bluuebunny/crossref_metadata_2025 huggingface dataset:
Binary oncolytic adenovirus in combination with HER2-specific autologous CAR VST for treatment of advanced HER2-positive solid tumors (VISTA).
Authors: Makawita Shalini , Gibbs Jerry M , McFadden Dustin R. , Porter Caroline , Shaw Amanda Rosewell , Robertson Catherine , Woods Mae Louise , Wang Tao , Grilley Bambi J , Heslop Helen E , Brenner Malcolm K , Suzuki Masataka
Published: July 2024

TPS2679

Background: Urgent therapies are needed for patients with refractory Human Epidermal Growth Factor Receptor 2 (HER2) positive solid malignancies. Our group has previously shown potent antitumor effect of a binary oncolytic/helper-dependent adenovirus (CAdVEC) with dual expression of IL-12 and PD-L1 blocker. Initial preclinical and clinical studies with direct tumor injection of CAdVEC has shown it to be safe and result in increased infiltration of CD8 T cells into the tumor microenvironment, with antitumor effect on locoregional and distant metastatic sites.1 Based on these results, we describe an ongoing study with addition of HER2-specific autologous chimeric antigen receptor (CAR)-T cell therapy to CAdVEC. Methods: This is a single arm, dose escalation phase I clinical trial guided by Bayesian Optimal Interval Design (BOIN) for patients with advanced HER2 positive solid tumors. Patients who are deemed unsuitable for curative treatments and progressed after at least one standard first line therapy are eligible. HER2 positivity is determined by IHC and defined as ≥2+. Patients are required to have at least one tumor site appropriate for intratumor injection and radiographically measurable disease per RECIST v1.1. Patients with autoimmune disease requiring systemic corticosteroids greater than 10mg/day and those with active/untreated CNS metastasis are excluded. Patients will receive increasing doses of CAdVEC intratumor injection alone (first two dose levels) or in combination with HER2 specific autologous CAR-T cells (dose levels 3-7). A total of 45 patients are planned. The primary endpoint of the study is to evaluate safety and maximum tolerated dose as assessed by incidence of dose limiting toxicities (DLT) of CAdVEC intratumor injection in combination with HER2-specific autologous CAR T cells. Secondary endpoints include anti-tumor activity of the combination measured by overall response rate (ORR), disease control rate (DCR), median progression free survival (PFS) and median overall survival (OS). Exploratory endpoints include assessing the immunogenicity of combination therapy by determining the impact of treatment on cellular and humoral immunity, as well as assessing long-term persistence and functional status of HER2 CAR T-cells. Correlative analysis of levels of adenovirus antibodies with clinical outcomes and immunological findings are also planned. This study is currently enrolling. 1. Wang D, Porter CE, Lim B, et al: Science Advances 9, 2023. Clinical trial information: NCT03740256 .
Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial
Authors: Ramchand Sabashini K. , Ghasem-Zadeh Ali , Hoermann Rudolf , White Shane , Yeo Belinda , Francis Prudence A. , Xu Cecilia L.H. , Coleman Olivia , Shore-Lorenti Cat , Ebeling Peter R. , Zajac Jeffrey D. , Seeman Ego , Grossmann Mathis
Published: July 2024

PURPOSE

Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)–positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women.

METHODS

In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months). Volumetric bone mineral density (BMD), microarchitecture, and estimated bone strength of the distal tibia and distal radius were measured using high-resolution peripheral quantitative computed tomography, and spine and hip BMD were measured using dual-energy X-ray absorptiometry at 0, 6, and 12 months. The primary end point and treatment effect was the mean adjusted between group difference (MAD; [95% CI]) in distal tibial total volumetric BMD over 12 months, with a single
P
value tested over all time points. The study is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; identifier: ACTRN12616001051437).

RESULTS

Intention-to-treat analysis included all 68 randomly assigned women. Over 12 months, compared with PBO, DMAB prevented the decrease in distal tibial total BMD (MAD, 20.8 mg HA/cm
3
[95% CI, 17.3 to 24.2]), cortical BMD (42.9 mg HA/cm
3
[95% CI, 32.1 to 53.9]), trabecular BMD (3.32 mg HA/cm
3
[95% CI, 1.45 to 5.20],
P
= .004), estimated stiffness (11.6 kN/m [95% CI, 7.6 to 15.6]), and failure load (563 N [95% CI, 388 to 736]). Findings were similar at the distal radius. Decreases in BMD at the lumbar spine (MAD, 0.13 g/cm
2
[95% CI, 0.11 to 0.15]), total hip (0.08 g/cm
2
[95% CI, 0.07 to 0.09], and femoral neck (0.06 g/cm
2
[95% CI, 0.05 to 0.07]) were also prevented. All
P
< .001 unless otherwise noted.

