bluuebunny/crossref_metadata_2025 huggingface dataset:
Representation of women in orthopaedic surgery: perception of barriers among undergraduate medical students in Saudi Arabia
Authors: Alomar Abdulaziz Z. , Almonaie Shahd , Nagshabandi Khalid Nabil , AlGhufaili Deema , Alomar Manar
Published: January 2023

Background

While female participation has improved in several surgical specialties over time globally, no such increase has been observed in orthopaedic surgery over the past decades. The potential barriers to female participation are likely present from the beginning of medical education. Therefore, this study assessed the apparent lag in equal representation among men and women in orthopaedic surgery in the Kingdom of Saudi Arabia.

Methods

This cross-sectional study used a questionnaire survey to investigate medical students’ and interns’ perceptions of women participating in orthopaedic surgery, their subspeciality preferences, and barriers preventing them from pursuing an orthopaedic career. The responses were analysed to understand general perceptions, gender-based differences, impact of clinical experiential learning, and exposure to orthopaedic surgery.

Results

Approximately 565 medical students (49% females, 51% males) participated in the survey. Only 17% of students (11% females, 23% males) considered orthopaedic surgery as their future career option. While 31% of female and 17% of male students disagreed with the concept of female-appropriate orthopaedic subspecialties, most of the remaining male and female students perceived paediatric orthopaedics as a female-appropriate subspecialty. Concerning equal representation of women, gender bias and lack of a strong physique were the most frequently selected barriers by female and male students, respectively. Patient preference for male orthopaedicians, gender discrimination, social and family commitments, and need for physical strength were all perceived as barriers for women in orthopaedics. Overall, clinical experience and orthopaedic exposure did not significantly improve the likelihood of female students in choosing orthopaedic surgery as a career.

Conclusions

The bias against women in orthopaedic careers is prevalent among medical students early in their academic years. Clinical experience and exposure to orthopaedic surgery should be improved to make a significant impact on female participation in orthopaedic careers. Career building efforts in terms of improved career opportunities, career counselling, flexible working hours, social and family related adjustments and implementation of mentorship/research/fellowship programmes for females are needed to reduce gender discrimination and improve female orthopaedic participation. Furthermore, process improvements may yield greater flexibility for women pursuing the challenging field while accommodating other barriers faced by women in orthopaedic surgery.
Extru-seq: a method for predicting genome-wide Cas9 off-target sites with advantages of both cell-based and in vitro approaches
Authors: Kwon Jeonghun , Kim Minyoung , Hwang Woochang , Jo Anna , Hwang Gue-Ho , Jung Minhee , Kim Un Gi , Cui Gang , Kim Heonseok , Eom Joon-Ho , Hur Junho K. , Lee Junwon , Kim Youngho , Kim Jin-soo , Bae Sangsu , Lee Jungjoon K.
Published: January 2023

We present a novel genome-wide off-target prediction method named Extru-seq and compare it with cell-based (GUIDE-seq), in vitro (Digenome-seq), and in silico methods using promiscuous guide RNAs with large numbers of valid off-target sites. Extru-seq demonstrates a high validation rate and retention of information about the intracellular environment, both beneficial characteristics of cell-based methods. Extru-seq also shows a low miss rate and could easily be performed in clinically relevant cell types with little optimization, which are major positive features of the in vitro methods. In summary, Extru-seq shows beneficial features of cell-based and in vitro methods.
Differential CpG DNA methylation of peripheral B cells, CD4+ T cells, and salivary gland tissues in IgG4-related disease
Authors: Wu Xunyao , Wang Anqi , Wang Mu , Peng Yu , Chen Yingying , Li Jieqiong , Liu Zheng , Lu Hui , Zhou Jiaxin , Peng Linyi , Zhao Yan , Zeng Xiaofeng , Fei Yunyun , Zhang Wen
Published: January 2023

Objectives

Immunoglobulin-G4-related disease (IgG4-RD) is a distinct systemic autoimmune-mediated disease manifesting as chronic inflammation and tissue fibrosis. Since the role of DNA methylation in the pathogenesis of IgG4-RD is still unclear, we conduct this study to investigate epigenetic modifications in IgG4-RD.

Methods

A genome-wide DNA methylation study was conducted with B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients and matched controls by using the Illumina HumanMethylation 850K BeadChip. We further performed pyrosequencing and immunohistochemistry assays to validate the methylation status of some targets of interest.

Results

We identified differentially methylated CpG sites including 44 hypomethylated and 166 hypermethylated differentially methylated probes (DMPs) in B cells and 260 hypomethylated and 112 hypermethylated DMPs in CD4+ T cells from 10 IgG4-RD patients compared with 10 healthy controls. We also identified 36945 hypomethylated and 78380 hypermethylated DMPs in salivary gland tissues of 4 IgG4-RD patients compared with 4 controls. DPM2 (cg21181453), IQCK (cg10266221), and ABCC13 (cg05699681, cg04985582) were hypermethylated and MBP (cg18455083) was hypomethylated in B cells, CD4+ T cells, and salivary gland tissues of IgG4-RD patients. We also observed the hypomethylated HLA-DQB2 in CD4+ T cells from IgG4-RD patients. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DMPs in salivary gland tissues of IgG4-RD patients revealed enrichment of pathways involved in the regulation of immune cell responses and fibrosis.

