bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding Access to Sickle Cell Disease Care in Sierra Leone: The EASEL Pilot Project
Authors: Jaja Cheedy , Gibson Robert W , Ibemere Stephanie , Edem-Hotah Joseph
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00 PM

Background

Sickle cell disease (SCD) is a major contributor to childhood morbidity and mortality in African countries like Sierra Leone (SL). Limited early diagnosis programs, the limited number of physicians with expertise in hematology, combined with a dearth of extant strategies to combat SCD have led to a paucity of care for children affected by the disease in SL, a problem further compounded by the lack of public understanding of SCD, which perpetuates social stigma and myths about disease causation and results in few people seeking appropriate treatment. We showcase the EASEL Project, a  pilot project designed to empower the nursing workforce in Sierra Leone to perform early diagnosis, genetic counseling, and clinical management of sickle cell disease in children.

Methods

The EASEL project is an academic and private partnership initiative designed to provide basic comprehensive care to children within community hospitals while building capacity within the healthcare system for ongoing improvements in SCD clinical outcomes. The EASEL project leverages the nurse champion model and implementation science to promote the uptake of evidence-based health practices for SCD care. Three aims inform the EASEL project; (1) Conduct a formative evaluation to assess barriers and facilitators to the primary health center provision of SCD case management with a Nurse Champion model; (2) Create an implementation plan for the Sickle Cell Disease Nurse Champion Intervention using Implementation Mapping; and (3) Implement the Nurse Champion model and evaluate its determinants and implementation costs.

Results

The EASEL project will support nurses with the technical capacity to manage and increase opportunities for children living with SCD to receive uninterrupted access to basic preventative wellness care to experience improved quality of life and reduce overall under-five child mortality.

Conclusions

There is a need to integrate affordable SCD evidence-based solutions into the existing healthcare system in Sierra Leone. Newborn screening is urgently needed. Quantifying the public health burden of SCD in Sierra Leone needs to be conducted, and there is an urgent need for public awareness campaigns to combat stigma and misunderstandings about SCD and to provide genetic counseling opportunities and initiatives that promote disease avoidance.
Menopause in Women with Sickle Cell Disease
Authors: Adedeji Monica , Andrews Elizabeth , Riddick-Burden Gaye , Rizk Sanaa
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00 PM

Background

Sickle cell disease (SCD) is the most common genetic disorder globally. With improved SCD management over the decades, more focus has been directed on long-term survival, and age-related complications. While menarche has been studied in adolescents with SCD and seems to be delayed, since women with SCD previously did not live long enough to experience menopause, there remains a paucity of data on menopause so far. This study sought to illicit the menopause experience in women with SCD including the age of onset and symptom severity. We hypothesized that women with SCD may have earlier onset menopause compared to women without SCD as reports have mentioned ovarian sickling as a proposed mechanism of premature ovarian failure, and iron overload as a possible cause of endocrinopathy--leading to impaired ovarian reserve.

Methods

Within the Jefferson Health Network, 37 menopausal Black women with SCD were interviewed using a standardized questionnaire inquiring about their menopause experience. Mean, median and standard deviation were calculated using basic statistics.

Results

Women with SCD, irrespective of genotype, underwent menopause at a median age of 48 years compared to 52 years--the national median age of menopause in Black women. Furthermore, women not on hydroxyurea had an increased incidence of menopausal symptoms including weight gain, hot flashes, sleep disturbances, vaginal dryness and mood swings, compared to women taking hydroxyurea.

Conclusions

While this study’s results are limited due to small sample size, it sheds light on the menopause experience in women with SCD and further highlights the need for further research on this topic.

Clinical Data of Menopause in Women with Sickle cell disease (SCD) With and Without Hydrea Therapy
Sickle Cell Patient Education Materials
Authors: Geway Gemechu , Salmi Adam , Ferdjallah Asmaa
Published: June 2024

Presentation Date: 6/8/2024

Presentation Start Time: 6:00 PM

Background

Sickle cell disease patients often lack awareness of how the disease progresses in their bodies, leading to inadequate self-care and adherence to treatment recommendations. This can result in irreversible damage, such as stroke, and affect their psychological health, leading to feelings of isolation, depression, anxiety, and frustration. The 3D Sickle Cell Patient Education Model can help bridge the gap by providing patients with a comprehensive and detailed explanation of their disease, illustrating how red blood cells function within different areas of the body, and showcasing the complications and ramifications of the disease. It can also promote consistency with treatment programs for all patients, making it an essential tool for SCD communities and healthcare industries worldwide.

Methods

Rochester, MN, Mayo Clinic Comprehensive Pediatric Sickle Cell Clinic, we utilized an innovative approach by incorporating a 3D model to educate children diagnosed with SCD.

Results

During our session at the Mayo Clinic Comprehensive Pediatric Sickle Cell Clinic, we utilized an innovative approach by incorporating a 3D model to educate children diagnosed with SCD. We were pleasantly surprised to witness a significant improvement in their understanding of SCD. The 3D Sickle Cell Patient Education Model is an incredibly effective tool that SCD communities and healthcare industries can leverage to promote better education and awareness of SCD.