CONCLUSION

Treatment with DMAB at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.
Cancer Therapy, Gonadal Function, and Fertility Preservation: Narrative Review
Authors: Eden Christopher O. , Haslam Alyson , Prasad Vinay
Published: July 2024

PURPOSE

Fertility preservation was designed to help young patients overcome complications of cancer treatments, but its effectiveness is unknown. We sought to investigate how often patients with cancer are offered fertility preservation and if patients offered fertility preservation are more likely to have offspring.

METHODS

We searched Embase (through 2022) and PubMed (through 2022). Our broad computerized search strategy was built upon using the keywords “chemotherapy,” “radiation,” and “fertility.” The search took place on December 1, 2022. We included randomized and observational studies and excluded reviews and case reports/series.

RESULTS

Eighty-five articles that answered at least one of the research questions were included. Studies assessing fertoprotective therapies often rely on surrogate markers for fertility. Multiple factors affect these markers of fertility. The median premature ovarian failure rate among the intervention group was 18% (IQR, 12%-20%), and among the control group, it was 25% (IQR, 19%-33%). Five of 11 studies reported a significant benefit from fertoprotective therapy. Pregnancies occurred in a median of 21% (IQR, 6%-52%) of patients in the intervention group and 11% (IQR, 7-44) of patients in the control group, with three of seven studies reporting a higher percentage of pregnancies among the intervention group.

CONCLUSION

We reviewed the literature on several questions surrounding fertility preservation and found that there is limited and low-quality research on these therapies in cancer. Hence, there is a strong need for studies, especially randomized studies, that follow patients with cancer who undergo fertility preservation and assess outcomes in which patients are most interested.
Designing and Validating a Comprehensive Patient-Reported Outcomes Measure for Ambulatory Cancer Settings: The Revised Edmonton Symptom Assessment System for Cancer
Authors: Watson Linda , Link Claire , Qi Siwei , DeIure Andrea , Chmielewski Lindsi , Hildebrand April , Barbera Lisa
Published: July 2024

PURPOSE

Patient-reported outcomes (PROs) information has been routinely collected in Cancer Care Alberta (CCA) for years using the revised Edmonton Symptom Assessment System (ESAS-r) and Canadian Problem Checklist (CPC). There was interest in combining these into a more comprehensive single measure tailored to ambulatory cancer settings. The purpose of this study was to validate an expanded and redesigned ESAS-r called the ESAS-r Cancer.

METHODS

Stakeholder engagement, a review of the literature, and 2 years of CPC data collected in the cancer program informed the addition of six symptoms to the ESAS-r. To assess and validate the measure, 1,600 randomly sampled patients were mailed paper copies of the ESAS-r Cancer, ESAS-r, and a validated, comprehensive PRO measure called the Memorial System Assessment Scale-Short Form (MSAS-SF), which is often used with patients with cancer. Canonical Correlation Analysis and exploratory factor analyses were performed to assess concurrent and construct validity of the ESAS-r Cancer against ESAS-r, using MSAS-SF as the reference measure for comparison. Cronbach α was calculated to assess reliability.

RESULTS

Four hundred and sixty-one patients (29% response rate) completed all three questionnaires. ESAS-r Cancer showed higher numerical correlation than ESAS-r and accounted for more information included on MSAS-SF, explaining slightly more variance than ESAS-r (75.2%
v
73.5%). The three-dimensional factor structure of ESAS-r Cancer outperformed the two-dimensional factor structure of ESAS-r. The reliability of ESAS-r Cancer was verified and found to be slightly higher than ESAS-r (Cronbach α = .903
v
.884).

CONCLUSION

ESAS-r Cancer is now in use with patients throughout CCA. This valid and reliable PRO measure can be used by other cancer or specialized health care programs who wish to routinely assess common symptoms.
Association Between Medicare Site-Based Payment Policy, Physician Practice Characteristics, and Vertical Integration Among Oncologists
Authors: Hu Xin , McCarthy Ian , Yabroff K. Robin , You Wen , Lipscomb Joseph , Graetz Ilana
Published: July 2024

PURPOSE

Medicare's differential payments for services delivered in physician offices versus hospital outpatient settings incentivize hospital-physician integration (ie, vertical integration) across many specialties, but evidence for oncologists is mixed. We examined the association of Medicare site-based payment policy and physician practice characteristics, including service volume and diversity, with vertical integration among oncologists in 2013-2019.

METHODS

Using the Medicare Provider Utilization and Payment Data and Medicare Data on Provider Practice and Specialty in 2013-2019, we extracted nonintegrated medical/hematologic oncologists (hereafter oncologists) in 2013 and followed them through 2019. We quantified the incentives from Medicare site-based payment policy using the hospital-office ratio—total Medicare payments if all services were delivered in the hospital outpatient department (HOPD) versus physician office. Vertical integration was defined as billing >10% of services to HOPD in a year. Multivariable linear probability regressions estimated the association between hospital-office ratio and vertical integration in 2014-2019 with and without accounting for provider characteristics.