Conclusion

This is the first DNA methylation study in peripheral B cells, CD4+ T cells, and salivary gland tissues from IgG4-RD patients. Our findings highlighted the role of epigenetic modification of DNA methylation and identified several genes and pathways possibly involved in IgG4-RD pathogenesis.
Continuity of care (COC) and amyloid-β PET scan: the CARE-IDEAS study
Authors: O’Brien Emily C. , Ford Cassie B. , Sorenson Corinna , Jutkowitz Eric , Shepherd-Banigan Megan , Van Houtven Courtney
Published: January 2023

Background

High continuity of care (COC) is associated with better clinical outcomes among older adults. The impact of amyloid-β PET scan on COC among adults with mild cognitive impairment (MCI) or dementia of uncertain etiology is unknown.

Methods

We linked data from the CARE-IDEAS study, which assessed the impact of amyloid-β PET scans on outcomes in Medicare beneficiaries with MCI or dementia of uncertain etiology and their care partners, to Medicare claims (2015–2018). We calculated a participant-level COC index using the Bice-Boxerman formula and claims from all ambulatory evaluation and management visits during the year prior to and following the amyloid-β PET scan. We compared baseline characteristics by scan result (elevated or non-elevated) using standardized differences. To evaluate changes in COC, we used multiple regression models adjusting for sociodemographics, cognitive function, general health status, and the Charlson Comorbidity Index.

Results

Among the 1171 cohort members included in our analytic population, the mean age (SD) was 75.2 (5.4) years, 61.5% were male and 93.9% were non-Hispanic white. Over two-thirds (68.1%) had an elevated amyloid-β PET scan. Mean COC for all patients was 0.154 (SD = 0.102; range = 0–0.73) prior to the scan and 0.158 (SD = 0.105; range = 0–1.0) in the year following the scan. Following the scan, the mean COC index score increased (95% CI) by 0.005 (−0.008, 0.019) points more for elevated relative to not elevated scan recipients, but this change was not statistically significant. There was no association between scan result (elevated vs. not elevated) or any other patient covariates and changes in COC score after the scan.

Conclusion

COC did not meaningfully change following receipt of amyloid-β PET scan in a population of Medicare beneficiaries with MCI or dementia of uncertain etiology. Future work examining how care continuity varies across marginalized populations with cognitive impairment is needed.
Bilateral collagenous fibroma of the hard palate: a case report and review of the literature
Authors: El-naggar Hagar A. , El-Mahallawy Yehia A. , Harby Mohamed I. , Abou Madawi Nourhan A.
Published: January 2023

Background

Collagenous fibroma or desmoplastic fibroblastoma is a rare benign fibrous tissue tumor. It usually presents as a painless, slowly growing mass. Collagenous fibroma arises ordinarily inside the subcutaneous tissues or skeletal muscles. Histopathologically, the tumor consists of scattered stellate and spindle cells in a hypovascular collagenous stroma without atypia or infiltration. The oral cavity is a very uncommon site for desmoplastic fibroblastoma. Only 15 published articles in the literature reported the intraoral location. We present a case of collagenous fibroma with a bilateral distribution on the hard palate. This is the second case of bilateral collagenous fibroma after a previously reported one in literature; however, our case was larger, occupying almost the whole palate. We discuss the management of this rare tumor and how we can reach definite diagnosis.

Case presentation

A 37-year-old Caucasian female patient had a huge bilateral firm palatal mass that caused breathing problems. There was no history of trauma and the patient had no relevant medical history Total surgical excision under general anesthesia was carried out and histopathological examination suggested a benign mesenchymal tumor. Immunohistochemistry was necessary to confirm the tumor origin and to exclude aggressive fibromatosis. A diagnosis of bilateral collagenous fibroma was reached. Six months after surgery, there was no recurring lesion and the patient’s health was good.

Conclusions

Collagenous fibroma is a benign fibrous tissue tumor of unknown cause that is treated with simple excision. The prognosis is good with no recurrence. Reaching an accurate diagnosis is mandatory to avoid aggressive treatment since collagenous fibroma may be misdiagnosed as aggressive fibromatosis in case of massive size. Clinicians and pathologists should be aware of this unusual tumor for conservative management without side effects.
Addictive brain-network identification by spatial attention recurrent network with feature selection
Authors: Gong Changwei , Chen Xinyi , Mughal Bushra , Wang Shuqiang
Published: January 2023

Addiction in the brain is associated with adaptive changes that reshape addiction-related brain regions and lead to functional abnormalities that cause a range of behavioral changes, and functional magnetic resonance imaging (fMRI) studies can reveal complex dynamic patterns of brain functional change. However, it is still a challenge to identify functional brain networks and discover region-level biomarkers between nicotine addiction (NA) and healthy control (HC) groups. To tackle it, we transform the fMRI of the rat brain into a network with biological attributes and propose a novel feature-selected framework to extract and select the features of addictive brain regions and identify these graph-level networks. In this framework, spatial attention recurrent network (SARN) is designed to capture the features with spatial and time-sequential information. And the Bayesian feature selection(BFS) strategy is adopted to optimize the model and improve classification tasks by restricting features. Our experiments on the addiction brain imaging dataset obtain superior identification performance and interpretable biomarkers associated with addiction-relevant brain regions.
Grading assessment of steel bar corrosion in concrete structures based on naive Bayesian model and spontaneous magnetic flux leakage effect
Authors: Li Beian , Li Shidong , Zhang Guangzhao , Ying Huajian , Xia Qianwen , Liu Shangkai
Published: January 2023

