bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactions among stress, behavioral inhibition, and delta–beta coupling predict adolescent anxiety during the COVID‐19 pandemic
Authors: Ramos Michelle L. , Zhou Anna M. , Lytle Marisa N. , Myruski Sarah , Pérez‐Edgar Koraly , Buss Kristin A.
Published: March 2024

The COVID‐19 pandemic brought about unprecedented changes and uncertainty to the daily lives of youth. The range of adjustment in light of a near‐universal experience of COVID restrictions highlights the importance of identifying factors that may render some individuals more susceptible to heightened levels of anxiety during stressful life events than others. Two risk factors to consider are temperamental behavioral inhibition (BI) and difficulties in emotion regulation (ER). As such, the current paper focused on BI examined prior to COVID, because of its developmental link to anxiety and ER, as difficulties may be associated with differences in anxiety. We examined a neurocognitive marker of ER processes, delta–beta coupling (DBC). The current paper had two goals: (1) to examine BI in relation to COVID‐related worry and social anxiety experienced during the pandemic, and (2) to explore the role of individual differences in early DBC in the relationship between BI and anxiety outcomes 6 months apart during COVID‐19 (n = 86; T1 Mage = 15.95, SD = 1.73; T6 Mage = 16.43, SD = 1.73). We found support for the moderating role of DBC in the relationship between BI levels and social anxiety disorder (SAD) symptom severity during the pandemic. Here, high BI was predictive of increased SAD symptom levels in adolescents with stronger DBC.
Consider creating a transition program for new students
Authors: Hamblet Elizabeth C.
Published: March 2024

For some students with disabilities, the transition to college represents a ­significant challenge. Some move from a small high school where the staff knew them and the peer group was limited to a large university where they are anonymous and their class contains thousands of other students. Many students have not yet developed self‐advocacy skills. They may lack academic skills, too. Some have never stayed away from home overnight.
New study identifies prevalence rate of adults with ID
Authors: Lyerly Eric
Published: March 2024

A new study has shed light on the prevalence of ­intellectual disabilities in U.S. adults. According to the study, only 1% of adults between the ages of 21 and 41 possess an intellectual disability (https://onlinelibrary.wiley.com/doi/10.1111/jir.13119). The researchers estimated that there were approximately 818,564 such individuals living in the United States as of 2021. They also noted that prevalence estimates were consistent with other international estimates.
Lineage‐specific requirements of Alx4 function in craniofacial and hair development
Authors: Lan Yu , Wu Zhaoming , Liu Han , Jiang Rulang
Published: March 2024

Background

Disruption of ALX4 causes autosomal dominant parietal foramina and autosomal recessive frontonasal dysplasia with alopecia, but the mechanisms involving ALX4 in craniofacial and other developmental processes are not well understood. Although mice carrying distinct mutations in Alx4 have been previously reported, the perinatal lethality of homozygous mutants together with dynamic patterns of Alx4 expression in multiple tissues have hindered systematic elucidation of the cellular and molecular mechanisms involving Alx4 in organogenesis and disease pathogenesis.

Results

We report generation of Alx4f/f conditional mice and show that tissue‐specific Cre‐mediated inactivation of Alx4 in cranial neural crest and limb bud mesenchyme, respectively, recapitulated craniofacial and limb developmental defects as found in Alx4‐null mice but without affecting postnatal survival. While Alx4‐null mice that survive postnatally exhibited dorsal alopecia, mice lacking Alx4 function in the neural crest lineage exhibited a highly restricted region of hair loss over the anterior skull whereas mice lacking Alx4 in the cranial mesoderm lineage exhibited normal hair development, suggesting that Alx4 plays partly redundant roles in multiple cell lineages during hair follicle development.

Conclusion

The Alx4f/f mice provide a valuable resource for systematic investigation of cell type‐ and stage‐specific function of ALX family transcription factors in development and disease.
Efficacy and safety of the Aria pulmonary endovascular device in pulmonary hypertension
Authors: Gerges Christian , Vollmers Karl , Skoro‐Sajer Nika , Dannenberg Varius , Hartig Valerie , Pritzker Marc R. , Scandurra John , Weir E. Kenneth , Lang Irene M.
Published: March 2024

Aims

A common feature of various forms of pulmonary hypertension (PH) is progressive decline of pulmonary arterial compliance (CPA), which correlates with reduced survival. In this acute study, we evaluated feasibility, safety and haemodynamic performance of the Aria pulmonary endovascular device in patients with PH associated with left heart disease (PH‐LHD) and chronic lung disease (PH‐CLD).

Methods and results

Eight patients with PH‐LHD and 10 patients with PH‐CLD were included in this study. The device was placed in the main pulmonary artery via the right femoral vein and was connected by a catheter to a gas‐filled reservoir outside the body. During systole, gas shifts from the balloon to the reservoir, leading to deflation of the balloon. In diastole, the gas returns from the reservoir to the balloon, leading to balloon inflation and enhancing diastolic blood flow to the distal pulmonary capillary bed. Haemodynamics were assessed at baseline, and again with device off, device on and device off. The primary safety endpoint was the incidence of serious adverse events through 30 days after the procedure. No complications or investigational device‐related serious adverse events occurred. Device activation in PH‐LHD and PH‐CLD patients decreased pulmonary arterial pulse pressure by 5.6 ± 4.2 mmHg (−12%; p = 0.003) and 4.2 ± 2.2 mmHg (−11%; p < 0.001), increased CPA by 0.4 ± 0.2 ml/mmHg (+23%; p = 0.004) and 0.4 ± 0.3 ml/mmHg (+25%; p = 0.001), and increased right ventricular‐to‐pulmonary vascular (RV‐PV) coupling by 0.24 ± 0.18 (+40%; p = 0.012) and 0.11 ± 0.07 (+21%; p = 0.001), respectively.