RESULTS

In 2013, the average hospital-office ratio was 1.63, which increased to 1.99 in 2018. A 25th-to-75th percentile increase in the hospital-office ratio was negatively associated with integration (–1.01 percentage points [ppts], 95% CI = −1.45 to −0.57,
p
< .001) not accounting for physician practice characteristics; this association was attenuated (–0.30 ppts, 95% CI = −0.67 to 0.07,
p
= .11) after adjusting for these characteristics. Higher baseline (ie, 2013) service volume (Quartile4
v
Quartile1 = –3.00 ppts, 95% CI = −4.42 to −1.59,
p
< .001), more diverse services (Quartile4
v
Quartile1 = –3.55 ppts, 95% CI = −4.97 to −2.13,
p
< .001), and urban location (–5.23 ppts, 95% CI = −6.89 to −3.57,
p
< .001) were more strongly associated with vertical integration.

CONCLUSION

Compared to Medicare site-based payment policy, oncologists' practice characteristics emerged as more potent factors for integration and should be considered to ensure the intended impacts of site-based payment reform. Our finding raises questions about the effectiveness of ongoing movements toward site-neutral payment for drug administration services to deter vertical integration in oncology.
GH Treatment in Children of Normal Height
Authors: Mendonca Berenice B , Arnhold Ivo J P
Published: July 2024

The increased availability of recombinant human GH (rhGH), albeit at a relatively high cost, has increased a demand for treatment of children and adolescents of normal height to increase their adult stature. There are no scientific reports on the efficacy and safety of rhGH therapy in this condition; therefore, the authors comment on the possible causes and consequences based on their personal opinion and experience. As in gigantism, when GH action and end-organ are normal, enough GH is expected to result in increased growth velocity. Short-term adverse effects related to rhGH therapy for approved indications of short stature in children have been very rare. Data on long-term adverse effects are still scarce. A small increase in height might be statistically significant but not functionally or socially relevant. Considering that an increase in height represents more a desire than a need, physicians should emphasize the normality and qualities of these children, discuss with families the alternatives, such as counseling, and refrain from supporting the concept that taller is better.
Reduced Nephrin Tyrosine Phosphorylation Enhances Insulin Secretion and Increases Glucose Tolerance With Age
Authors: Williamson Casey R , Jones Nina
Published: July 2024

Background

Nephrin is a transmembrane protein with well-established signaling roles in kidney podocytes, and a smaller set of secretory functions in pancreatic β cells are implicated in diabetes. Nephrin signaling is mediated in part through its 3 cytoplasmic YDxV motifs, which can be tyrosine phosphorylated by high glucose and β cell injuries. Although in vitro studies demonstrate these phosphorylated motifs can regulate β cell vesicle trafficking and insulin release, in vivo evidence of their role in this cell type remains to be determined.

Methods

To further explore the role of nephrin YDxV phosphorylation in β cells, we used a mouse line with tyrosine to phenylalanine substitutions at each YDxV motif (nephrin-Y3F) to inhibit phosphorylation. We assessed islet function via primary islet glucose-stimulated insulin secretion assays and oral glucose tolerance tests.

Results

Nephrin-Y3F mice successfully developed pancreatic endocrine and exocrine tissues with minimal structural differences. Unexpectedly, male and female nephrin-Y3F mice showed elevated insulin secretion, with a stronger increase observed in male mice. At 8 months of age, no differences in glucose tolerance were observed between wild-type (WT) and nephrin-Y3F mice. However, aged nephrin-Y3F mice (16 months of age) demonstrated more rapid glucose clearance compared to WT controls.

Conclusion

Taken together, loss of nephrin YDxV phosphorylation does not alter baseline islet function. Instead, our data suggest a mechanism linking impaired nephrin YDxV phosphorylation to improved islet secretory ability with age. Targeting nephrin phosphorylation could provide novel therapeutic opportunities to improve β cell function.
Unsettled Labors
Authors: Brown Rachel H.
Published: July 2024

In Unsettled Labors, Rachel H. Brown explores the overlooked labor of migrant workers in Israel’s eldercare industry. Brown argues that live-in eldercare in Palestine/Israel, which is primarily done by migrant workers, is an often invisible area where settler colonialism is reproduced culturally, economically, and biologically. Situating Israeli labor markets within a longer history of imperialism and dispossession of Palestinian land, Brown positions migrant eldercare within the resulting tangle of Israeli laws, policies, and social discourses. She draws from interviews with caretakers, public statements, court documents, and first-hand fieldwork to uncover the inherently contradictory nature of elder care work: the intimate presence of South and Southeast Asian workers in the home unsettles the idea of the Israeli home as an exclusively Jewish space. By paying close attention to the comparative racialization of migrant workers, Palestinians, asylum seekers, and Mizrahi and Ashkenazi settlers, Brown raises important questions of labor, social reproduction, displacement, and citizenship told through the stories of collective care provided by migrant workers in a settler colonial state.
Bridging the Senses: Medium and Materiality from Music Videos to Graphic Lyrics
Authors: Ty Andrew
Published: July 2024

