bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and modelling of an anisotropic continuum robot end-effector for single-port access surgery suturing
Authors: Vandebroek Tom , Legrand Julie , Vercauteren Tom , Ourselin Sebastien , Deprest Jan , Vander Poorten Emmanuel
Published: February 2023

Single port access surgery has brought many advantages and new challenges to the field of minimally invasive surgery. In principle, many of these challenges can be addressed through robotics. Continuum robots in particular have seen a surge in interest in recent years for their miniaturisation potential. However, many applications with these robots have been developed for contactless or low-force tasks. This paper tackles several barriers to high-force tasks with continuum robots such as suturing for Open Spina Bifida repair. A novel continuum robot end-effector is proposed. The end-effector is composed of a distal bending segment and hybrid gripper. First, the novel hybrid gripper specifically designed for continuum robots is introduced. The hybrid gripper can function both as a general surgical gripper and as a needle driver while overall keeping the required input force limited. Second, an optimisation of the continuum structure of the distal bending segment is conducted. The objective of this optimisation is to sustain high tip forces – required by the said high-force contact tasks – while keeping deformations acceptable. Third, a quasi-static model that predicts the coupled effect of bending and gripping is derived. This model predicts the deformation of the continuum structure that is induced by the gripping action itself. It could hence be used to compensate for such deformation and establish a stable grip with the otherwise flexible instruments. Finally, experiments are conducted to validate the new designs and the model. The hybrid gripper has a diameter of [Formula: see text] mm, a length of [Formula: see text] mm and can hold securely a needle with a [Formula: see text] N input force, outputting a [Formula: see text] N gripping force. The optimised bending segment is validated for Open Spina Bifida suture: it can bend freely up to 90° and it can support a [Formula: see text] N tip load up to a 35° bending angle. The bending and gripper model error varies between 1% and 14.55%, yielding useful results to predict the shape of the bending segment and potentially compensate for the disturbance created by actuating the gripper.
NFATc2-dependent epigenetic downregulation of the TSC2/Beclin-1 pathway is involved in neuropathic pain induced by oxaliplatin
Authors: Liu Meng , Mai Jing-Wen , Luo De-Xing , Liu Guan-Xi , Xu Ting , Xin Wen-Jun , Lin Su-Yan , Li Zhen-Yu
Published: February 2023

Neuropathic pain is a common dose-limiting side effect of oxaliplatin, which hampers the effective treatment of tumors. Here, we found that upregulation of transcription factor NFATc2 decreased the expression of Beclin-1, a critical molecule in autophagy, in the spinal dorsal horn, and contributed to neuropathic pain following oxaliplatin treatment. Meanwhile, manipulating autophagy levels by intrathecal injection of rapamycin (RAPA) or 3-methyladenine (3-MA) differentially altered mechanical allodynia in oxaliplatin-treated or naïve rats. Utilizing chromatin immunoprecipitation-sequencing (ChIP-seq) assay combined with bioinformatics analysis, we found that NFATc2 negatively regulated the transcription of tuberous sclerosis complex protein 2 (TSC2), which contributed to the oxaliplatin-induced Beclin-1 downregulation. Further assays revealed that NFATc2 regulated histone H4 acetylation and methylation in the TSC2 promoter site 1 in rats’ dorsal horns with oxaliplatin treatment. These results suggested that NFATc2 mediated the epigenetic downregulation of the TSC2/Beclin-1 autophagy pathway and contributed to oxaliplatin-induced mechanical allodynia, which provided a new therapeutic insight for chemotherapy-induced neuropathic pain.
Toll-like receptor 4 signaling pathway in sensory neurons mediates remifentanil-induced postoperative hyperalgesia via transient receptor potential ankyrin 1
Authors: Liu Xiaowen , Gong Ruisong , Peng Liang , Zhao Jing
Published: February 2023