Conclusions

Temporary implantation of the Aria endovascular device was feasible and safe. Device activation resulted in acute improvement of CPA and RV‐PV coupling.
Validation of Salamander Dermal Mucus Swabs as a Novel, Nonlethal Approach for Amphibian Metabolomics and Glutathione Analysis Following Pesticide Exposure
Authors: Van Meter Robin J. , Glinski Donna A. , Wanat Jennifer J. , Thomas Purucker S. , Matthew Henderson W.
Published: March 2024

Evaluating biomarkers of stress in amphibians is critical to conservation, yet current techniques are often destructive and/or time-consuming, which limits ease of use. In the present study, we validate the use of dermal swabs in spotted salamanders (Ambystoma maculatum) for biochemical profiling, as well as glutathione (GSH) stress response following pesticide exposure. Thirty-three purchased spotted salamanders were acclimated to laboratory conditions at Washington College (Chestertown, MD, USA) for 4 weeks. Following acclimation, salamanders were randomly sorted into three groups for an 8-h pesticide exposure on soil: control with no pesticide, 2,4-dichlorophenoxyacetic acid (2,4-D), or chlorpyrifos. Before and after exposure, mucus samples were obtained by gently rubbing a polyester-tipped swab 50 times across the ventral and dorsal surfaces. Salamanders were humanely euthanized and dissected to remove the brain for acetylcholinesterase and liver for GSH and hepatic metabolome analyses, and a whole-body tissue homogenate was used for pesticide quantification. Levels of GSH were present in lower quantities on dermal swabs relative to liver tissues for chlorpyrifos, 2,4-D, and control treatments. However, 2,4-D exposures demonstrated a large effect size increase for GSH levels in livers (Cohen's d = 0.925, p = 0.036). Other GSH increases were statistically insignificant, and effect sizes were characterized as small for 2,4-D mucosal swabs (d = 0.36), medium for chlorpyrifos mucosal swabs (d = 0.713), and negligible for chlorpyrifos liver levels (d = 0.012). The metabolomics analyses indicated that the urea cycle, alanine, and glutamate metabolism biological pathways were perturbed by both sets of pesticide exposures. Obtaining mucus samples through dermal swabbing in amphibians is a viable technique for evaluating health in these imperiled taxa. Environ Toxicol Chem 2024;43:1126–1137. © 2024 SETAC
Disability studies in war and care: How to do work otherwise? A conversation between anthropology‐and‐disability‐studies scholars in relation to Russia's invasion of Ukraine
Authors: Zaremba‐Kosovych Hanna , Verbilovich Volha , Phillips Sarah D. , Hemment Julie
Published: March 2024

This piece weaves together the voices of four feminist disability studies scholars and anthropologists whose work has been profoundly shaped by Russia's war of aggression. Composed via a dialogic encounter, it is based on a panel presentation on the topic of disability studies in war and care that took place at the University of Massachusetts Amherst just before the 1‐year mark of the full‐scale invasion. We came together to share insights and consider the best ways to practice horizontal solidarity, our approach inspired by recent work on feminist epistemology and methodology and scholarship on care, and disability studies. The text assumes a dialogic form, presenting our reflections as well as the contexts that shape our knowledge production and sharing the process of scaffolding our “Dis‐Fem” conversation. In dialogue with the decolonizing discussions that animate feminist, anthropological, and Slavic Studies, as well as critical disability scholarship, it centers on the work of Ukrainian scholar‐activists associated with the organization of people with disabilities (OPD) Fight For Right. In foregrounding their work, it traces the creative ways they've mobilized data and the experimental and collaborative data practices they've harnessed. Finally, it asks questions about trans‐local solidarities we can enact and ways we might forge novel, “otherwise” ways to collaborate.
The role of husk traits in maize susceptibility to Fusarium verticillioides: A multi‐location study in northern Italy
Authors: Magarini Andrea , Colombo Federico , Cassani Elena , Ghidoli Martina , Landoni Michela , Sangiorgio Stefano , Pilu Roberto
Published: March 2024