Inter- and extratextual media platforms define much of the realm of fandom and franchising. In “Bridging the Senses: Medium and Materiality from Music Video to Graphic Lyric,” Andrew Ty analyzes a set of illustrated books based on BTS songs and music videos that first introduced the The most beautiful moment in life albums’ Bangtan Universe storylines. Ty highlights how the physical objects of the Graphic Lyric books—the way they are physically designed—invite readers to manually handle the texts to engage with tactility. Ty argues that this “old” media, particularly in the rich transmedia landscape of Bangtan Universe and K-Pop in general, produces new ways of experiencing the audio and visual experiences of the songs and videos, which further enrich the fans’ engagement and memory of the original material.
“Gender DOES NOT Exist Outside of Patriarchy”: Flower Boys, Gender Envy, and the Radical Possibilities of JIMIN GENDER
Authors: Lee S. Heijin
Published: July 2024

In “‘Gender DOES NOT Exist Outside of Patriarchy’: Flower Boys, Gender Envy, and the Radical Possibilities of JIMIN GENDER,” S. Heijin Lee examines the intersection between South Korean and North American constructions of masculinity and how North American fans perceive BTS member Jimin as a gender category unto himself. Lee tracks the emergence of the flower boy aesthetic in Asia, with attention to how the South Korean idol industry and BTS, in particular, links it with luxury brand identification and desire. Images of Jimin, as the personification of this emergent racial, classed, and gendered persona, circulate on social media and are overlaid with fan projections of their own desires about gender. The chapter focuses on social media expressions about Jimin to argue that Jimin’s persona provides a medium for fans to critique gender binaries and definitions.
Full Endoscopic Transpedicular Discectomy for a Rostrally Migrated L5-S1 Disc Herniation in the Setting of Previous Lumbar Surgery: A Case Report With Intraoperative Video
Authors: Mambelli Dorian , Farrell Ryan , Huang Meng
Published: July 2024

BACKGROUND AND IMPORTANCE:

The surgical management of rostral disc herniations at L5-S1 poses challenges for conventional endoscopic approaches, particularly in patients who have had previous lumbar surgery. We present a full endoscopic transpedicular discectomy (FETD), whereby a pediculotomy is created to pass an endoscope through the pedicle for intracanal access. This addresses anatomic obstacles and potential complications associated with other endoscopic and minimally invasive or open techniques. To date, this is the only article to highlight this approach with a case report and intraoperative video.

CLINICAL PRESENTATION:

A 76-year-old man with a history of L3-S1 laminectomy presented with left leg pain and a near-complete left foot drop. An MRI revealed a left paracentral rostrally migrated disc herniation arising from L5-S1 with impingement of the exiting left L5 nerve root at the inferomedial aspect of the pedicle of L5. The patient consented to the FETD procedure. Using sequential reamers of increasing diameter and a high-speed burr, a superolateral to inferomedial pediculotomy was performed. This approach allowed us to target the pathology at the point of maximum compression without traversing the prior operative field. A transforaminal endoscopic approach was not possible with the iliac crest obstructing rostral angulation. The disc was successfully removed without any intraoperative complications, and after surgery, the patient's radiculopathy resolved without any radiographic evidence of instability.

CONCLUSION:

FETD is a unique approach that demonstrates the versatility of endoscopic spine surgery, offering advantages over conventional approaches particularly for rostral disc herniations at L5-S1 in the setting of prior lumbar surgery.
Effective and appropriate use of weight loss medication in pediatric obesity: a narrative review
Authors: Chung Yoojin Lindsey
Published: July 2024

Over the past few decades, there has been a notable increase in the incidence of pediatric obesity, which is a significant public health concern. Children who are obese have a greater risk of type 2 diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, obstructive sleep apnea, and adult obesity. Lifestyle modification therapy is typically the initial approach to treat pediatric obesity. For patients who do not achieve success with lifestyle modification therapy alone, pharmacotherapy is the next logical treatment option. When selecting an anti-obesity medication (AOM), it is essential to first ascertain the medical background of the patient, including current medications and obesity-associated comorbidities. Evaluation of obesity phenotypes in patients may also be beneficial. AOMs for pediatric obesity include metformin, orlistat, glucagon-like peptide 1 agonists, phentermine, and the phentermine/topiramate combination. Sufficient lifestyle modification therapy should be administered before considering pharmacotherapy and continued after the initiation of AOM. To ensure healthy development, monitoring growth and puberty development during anti-obesity treatments is essential.
Comparing Antimicrobial Effects of Heterotrigona itama Propolis from Two Regions of Malaysia Against Enterococcus faecalis
Authors: Ibrahim Nur Syaza Amni , Helmi Ramli Muhammad Rafizul , Gulam Khan Hasnah Begum Said , Al-Bayaty Fouad Hussain M.H , Ismail Ikmal Hisham
Published: July 2024