In order to explore an accurate method to evaluate the corrosion of reinforced concrete structures, the spontaneous magnetic flux leakage (SMFL) signal distribution on the surface of reinforced concrete specimens under different corrosion degrees was scanned based on SMFL technology. The influence of steel bar length, steel bar diameter, and other parameters on the distribution of SMFL signal was studied. The correlation between steel bar corrosion and the characteristic magnetic index of concrete structure was explored. Based on the naive Bayesian model, the classification evaluation of the steel bar corrosion degree of concrete structure was carried out. The results show that the variation of SMFL signal is affected by the corrosion degree α. When the lift-off height and the thickness of concrete protective layer remain unchanged, the slope between the peak and trough of Bz (magnetic induction intensity along z direction) curve increases with the increase of α, and the trough of Bx (magnetic induction intensity along x direction) curve decreases with the increase of the corrosion degree α. The peak and trough of magnetic signal curve can be used as the basis for determining the corrosion position. There is a strong correlation between the magnetic characteristic index β, γ, and the steel corrosion degree α obtained by SMFL. Through the characterization relationship between α, β, and γ, the corresponding models of single and comprehensive index β and γ were established. The results showed that the accuracy of β and γ integrated discriminant Naive Bayesian model-III reached 90.7%, which proved that the evaluation method has high reliability. This study explores the application of SMFL in corrosion detection of concrete structures.
Lessons from CDER’s Quality Management Maturity Pilot Programs
Authors: Maguire Jennifer , Fisher Adam , Harouaka Djamila , Rakala Nandini , Lundi Carla , Yambot Marcus , Viehmann Alex , Stiber Neil , Gonzalez Kevin , Canida Lyle , Buhse Lucinda , Kopcha Michael
Published: January 2023

Between October 2020 and March 2022, FDA’s Center for Drug Evaluation and Research (CDER) completed two pilot programs to assess the quality management maturity (QMM) of drug manufacturing establishments. Mature quality systems promote proactive detection of vulnerabilities, prevent problems before they occur, and foster a culture that rewards process and system improvements. A CDER QMM program may help to advance supply chain resiliency and robustness and mitigate drug shortages. One pilot program evaluated seven establishments located within the U.S. that produce finished dosage form products marketed in the U.S. A second pilot program evaluated eight establishments located outside the U.S. that produce active pharmaceutical ingredients used in drug products marketed in the U.S. The execution of these pilot programs afforded FDA the opportunity to learn important lessons about the establishment QMM assessment process, scoring approach, assessor behaviors, and perceptions of the assessment questions, reports, and ratings. Many of the participating establishments reported that the QMM pilot assessments helped to identify their strengths, weaknesses, and new areas for improvement which they had not previously identified through internal audits or CGMP inspections. There has been a great deal of interest in the outcomes of CDER’s QMM pilot programs and this paper describes, for the first time, the lessons CDER learned and will continue to heed in the development of a QMM program.

Graphical Abstract
Coconut Oil Saturated Fatty Acids Improved Energy Homeostasis but not Blood Pressure or Cognition in VCD-Treated Female Mice
Authors: Sui Ke , Yasrebi Ali , Longoria Candace R , MacDonell Avery T , Jaffri Zehra H , Martinez Savannah A , Fisher Samuel E , Malonza Natasha , Jung Katie , Tveter Kevin M , Wiersielis Kimberly R , Uzumcu Mehmet , Shapses Sue A , Campbell Sara C , Roepke Troy A , Roopchand Diana E
Published: January 2023

Obesity, cardiometabolic disease, cognitive decline, and osteoporosis are symptoms of postmenopause, which can be modeled using 4-vinylcyclohexene diepoxide (VCD)–treated mice to induce ovarian failure and estrogen deficiency combined with high-fat diet (HFD) feeding. The trend of replacing saturated fatty acids (SFAs), for example coconut oil, with seed oils that are high in polyunsaturated fatty acids, specifically linoleic acid (LA), may induce inflammation and gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed a HFD (45% kcal fat) with a high LA:SFA ratio (22.5%: 8%), referred to as the 22.5% LA diet, or a HFD with a low LA:SFA ratio (1%: 31%), referred to as 1% LA diet, for a period of 23 to 25 weeks. Compared with VCD-treated mice fed the 22.5% LA diet, VCD-treated mice fed the 1% LA diet showed lower weight gain and improved glucose tolerance. However, VCD-treated mice fed the 1% LA diet had higher blood pressure and showed evidence of spatial cognitive impairment. Mice fed the 1% LA or 22.5% LA diets showed gut microbial taxa changes that have been associated with a mix of both beneficial and unfavorable cognitive and metabolic phenotypes. Overall, these data suggest that consuming different types of dietary fat from a variety of sources, without overemphasis on any particular type, is the optimal approach for promoting metabolic health regardless of estrogen status.
Minimum Clinically Important Difference in Patients Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion
Authors: Nie James W. , Hartman Timothy J. , MacGregor Keith R. , Oyetayo Omolabake O. , Zheng Eileen , Singh Kern
Published: January 2023

BACKGROUND:

Few studies have established the minimum clinically important difference (MCID) in patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for physical function and pain.