Conclusions

SCD can be complex for patients and their loved ones to manage. However, with proper care and management, those affected by the disease can still live a better life. These Sickle Cell Patient Learning resources can provide valuable tools and resources for caregivers and healthcare providers to manage the condition more effectively, leading to improved patient outcomes. Additionally, this model can also serve as an educational tool in schools from diverse backgrounds, including urban, rural, and suburban areas where access to education resources may be limited. By utilizing these resources, we can help ensure that those affected by SCD have the support and tools they need to thrive.

3D Sickle Cell Patient Education Model
Ex-situ liver resection for complex Echinococcus multilocularis infection: a case report
Authors: Kjeseth Trond , Line Pål-Dag , Khan Ammar , Solheim Jon M , Bjørk Ida G , Sundal Jon , Jensenius Mogens , Yaqub Sheraz
Published: June 2024

Echinococcus multilocularis, the fox dwarf tapeworm, causes alveolar echinococcosis (AE), a critical and life-threatening condition. A radical surgical approach represents the only curative option. In this case study, we present a 37-year-old man diagnosed with extensive hepatic AE requiring ex-situ extended right-sided liver resection including the caudate lobe and retro-hepatic vena cava. The left liver segments were auto-transplanted with reconstruction of the left hepatic vein and an inferior vena cava graft. In the post-operative course, the patient developed a bile leak, which was successfully managed with endoscopic stent intervention. He was discharged after a three-week hospitalization. Medical treatment with albendazole was initiated preoperatively and continued postoperatively.
A Review of JAK Inhibitors for Treatment of Alopecia Areata in the Military Health Care System
Authors: Song Christian J , Riley Christopher A , Wilkison Bart D , Cho Sunghun
Published: June 2024

Introduction

Alopecia areata (AA) is a disease that manifests as patchy hair loss on the scalp and other parts of the body; severe disease may result in disfigurement, functional impairment, and significant psychological distress. This condition is understood to be caused by autoimmunity to the hair follicle and subsequent arrest of hair growth. New medications, baricitinib and ritlecitinib, belong to the Janus kinase (JAK) inhibitor family and are among the first FDA-approved treatments for severe AA. In this manuscript, we aim to answer the question: What treatment options exist for AA in the military health care system (MHS)? In doing so, we review the pathogenesis, physical and psychosocial impact of AA, conventional treatment of AA, and the efficacy and safety of baricitinib and ritlecitinib.

Methods

A literature search was performed using PubMed, Embase, and Ovid for the history and pathogenesis of AA, psychosocial impact of disease, functional impairments, and current treatments. Keywords “alopecia areata,” “current therapy for alopecia areata,” “pathogenesis alopecia areata,” “baricitinib,” “ritlecitinib,” “JAK inhibitor alopecia,” “JAK inhibitor safety,” “baricitinib efficacy,” “alopecia eyelash,” “alopecia nails,” and “psychosocial impact of alopecia” were used for the search. The TRICARE manual was searched for guidelines applicable to the treatment of AA, DoD Instruction 6130.03 Volume 2 for medical standards for military service, and the U.S. Central Command Modification 15 for fitness of deployment to Central Command area of operations.

Results

Traditional treatments such as intralesional steroids may be effective for some patients, but difficulty lies in controlling extensive or refractory disease. Janus kinase inhibitors, baricitinib and ritlecitinib, are found effective at improving severe refractory disease; baricitinib induced hair regrowth in 32.6% more patients than placebo, and ritlecitinib was found to be superior to placebo by at least 24%. Currently, there is no coverage for therapeutic treatment of hair growth in the MHS. Additionally, military members are disqualified for continued service if they require immunomodulator medications such as baricitinib and ritlecitinib. Those on immunomodulators are unable to deploy worldwide.

Conclusions

Baricitinib and ritlecitinib are effective treatments for widespread, progressive, and refractory AA. Although JAK inhibitors demonstrate improved effectiveness compared to non-immunomodulator treatments, their use in the MHS for this purpose is limited.
The Association Between Diets With High Inflammatory Potential and Sleep Quality and Its Parameters: A Systematic Review
Authors: Kheirouri Sorayya , Alizadeh Mohammad
Published: June 2024

Context

Dietary components or its overall properties can influence an individual's sleep status.

Objective

The aim for this study was to critically search, appraise, and synthesize research evidence on the association between dietary inflammatory index (DII) and sleep quality and its parameters.

Data Sources

Original published studies on adults were obtained from the PubMed, SCOPUS, ScienceDirect, Cochrane Library, and Google Scholar databases.

Data Extraction

The search was conducted without date limitation until April 2023. Duplicated and irrelevant investigations were screened out, and the results of the remaining articles were descriptively summarized, then critically appraised and analyzed. Possible mechanistic pathways regarding diet, systemic inflammation, and sleep status were discussed.

Data Analysis

Of the 102 studies searched, 23 articles (n = 4 cohort studies, 18 cross-sectional studies, and 1 intervention study) were included in the final review. The association between DII and sleep status was investigated subjectively in 21 studies and objectively in 6 studies. The main studied sleep outcomes were sleep quality, duration, latency, efficiency, apnea, disturbances, the use of sleeping medications, daytime dysfunctions, wakefulness after sleep onset, and rapid eye movement.