Objective: This present study aimed to determine and compare the antimicrobial properties of Malaysian propolis (MP) produced by Heterotrigona Itama from different regions of Malaysia, against E. faecalis.
Methods: The propolis were obtained in Lenggong MLP (North Peninsula Malaysia) and Raub MRP - (Central Peninsula Malaysia). The antibacterial activities of the ethanolic extracts of propolis were conducted using antimicrobial susceptibility test (AST), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). The effect of these extracts on the cell morphology were observed using scanning electron microscopy (SEM). Calcium hydroxide and 5% dimethyl sulfoxide (DMSO) were used as controls.
Results: Statistical analysis was done using unpaired t-test to differentiate the difference of the two averages. The ethanol extracts of MLP showed higher activity compared to MRP at 50mg/ml on E. faecalis with zone of inhibition of 14.33mm and 10.00mm respectively. MIC test for MRP and MLP was 0.78125mg/ml and 3.125mg/ml respectively. Whereas the MBC value for both MRP and MLP was 12.50mg/ml and 50.00mg/ml respectively. SEM analysis showed that MP disrupted the size, cell morphology and the structure of the bacteria cell wall.
Conclusion: Our study showed MRP outperformed MLP against E. faecalis via MIC, MBC and SEM. Dissimilarities of surrounding trees in Raub and Lenggong may provide the variable chemical source contributing to this contrast. Thus, these stingless bees have a very special relationship with plant resins, relying on them for the very survival of their nests.
New Equations Describing the Rheological Behavior of Chocolate
Authors: Stanciu Ioana
Published: July 2024

The first archaeological mentions of cacao date back nearly 4,000 years and were discovered by researchers in Central America and Mexico. Chocolate is a compound that contains milk powder, cocoa, sugar, vanilla sugar and water. The objective of this article is determination two rheological equations determined by the method of least squares and whose coefficients depend on the chocolate concentration and temperature. We used a DV-3P Anton Paar digital rotational viscometer.
Validez de contenido por juicio de expertos: Integración cuantitativa y cualitativa en la construcción de instrumentos de medición
Authors: Maldonado-Suárez Neiber , Santoyo-Telles Felipe
Published: July 2024

INTRODUCCIÓN. Algunas expresiones como la inteligencia, la personalidad, las emociones o las percepciones no son tangibles, por lo que se miden mediante constructos compuestos por dimensiones, evaluadas con ítems; esto requiere el desarrollo de instrumentos de medición que permitan inferir la presencia de dichas variables.
MÉTODO. La construcción de estos instrumentos es un proceso complejo, iterativo, con diversas fases de revisión y validación empírica. La validez de contenido por juicio de expertos es una de estas fases; implica someter los ítems al juicio de especialistas para identificar vacíos, ambigüedades o sesgos. Aunque esto asegura la representatividad y relevancia de los ítems, rara vez se informa este procedimiento en la validación de instrumentos.
RESULTADOS. Este artículo sintetiza el procedimiento de validez de contenido por juicio de expertos en la construcción de un instrumento de medición; además, muestra la ejecución del análisis cuantitativo mediante el Coeficiente de Validez de Contenido con apoyo de una macro de Excel, así como la integración cualitativa de las observaciones proporcionadas por los jueces.
CONCLUSIÓN. Se concluye con la importancia de sistematizar e informar sobre las decisiones tomadas en este proceso, a fin de garantizar el rigor y trazabilidad en la construcción de instrumentos de medición.
The Mother in Kore-eda's Broker : Striking New Reverberations in the Korean Context
Authors: An Ji-yoon
Published: July 2024

Abstract: This article's interest in Hirokazu Kore-eda's Broker (2022) is twofold. First, it analyzes the visual text to unwrap the ideas of conventionality that are subtly debunked in the making of an unconventional family, amidst which it analyzes the mother character to be a central force of redemption and union. Ultimately, it argues the role of motherhood in this new family unit to be that of an imaginary and ideological vessel. Second, it positions this idea against the history of Korean cinema, where decades of films have similarly glorified motherhood as an unconditional love that redeems. Yet Kore-eda's radical image of a teenage sex worker as the bearer of this ideology simultaneously resonates with a different strand of Korean films: half-commercial half-arthouse films from the mid-1990s and 2000s known as "high-quality films." Motherhood is one of two connections that can be drawn between Broker and high-quality films. While the mother aligns with the female precedents of these films by together pushing the boundaries of the Korean cinematic mother, her pivotal role in the making of a new kind of family also connects to depictions of "alternative families." Such reverberations are meaningful not only in allowing Broker to be positioned within the context of Korean film history as a story that interlaces with the ideas of Korean films despite being made by a non-Korean auteur, but also in illuminating the trans- and multi-national nature of (art) films today, where the lowering of the national boundaries surrounding auteurs are leading to multi-contextual films.
Probabilistic Models and Statistics for Electronic Financial Markets in the Digital Age
Authors: Bibinger Markus
Published: July 2024