OBJECTIVE:

To establish MCID for physical function and pain patient-reported outcome measures (PROMs) for MIS-TLIF through anchor- and distribution-based methods using the Oswestry Disability Index (ODI) as the anchor.

METHODS:

Ninety-eight patients undergoing primary MIS-TLIF with preoperative and 1-year postoperative ODI scores were identified. MCID was calculated using anchor- and distribution-based methods. ODI responders were classified as patients who decreased by 1 disability classification. PROMs of Patient-Reported Outcome Measurement Information System-Physical Function (PROMIS-PF), 12-Item Short Form Physical Component Score (SF-12 PCS), Visual Analog Scale (VAS) back/leg, and ODI were collected preoperatively and 1-year postoperatively. Anchor-based methods were average change, minimum detectable change, change difference, receiver operating characteristic curve, and cross-sectional analysis. Distribution-based methods were standard error of measurement, receiver change index, effect size, and 0.5 ∗ ΔSD.

RESULTS:

Anchor-based methods ranged from 4.2 to 11.9 for PROMIS-PF, 6.0 to 15.8 for SF-12 PCS, 1.8 to 4.6 for VAS back, and 2.1 to 4.0 for VAS leg. The area under the curve for receiver operating characteristic analysis ranged from 0.66 to 0.81. Distribution-based methods ranged from 1.1 to 3.9 for PROMIS-PF, 1.6 to 10.4 for SF-12 PCS, 0.5 to 1.6 for VAS back, and 0.6 to 1.8 for VAS leg.

CONCLUSION:

Patients undergoing MIS-TLIF had a wide range of MCID values. The receiver operating characteristic curve was selected as the most clinically appropriate method. The corresponding MCID values were 4.2 for PROMIS-PF, 6.8 for SF-12 PCS, 1.8 for VAS back, and 2.4 for VAS leg.
The Thin Moral Concept of Evil
Authors: Wilby Michael
Published: January 2023

Evil-scepticism comes in two varieties: one variety is descriptive, where it is claimed that the concept of evil does not successfully denote anything in the world; the other variety is normative, where it is claimed that the concept of evil is not a helpful or useful concept to be employing in either our social or interpersonal lives. This paper argues that evil-scepticism can be responded to by understanding the concept of evil as a thin moral concept. Understood in this thin way, the descriptive challenge fades, because the concept of evil does not even purport to denote anything in the world (it is purely evaluative), and so does the normative argument, since the thinness of the concept means that, first, it is ineliminable anyway, and, second, its malleability allows for it to be used for progressive and constructive means.
Nature Without the State: An Anarchist Critique of ‘Animalistic Evil’
Authors: Day Jason K.
Published: January 2023

I here present an anarchist critique of the idea of ‘animalistic evil’ and its common use as a justification for the State’s existence and use of force. On this view, ‘evil’ is a privation of morality, justice, and civilised behaviour. It is then identified with the ‘animalistic’ since animals are often thought to be defined by the aforesaid privation. I first clarify the idea of animalistic evil within the history of philosophy and science. Aristotle (384–322 BCE), Thomas Hobbes (1588–1679), and Thomas H. Huxley (1825–1895) prominently argue that all that prevents humanity from devolving into animalistic evil, a state of violent and individualistic struggle for bare survival, is the power of State government to forcibly control the animalistic drives within its citizens. I subsequently pose two questions. (1) Is it justified to associate animal life with evil when this is (a) understood as a privation of a morality, justice and society and (b) characterised as an individualistic struggle for survival? (2) If this is not justified, what is the political harm of doing so? Building on the work of the anarchist thinker Peter Kropotkin (1842–1921), I argue that any conception of animalistic evil is unjustifiable, that it is a false justification for the State’s existence and use of force, and that the State, upon making the empty threat of animalistic evil, both violently harms individuals and impedes the socially beneficial practice of mutual aid.
Prácticas pedagógicas desde la pertinencia cultural en escuelas multigrado del Norte Mexicano.
Authors: Castillo Morán Amelia , Medina López Julio Erick
Published: January 2023

El presente documento, da cuenta de los resultados investigativos para develar la pertinencia cultural de las prácticas pedagógicas desde la perspectiva de los actores, en escuelas multigrado que forman parte del nivel de Educación Básica Primaria General, en cuanto determinante para la implementación de la educación intercultural en el norte de México. El trabajo de investigación presenta una metodología cualitativa de tipo interpretativo, con un diseño de estudio de casos múltiples. El muestreo que se realiza es intencionado estructural con la participación de 20 profesores docentes y 4 directivos en entrevistas en profundidad y 2 grupos focales. El modelo seleccionado para la interpretación de los datos es de tipo inductivo, lo que permite dar cuenta de que las prácticas pedagógicas realizadas en contexto multigrado, desde la perspectiva de los actores, permite la implementación de la educación intercultural, sin embargo, los resultados dan cuenta un vacío relacionado con la intencionalidad de hacer educación intercultural por parte de los actores derivado del análisis de las categorías emergentes tales como la didáctica, currículo, gestión y experiencias de estudiantes.
Variables asociadas al uso de pantallas al término de la primera infancia
Authors: Ortiz-de-Villate Carla , Gil-Flores Javier , Rodríguez-Santero Javier
Published: January 2023