Conclusions

According to most of the evidence, DII may not be related to overall sleep quality, sleep duration, latency, efficiency, and the use of sleeping medications. The evidence of positive association was greater between a high DII score (pro-inflammatory diet) with daytime dysfunctions, wakefulness after sleep onset, and sleep apnea. There is insufficient evidence to make any conclusion regarding sleep disturbances and rapid eye movement.
The Function of Legal Ritual in the Peace Palace
Authors: Jeutner Valentin
Published: June 2024

The article argues that oral proceedings before the International Court of Justice (ICJ) can be understood as a particular type of legal ritual. Following an introduction, Section 2 provides an account of the oral proceedings before the ICJ. With reference to Catherine Bell’s six characteristics of ritual-like practices, Section 3 shows that the ICJ’s oral proceedings are formal and traditional, relatively static and rule-governed, employ sacral symbolism, and resemble a performance. Section 4 considers the function and meaning of the legal ritual of oral proceedings before the ICJ. It argues that the ICJ’s legal ritual creates a sense of community among the international legal order’s different stakeholders and establishes the legitimacy of this community and the values it represents. The article concludes by noting that the ICJ’s legal ritual is one of the court’s most important means of enforcing the terms of the international legal order.
The new world order and the Global South
Authors: Stuenkel Oliver Della Costa
Published: June 2024

The shift of power away from the West is often seen as a key element of the crisis of liberal international order. The reluctance by most non-Western powers to side with the West vis-à-vis Russia’s invasion of Ukraine has contributed to the notion that the emerging order will be shaped by a contested system of spheres of influence, geopolitical tensions, and a much smaller common denominator vis-à-vis the normative elements of global order. Yet views across the Global South vis-à-vis the liberal order are far more nuanced, and pointing to non-Western powers as a culprit for the crisis of global order would be simplistic. Indeed, many countries in the Global South tend to be less opposed to the values themselves that undergird liberal order but question the Western-centric ways in which the rules and norms are applied and the in-built hierarchies and inequalities of liberal order. The main challenge of existing structures of global governance thus does not seem to be non-Western countries’ rejection of the underlying rules, but the question of whether today’s system is capable of functioning in a genuinely multipolar order, where power and privilege are less concentrated than in the past. The recent ‘geopoliticization’ of the global economy and the emerging ‘tech war’ suggest this process of adaptation will be enormously difficult. At the same time, while specific subgroups are explicitly opposed to a rules-based order, there are few signs that the Global South—a concept of little analytical usefulness beyond denoting the non-West—would be interested or capable of articulating a genuinely novel or alternative approach sufficiently attractive to garner broad support.
Final results of the search for new Milky Way satellites in the Hyper Suprime-Cam Subaru Strategic Program survey: Discovery of two more candidates
Authors: Homma Daisuke , Chiba Masashi , Komiyama Yutaka , Tanaka Masayuki , Okamoto Sakurako , Tanaka Mikito , Ishigaki Miho N , Hayashi Kohei , Arimoto Nobuo , Lupton Robert H , Strauss Michael A , Miyazaki Satoshi , Wang Shiang-Yu , Murayama Hitoshi
Published: June 2024

We present the final results of our search for new Milky Way (MW) satellites using the data from the Hyper Suprime-Cam (HSC) Subaru Strategic Program (SSP) survey over ∼1140 deg2. In addition to three candidates that we have already reported, we have identified two new MW satellite candidates in the constellations of Sextans, at a heliocentric distance of D⊙ ≃ 126 kpc, and Virgo, at D⊙ ≃ 151 kpc, named Sextans II and Virgo III, respectively. Their luminosities (Sext II: MV ≃ −3.9 mag; Vir III: MV ≃ −2.7 mag) and half-light radii (Sext II: rh ≃ 154 pc; Vir III: rh ≃ 44 pc) place them in the region of size–luminosity space of ultra-faint dwarf galaxies (UFDs). Including four previously known satellites, there are a total of nine satellites in the HSC-SSP footprint. This discovery rate of UFDs is much higher than that predicted from the recent models for the expected population of MW satellites in the framework of cold dark matter models, thereby suggesting that we encounter a too many satellites problem. Possible solutions to settle this tension are also discussed.
Gradual ER calcium depletion induces a progressive and reversible UPR signaling
Authors: Pontisso Ilaria , Ornelas-Guevara Roberto , Chevet Eric , Combettes Laurent , Dupont Geneviève
Published: June 2024