Fusarium disease and the consequent mycotoxin accumulation pose significant problem in maize cultivation, with fumonisins produced by Fusarium verticillioides posing a global health concern. To address this issue, a range of preventive measures (e.g. crop management techniques) can be implemented to minimize fungal infections. A promising strategy to counteract this issue involves the selection of genotypes with greater resistance to fungal pathogens. This approach has the potential to reduce the reliance on chemical inputs for controlling fungus growth or indirect infection vectors. Leveraging genetic approaches can help improve the economic sustainability of agriculture in the face of climate change challenges. In the present work, we assessed the importance of two husk leaf traits (coverage and number), their association with F. verticillioides infection, fumonisin content, and their potential influence on crop yield. The study was conducted in three locations in the North of Italy and 38 hybrids with varying resistance to F. Verticillioides were compared. The results obtained showed that husk coverage has a pivotal role not only in protecting maize ears from Fusarium infection but have also a significant impact on crop yield: a significant positive correlation was found between husk coverage and yield in all three locations (r = 0.33185; r = 0.51327 and r = 0.51207, respectively). Furthermore, in the field of Vicenza, a significant negative correlation was found between husk coverage and Fusarium severity (r = −0.41492). Husk coverage emerges as an important trait that merits inclusion in maize breeding programs, given its protective role against fungal infections and its favourable influence on both yield and grain quality.
Adenosine receptors are the on‐and‐off switch of astrocytic cannabinoid type 1 (CB1) receptor effect upon synaptic plasticity in the medial prefrontal cortex
Authors: Gonçalves‐Ribeiro Joana , Savchak Oksana K. , Costa‐Pinto Sara , Gomes Joana I. , Rivas‐Santisteban Rafael , Lillo Alejandro , Sánchez Romero Javier , Sebastião Ana M. , Navarrete Marta , Navarro Gemma , Franco Rafael , Vaz Sandra H.
Published: March 2024

The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1R, A2AR), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R‐A2AR or CB1R‐A1R heteromers that ultimately impact mPFC synaptic plasticity. CB1R‐mediated Ca2+ transients increased and decreased when A1R and A2AR were activated, respectively, unveiling adenosine receptors as modulators of astrocytic CB1R. CB1R activation leads to an enhancement of long‐term potentiation (LTP) in the mPFC, under the control of A1R but not of A2AR. Notably, in IP3R2KO mice, that do not show astrocytic Ca2+ level elevations, CB1R activation decreases LTP, which is not modified by A1R or A2AR. The present work suggests that CB1R has a homeostatic role on mPFC LTP, under the control of A1R, probably due to physical crosstalk between these receptors in astrocytes that ultimately alters CB1R Ca2+ signaling.
The impact of juvenile curfews on teenage birth rates
Authors: Gamino Aaron M.
Published: March 2024

I examine the effect of city‐level juvenile curfews on teenage birth rates using the National Center for Health Statistics birth data from 1982 to 2002. I compare differences in birth rates between younger and older age groups in cities with and without curfew ordinances. Before curfew adoption, the age differential in birth rates trended similarly for cities that did and did not adopt a curfew. There were significant decreases in the age differential birth rates in cities that adopted a curfew relative to cities that did not. Curfews reduced birth rates by approximately 3 births per 1000 women ages 15–17. I find a decrease in birth rates among white women. The main results are corroborated using a variety of robustness checks and specifications.
Soil-specific outcomes in the OECD 216 Nitrogen Transformation Test
Authors: Sweeney Christopher J. , Bottoms Melanie , Schulz Lennart
Published: March 2024

The Organisation for Economic Co-operation and Development (OECD) 216 test guideline investigates the impact of agrochemicals on soil nitrogen transformation. After an evaluation of 465 OECD 216 studies, we describe two distinct yet contrasting outcomes in control nontreated samples that are possible in this testing framework, which we term the “rise” (consistent increases in nitrate concentrations throughout the test period) and “dip” (initial decline in nitrate concentration between Days 0–7, followed by a net-generation of nitrate across Days 7–28) responses. We raise significant concerns that control data from standardized, internationally recognized test guidelines can demonstrate such dissimilar patterns. We propose that, when present, the dip response undermines the intended functioning of the test system and removes the ability to draw appropriate ecotoxicological inferences from the data. In this work, we hypothesize the dip response is a product of conducting the study in low nitrogen content soils. Our results indicate that the dip response can be alleviated by using ammonium sulfate as an immediately available inorganic nitrogen source in place of the guideline-mandated complex, organic lucerne meal, demonstrating the influence of nitrogen availability and accessibility. However, not all low nitrogen soils exhibited the dip response, indicating the involvement of additional unidentified factors. Using our data and real-world regulatory examples, we advocate that datasets displaying the dip response should not be considered valid OECD 216 studies due to the influence of soil properties precluding an assessment of whether any impacts observed are driven solely by the test compound in question or are instead a product of the soil used. We propose methods to account for these soil-specific responses that could be integrated into the conduct and interpretation of OECD 216 studies. Such amendments will improve the reliability and robustness of the study system and enhance confidence in ecotoxicological conclusions derived from OECD 216 datasets. Integr Environ Assess Manag 2024;20:1611–1624. © 2024 SETAC

Key Points

We report on two soil-specific outcomes within control data originating in the OECD 216 Nitrogen Transformation Test, which we term the “dip” and “rise” responses. We suggest the dip response represents the test system behaving in an adverse and unintended manner and can affect ecotoxicological inferences made from the data. We demonstrate the dip response is linked to nitrogen availability and accessibility; however, our data also demonstrate the involvement of additional, unidentified factors. We propose amendments to the OECD 216 guideline to better account for the differential performance of soils within the test system and improve the reliability and robustness of OECD 216 data.
Self‐assembled monolayers for perovskite solar cells
Authors: Xu Dongdong , Wu Pu , Tan Hairen
Published: March 2024