Background: Remifentanil-induced postoperative hyperalgesia (RIH) refers to a state of hyperalgesia or aggravated pre-existing pain after remifentanil exposure. There has been considerable interest in understanding and preventing RIH. However, the mechanisms responsible for RIH are still not completely understood. Toll-like receptor 4 (TLR4), a classic innate immune receptor, has been detected in sensory neurons and participates in various nociceptive conditions, whereas its role in RIH remains unclear. Transient receptor potential ankyrin 1 (TRPA1) always serves as a nociceptive channel, whereas its role in RIH has not yet been investigated. This study aimed to determine whether the TLR4 signaling pathway in sensory neurons engaged in the development of RIH and the possible involvement of TRPA1 during this process. Methods: A rat model of remifentanil-induced postoperative hyperalgesia (RIH) was established, which presented decreased paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). The mRNA and protein expression levels of TLR4, phosphorylated NF-κB, and TRPA1 in the dorsal root ganglion (DRG) from RIH model were analyzed by real-time PCR, western blot, and immunofluorescence. The TLR4 antagonist TAK-242 and the TRPA1 antagonist HC-030031 were applied to determine the role of sensory neuron TLR4 signaling and TRPA1 in RIH. Results: Compared with control, PWMT and PWTL were significantly decreased in RIH model. Moreover, the mRNA and protein expression of TLR4 and TRPA1 in DRG were upregulated after remifentanil exposure together with increased NF-κB phosphorylation. TLR4 antagonist TAK-242 mitigated mechanical pain in RIH together with downregulated expression of TLR4, phosphorylated NF-κB, and TRPA1 in DRG neurons. In addition, TRPA1 antagonist HC-030031 also alleviated mechanical pain and decreased TRPA1 expression in RIH without affecting TLR4 signaling in DRG. Conclusions: Taken together, these results suggested that activation of TLR4 signaling pathway engaged in the development of RIH by regulating TRPA1 in DRG neurons. Blocking TLR4 and TRPA1 might serve as a promising therapeutic strategy for RIH.
Differences and variability of physical and technical characteristics among rugby union small-sided games performed within a preseason
Authors: Zanin Marco , Ranaweera Jayamini , Darrall-Jones Joshua , Roe Gregory
Published: February 2023

This study aimed to investigate the differences in physical and technical characteristics among three specific rugby union small-sided games (SSG) and to examine the variability of these characteristics over three weeks within a preseason of a professional rugby union club. Eighteen backs and 22 forwards were recruited for the study. The three SSG designs were: backs only (SSG-B), forwards only (SSG-F) and both backs and forwards (SSG-BF). Physical characteristics were quantified using external (e.g., total distance covered [m·min−1]) and internal (i.e., Stagno's training impulse [AU·min−1]) load measures. Technical characteristics were quantified using the number of rucks, successful passes, unsuccessful passes, line breaks and tries per minute. The SSG-BF produced a greater high speed (>61%) running distance covered in comparison with SSG-B (1.97 vs. 1.32 m·min−1) and SSG-F (1.26 vs. 0.94 m·min−1), and more successful passes (9.47 vs. 9.36 count·min−1) and line breaks (0.98 vs. 0.65 count·min−1) than SSG-F. Conversely, all the other physical and technical characteristics were higher in SSG-B and SSG-F. All the physical and technical characteristics, except high speed (>61%) distance covered in forwards and unsuccessful passes and tries per minute, changed over days showing either a linear or quadratic pattern. Based on these findings, practitioners may implement position-specific SSG (i.e., SSG-B and SSG-F) to expose players to greater physical and technical characteristics. Furthermore, if SSGs were to be repeated across multiple days, practitioners should be aware of the possible variability in physical and technical characteristics due to potential adaptations to the constraints or the onset of fatigue.
Energy loss in oblique collisions
Authors: Cross Rod
Published: February 2023

The decrease in kinetic energy of a ball incident vertically on a rigid horizontal surface depends on the normal coefficient of restitution, [Formula: see text]. It is shown in the present paper that if the ball is incident obliquely on the surface then the total decrease in kinetic energy has two independent contributions, one depending on [Formula: see text], the other depending on the tangential coefficient of restitution, [Formula: see text].
Clinical significance of adjuvant chemotherapy for pathological complete response rectal cancer patients with acellular mucin pools after neoadjuvant chemoradiotherapy
Authors: Chen Mian , Zhang Jianwei , Hou Yujie , Liu Huashan , Fan Xinjuan , Luo Shuangling , Liu Zhanzhen , Hu Huanxin , Lai Sicong , Kang Liang , Huang Liang
Published: February 2023

Background:

Approximately 15–30% of locally advanced rectal cancer (LARC) patients achieved pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision, but the clinical significance of adjuvant chemotherapy (ACT) for pCR patients remains unclear.

Objectives:

To determine whether LARC pCR patients can benefit from the administration of ACT.

Design:

Single center retrospective study.

Methods:

This study retrospectively included 280 LARC patients who achieved pCR after CRT and surgery from 2011 to 2019. The information of patients was recorded. Main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival. Subgroup analysis was conducted on whether pCR patients with acellular mucin pools received ACT or not.

Results:

A total of 74/280 (26.4%) patients were identified with acellular mucin pools. Disease recurrence occurred in 38/280 (13.6%) patients, and in the subgroup of patients with acellular mucin pools, 15/74 (20.3%) patients developed distant metastases. The existence of acellular mucin pools was associated with worse DFS (79.7% versus 88.8%, P = 0.037). Among pCR patients with acellular mucin pools, 9/25 (36.0%) of non-ACT patients occurred recurrence, and ACT was beneficial for improving DFS (hazard ratio: 0.245; 95% confidence interval: 0.084–0.719; P = 0.010).