The unfolded protein response (UPR) is a widespread signal transduction pathway triggered by endoplasmic reticulum (ER) stress. Because calcium (Ca2+) is a key factor in the maintenance of ER homeostasis, massive Ca2+ depletion of the ER is a potent inducer of ER stress. Although moderate changes in ER Ca2+ drive the ubiquitous Ca2+ signaling pathways, a possible incremental relationship between UPR activation and Ca2+ changes has yet to be described. Here, we determine the sensitivity and time-dependency of activation of the three ER stress sensors, inositol-requiring protein 1 alpha (IRE1α), protein kinase R-like ER kinase (PERK), and activating transcription factor 6 alpha (ATF6α) in response to controlled changes in the concentration of ER Ca2+ in human cultured cells. Combining Ca2+ imaging, fluorescence recovery after photobleaching experiments, biochemical analyses, and mathematical modeling, we uncover a nonlinear rate of activation of the IRE1α branch of UPR, as compared to the PERK and ATF6α branches that become activated gradually with time and are sensitive to more important ER Ca2+ depletions. However, the three arms are all activated within a 1 h timescale. The model predicted the deactivation of PERK and IRE1α upon refilling the ER with Ca2+. Accordingly, we showed that ER Ca2+ replenishment leads to the complete reversion of IRE1α and PERK phosphorylation in less than 15 min, thus revealing the highly plastic character of the activation of the upstream UPR sensors. In conclusion, our results reveal a dynamic and dose-sensitive Ca2+-dependent activation/deactivation cycle of UPR induction, which could tightly control cell fate upon acute and/or chronic stress.
Systematic Skewness and Stock Returns
Authors: Karehnke Paul
Published: June 2024

This paper revisits the relation between systematic skewness and returns, showing two main findings. First, the systematic skewness premium in individual stocks is time varying. When either skewness preference or systematic skewness is above rather than below the median, the premium is 4% higher. The combined effect of the two induces time variation in the premium of about 7%. Second, systematic skewness has significant additional explanatory power in explaining returns relative to most common characteristics, except size and momentum. These two results imply that skewness preference is an important determinant of expected returns providing a possible rationale for size and momentum. (JEL G11, G12)
Mesenchymal stromal cells ameliorate mitochondrial dysfunction in α cells and hyperglucagonemia in type 2 diabetes via SIRT1/FoxO3a signaling
Authors: Song Jia , Wang Lingshu , Wang Liming , Guo Xinghong , He Qin , Cui Chen , Hu Huiqing , Zang Nan , Yang Mengmeng , Yan Fei , Liang Kai , Wang Chuan , Liu Fuqiang , Sun Yujing , Sun Zheng , Lai Hong , Hou Xinguo , Chen Li
Published: June 2024

Dysregulation of α cells results in hyperglycemia and hyperglucagonemia in type 2 diabetes mellitus (T2DM). Mesenchymal stromal cell (MSC)-based therapy increases oxygen consumption of islets and enhances insulin secretion. However, the underlying mechanism for the protective role of MSCs in α-cell mitochondrial dysfunction remains unclear. Here, human umbilical cord MSCs (hucMSCs) were used to treat 2 kinds of T2DM mice and αTC1-6 cells to explore the role of hucMSCs in improving α-cell mitochondrial dysfunction and hyperglucagonemia. Plasma and supernatant glucagon were detected by enzyme-linked immunosorbent assay (ELISA). Mitochondrial function of α cells was assessed by the Seahorse Analyzer. To investigate the underlying mechanisms, Sirtuin 1 (SIRT1), Forkhead box O3a (FoxO3a), glucose transporter type1 (GLUT1), and glucokinase (GCK) were assessed by Western blotting analysis. In vivo, hucMSC infusion improved glucose and insulin tolerance, as well as hyperglycemia and hyperglucagonemia in T2DM mice. Meanwhile, hucMSC intervention rescued the islet structure and decreased α- to β-cell ratio. Glucagon secretion from αTC1-6 cells was consistently inhibited by hucMSCs in vitro. Meanwhile, hucMSC treatment activated intracellular SIRT1/FoxO3a signaling, promoted glucose uptake and activation, alleviated mitochondrial dysfunction, and enhanced ATP production. However, transfection of SIRT1 small interfering RNA (siRNA) or the application of SIRT1 inhibitor EX-527 weakened the therapeutic effects of hucMSCs on mitochondrial function and glucagon secretion. Our observations indicate that hucMSCs mitigate mitochondrial dysfunction and glucagon hypersecretion of α cells in T2DM via SIRT1/FoxO3a signaling, which provides novel evidence demonstrating the potential for hucMSCs in treating T2DM.
Success of Resident Research Grants in Orthopaedic Trauma From 2000 to 2022: A Retrospective Review
Authors: Stanley Mackinzie A. , Tseng Joyee , Bird Mackenzie , Marecek Geoffrey S.
Published: June 2024

OBJECTIVES:

The objective of this study was to determine the publication rate for orthopaedic trauma resident research projects that receive grant funding and the long-term academic involvement of the grant recipients.

METHODS:

Design:

Retrospective.

Setting:

Publically available records for resident research grant recipients.

Patient Selection Criteria:

Resident research grants on orthopaedic trauma topics from Orthopaedic Trauma Association (OTA), AO North America (AONA), and Orthopaedic Research and Education Foundation from 2000 to 2022.

Outcome Measures and Comparisons:

Subsequent related publications, grant size, time to publication, sustained academic involvement of the residents as measured by academic position, total number of publications, and h-index.

RESULTS:

Three hundred ninety-seven orthopaedic trauma grants (OTA 117, AONA 225, and OREF 55) were identified. A total of 38% (151) of grants resulted in a publication with no significant difference between agencies (P = 0.94). The average amount awarded was $9,843, with no correlation to publication (P = 0.63). The mean time to publication was 3.57 ± 2.33 years. The time to publication for AONA was significantly longer than for OTA (4.14 vs. 2.83 years, P = 0.004). There was no difference in total publications, h-index, or NIH grants between grant recipients from different agencies. More OTA grant recipients held an academic position compared with AONA grant recipients (63% vs. 43%, P = 0.003). Grant awardees with initial publication success were 1.7 times as likely to have a future academic appointment (P = 0.014) and had 1.9 times the number of publications than those without (P = 0.001). Awardees with an h-index in the top quartile were significantly more likely to have published than those with an h-index in the bottom quartile (P = 0.007).