El actual desarrollo de las TIC ha generalizado el uso de pantallas. Los riesgos de un tiempo excesivo de exposición a pantallas son especialmente relevantes para los niños, desde edades tempranas. Este trabajo analiza la relación entre tiempo de pantallas y otras variables personales y contextuales en la infancia. Participan 94092 niños de aproximadamente 8 años, escolarizados en centros educativos de Andalucía (España). Los datos fueron generados en una evaluación a gran escala promovida por la Administración educativa regional, que supuso la aplicación de pruebas para medir aprendizajes y de cuestionarios de contexto familiar. Los análisis se basan en las pruebas t y chi-cuadrado, para comprobar las diferencias entre los grupos, y en la construcción de un modelo de regresión logística binaria para valorar el peso de las variables en la explicación del tiempo de pantallas. Los resultados indican que un elevado tiempo de pantallas se asocia a menor rendimiento en comunicación lingüística y razonamiento matemático. El género, la hora de acostarse y el nivel socioeconómico familiar son variables que contribuyen a explicar el tiempo de pantallas. A partir de estos resultados se formulan recomendaciones de cara a la intervención preventiva por parte de las familias y otros agentes educativos.
Redes sociales y smartphones como recursos para la enseñanza: percepción del profesorado en España
Authors: Lena-Acebo Francisco-Javier , Pérez-Escoda Ana , García-Ruiz Rosa , Fandos-Igado Manuel
Published: January 2023

Los nuevos entornos de aprendizaje y las redes sociales han supuesto un paso adelante con su uso en el aula llegando, incluso, a mostrarse como un importante refuerzo para la educación durante una situación de excepcionalidad provocada por la pandemia mundial del COVID-19. Las acciones y percepciones de los docentes al respecto han sido fundamentales para una respuesta rápida en un confinamiento global en el que las tecnologías móviles han jugado un papel fundamental. Este estudio presenta una investigación descriptiva correlacional con dos objetivos principales: en primer lugar, conocer la accesibilidad y el uso autodirigido de las redes sociales y, en segundo lugar, describir la utilidad percibida en SMD (dispositivos móviles inteligentes) y SNS (sitios de redes sociales) para los profesores. Con un enfoque metodológico cuantitativo y cualitativo se analizaron las correlaciones entre variables establecidas en una muestra de 2.048 profesores españoles. Los resultados destacan, en primer lugar, la ausencia de diferencias en cuanto a edad y género, demostrando así su máxima penetración entre los docentes; en segundo lugar, mostrando la relación entre la frecuencia de uso y la percepción positiva hacia la pertinencia en la actividad pedagógica. Las conclusiones abordadas desde el enfoque cualitativo muestran cuestiones interesantes que apuntan a la falta de conocimiento, sentido de responsabilidad y riesgos asociados cuando los docentes expresan sus percepciones sobre el uso de SMD y SNS en una integración pedagógica. Esto implica una perspectiva positiva ya que los docentes demandan apoyo y capacitación, pero no muestran rechazo como cabría esperar.
On the Value of Dynamism in Transit Networks
Authors: Martínez Mori J. Carlos , Speranza M. Grazia , Samaranayake Samitha
Published: January 2023

The rise of on-demand mobility technologies over the past decade has sparked interest in the integration of traditional transit and on-demand systems. One of the main reasons behind this is the potential to address a fundamental trade-off in transit: the ridership versus coverage dilemma. However, unlike purely fixed systems or purely on-demand systems, integrated systems are not well understood; their planning and operational problems are significantly more challenging, and their broader implications are the source of a heated debate. Motivated by this debate, we introduce the dynamicity gap, a general concept that quantifies the attainable benefit of allowing (but not requiring) dynamic components in the response strategy to a multistage optimization problem. Although computing the dynamicity gap exactly may be intractable, we develop an analytical framework with which to approximate it as a function of problem input parameters. The framework allows us to certify the value of dynamism (i.e., a dynamicity gap greater than one) for certain combinations of problem input parameters. We showcase our approach with two sets of computational experiments, from which we gain both qualitative and quantitative insights about the settings in which the integration of transit and on-demand systems may certifiably be a worthwhile investment.

Funding: This work was partially supported by the National Science Foundation [Grants DMS-1839346 and CNS-1952011]. Part of this research was performed while the authors were visiting the Institute for Pure and Applied Mathematics, which is supported by the National Science Foundation [Grant DMS-1925919].

Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2022.1193 .
Un ratón que nada y come peces
Authors: Martín-Regalado Natalia , Briones-Salas Miguel
Published: January 2023

Sabemos que los ratones tienen hábitos terrestres o arborícolas, que comen hierbas o semillas, pero que naden y se alimenten de peces e insectos acuáticos sí que es increíble de imaginar, pero existen y viven en México.
Reflecting on patient safety in 2022
Authors: Tingle John
Published: January 2023

John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, discusses some major patient safety reports published in 2022, and considers the lessons to take away from them
Considering changes to education
Authors: Foster Sam
Published: January 2023

Sam Foster, Chief Nurse, Oxford University Hospitals, looks at research commissioned by the Nursing and Midwifery Council into views on changing the standards for pre-registration nursing education programmes
Intentional non-adherence in the context of antiretroviral therapy
Authors: Foote Liz
Published: January 2023