Conclusions:

The existence of acellular mucin pools may represent a sign of invasive tumor biology, which indicated a negative prognosis. ACT can improve the prognosis of patient with acellular mucin pools, so ACT should be considered for them.
Back pain in adolescent idiopathic scoliosis: A comprehensive review
Authors: An Juhyung K , Berman Daniel , Schulz Jacob
Published: February 2023

Purpose:

Adolescent idiopathic scoliosis (AIS) is a common spinal deformity that affects millions of children worldwide. A variety of treatment algorithms exist for patients based on radiographic parameters such as the Cobb angle and the Risser stage. However, there has been a growing focus on nonradiographic outcomes such as back pain, which can cause functional disability and reduced quality of life for patients. In spite of this, back pain in AIS is poorly characterized in the literature. We aimed to summarize various factors that may influence back pain in AIS and the impact of different treatment methods on pain reduction.

Methods:

A comprehensive systematic review was undertaken using the PubMed and Cochrane database. Keywords that were utilized and combined with “Adolescent Idiopathic Scoliosis” included, “back pain,” “treatment,” “biomechanics,” “biochemistry,” “epidemiology,” and “biopsychosocial.” The literature was subsequently evaluated and deemed relevant or not relevant for inclusion.

Results:

A total of 93 articles were ultimately included in this review. A variety of contradictory literature was present for all sections related to epidemiology, underlying biomechanics and biochemistry, biopsychosocial factors, and treatment methodologies.

Conclusion:

Back pain in AIS is common but remains difficult to predict and treat. The literature pertaining to causative factors and treatment options is heterogeneous and inconclusive. Longer-term prospective studies combining biopsychosocial intervention in conjunction with existing curve correction techniques would be meaningful.
Professional Identity in Nursing: A Narrative Essay
Authors: Mazyck Donna
Published: February 2023

Newer language exists regarding nurse professionalism. The term Professional Identity in Nursing (PIN) is taking hold in academic and clinical settings. This narrative essay provides descriptions of my school nursing experience and the formation of my PIN. This essay introduces PIN definition and domains. School nurses are encouraged to develop their PIN.
Promoting health equity in HIV prevention and treatment research: a practical guide to establishing, implementing, and sustaining community advisory boards
Authors: Weinstein Elliott R. , Herrera Christian M. , Pla Serrano Lorenzo , Martí Kring Edward , Harkness Audrey
Published: February 2023

Over the last 25 years, community-based participatory research (CBPR) has emerged as an innovative methodological approach to break down the barriers toward health equity in biopsychosocial research. Although there are several methods one can use to conduct CBPR research, one widely used established tool that has shown to be effective for engaging community meaningfully in research is community advisory boards (CABs). CABs are formalized collaborative bodies consisting of community and research stakeholders and have been integral in engaging underserved groups experiencing HIV-related health inequities at the early stages of the AIDS crisis. Even though evidence suggests that CABs are an effective tool for conducting high-quality, rigorous, and community-centered HIV-related research, there are minimal guidelines summarizing the steps needed for developing and maintaining a CAB. Therefore, to fill this gap in the literature, this article offers a practical guide to help researchers with minimal experience, particularly graduate students and early-stage investigators, feel more comfortable with establishing a CAB for equity-focused HIV-related research. This article synthesizes already established guidelines and frameworks for CAB development while specifically outlining unique steps related to the three main stages of CAB formation – establishment, implementation, and sustainment. Throughout this article, the authors offer tension points, generated from the literature and with consultation from a CAB working alongside the authors, that researchers and community partners may need to navigate during each of these three stages. In addition, best practices from the literature are identified for each step in the guidelines so that readers can see firsthand how research groups have carried out these steps in their own practice.
Examining Preoperative MRI for Medial Meniscal Ramp Lesions in Patients Surgically Treated for Acute Grade 3 Combined Posterolateral Corner Knee Injury
Authors: Moran Jay , Jimenez Andrew E. , Katz Lee D. , Wang Annie , McLaughlin William M. , Gillinov Stephen M. , Patel Rohan R. , Kunze Kyle N. , Hewett Timothy E. , Alaia Michael J. , LaPrade Robert F. , Medvecky Michael J.
Published: February 2023

Background:

While medial meniscocapsular tears (ramp lesions) are commonly associated with isolated anterior cruciate ligament injuries, there are limited descriptions of these meniscal injuries in multiligament knee injuries (MLKIs).