CONCLUSIONS:

Fewer than half of orthopaedic trauma-related resident research grants resulted in a publication with comparable rates across agencies. Grant size did not predict publication success. Publication success was a positive predictor of continued academic involvement. Most publications occurred within 5 years, suggesting that these grants may be most helpful in career development if awarded during the first 1–2 years of a 5-year orthopaedic residency program.
Operative Time Associated With Increased Length of Stay After Single-level Cervical Disk Arthroplasty
Authors: Ng Mitchell K. , Tracey Olivia , Vasireddi Nikhil , Emara Ahmed , Lam Aaron , Wellington Ian J. , Ford Brian , Ahn Nicholas U. , Houten John K. , Saleh Ahmed , Razi Afshin E.
Published: June 2024

Study Design:

Level III evidence—retrospective cohort.

Objective:

The purpose of this study was to (1) determine whether longer CDA operative time increases the risk of 30-day postoperative complications, (2) analyze the association between operative time and subsequent health care utilization, and (3) discharge disposition.

Background:

Cervical disk arthroplasty (CDA) most commonly serves as an alternative to anterior cervical discectomy and fusion (ACDF) to treat cervical spine disease, however, with only 1600 CDAs performed annually relative to 132,000 ACDFs, it is a relatively novel procedure.

Methods:

A retrospective query was performed identifying patients who underwent single-level CDA between January 2012 and December 2018 using a nationwide database. Differences in baseline patient demographics were identified through univariate analysis. Multivariate logistic regression was performed to identify associations between operative time (reference: 81–100 min), medical/surgical complications, and health care utilization.

Results:

A total of 3681 cases were performed, with a mean patient age of 45.52 years and operative time of 107.72±49.6 minutes. Higher odds of length of stay were demonstrated starting with operative time category 101–120 minutes (odds ratio: 2.164, 95% CI: 1.247–3.754, P=0.006); however, not among discharge destination, 30-day unplanned readmission, or reoperation. Operative time <40 minutes was associated with 10.7x odds of nonhome discharge, while >240 minutes was associated with 4.4 times higher odds of LOS>2 days (P<0.01). Increased operative time was not associated with higher odds of wound complication/infection, pulmonary embolism, deep venous thrombosis, or urinary tract infections.

Conclusions:

Prolonged CDA operative time above the reference 81–100 minutes is independently associated with increased length of stay, but not other significant health care utilization parameters, including discharge disposition, readmission, or reoperation. There was no association between prolonged operative time and 30-day medical/surgical complications, including wound complications, infections, pulmonary embolism, or urinary tract infection.
Multimodal learning system integrating electronic medical records and hysteroscopic images for reproductive outcome prediction and risk stratification of endometrial injury: a multicenter diagnostic study
Authors: Li Bohan , Chen Hui , Lin Xiaona , Duan Hua
Published: June 2024

Objective:

To develop a multimodal learning application system that integrates electronic medical records (EMR) and hysteroscopic images for reproductive outcome prediction and risk stratification of patients with intrauterine adhesions (IUAs) resulting from endometrial injuries.

Materials and methods:

EMR and 5014 revisited hysteroscopic images of 753 post hysteroscopic adhesiolysis patients from the multicenter IUA database we established were randomly allocated to training, validation, and test datasets. The respective datasets were used for model development, tuning, and testing of the multimodal learning application. MobilenetV3 was employed for image feature extraction, and XGBoost for EMR and image feature ensemble learning. The performance of the application was compared against the single-modal approaches (EMR or hysteroscopic images), DeepSurv and ElasticNet models, along with the clinical scoring systems. The primary outcome was the 1-year conception prediction accuracy, and the secondary outcome was the assisted reproductive technology (ART) benefit ratio after risk stratification.

Results:

The multimodal learning system exhibited superior performance in predicting conception within 1-year, achieving areas under the curves of 0.967 (95% CI: 0.950–0.985), 0.936 (95% CI: 0.883–0.989), and 0.965 (95% CI: 0.935–0.994) in the training, validation, and test datasets, respectively, surpassing single-modal approaches, other models and clinical scoring systems (all P<0.05). The application of the model operated seamlessly on the hysteroscopic platform, with an average analysis time of 3.7±0.8 s per patient. By employing the application’s conception probability-based risk stratification, mid-high-risk patients demonstrated a significant ART benefit (odds ratio=6, 95% CI: 1.27−27.8, P=0.02), while low-risk patients exhibited good natural conception potential, with no significant increase in conception rates from ART treatment (P=1).