Adherence to antiretroviral therapy (ART) is a crucial determinant of treatment success in HIV. This article seeks to look closely at intentional non-adherence and why some patients choose to opt out of life-sustaining treatment. There is a range of reasons why patients intentionally stop taking their ART and the author take a more detailed look at some of those reasons, specifically religion, the need for control and social isolation. Case studies are included throughout the discussion to give more depth and increase understanding. The author goes to explore strategies that can be employed to help nurses in their response, as health professionals, to support patients and deliver high-quality and non-judgemental care.
Reaction v response
Authors: Webster Chloe
Published: January 2023

So much research has been conducted on understanding and supporting children's behaviour in the early years, but as practitioners we need to look more critically at ourselves and our own reactions and responses to be able to fully understand and support children's behaviour.
Positioning play
Authors: Grimmer Tamsin
Published: January 2023

Have you ever re-stacked the dishwasher after someone else helped you to load it? The position of objects is very important at times and even adults may become obsessed with putting things in order or straightening a picture on the wall. The latest article in this series explores this in more detail.

Positioning–children show an interest in where things are, positioning items in lines, rows or by size. They may be fascinated with different types of lines (vertical or horizontal) or walk around sand tray edges or balance on walls. Some children may even prefer certain foods not to touch other foods or may be interested in the position of their bodies by lying on floors or under tables.
Franchising with family
Authors: Jennings Victoria
Published: January 2023

Working with family is no easy task, people often avoid it all together.

Here Victoria Jennings provides some tips into how to make this easier if you do decide to take this step.
Damien Hirsts' spot paintings
Authors: Marycz Adam
Published: January 2023

I believe one of the most undervalued areas in education holistically, not just in early years is art. In my setting I want this to be different. I work to educate both myself and the children about artists and their work. One way is by providing the children with invitations/provocations exploring the work of different artists like this one studying Damien Hirst.
Babies born during the COVID-19 pandemic
Authors: Johnson Louisa
Published: January 2023

In upcoming issues of EYE, Louisa Johnson, an early childhood studies graduate from University of Chichester, will be sharing her research on the impact of the COVID-19 pandemic on families with babies. Here she introduces her research..
Doing harm: the impact of UK’s GCRF cuts on research ethics, partnerships and governance
Authors: Nwako Zibah , Grieve Tigist , Mitchell Rafael , Paulson Julia , Saeed Tania , Shanks Kelsey , Wilder Rachel
Published: January 2023

In spring 2021, during the COVID-19 pandemic, research projects funded by the UK’s Global Challenges Research Fund (GCRF) were subjected to budget cuts. The cuts were the result of UK government’s decision to reduce its Official Development Assistance (ODA), which had devastating effects for humanitarian, development and research work. This article draws on focus group discussions with project teams working on three large GCRF-funded projects to explore the effects of these cuts. The article documents how the cuts curtailed project aspirations and impact, had a negative toll on the mental health of researchers, and imperilled the trusting relationships upon which international research collaborations are built. The article argues that the cuts expose the shallow commitments to research ethics and equitable partnerships of powerful actors in the UK research ecosystem, including research councils and government. In ‘doing harm’ via these cuts, the article explores the failure of research governance structures and the continued coloniality underpinning the UK’s approach to researching ‘global challenges’.
Effects of dispersion and pumping scheme on soliton-comb regimes in χ
(2) microresonators
Authors: Smirnov S. , Podivilov E. , Sturman B.
Published: January 2023

Monochromatic pumping of

χ

(
2
)

microresonators is promising for frequency comb generation. Two main generation schemes refer to pumping into the phase-matched first harmonic (FH) and second harmonic (SH)—FH and SH pumping. The phase matching can be natural or artificial (employing periodic poling). Also, minimization of the FH and SH group velocity difference (temporal walk-off) is needed for effective comb generation. So far, perspective soliton-comb regimes were predicted for SH pumping in lithium niobate (LN)-based resonators at a special poling. Here we explore, analytically and numerically, the possibilities for realizing the

χ

(
2
)

comb generation for the remaining options of pumping as applied to LN microresonators. This includes the FH pumping case for the pump wavelength

λ
p

≃
2698

n
m

in radially poled resonators and also FH and SH pumping schemes at natural phase matching,

λ
p

≃
1664

and 832 nm. It is found that the nonlinear regimes are substantially different and less efficient here as compared to the primary SH pumping case. This is caused by a profound difference between the FH and SH excitation schemes and also by different combinations of signs of the dispersion coefficients for FH and SH resonator modes.
High-efficiency spectral beam combining of an individual laser diode bar with polarization multiplexing
Authors: Zhang Weiqiao , Cao Peng , Ting Fu , Zhou Xuyan , Zheng Wanhua
Published: January 2023

In this Letter, a new strategy for the spectral beam combining (SBC) of an individual laser diode (LD) bar based on a polarization multiplexing external cavity is proposed and demonstrated. The maximum combining efficiency is up to 95.51%, which leads to an output power of 76.6 W and an electro-optic conversion efficiency of 48.33% under continuous wave operation at a current of 100 A. Compared to the conventional SBC, the combining efficiency, the output power, and the electro-optical conversion efficiency present improvements of 12%, 10W, and 6%, respectively. The results show that this novel SBC method is a prospective technique for increasing the combining efficiency of LD bars.
Ecological landscapes guide the assembly of optimal microbial communities
Authors: George Ashish B. , Korolev Kirill S.
Published: January 2023