In metal‐halide perovskite solar cells (PSCs), various carrier recombination losses occur at the interface between metal oxides (MOs) and perovskite (PVK) due to the imperfect lattice structure of the crystal surface. Additionally, the nonoptimal energy levels of MOs and PVK, as well as ion diffusion and chemical corrosion between the two materials, severely hinder carrier transport at the interface. Therefore, there is an urgent need to introduce multifunctional materials between MOs and PVK to mitigate interface defects, carrier transport limitations, chemical corrosion, and other related issues. In recent years, self‐assembled monolayers (SAMs) have emerged as essential organic interfacial materials for effectively bridging MOs and PVK, playing a pivotal role in enhancing cells’ performance. Based on this, we provide a detailed overview of the origin and development of SAMs in PSCs and summarize the importance and potential of SAMs from various aspects, including their chemical structure, interface passivation, energy level tuning, and interface corrosion. We finally discuss the prospects of SAMs in terms of molecular structure, deposition methods, and their application in narrow‐band gap PSCs. With these insights, it is anticipated that SAMs will assist in realizing larger, highly efficient, stable, and cost‐effective PSCs, thereby enhancing the competitiveness of PSCs in the solar photovoltaics market.
Nowcasting directional change in high frequency FX markets
Authors: Tsang Edward P. K. , Ma Shuai , Chinthalapati V. L. Raju
Published: March 2024

Directional change (DC) is an alternative to time series in recording transactions: it only records the transactions at which price changes to the opposite direction of the current trend by a threshold specified by the observer. DC can only be confirmed in hindsight: one does not know that direction has changed until it is confirmed by a later transaction. The transaction in which the price confirms a DC is called a DC confirmation point. DC nowcasting is an attempt to recognize DC before the DC confirmation point. Accurate DC nowcasting will benefit trading. In this paper, we propose a method for DC nowcasting. This method is entirely data driven: it is based on the historical distribution of DC‐related indicators. Empirical results suggest that DC nowcasting is possible, even under a naïve rule. This opens the door to a promising research direction on an important topic.
Cancer anorexia‐cachexia syndrome is characterized by more than one inflammatory pathway
Authors: Gagnon Bruno , Murphy Jessica , Simonyan David , Penafuerte Claudia A. , Sirois Jacinthe , Chasen Martin , Tremblay Michel L.
Published: March 2024

Background

The interdependence of cytokines and appetite‐modifying hormones implicated in cancer anorexia‐cachexia syndrome (CACS) remains unclear. This study aimed to regroup these cytokines and hormones into distinct inflammatory (or non‐inflammatory) pathways and determine whether these pathways can classify patients with CACS phenotypes.

Methods

Clinical characteristics of 133 patients [61.7% male; mean age = 63.4 (SD: 13.1) years] with advanced cancer prior to oncology treatments were documented, including weight loss history. Patients completed the Functional Assessment of Anorexia‐Cachexia Therapy (FAACT) questionnaire and Timed Up and Go test and had their sex‐standardized skeletal muscle index (z‐SMI) and fat mass index (z‐FMI) derived using computed tomography scans. Their plasma levels of cytokines and appetite‐modifying hormones were also determined. Date of death was recorded. Exploratory factor analysis (EFA) was used to regroup 15 cytokines and hormone into distinct inflammatory pathways (factors). For each patient, regression factor scores (RFS), which tell how strongly the patient associates with each factor, were derived. Two‐step cluster analysis on the RFS was used to classify patients into groups. CACS phenotypes were correlated with RFS and compared between groups. Groups' survival was estimated using Kaplan–Meier analysis.

Results

Patients had low z‐SMI (mean = −3.78 cm2/m2; SD: 8.88) and z‐FMI (mean = 0.08 kg2/m2; SD: 56.25), and 62 (46.6%) had cachexia. EFA identified three factors: (F‐1) IFN‐γ, IL‐1β, Il‐4, IL‐6, IL‐10, IL‐12, TGFβ1 (positive contribution), and IL‐18 (negative); (F‐2) IL‐8, IL‐18, MCP‐1, TGFβ1, TNF‐α (positive), and ghrelin (negative); and (F‐3) TRAIL and leptin (positive), and TGFβ1 and adiponectin (negative). RFS‐1 was associated with cachexia (P = 0.002); RFS‐2, with higher CRP (P < 0.0001) and decreased physical function (P = 0.01); and RFS‐3 with better appetite (P = 0.04), lower CRP (P = 0.002), higher z‐SMI (P = 0.04) and z‐FMI (P < 0.0001), and less cachexia characteristics (all P < 0.001). Four patient groups were identified with specific RFS clusters aligning with the CACS continuum from no cachexia to pre‐cachexia, cachexia, and terminal cachexia. Compared to the other two groups, groups 1 and 2 had higher plasma levels of IL‐18 and TRAIL. Group 1 also had lower inflammatory cytokines, adiponectin, and CRP compared to the other three groups. Group 3 had inflammatory cytokine levels similar to group 2, except for TNF‐α and leptin which were lower. Group 4 had very high inflammatory cytokines, adiponectin, and CRP compared to the other 3 groups (all P < 0.0001). Groups 3 and 4 had worse cachexia characteristics (P < 0.05) and shorter survival (log rank: P = 0.0009) than the other two groups.