Conclusions:

The multimodal learning system using hysteroscopic images and EMR demonstrates promise in accurately predicting the natural conception of patients with IUAs and providing effective postoperative stratification, potentially contributing to ART triage after IUA procedures.
Correlation between fetal ventricular echogenic foci in pregnancy and fetus chromosomal anomaly: a case-control study in Bandar Abbas city
Authors: Rastegar Mazyar , Rajaei Shahrokh , Yazdian Anari Negin , Hashemi Seyyed Mohammad , Entezar Baghiatallah Amir , Ghazalgoo Arezoo , Namazi Sholes , Soltani Moghadam Saman , Aleali Maryam Sadat , Keivanlou Mohammad-Hossein , Amini-Salehi Ehsan
Published: June 2024

Background:

Ventricular echogenic foci are small structures within the hearts of some fetuses. These small areas result from increased echogenicity in the ventricles of fetuses located near the papillary muscles. An association between these foci and chromosomal abnormalities in fetuses has been reported. Considering that chromosomal abnormalities are a major cause of prenatal death, this study aimed to determine the value of fetal echogenic foci as markers for chromosomal abnormalities.

Materials and methods:

Fetal echocardiography was performed by an experienced cardiologist on 149 pregnant women in the second trimester. Of these, 75 were reported to have positive echogenic foci, and 74 were reported to have no echogenic foci. Subsequently, the three chromosomal anomalies including trisomies 21, 18, and 13 were examined. The information of the individuals, including gestational age and echogenic foci, was recorded.

Results:

Based on the findings of the present study, seven infants (4.7%) had trisomy 21, four infants (2.7%) had trisomy 13, and six infants (4.1%) had trisomy 18. The mean gestational age of pregnant women with positive and negative echogenic foci was 21.07±3.23 and 21.03±3.09, respectively. No significant relationship was found between ventricular echogenic foci and trisomy 21, 18, or 13.

Conclusion:

The present study suggests no significant relation between the presence of echogenic foci and chromosomal trisomies. This finding indicates that additional tests are required to confirm chromosomal abnormalities when echogenic intracardiac foci are present, especially in high-risk fetuses. Moreover, the absence of echogenic focus does not rule out chromosomal disorders.
An Intact Periosteum is Required for Recombinant Human Jagged1 Guided Bone Regeneration in Calvaria Critical-size Defect Healing
Authors: Senos Rafael , Chen Matheus Ton Yan , Panse Isabella , Stella Jose Joaquin , Hankenson Kurt D.
Published: June 2024

The need to promote calvaria bone healing as a consequence of injury or craniotomy is a major clinical issue. Previous reports tested recombinant human Jagged1 (rhJagged1) treatment for critical-size calvaria defects in the absence of periosteum, and this resulted in significant new bone formation. As the periosteum contributes to healing by serving as a source of progenitor cells, the present study aimed to examine whether significantly more bone is formed when the periosteum is intact for using rhJagged1 to treat critical-size parietal bone defects in mice. Fifteen healthy adult mice, 34 to 65 weeks of age, 26.9 to 48.2 g, were divided into different groups that compared the critical-size defects treated with either phosphate-buffered saline or rhJagged1 protein in either the presence or absence of periosteum. The results indicated that more bone was formed in the presence of periosteum when rhJagged1 is delivered [35% bone volume per tissue volume (BV/TV); P = 0.02] relative to nonperiosteum. Recombinant human Jagged1 protein delivered in the absence of periosteum had the next most new bone formed (25% BV/TV). Defects with phosphate-buffered saline delivered in the absence or presence of periosteum had the least new bone formed (15% and 18% BV/TV, respectively; P = 0.48). The results also show that rhJagged1 does not form ectopic or hypertrophic bone. The usage of rhJagged1 to treat critical-size defects in calvaria is promising clinically, but to maximize clinical efficacy it will require that the periosteum be intact on the noninjured portions of calvaria.
Inferential reasoning abilities in wild-caught bumblebees
Authors: Martin-Ordas Gema
Published: June 2024

The ability to make a decision by excluding alternatives (i.e. inferential reasoning) is a type of logical reasoning that allows organisms to solve problems with incomplete information. Several species of vertebrates have been shown to find hidden food using inferential reasoning abilities. Yet little is known about invertebrates’ logical reasoning capabilities. In three experiments, I examined wild-caught bumblebees’ abilities to locate a ‘rewarded’ stimulus using direct information or incomplete information—the latter requiring bees to use inferential reasoning. To do so, I adapted three paradigms previously used with primates—the two-cup, three-cup and double two-cup tasks. Bumblebees saw either two paper strips (experiment 1), three paper strips (experiment 2) or two pairs of paper strips (experiment 3) and experienced one of them being rewarded or unrewarded. At the test, they could choose between two (experiment 1), three (experiment 2) or four paper strips (experiment 3). Bumblebees succeeded in the three tasks and their performance was consistent with inferential reasoning. These findings highlight the importance of comparative studies with invertebrates to comprehensively track the evolution of reasoning abilities, in particular, and cognition, in general.
Emotional salience modulates the forward-flow of memory
Authors: Peris-Yague Alba , Frank Darya , Hellerstedt Robin , Strange Bryan A.
Published: June 2024