Assembling optimal microbial communities is key for various applications in biofuel production, agriculture, and human health. Finding the optimal community is challenging because the number of possible communities grows exponentially with the number of species, and so an exhaustive search cannot be performed even for a dozen species. A heuristic search that improves community function by adding or removing one species at a time is more practical, but it is unknown whether this strategy can discover an optimal or nearly optimal community. Using consumer-resource models with and without cross-feeding, we investigate how the efficacy of search depends on the distribution of resources, niche overlap, cross-feeding, and other aspects of community ecology. We show that search efficacy is determined by the ruggedness of the appropriately-defined ecological landscape. We identify specific ruggedness measures that are both predictive of search performance and robust to noise and low sampling density. The feasibility of our approach is demonstrated using experimental data from a soil microbial community. Overall, our results establish the conditions necessary for the success of the heuristic search and provide concrete design principles for building high-performing microbial consortia.
Chaotic dynamics in spatially distributed neuronal networks generate population-wide shared variability
Authors: Mosheiff Noga , Ermentrout Bard , Huang Chengcheng
Published: January 2023

Neural activity in the cortex is highly variable in response to repeated stimuli. Population recordings across the cortex demonstrate that the variability of neuronal responses is shared among large groups of neurons and concentrates in a low dimensional space. However, the source of the population-wide shared variability is unknown. In this work, we analyzed the dynamical regimes of spatially distributed networks of excitatory and inhibitory neurons. We found chaotic spatiotemporal dynamics in networks with similar excitatory and inhibitory projection widths, an anatomical feature of the cortex. The chaotic solutions contain broadband frequency power in rate variability and have distance-dependent and low-dimensional correlations, in agreement with experimental findings. In addition, rate chaos can be induced by globally correlated noisy inputs. These results suggest that spatiotemporal chaos in cortical networks can explain the shared variability observed in neuronal population responses.
Ubiquitination of stalled ribosomes enables mRNA decay via HBS-1 and NONU-1 in vivo
Authors: Monem Parissa C. , Vidyasagar Nitin , Piatt Audrey L. , Sehgal Enisha , Arribere Joshua A.
Published: January 2023

As ribosomes translate the genetic code, they can encounter a variety of obstacles that hinder their progress. If ribosomes stall for prolonged times, cells suffer due to the loss of translating ribosomes and the accumulation of aberrant protein products. Thus to protect cells, stalled ribosomes experience a series of reactions to relieve the stall and degrade the offending mRNA, a process known as No-Go mRNA Decay (NGD). While much of the machinery for NGD is known, the precise ordering of events and factors along this pathway has not been tested. Here, we deploy C. elegans to unravel the coordinated events comprising NGD. Utilizing a novel reporter and forward and reverse genetics, we identify the machinery required for NGD. Our subsequent molecular analyses define a functional requirement for ubiquitination on at least two ribosomal proteins (eS10 and uS10), and we show that ribosomes lacking ubiquitination sites on eS10 and uS10 fail to perform NGD in vivo. We show that the nuclease NONU-1 acts after the ubiquitin ligase ZNF-598, and discover a novel requirement for the ribosome rescue factors HBS-1/PELO-1 in mRNA decay via NONU-1. Taken together, our work demonstrates mechanisms by which ribosomes signal to effectors of mRNA repression, and we delineate links between repressive factors working toward a well-defined NGD pathway.
Predictive value of hemogram parameters in malignant transformation of the endometrium in patients with different risk factors
Authors: Firat Aysun , Ercan Aysegul , Mordeniz Cengiz , Verit Atmaca Fatma Ferda
Published: January 2023

Objectives

To investigate whether the pretreatment hemogram parameters and their ratios can be used in predicting the endometrial transformation in patients with abnormal uterine bleeding.

Material and methods

Records of all patients who underwent an endometrial histopathological evaluation between 2011 and 2021 were investigated. Hemogram, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were analyzed. Chi square and Mann Whitney U tests were used for analysis. P<0.05 was considered statistically significant.

Results

427 patients were included, of whom 117 were presented with endometrial hyperplasia without atypia (27.4%; mean age, 42±9.7; Group II), 70 with atypia (16.3%; mean age, 53.4±9; Group III), 102 with early endometrial cancer (EC) (23.8%; mean age, 63±7.8; Group IV) and 38 with advanced disease (8.8%; mean age, 63.3±10.5; Group V). Patients without pathology constituted the control group (23.4%; mean age, 42.2±9.5; Group I). Risk factors for atypia and carcinoma were determined as age, postmenopausal state, obesity, diabetes, and increased estrogen exposure (each, p<0.05). There was no significant difference in NLR and PLR (p>0.05). However, hemoglobin and hematocrit levels were higher in Groups IV and V (13.9 vs 13.1 mg/dL, and 39.1 vs 38.8%, respectively; p<0.01). Platelet value was significantly higher in Groups III to V (282x109/L, 283x109/L and 295x109/L; p<0.05, p<0.05 and p<0.01, respectively).