The scope of this manuscript is to review some recent developments in statistics for discretely observed semimartingales which are motivated by applications for financial markets. Our journey through this area stops to take closer looks at a few selected topics discussing recent literature. We moreover highlight and explain the important role played by some classical concepts of probability and statistics. We focus on three main aspects: Testing for jumps; rough fractional stochastic volatility; and limit order microstructure noise. We review jump tests based on extreme value theory and complement the literature proposing new statistical methods. They are based on asymptotic theory of order statistics and the Rényi representation. The second stage of our journey visits a recent strand of research showing that volatility is rough. We further investigate this and establish a minimax lower bound exploring frontiers to what extent the regularity of latent volatility can be recovered in a more general framework. Finally, we discuss a stochastic boundary model with one-sided microstructure noise for high-frequency limit order prices and its probabilistic and statistical foundation.
Missing the vulnerable—Inequalities in social protection in 13 sub-Saharan African countries: Analysis of population-based surveys
Authors: Chipanta David , Amo-Agyei Silas , Hertzog Lucas , Hosseinpoor Ahmad Reza , Smith Michael , Mahoney Caitlin , Jaramillo Meija Juan Gonzalo , Keiser Olivia , Estill Janne
Published: July 2024

We assessed socioeconomic inequalities in social protection coverage among the public, men and women living with the human immunodeficiency virus (MLHIV, WLHIV), and adolescent girls and young women (AGYW). We used population-based data from Cameroon, Côte d’Ivoire, Ethiopia, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. We constructed concentration curves (CC) and computed concentration indices (CIX) for each country and population group. A CC represents the cumulative percentage of social protection coverage plotted on the y-axis against the cumulative proportion of the population—ranked by socioeconomic status from the poorest to the richest—on the x-axis. The CIX quantifies the concentration of social protection coverage among the poor or the rich. The sample size ranged from 10,197 in Eswatini to 29,577 in Tanzania. Social protection coverage among the public varied from 5.2% (95% Confidence Interval 4.5%–6.0%) in Ethiopia to 39.9% (37.0%–42.8%) in Eswatini. It ranged from 6.9% (5.7%–8.4%) MLHIV in Zambia to 45.0% (41.2–49.0) among WLHIV in Namibia. Among AGYW, it varied from 4.4% (3.6–5.3) in Ethiopia to 44.6% (40.8–48.5) in Eswatini. Socioeconomic inequalities in social protection coverage favored the poor in 11/13 countries surveyed. It favored the rich in Cameroon and was undefined in Côte d’Ivoire. The CIX in these 11 countries ranged from −0.080 (p = 0.002) among the public in Malawi to −0.372 (p< 0.001) among WLHIV in Zimbabwe. In 8 of these 11 countries, ≥15% of people from the poorest households reported receiving social protection. Only in countries with higher levels of social protection coverage did most people from the poorest households achieve high coverage. Social protection coverage was low and favored the poor. Pro-poor social protection is insufficient to reach the poor. Research is required to reach the poorest households with social protection in Africa.
Characteristics of surveillance systems for suicide and self-harm: A scoping review
Authors: Silva Aline Conceição , Vanzela Amanda Sarah , Pedrollo Laysa Fernanda Silva , Baker John , de Carvalho José Carlos Marques , Sequeira Carlos Alberto da Cruz , Vedana Kelly Graziani Giacchero , Santos José Carlos Pereira dos
Published: July 2024

Background

Suicide is a complex public health issue. Surveillance systems play a vital role in identifying trends and epidemiologic needs, informing public health strategies, and tailoring effective context-based suicide prevention interventions.

Aim

To identify and summarise the characteristics of specific surveillance systems and general health behaviour that include data onsuicide and self-harm.

Method

A scoping review following the JBI recommendations and PRISMA-ScR guidelines identified 29 relevant studies on suicide and self-harm surveillance systems. A systematic search was performed on Cinahl, Embase, Lilacs—Latin American and Caribbean Health Sciences Literature, PubMed—US National Library of Medicine, Scopus, and Google Scholar. The eligibility criteria include papers that use qualitative, quantitative or mixed methods with no restrictions on time or language. The following papers were excluded regarding euthanasia and assisted suicide, as well as papers that did not explicitly describe suicide, self-harm, and surveillance systems. Two researchers independently screened the materials for eligibility and extracted data from the included studies. Data analysis was conducted using content analysis.

Results

Twenty-nine references were included, and 30 surveillance systems were identified and classified into general health behaviour surveillance (n = 15) and specific systems for suicide and self-harm (n = 15). General health behaviour systems often operate at national data collection level, collecting non-fatal data in healthcare settings, mainly emergency departments. The specific systems exhibited greater variability in terms of context, involved actors, data collection level, data collection procedures, and case classification. Limitations found by the studies pointed mostly to case definitions and data quality. Co-production, intersectoral collaboration, clear case definition criteria and data standardisation are essential to improve surveillance systems for suicide and self-harm.