As we navigate our day-to-day lives, we regularly adapt our behaviour according to what we predict may happen next in a given context. When an unexpected event occurs, our predictions about the world are disrupted and must be updated. Unexpected, isolated events, particularly with high emotionality, are also better recalled. In the present work, we investigated how oddballs affect recall dynamics. Seventy young, healthy participants encoded word lists containing either emotional or perceptual oddballs at varying stimulus onset asynchronies followed by free recall. It is well established that after recalling an item, we have a higher probability of recalling items encoded nearby, particularly those that were encoded after the item was recalled, a phenomenon known as forward contiguity of recall. We tested how novelty (oddballs versus control words) modulated forward contiguity as a function of salience type (emotional versus perceptual). The present results provide empirical evidence of forward contiguity modulation selectively by emotional salience and suggest that recall patterns after presenting emotional and perceptual oddballs are mediated by different mechanisms.
Relation between soft tissue energy dissipation and leg stiffness in running at different step frequencies
Authors: Dewolf Arthur H , Ivaniski-Mello André , Peyré-Tartaruga Leonardo Alexandre , Mesquita Raphael M.
Published: June 2024

This study aims to investigate the relationship between soft tissue energy dissipation and leg stiffness during running. Eight recreational healthy male runners (age: 22.2 ± 1.0 years; height: 1.84 ± 0.03 m; mass: 73.7 ± 5.7 kg) were asked to run at different speeds and step frequencies. Their soft tissue energy dissipation was estimated by the difference between the total mechanical work of the body, measured as the work done to move the body centre of mass relative to the surroundings plus the work to move the limbs relative to the body centre of mass, and lower-limb joint work. A mass-spring model with an actuator was used to analyse the force–length curve of the bouncing mechanism of running. In this way, the stiffness and damping coefficient were assessed at each speed and step frequency. Pearson's correlations were used to describe the relationship between the deviation from the spring-mass model and soft tissue energy fluctuations. The soft tissue dissipation was found to be significantly influenced by step frequency, with both positive and negative work phases decreasing when step frequency increases. Moreover, deviation from a spring-mass model was positively associated with the amount of soft tissue dissipation (
r
> 0.6). The findings emphasize the substantial role of soft tissues in dissipating or returning energy during running, behaving in a damped-elastic manner. Also, we introduce a novel approach for evaluating the elastic rebound of the body during running. The insights gained may have broad implications for assessing running mechanics, with potential applications in various contexts.
Quantum simulation of discrete linear dynamical systems and simple iterative methods in linear algebra
Authors: Jin Shi , Liu Nana
Published: June 2024

Quantum simulation is capable of simulating certain dynamical systems in continuous time—Schrödinger’s equations being the most direct and well known—more efficiently than classical simulation. Any linear dynamical system can in fact be transformed into a system of Schrödinger’s equations via a method called Schrödingerisation (Jin
et al.
2022. Quantum simulation of partial differential equations via Schrödingerisation. (
https://arxiv.org/abs/2212.13969
) and Jin
et al.
2023.
Phys. Rev. A
108
, 032603. (
doi:10.1103/PhysRevA.108.032603
)). We show how Schrödingerisation allows quantum simulation to be directly used for the simulation of continuous-time versions of general (explicit) iterative schemes or discrete linear dynamical systems. In particular, we use this new method to solve linear systems of equations and for estimating the maximum eigenvector and eigenvalue of a matrix, respectively. This method is applicable using either discrete-variable quantum systems or on hybrid continuous-variable and discrete-variable quantum systems. This framework provides an interesting alternative to solve linear algebra problems using quantum simulation.
Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity
Authors: Huang Shuhan , Rizzo Daniella , Wu Sherry Jingjing , Xu Qing , Ziane Leena , Alghamdi Norah , Stafford David A. , Daigle Tanya L. , Tasic Bosiljka , Zeng Hongkui , Ibrahim Leena Ali , Fishell Gord
Published: June 2024

Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their volume transmission output property. However, their activity and function within cortical circuits remain unclear. Here, we developed two genetic tools to target these neurons and examine their function in the primary visual cortex. We found that the spontaneous activity of neurogliaform cells positively correlated with locomotion. Silencing these neurons increased spontaneous activity during locomotion and impaired visual responses in L2/3 pyramidal neurons. Furthermore, the contrast-dependent visual response of neurogliaform cells varies with their laminar location and is constrained by their morphology and input connectivity. These findings demonstrate the importance of neurogliaform cells in regulating cortical behavioral state-dependent spontaneous activity and indicate that their functional engagement during visual stimuli is influenced by their laminar positioning and connectivity.
VCAb: A web-tool for structure-guided antibody engineering
Authors: Guo Dongjun , Ng Joseph Chi-Fung , Dunn-Walters Deborah K. , Fraternali Franca
Published: June 2024