Conclusions

Our findings support the impact of inflammation on malign transformation from normal endometrial mucosa to atypia and carcinoma. NLR and PLR values showed no statistical difference. Instead, thrombocytosis may have a predictive role in EC.
Spatial-temporal variability and influence factors of Cd in soils of Guangxi, China
Authors: Tian Mi , Wang Xueqiu , Liu Futian , Hu Qinghai , Qiao Yu , Wang Qiang
Published: January 2023

In this study, the regional spatial-temporal variability of cadmium (Cd) in the topsoil of Guangxi, China from 2010 to 2016 was studied from data obtained from the China Geochemical Baseline Project (CGB Ⅰ and CGB Ⅱ). The driving forces of natural and anthropogenic variables were quantitatively analyzed using a geographically and temporally weighted regression model. The results showed that 1) soil Cd was highly enriched in 2010 and in soils of Hechi city in northwest Guangxi, a non-ferrous metal mining and metallurgy area, ~17% of the samples exceeded the soil contamination risk limit. In contrast, in 2016, the topsoil Cd content decreased significantly, with 7% of sites exceeding the soil risk limit. 2) Multiple factors jointly influenced the regional spatial variability of Cd. pH and organic carbon were found to be the main factors influencing Cd content and were strongly spatially correlated with Cd. Anthropogenic activities, including mining and industrial emissions, resulted in significant Cd enrichment in local areas, whereas agricultural and domestic pollutants were relatively weakly correlated with Cd. The weathering products of carbonates were significantly enriched in Cd; thus, the geological background played a significant role in the spatial variability of Cd. Soil-forming factors, including temperature, precipitation, and elevation influenced the spatial distribution of Cd, especially in the Cd background area. 3) Anthropogenic activities were the key factors influencing temporal changes in Cd. Mining caused significant enrichment of Cd in CGB Ⅰ, while industrial emissions were the primary factor for Cd enrichment in CGB Ⅱ. In addition, natural factors also played an important role; the increased Normalized Difference Vegetation Index suggested reduced desertification and reduction of soil erosion in the watershed and in pollutants transported from upstream.
Cannabis companies and the sponsorship of scientific research: A cross-sectional Canadian case study
Authors: Grundy Quinn , Imahori Daphne , Mahajan Shreya , Garner Gord , Timothy Roberta , Sud Abhimanyu , Soklaridis Sophie , Buchman Daniel Z.
Published: January 2023

Corporations across sectors engage in the conduct, sponsorship, and dissemination of scientific research. Industry sponsorship of research, however, is associated with research agendas, outcomes, and conclusions that are favourable to the sponsor. The legalization of cannabis in Canada provides a useful case study to understand the nature and extent of the nascent cannabis industry’s involvement in the production of scientific evidence as well as broader impacts on equity-oriented research agendas. We conducted a cross-sectional, descriptive, meta-research study to describe the characteristics of research that reports funding from, or author conflicts of interest with, Canadian cannabis companies. From May to August 2021, we sampled licensed, prominent Canadian cannabis companies, identified their subsidiaries, and searched each company name in the PubMed conflict of interest statement search interface. Authors of included articles disclosed research support from, or conflicts of interest with, Canadian cannabis companies. We included 156 articles: 82% included at least one author with a conflict of interest and 1/3 reported study support from a Canadian cannabis company. More than half of the sampled articles were not cannabis focused, however, a cannabis company was listed amongst other biomedical companies in the author disclosure statement. For articles with a cannabis focus, prevalent topics included cannabis as a treatment for a range of conditions (15/72, 21%), particularly chronic pain (6/72, 8%); as a tool in harm reduction related to other substance use (10/72, 14%); product safety (10/72, 14%); and preclinical animal studies (6/72, 8%). Demographics were underreported in empirical studies with human participants, but most included adults (76/84, 90%) and, where reported, predominantly white (32/39, 82%) and male (49/83, 59%) participants. The cannabis company-funded studies included people who used drugs (37%) and people prescribed medical cannabis (22%). Canadian cannabis companies may be analogous to peer industries such as pharmaceuticals, alcohol, tobacco, and food in the following three ways: sponsoring research related to product development, expanding indications of use, and supporting key opinion leaders. Given the recent legalization of cannabis in Canada, there is ample opportunity to create a policy climate that can mitigate the harms of criminalization as well as impacts of the “funding effect” on research integrity, research agendas, and the evidence base available for decision-making, while promoting high-priority and equity-oriented independent research.
Spillover effect analysis of home-purchase limit policy on housing prices in large and medium-sized cities: Evidence from China
Authors: Wu Guancen , Guo Wenjing , Niu Xing
Published: January 2023

Home-purchase limit is a unique administrative housing policy of China and has non-negligible influences on the housing price. The objective of this study is to analyze the spillover effect of home-purchase limit policy on housing prices in 35 large and medium-sized cities. The panel data of these cities and the spatial Durbin model are employed in this study. The results indicate that the spillover effect of home-purchase limit policy is positive and significant in all of 35 cities. However, when we categorize these cities into high-risk, medium-risk, and low-risk based on housing price characteristics, the spillover effect of home-purchase limit policy is different. It is not significant in high-risk cities, is negatively significant in medium-risk cities, and is positively significant in low-risk cities. This paper suggests that local governments can pay more attention to the precise design and implementation of home-purchase limit policy, and maintain policy continuity to avoid further spillover fluctuations in housing prices.