Conclusions

This review identified the characteristics of surveillance systems for suicide and self-harm. Monitoring and evaluation are crucial for ongoing relevance and impact on prevention efforts.
Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram
Authors: Ramaswamy Sowmya M. , Kuizenga Merel H. , Weerink Maud A. S. , Vereecke Hugo E. M. , Nagaraj Sunil B. , Struys Michel M. R. F.
Published: July 2024

Background

Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings.

Methods

Multichannel EEG datasets from two different sources were used in this study: (1) sedation dataset consisting of 102 healthy volunteers receiving propofol (N = 36), sevoflurane (N = 36), or dexmedetomidine (N = 30), and (2) publicly available sleep EEG dataset (N = 994). Forty-four quantitative time, frequency and entropy features were extracted from EEG recordings and were used to train the machine learning algorithms on sleep dataset to predict sleep stages in the sedation dataset. The predicted sleep states were then compared with the Modified Observer’s Assessment of Alertness/ Sedation (MOAA/S) scores.

Results

The performance of the model was poor (AUC = 0.55–0.58) in differentiating sleep stages during propofol and sevoflurane sedation. In the case of dexmedetomidine, the AUC of the model increased in a sedation—dependent manner with NREM stages 2 and 3 highly correlating with deep sedation state reaching an AUC of 0.80.

Conclusions

We addressed an important clinical question to identify biological sleep promoting sedatives using EEG signals. We demonstrate that propofol and sevoflurane do not promote EEG patterns resembling natural sleep while dexmedetomidine promotes states resembling NREM stages 2 and 3 sleep, based on current sleep staging standards.
The impact of Astragaloside IV on the inflammatory response and gut microbiota in cases of acute lung injury is examined through the utilization of the PI3K/AKT/mTOR pathway
Authors: Luo Cheng , Ye Yuanhang , Lv Anqi , Zuo Wanzhao , Yang Yi , Jiang Cheng , Ke Jia
Published: July 2024

Objectives

Astragaloside IV (AS-IV) is a natural triterpenoid saponin compound with a variety of pharmacological effects, and several studies have clarified its anti-inflammatory effects, which may make it an effective alternative treatment against inflammation. In the study, we aimed to investigate whether AS-IV could attenuate the inflammatory response to acute lung injury and its mechanisms.

Methods

Different doses of AS-IV (20mg·kg-1, 40mg·kg-1, and 80mg·kg-1) were administered to the ALI rat model, followed by collection of serum and broncho alveolar lavage fluid (BALF) for examination of the inflammatory response, and HE staining of the lung and colon tissues, and interpretation of the potential molecular mechanisms by quantitative real-time PCR (qRT-PCR), Western blotting (WB). In addition, fecal samples from ALI rats were collected and analyzed by 16S rRNA sequencing.

Results

AS-IV decreased the levels of TNF-α, IL-6, and IL-1β in serum and BALF of mice with Acute lung injury (ALI). Lung and colon histopathology confirmed that AS-IV alleviated inflammatory infiltration, tissue edema, and structural changes. qRT-PCR and WB showed that AS-IV mainly improved inflammation by inhibiting the expression of PI3K, AKT and mTOR mRNA, and improved the disorder of intestinal microflora by increasing the number of beneficial bacteria and reducing the number of harmful bacteria.

Conclusion

AS-IV reduces the expression of inflammatory factors by inhibiting the PI3K/AKT/mTOR pathway and optimizes the composition of the gut microflora in AIL rats.
Mild hypothermia pretreatment improves hepatic ischemia-reperfusion injury: A systematic review and meta-analysis of animal experiments
Authors: Wei Li-juan , Wei Ke , Lu Shu-yu , Wang Min , Chen Chun-xi , Huang Hui-qiao , Pan Xiao , Tao Pin-yue
Published: July 2024

Background and aim

Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury.

Methods

We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32–34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software.

Results

Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008].

Conclusion

Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.
Prevalence of major depressive disorder and its determinants among young married women and unmarried girls: Findings from the second round of UDAYA survey
Authors: Dhara Shromona , Thakur Joyeeta , Pandey Neelanjana , Mozumdar Arupendra , Roy Subho
Published: July 2024

Introduction

Depression is a prevalent and debilitating mental illness affecting young women worldwide. This study aimed to identify psychosocial determinants of major depressive disorder (MDD) among young women in Bihar and Uttar Pradesh, India.

Methods

Data from "Understanding the Lives of Adolescents and Young Adults" (UDAYA) study (2018-19) for young women aged 12-23 years, both married and unmarried was used for this paper. MDD was evaluated using the Patient Health Questionnaire PHQ-9 with a cut-off score of ≤10. The determinants of MDD were identified through multilevel binary logistic regression analysis.