Conclusions

This exploratory study identified three distinct pathways of inflammation, or lack thereof, characterizing different CACS phenotypes.
Prediction of severity of dengue infection in children based on hepatic involvement
Authors: Alam Rubaiyat , Fathema Kaniz , Yasmin Afsana , Roy Urmi , Hossen Kamal , Rukunuzzaman Md
Published: March 2024

Background and Aim

To assess the spectrum of hepatic involvement in children with dengue fever (DF) and prediction of severity of dengue infection by early detection of elevated liver enzymes.

Methods

This prospective observational study was conducted at a tertiary care hospital from June 2019 to September 2019. Children admitted with DF were included. Severity of DF was graded as dengue without warning sign (DNWS), with warning sign (DWS), and severe dengue fever (SDF) according to WHO criteria. Liver injury (LI) was defined as alanine aminotransferase (ALT) more than upper limit of normal irrespective of sex.

Results

Of 190 children (male, 109) with DF, 60 had DNWS, 49 had DWS, and 81 had SDF. A total of 100 children (52.6%) had LI. The distribution of hepatic involvement spectrum involves hepatomegaly (26.3%), hepatic tenderness (25.2%), features of acute liver failure (1.5%), raised level of ALT (52.6%), raised level of aspartateaminotransferase (AST) (65.8%), prolonged prothrombin time (7.3%), and reduced level of serum albumin (44.7%) in children. Of them, 5.8% and 6.8% of children had >tenfold increase in ALT and AST values. The degree of liver function derangement significantly (P < 0.05) increased with DF severity. In our study, ALT at 422 IU/L (10 times upper limit of normal [ULN]) and AST 689 IU/L (17 times ULN) had similar sensitivity and specificity as WHO recommended cutoff of 1000 IU/L (25 times of ULN) to detect SDF.

Conclusion

ALT ≥10 times and AST ≥17 times of ULN are as sensitive as ≥25 times (as recommended by WHO) to detect SDF.
Rapid and sensitive lateral flow biosensor for the detection of GII human norovirus based on immunofluorescent nanomagnetic microspheres
Authors: Gao Junshan , Xue Liang , Li Yijing , Cai Weicheng , Miao Shuidi , Meng Luobing , Ren Shaolei , Zhang Jumei , Wang Juan , Wu Shi , Ye Qinghua , Chen Ling , Gu Qihui , Wu Qingping
Published: March 2024

Human norovirus (HuNoV) is the most predominant viral agents of acute gastroenteritis. Point‐of‐care testing (POCT) based on lateral flow immunochromatography (LIFC) has become an important tool for rapid diagnosis of HuNoVs. However, low sensitivity and lack of quantitation are the bottlenecks of traditional LIFC. Thus, we established a rapid and accurate technique that combined immunomagnetic enrichment (IM) with LFIC to identify GII HuNoVs in fecal specimens. Before preparing immunofluorescent nanomagnetic microspheres and achieving the effect of HuNoV enrichment in IM and fluorescent signal in LFIC, amino‐functionalized magnetic beads (MBs) and carboxylated quantum dots (QDs) were coupled at a mass ratio of 4:10. Anti‐HuNoV monoclonal antibody was then conjugated with QDs‐MB. The limit of detection was 1.56 × 104 copies/mL, and the quantitative detection range was 1.56 × 104 copies/mL–1 × 106 copies/mL under optimal circumstances. The common HuNoV genotypes GII.2, GII.3, GII.4, and GII.17 can be detected, there was no cross‐reaction with various enteric viruses, including rotavirus, astrovirus, enterovirus, and sapovirus. A comparison between IM‐LFIC and RT‐qPCR for the detection of 87 fecal specimens showed a high level of agreement (kappa = 0.799). This suggested that the method is rapid and sensitive, making it a promising option for point‐of‐care testing in the future.
Correlation between high‐risk HPV infection and p16/Ki‐67 abnormalities in Pap samples in a South Eastern Europe cohort
Authors: Shalaby Nevine A. , Tudorescu‐Morjan Claudiu , Manole Catalin Gabriel , Iacata Alexandra‐Antonela , Popovici Mirela Laura , Grecu Laura Iulia , Curici Antoanela
Published: March 2024

Cervical cancer (CC) is the fourth most common cause of cancer‐related deaths amongst women worldwide. CC represents a major global healthcare issue, and Romania ranks the worst in mortality rates amongst EU countries. However, the early detection of CC can be lifesaving. To understand the testing process undergone by women in Romania, we performed a retrospective study, and investigated a cohort of 83 785 cervical cases from Romanian women aged 15−70, obtained in private‐based opportunistic screening. We examined the correlation between Pap smear results, human papilloma virus (HPV) genotyping, and the expression of cell cycle markers p16 and Ki‐67. Analysis of Pap results revealed approximately 10% abnormal cases, of which high‐grade squamous intraepithelial lesions constituted 4.9%. HPV genotyping of 12 185 cases with available Pap results unveiled a range of high‐risk HPV (hrHPV) types associated with cervical abnormalities. Notably, 26% of hrHPV‐positive cases showed no observable abnormalities. In a subset of cases with abnormal Pap and a type of hrHPV, P16/Ki‐67 double‐staining was also positive. This study suggests the importance of an integrated diagnostic algorithm that should consider the HPV genotype, Pap smear, and p16/Ki‐67 staining. This algorithm should enhance the CC screening accuracy and its management strategies, particularly in those regions with a high disease burden, such as Romania.
Disease severity versus pain severity: Range of motion differences during single‐ and multiplanar tasks in women with carpometacarpal osteoarthritis
Authors: Ordonez Diaz Tamara , Licht Samuel , Wright Thomas W. , Nichols Jennifer A.
Published: March 2024