Effective responses against different immune challenges require secretion of antibodies with various isotypes performing specific effector functions. Structural information on these isotypes is essential to engineer antibodies with desired physico-chemical features of their antigen-binding properties, and optimal stability and developability as potential therapeutic antibodies.In silicomutational scanning profiles on antibody structures would further pinpoint candidate mutations for enhancing antibody stability and function. Although a number of antibody structure databases exist, a public data resource which provides clear, consistent annotation of isotypes, species coverage of 3D antibody structures and their deep mutation profiles is currently lacking. TheVandCregion bearingantibody (VCAb) web tool is established with the purpose to clarify these annotations and provide an accessible and easily consultable resource to facilitate antibody engineering. VCAb currently provides data on 6,948 experimentally determined antibody structures including both V and C regions from different species. Additionally, VCAb provides annotations of species and isotypes with both V and C region numbering schemes applied, which can be interactively queried or downloaded in batch. Multiplein silicomutational scanning methods are applied on VCAb structures to provide an easily accessible interface for querying the impact of mutations on antibody stability. These features are implemented in a R shiny application to enable interactive data interrogation. VCAb is freely accessible athttps://fraternalilab.cs.ucl.ac.uk/VCAb/. The source code to generate the VCAb database and the online R shiny application is available athttps://github.com/Fraternalilab/VCAb, enabling users to set up local VCAb instances.
Pathway activation model for personalized prediction of drug synergy
Authors: Trac Quang Thinh , Huang Yue , Erkers Tom , Östling Päivi , Bohlin Anna , Österroos Albin , Vesterlund Mattias , Jafari Rozbeh , Siavelis Ioannis , Bäckvall Helena , Kiviluoto Santeri , Orre Lukas M. , Rantalainen Mattias , Lehtiö Janne , Lehmann Sören , Kallioniemi Olli , Pawitan Yudi , Vu Trung Nghia
Published: June 2024

Targeted monotherapies for cancer often fail due to inherent or acquired drug resistance. By aiming at multiple targets simultaneously, drug combinations can produce synergistic interactions that increase drug effectiveness and reduce resistance. Computational models based on the integration of omics data have been used to identify synergistic combinations, but predicting drug synergy remains a challenge. Here, we introduce DIPx, an algorithm for personalized prediction of drug synergy based on biologically motivated tumor- and drug-specific pathway activation scores (PASs). We trained and validated DIPx in the AstraZeneca-Sanger (AZS) DREAM Challenge dataset using two separate test sets: Test Set 1 comprised the combinations already present in the training set, while Test Set 2 contained combinations absent from the training set, thus indicating the model”s ability to handle novel combinations. The Spearman correlation coefficients between predicted and observed drug synergy were 0.50 (95% CI: 0.47–0.53) in Test Set 1 and 0.26 (95% CI: 0.22–0.30) in Test Set 2, compared to 0.38 (95% CI: 0.34–0.42) and 0.18 (95% CI: 0.16–0.20), respectively, for the best performing method in the Challenge. We show evidence that higher synergy is associated with higher functional interaction between the drug targets, and this functional interaction information is captured by PAS. We illustrate the use of PAS to provide a potential biological explanation in terms of activated pathways that mediate the synergistic effects of combined drugs. In summary, DIPx can be a useful tool for personalized prediction of drug synergy and exploration of activated pathways related to the effects of combined drugs.
Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system
Authors: Clancy Shaylyn , Xie Nicholas , Eluvathingal Muttikkal Tess , Wang Jasmine , Fateh Esha , Smith Margaret , Wilson Phillip , Smith Matthew , Hogan Arielle , Sutherland Ann , Lu Xiaowei
Published: June 2024

Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs) that connect the sound receptors in the organ of Corti (OC) to the cochlear nuclei of the hindbrain. Type I SGNs innervate inner hair cells (IHCs) to transmit sound signals, while type II SGNs (SGNIIs) innervate outer hair cells (OHCs) to detect moderate-to-intense sound. During development, SGNII afferents make a characteristic 90-degree turn toward the base of the cochlea and innervate multiple OHCs. It has been shown that the Planar Cell Polarity (PCP) pathway acts non-autonomously to mediate environmental cues in the cochlear epithelium for SGNII afferent turning towards the base. However, the underlying mechanisms are unknown. Here, we present evidence that PCP signaling regulates multiple downstream effectors to influence cell adhesion and the cytoskeleton in cochlear supporting cells (SCs), which serve as intermediate targets of SGNII afferents. We show that the core PCP gene Vangl2 regulates the localization of the small GTPase Rac1 and the cell adhesion molecule Nectin3 at SC-SC junctions through which SGNII afferents travel. Throughin vivogenetic analysis, we also show that loss of Rac1 or Nectin3 partially phenocopied SGNII peripheral afferent turning defects inVangl2mutants, and that Rac1 plays a non-autonomous role in this process in part by regulating PCP protein localization at the SC-SC junctions. Additionally, epistasis analysis indicates that Nectin3 and Rac1 likely act in the same genetic pathway to control SGNII afferent turning. Together, these experiments identify Nectin3 and Rac1 as novel regulators of PCP-directed SGNII axon guidance in the cochlea.

Significance statement

Planar Cell Polarity (PCP) signaling plays a non-autonomous role in the guidance of type II spiral ganglion neuron (SGNII) afferent projections that innervate cochlear hair cells. However, little is known about the underlying mechanisms. Here, we identify the small GTPase Rac1 and the cell adhesion molecule Nectin3 as two downstream effectors of PCP signaling in SGNII afferent guidance. We show that PCP signaling regulates Rac1 and Nectin3 localization in cochlear supporting cells that serve as intermediate targets for SGNII afferents and that Rac1 and Nectin3 likely act in the same genetic pathway to non-autonomously regulate SGNII afferent guidance. These findings significantly advance our understanding of auditory circuit assembly and shed light on PCP-directed axon guidance mechanisms.