Results

The prevalence of MDD was 13.6% (95% CL 12.2-15.2) and 5.1% (95% CL 4.2-6.1) for young married women and unmarried girls, respectively. Among the young married women, community-level variables like dowry-related humiliation (1.74, 95% CI 1.15-2.64), and sexual assaults (2.15, 95% CI 1.24-3.73) were significantly associated with MDD. For unmarried girls, reporting of family violence <10% of participants (0.45, 95% CI 0.24-0.85), family violence (≥10% of participants) % (0.35 95% CI 0.19-0.68) and interpartner violence (>25% of participants) (0.42; 95% CI 0.23-0.74) remain significant predictors of MDD. At individual level, for both the groups, age, participation in decision making (on education), social capital (currently attending school/educational course and number of friends), self-efficacy, telephonic harassment, and physical activity were associated with MDD. Wealth index, job seeking, participation in decision making (on health-seeking), parental interactions and physical abuse (for unmarried girls only) and education, reported last sexual intercourse, pressure from the in-laws’ to conceive (for young married women only) were associated with MDD.

Conclusions

For young married women, community level targeted interventions should focus on the social ecology to foster a sense of safe community environment. For unmarried girls, additionally, interventions should aim to optimize their family environment for effective mental health outcomes.
Geographical variations, prevalence, and molecular dynamics of fastidious phloem-limited pathogens infecting sugar beet across Central Europe
Authors: Duduk Bojan , Stepanović Jelena , Fránová Jana , Zwolińska Agnieszka , Rekanović Emil , Stepanović Miloš , Vučković Nina , Duduk Nataša , Vico Ivana
Published: July 2024

In Europe, two fastidious phloem-limited pathogens, ’Candidatus Phytoplasma solani’ (16SrXII-A) and ’Candidatus Arsenophonus phytopathogenicus’, are associated with rubbery taproot disease (RTD) and syndrome basses richesses (SBR) of sugar beet, respectively. Both diseases can significantly reduce yield, especially when accompanied by root rot fungi. This study investigates the presence, geographic distribution and genetic traits of fastidious pathogens and the accompanying fungus, Macrophomina phaseolina, found on sugar beet across four geographically separated plains spanning seven countries in Central Europe. The survey revealed variable incidences of symptoms linked to these fastidious pathogens in the Pannonian and Wallachian Plains, sporadic occurrence in the North European Plain, and no symptomatic sugar beet in the Bohemian Plain. Molecular analyses unveiled the occurrence of both ’Ca. P. solani’ and ’Ca. A. phytopathogenicus’ throughout Central Europe, with a predominance of the phytoplasma. These fastidious pathogens were detected in all six countries surveyed within the Pannonian and Wallachian Plains, with only a limited presence of various phytoplasmas was found in the North European Plain, while no fastidious pathogens were detected in Bohemia, aligning with observed symptoms. While 16S rDNA sequences of ’Ca. P. solani’ remained highly conserved, multi-locus characterization of two more variable loci (tuf and stamp) unveiled distinct variability patterns across the plains. Notably, the surprising lack of variability of tuf and stamp loci within Central Europe, particularly the Pannonian Plain, contrasted their high variability in Eastern and Western Europe, corresponding to epidemic and sporadic occurrence, respectively. The current study provides valuable insights into the genetic dynamics of ’Ca. P. solani’ in Central Europe, and novel findings of the presence of ’Ca. A. phytopathogenicus’ in five countries (Slovakia, Czech Republic, Austria, Serbia, and Romania) and M. phaseolina in sugar beet in Slovakia. These findings emphasize the need for further investigation of vector–pathogen(s)–plant host interactions and ecological drivers of disease outbreaks.
Comparison of model feature importance statistics to identify covariates that contribute most to model accuracy in prediction of insomnia
Authors: Huang Alexander A. , Huang Samuel Y.
Published: July 2024

Importance

Sleep is critical to a person’s physical and mental health and there is a need to create high performing machine learning models and critically understand how models rank covariates.

Objective

The study aimed to compare how different model metrics rank the importance of various covariates.

Design, setting, and participants

A cross-sectional cohort study was conducted retrospectively using the National Health and Nutrition Examination Survey (NHANES), which is publicly available.

Methods

This study employed univariate logistic models to filter out strong, independent covariates associated with sleep disorder outcome, which were then used in machine-learning models, of which, the most optimal was chosen. The machine-learning model was used to rank model covariates based on gain, cover, and frequency to identify risk factors for sleep disorder and feature importance was evaluated using both univariable and multivariable t-statistics. A correlation matrix was created to determine the similarity of the importance of variables ranked by different model metrics.

Results

The XGBoost model had the highest mean AUROC of 0.865 (SD = 0.010) with Accuracy of 0.762 (SD = 0.019), F1 of 0.875 (SD = 0.766), Sensitivity of 0.768 (SD = 0.023), Specificity of 0.782 (SD = 0.025), Positive Predictive Value of 0.806 (SD = 0.025), and Negative Predictive Value of 0.737 (SD = 0.034). The model metrics from the machine learning of gain and cover were strongly positively correlated with one another (r > 0.70). Model metrics from the multivariable model and univariable model were weakly negatively correlated with machine learning model metrics (R between -0.3 and 0).

Conclusion

The ranking of important variables associated with sleep disorder in this cohort from the machine learning models were not related to those from regression models.