In carpometacarpal osteoarthritis (CMC OA) of the thumb, to what extent treatments should be directed by radiographic disease severity versus pain‐based indicators remains an open question. To address this gap, this study investigated the relative impact of disease severity and pain severity on the range of motion in participants with CMC OA. We hypothesized larger differences would exist between extremes in the pain severity cohort than the disease severity cohort, suggesting pain modulates movement to a greater extent than joint degradation. Thirty‐one female participants (64.6 ± 10.9 years) were grouped as symptomatic or asymptomatic (pain severity cohort) and early stage OA or end‐stage OA (disease severity cohort) using radiographs and questionnaires. Kinematics were measured during single‐planar and multiplanar range of motion tasks. Joint angle differences between groups were statistically compared. Differences in self‐reported pain, function, and disability were evident in both participant cohorts. Notably, substantial distinctions emerged exclusively during multiplanar tasks, with a greater prevalence in the disease severity cohort compared to the pain severity cohort. Participants with end‐stage OA also exhibited similar overall area covered during circumduction in comparison to those with early‐stage OA, despite having a decreased range of motion at the CMC joint. The study underscores the importance of assessing multiplanar tasks, potentially leading to earlier identification of CMC OA. While movement compensations such as employing the distal thumb joints over the CMC joint were observed, delving deeper into the interplay between pain and movement could yield greater insight into the underlying factors steering these compensatory mechanisms.
Real‐world effectiveness of ustekinumab and vedolizumab in TNF‐exposed pediatric patients with ulcerative colitis
Authors: Patel Perseus V. , Zhang Amy , Bhasuran Balu , Ravindranath Vignesh G. , Heyman Melvin B. , Verstraete Sofia G. , Butte Atul J. , Rosen Michael J. , Rudrapatna Vivek A. ,   ImproveCareNow Pediatric IBD Learning Health System
Published: March 2024

Objectives

Vedolizumab (VDZ) and ustekinumab (UST) are second‐line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti‐TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti‐TNF refractory UC.

Methods

We performed a propensity‐score weighted regression analysis to compare corticosteroid‐free clinical remission (CFCR) at 6 months from starting second‐line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk.

Results

Our cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41–1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76–2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness.

Conclusions

UST and VDZ are similarly effective for inducing clinical remission in anti‐TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies.
Surgical excision and radiotherapy for brain metastasis from colorectal cancer: How frailty and comorbidity indices influence outcome
Authors: Wong Chia‐En , Chang Yu , Huang Chi‐Chen , Hsu Hao‐Hsiang , Lai Yu‐Hsuan , Chang Kwang‐Yu , Huang Chih‐Yuan , Wang Liang‐Chao , Lee Jung‐Shun , Lee Po‐Hsuan
Published: March 2024

The incidence of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study aims to identify the clinical prognosticators and evaluate the prognostic validity of common comorbidity indices in patients with BM from CRC. This retrospective single‐center study analyzed 93 patients with BM from CRC who received surgical excision and/or radiotherapy. The clinical characteristics and prognostic indices including the 5‐item modified frailty index (mFI‐5) and prognostic nutritional index (PNI) were calculated from the collected patient data and analyzed. In this study, 66 (71.0%), 10 (10.8%), and 17 (18.3%) patients received whole‐brain radiotherapy (WBRT) alone, surgery alone, and surgery plus WBRT, respectively. The median survival of all patients was 3.98 months (IQR: 1.74–7.99). The 2‐ and 3‐year survival rates were 7.4% and 3.7%, respectively. Controlled primary tumor (p = 0.048), solitary BM (p = 0.001), surgery + radiation (p < 0.001), and greater PNI (p = 0.001) were independent predictors of favorable survival. In surgically treated patients, uncontrolled primary tumor (p = 0.006), presence of multiple BM (p < 0.001), and MFI‐5 ≥ 2 (p = 0.038) were independent prognosticators. For patients who received WBRT, the presence of two (p = 0.004) or multiple (p < 0.001) BM and PNI (p < 0.001) were independent survival predictors MFI‐5, multiple BM, and the status of the primary tumor were independent prognosticators for patients who underwent surgery for CRCBM. For patients who received WBRT, the PNI and the number of BM were independent survival predictors.
An ethics framework for the transition to an operational learning healthcare system
Authors: Hollestelle Marieke J , van der Graaf Rieke , Sturkenboom Miriam CJM , van Delden Johannes JM
Published: March 2024

Introduction

While Learning Healthcare Systems (LHSs) have received increasing attention in health care and research, the amount of operational LHSs remains limited. Given the investment of resources in these projects, a moral responsibility to pursue the transition toward an LHS falls on projects and their participating stakeholders. This paper provides an ethics framework for projects that have taken steps toward building an LHS and are in the position to transition to an operational LHS.

