B , Souter Irene , Rexrode Kathryn M , Hauser Russ , Chavarro Jorge E
Published: January 2024

Context

The association between women's stress and pregnancy glucose levels remain unclear, specifically when considering the preconception period as a sensitive window of exposure.

Objective

We investigated whether preconception perceived stress was associated with glucose levels during pregnancy among women attending a fertility center (2004-2019).

Methods

Before conception, women completed a psychological stress survey using the short version of the validated Perceived Stress Scale 4 (PSS-4), and blood glucose was measured using a 50-gram glucose load test during late pregnancy as a part of screening for gestational diabetes. Linear and log-binomial regression models were used to assess associations of total PSS-4 scores with mean glucose levels and abnormal glucose levels ( ≥ 140 mg/dL), adjusting for age, body mass index, race, smoking, education, physical activity, primary infertility diagnosis, number of babies, and mode of conception.

Results

Psychological stress was positively associated with mean abnormal glucose levels. The adjusted marginal means (95% CI) of mean glucose levels for women in the first, second, and third tertiles of psychological stress were 115 (110, 119), 119 (115, 123), and 124 (119, 128), and mg/dL, respectively (P for trend = .007). Also, women in the second and third tertiles of psychological stress had 4% and 13% higher probabilities of having abnormal glucose compared with women in the first tertile of psychological stress (P trend = .01).

Conclusion

These results highlight the importance of considering preconception when evaluating the relationship between women's stress and pregnancy glucose levels.
Integrated single-cell multiomics uncovers foundational regulatory mechanisms of lens development and pathology
Authors: Tangeman Jared A. , Rebull Sofia M. , Grajales-Esquivel Erika , Weaver Jacob M. , Bendezu-Sayas Stacy , Robinson Michael L. , Lachke Salil A. , Del Rio-Tsonis Katia
Published: January 2024

Ocular lens development entails epithelial to fiber cell differentiation, defects in which cause congenital cataracts. We report the first single-cell multiomic atlas of lens development, leveraging snRNA-seq, snATAC-seq and CUT&RUN-seq to discover previously unreported mechanisms of cell fate determination and cataract-linked regulatory networks. A comprehensive profile of cis- and trans-regulatory interactions, including for the cataract-linked transcription factor MAF, is established across a temporal trajectory of fiber cell differentiation. Furthermore, we identify an epigenetic paradigm of cellular differentiation, defined by progressive loss of the H3K27 methylation writer Polycomb repressive complex 2 (PRC2). PRC2 localizes to heterochromatin domains across master-regulator transcription factor gene bodies, suggesting it safeguards epithelial cell fate. Moreover, we demonstrate that FGF hyper-stimulation in vivo leads to MAF network activation and the emergence of novel lens cell states. Collectively, these data depict a comprehensive portrait of lens fiber cell differentiation, while defining regulatory effectors of cell identity and cataract formation.
Public Chronic Traumatic Encephalopathy Knowledge: Sources, Accuracy and Confidence
Authors: Zurlinden Taylor , Falletta Gillian , Schneider Kate , Sorrell Anne E. , Savransky Anya , Everhart D. Erik
Published: January 2024

The goal of this study was to examine the general public's level of accuracy and confidence in knowledge of chronic traumatic encephalopathy (CTE), as well as information sources. This study also explored how these factors affected comfort in allowing children to play a high-contact sport. This study utilized online surveys and included 529 participants. Overall, CTE knowledge accuracy was 48.02% (standard deviation = 0.23). Inaccuracies regarding the etiology and diagnosis of CTE were most common, whereas the symptoms and lack of treatments for CTE were more widely known. Despite overall low CTE knowledge accuracy, CTE knowledge confidence was positively correlated with comfort in allowing children to play a high-contact sport (r = 0.199, P ≤ 0.001). Participants identified television/movies followed by web sites and social media as the most utilized CTE information sources. These results further support the need for clinicians and researchers to address misconceptions about CTE.
Movimento feminista e interseccionalidade: Repertórios de ação e de interação com o Estado
Authors: Silva Mônica , Bronzo Carla , Brasil Flávia
Published: January 2024

O artigo teve como objetivos identificar e analisar os repertórios de ação e interação das mulheres negras com o poder público. O trabalho apoia-se em desenvolvimentos teóricos no campo de estudos dos movimentos sociais e na vertente dos feminismos negros, mobilizando a literatura clássica e contemporânea no campo das ciências sociais. O período de análise compreende de 2010, ano em que foi instituído o Estatuto da Igualdade Racial, até o ano de 2020 e tem como foco o Brasil. A metodologia baseia-se em fontes secundárias, por meio de uma revisão bibliográfica e documental sobre o tema. O trabalho identifica uma diversidade de repertórios de ação dos movimentos em foco e de sua interação com o Estado, na linha propositiva e dialógica, bem como na linha de resistência e ativismo, incidindo na proposição, para o poder público, de pautas e agendas centrais do feminismo negro.