Method

To articulate relevant ethical requirements, we analyze established ethics frameworks in the fields of LHSs, data‐intensive health research, and transitioning or innovating health systems. The overlapping content and shared values are used to articulate overarching ethical requirements. To provide necessary context, we apply the insights from the analysis to the Innovative Medicines Initiative ConcePTION project. This project is specifically designed to generate knowledge on the safety of medications used during pregnancy and lactation through the establishment of an LHS.

Results

Upon analyzing the consulted frameworks, we identified four overlapping ethical requirements that are also of significant relevance within the scope of our ethics framework. These requirements are: (1) public benefit and favorable harm–benefit ratio; (2) equity and justice; (3) stakeholder engagement; and (4) sustainability. Additionally, we apply these ethical requirements to the context of an LHS for pregnant and lactating people.

Conclusion

Although tailored to the context of pregnancy and lactation, our ethics framework can provide guidance for the transition to an operational LHS across diverse healthcare domains.
Dissipative Particle Dynamics Study on the Phase Region of Spatial Gradient Materials Produced by Photoinduced Isomerization
Authors: Li Hui , Gao Kaiming , Zhao Haitao , Xue Zijian , Chen Zhenbin , Lu Xuefeng , Liu Hong
Published: March 2024

Spatial gradient materials occupy an important research position in the field of functional materials with their unique porous structure. Gradient changes in pore size and density distribution have received extensive attention in the fields of biomimetic and smart materials. The gradient transition law is mathematically related to the driving force of isomerization reaction and component phase separation. In this study, a dissipative particle dynamics simulation is used to introduce photoisomerization reactions into the system. Lambert's law is used to construct a reaction model for the variation of light intensity with irradiation depth, and a gradient structure with a spatial transition law is obtained. The effects of the extinction coefficient ε, the initial reaction probability Pr0, and the interactions α(A,B) between the isomerized molecules as well as the viscosity on the formation of the gradient structure are investigated in detail. Furthermore, the mathematical proportionality between the size of the phase region and interfacial energy of the two phases is elucidated. This study provides preliminary computational insights into the factors affecting the photoinduced phase separation process of polymeric gradient materials. It may help to develop effective strategies to improve the phase separation and properties of polymer gradient materials in subsequent studies.
The geometrical and physical interpretation of fractional order derivatives for a general class of functions
Authors: Ruby  , Mandal Moumita
Published: March 2024

The aim of this article is to find a geometric and physical interpretation of fractional order derivatives for a general class of functions defined over a bounded or unbounded domain. We show theoretically and geometrically that the absolute value of the fractional derivative value of a function is inversely proportional to the area of the triangle. Further, we prove geometrically that the fractional derivatives are inversely proportional to the classical integration in some sense. The established results are verified numerically for non‐monotonic, trigonometric, and power functions. Further, this article establishes a significant connection between the area of the projected fence and the area of triangles. As the area of triangles decreases, the area of the projected fence increases, and vice versa. We calculate the turning points of the fractional derivative values of different functions with respect to order
, including non‐monotonic, trigonometric, and power functions. In particular, we demonstrate that for the power function
, with
being a positive real number, the value
is a turning point when
. However, for
, the turning point shifts to the left of point
and shifts to the right of point
for
We discuss the physical interpretation of fractional order derivatives in terms of fractional divergence. We present some applications of fractional tangent lines in the field of numerical analysis.
Survival among patients receiving eteplirsen for up to 8 years for the treatment of Duchenne muscular dystrophy and contextualization with natural history controls
Authors: Iff Joel , Done Nicolae , Tuttle Edward , Zhong Yi , Wei Fangzhou , Darras Basil T. , McDonald Craig M. , Mercuri Eugenio , Muntoni Francesco
Published: March 2024

Introduction/Aims

Eteplirsen, approved in the US for patients with Duchenne muscular dystrophy (DMD) with exon 51 skip‐amenable variants, is associated with attenuated ambulatory/pulmonary decline versus DMD natural history (NH). We report overall survival in a US cohort receiving eteplirsen and contextualize these outcomes versus DMD NH.

Methods

US patients with DMD receiving eteplirsen were followed through a patient support program, with data collected on ages at eteplirsen initiation and death/end of follow‐up. Individual DMD NH data were extracted by digitizing Kaplan–Meier (KM) curves from published systematic and targeted literature reviews. Overall survival age was analyzed using KM curves and contextualized with DMD NH survival curves; subanalyses considered age groups and duration of eteplirsen exposure. Overall survival time from treatment initiation was also evaluated.

Results

A total of 579 eteplirsen‐treated patients were included. During a total follow‐up of 2119 person‐years, median survival age was 32.8 years. DMD NH survival curves extracted from four publications (follow‐up for 1224 DMD NH controls) showed overall pooled median survival age of 27.4 years. Eteplirsen‐treated patients had significantly longer survival from treatment initiation versus age‐matched controls (age‐adjusted hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44–0.98; p < .05). Longer treatment exposure was associated with improved survival (HR, 0.15; 95% CI, 0.05–0.41; p < .001). Comparisons using different DMD NH cohorts to address common risks of bias yielded consistent findings.

Discussion

Data suggest eteplirsen may prolong survival in patients with DMD across a wide age range. As more data become available, the impact of eteplirsen on survival will be further elucidated.
Sequelae and post‐thrombotic syndrome after venous thromboembolism in acute lymphoblastic leukemia survivors treated on the NOPHO ALL2008 protocol
Authors: Dam Merete , Lynggaard Line Stensig , Jónsson Ólafur G. , Saulyte Trakymiene Sonata , Palk Katrin , Jarvis Kirsten , Andrés‐Jensen Liv , Tuckuviene Ruta , Albertsen Birgitte Klug
Published: March 2024

The treatment of acute lymphoblastic leukemia (ALL) is frequently complicated by toxicity, including venous thromboembolism (VTE) affecting roughly 8% of patients. VTE can lead to post‐thrombotic syndrome (PTS), a group of signs and symptoms developed as a complication to deep venous thrombosis (DVT), imposing risk of permanent disability and reduced quality of life (QoL). PTS prevalence ranges from 0% to 70%, reflecting very heterogenous cohorts and assessment tools. We aimed to estimate sequelae, including PTS and QoL in children and adults (<45 years old) who had a DVT during ALL treatment. PTS and QoL scores were obtained through use of Villalta and Modified Villalta Scale, PedsQL, and Short Form‐36 questionnaires. The cohort comprised 20 children (<18 years) and seven adults (median age: 12.9 years, range: 2–44 years) at the time of DVT diagnosis. In total, 25 ALL survivors underwent PTS examination. The examination took place when survivors were 7–48 years (median age: 20.3 years, median follow‐up time 6.8 years). QoL was assessed correlating cases with three matching ALL survivors without VTE. Two adults (15.4%) showed mild or moderate PTS. Eight children (66.7%) were diagnosed with mild PTS, while three cases had collaterals as sole symptoms. Pain or symptoms affecting daily life were reported by 16%. No difference in QoL was found (p = .9). This study underscores the need for comprehensive population‐based investigations with validation of PTS instruments in ALL survivors.
Resiliency in the Jackson Water Crisis: Investigating the roles of social vulnerability and U.S. Federal Subsidiarity Assistance
Authors: Arterberry Latara M. , Nukpezah Julius A.
Published: March 2024

The City of Jackson, Mississippi, has faced numerous problems related to its water supply in the last three decades. The most recent water crisis stemmed from the flooding of two water treatment plants, resulting in contamination and the shutting down of the water supply. The study examines antecedents to the Jackson Water Crisis and how it was addressed. The article investigates the following questions: (1) What is the effect of jurisdictional vulnerability on the resiliency of the Jackson Water Crisis, and (2) What role does the subsidiarity principle play in the resiliency of the Jackson Water Crisis? The study draws from social vulnerability theory to investigate Jackson's changing racial demographics starting in 1970 to understand the crisis. It then draws from the subsidiarity principle that underpins federal assistance to subnational governments to explain how multilevel governments cooperate to address social inequity and create a more resilient community.
Fault estimation for a class of nonlinear systems using the improved intermediate estimator
Authors: Goli Mahdi , Bolandi Hossein , Ebadollahi Saeed
Published: March 2024

This paper focused on fault estimation in Lipschitz nonlinear systems by providing an improved intermediate estimator (IIE). The core feature of an intermediate estimator is to simultaneously estimate the fault and states of the system without considering the matching condition. Since fault estimation is the first step of the process to compensate for its effect, the system performance can be further improved by making more accurate fault estimation. The structure of the nominal intermediate estimator (NIE) was modified by being inspired by the proportional‐integral (PI) controller to improve the performance characteristics of the estimator, such as convergence rate, overshoot, and steady‐state error. The estimation equation was assumed as such in the proposed estimator structure that the estimated fault would have a PI structure of the output estimation error. This has increased the number of design parameters, improving the estimator performance in transient and steady‐state. The NIE can be indeed known as a particular case of the IIE since the proposed estimator benefits from all the advantages of an NIE while improving the estimation performance. The states of the error system were proven to be uniformly ultimately bounded according to Lyapunov stability theory and using the LMI method, as well as the appropriate selection of parameters. The analysis of the theory, simulation, and comparing the results of the proposed method with the NIE method reveal the capabilities and advantages of the proposed method.
Attack reconstruction‐based resilient consensus tracking for multi‐agent systems with distributed adaptive control protocol
Authors: Li Zifei , Wang Wei , Huang Jiangshuai
Published: March 2024

This article considers the distributed secure consensus tracking control problem for multi‐agent systems (MASs) with relative output information. To tackle the potential false‐data‐injection (FDI) attacks on both the communication between physical components and the control center at the agent level, as well as the message transmission between connected agents, local sliding mode observers (SMO) and distributed observers are proposed for each agent. By introducing reconstructed signals for attacks and smooth terms to compensate the unknown input in the leader agent's dynamics, a distributed adaptive consensus protocol with relative output information is proposed. The closed‐loop stability is analyzed by introducing a novel Lyapunov function. It is shown that all closed‐loop signals are globally uniformly bounded and asymptotically consensus tracking can be achieved. Simulation results are provided to validate the theoretical findings.