Purpose:

To (1) retrospectively evaluate preoperative magnetic resonance imaging (MRI) scans for the presence of ramp lesions in patients surgically treated for acute grade 3 combined posterolateral corner (PLC) knee injuries and (2) determine if a preoperative posteromedial tibial plateau (PMTP) bone bruise is associated with the presence of preoperative ramp lesions on MRI in these same patients.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

Data on consecutive patients at a level 1 trauma center with MLKIs between 2001 and 2021 were retrospectively reviewed. Only patients with acute grade 3 combined PLC injuries who received an MRI scan within 30 days of injury were assessed. Two musculoskeletal radiologists retrospectively reviewed each patient’s preoperative MRI for evidence of ramp lesions and bone bruises. Intraclass correlation coefficients (ICCs) were used to calculate reliability among the reviewers. Multivariate analysis was used to evaluate the relationship between PMTP bruising and the presence of a ramp lesion on MRI.

Results:

A total of 68 patients (79.4% male; mean age, 33.8 ± 13.7 years) with an acute grade 3 combined PLC injury were included in the study. On MRI, the ICCs for detection of ramp lesions and PMTP bone bruising were 0.921 and 0.938, respectively. Medial meniscal ramp lesions were diagnosed in 18 of 68 (26.5%) patients. Eleven of 18 (61.1%) patients with ramp lesions also showed evidence of PMTP bruising, while 13 of 50 (26.0%) patients without ramp lesions had PMTP bruising ( P = .008). When controlling for age and sex, PTMP bruising was significantly associated with the presence of a ramp lesion in combined PLC injuries (odds ratio, 4.62; P = .012).

Conclusion:

Preoperative medial meniscal ramp lesions were diagnosed on MRI in 26.5% of patients with acute grade 3 combined PLC injuries. PMTP bone bruising was significantly associated with the presence of a ramp lesion on MRI. These findings reinforce the need to assess for potential ramp lesions at the time of multiligament reconstruction.
Effectiveness of Health Education Interventions Methods to Improve Contraceptive Knowledge, Attitude, and Uptake Among Women of Reproductive Age, Ethiopia: A Systematic Review and Meta-Analysis
Authors: Gelgelo Dawit , Abeya Sileshi Garoma , Hailu Dejene , Edin Alo , Gelchu Shiferaw
Published: February 2023

Background

Globally, about 600,000 women die yearly as a result of pregnancy-related causes. Access to contraceptive health education has been described as one of the crucial interventions to confront maternal mortality. Nevertheless, the effectiveness of these interventions has not been systematically reviewed.

Objective

To access the effectiveness of health education intervention methods to improve contraceptive knowledge, attitude, and uptake among reproductive age group women.

Methods

This systematic review was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines through a systematic literature search of articles published between 2010 and 2022 comprising information on the effects of health education on contraceptive knowledge, attitude, attitude, and utilization among the reproductive age group of women. The most known bibliographic databases and libraries: PubMed/Medline, Embase, and Cochrane library were used.

Result

Eleven quasi-experimental studies fulfilled the inclusion criteria were included in the review. In a random effects model, the pooled estimate of the health education effect became 0.15 (95% CI = 0.104–0.206) at a P value of .001, and the pooled confidence intervals of the combined estimate of effect size occur on the positive side of zero. Therefore, contraceptive health education has a statistically significant positive effect on the contraceptive outcome despite variation between interventional and control groups.

Conclusion and recommendation

This review found that interactive communication supported by various health education delivery methods like brochures, booklets, peer educators, and the use of different behavioral change theories are more effective than the one-way and routine counseling of the family planning (FP) health education approach.
Financial, Occupational and Physical Challenges and Blood Glucose Monitoring in Type 2 Diabetes
Authors: Marvin Jacob , Powe Nicolette
Published: February 2023

Background

Blood glucose monitoring effects are changing for people living with type 2 diabetes. However, there is a lack of recent data surrounding financial, occupational, or physical stressors that affect the adherence of diabetes self-management practices. This article looks to examine specific financial, physical, and occupational challenges in adherence to blood glucose monitoring in type 2 diabetes.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 Pre-Pandemic data of adults 18+ were analyzed. These data were used to examine the relationships between insurance coverage, health status, occupation, and self-monitoring of blood glucose levels in the United States.

Results

This study found that respondents had a statistically significant association with five variables: prescription drug coverage (in-part or full), occupation status, gender, age, and three race subcategories (non-Hispanic White, Black, and Other-Multiracial) with blood glucose monitoring.

Conclusion

This study may help certified health education specialists (CHES) and diabetes care and educator specialists (DCES) to better identify which groups of individuals are at highest risk for poor adherence to specific blood glucose monitoring in type 2 diabetes.
Assessing impacts of the built environment on mobility: A joint choice model of travel mode and duration
Authors: Yang Yang , Samaranayake Samitha , Dogan Timur
Published: February 2023

This paper introduces a joint choice model for travel mode and duration to quantify the mobility impacts of urban design changes on the built environment. The model is formulated as a Random Forest classifier that predicts the mode-duration probabilities of a given trip. A novel series of predictor features are proposed which measure the urban form, demographics, and service densities on different scales of the transportation network. Through a sensitivity analysis and a proof-of-concept case study, we find that a dense, mixed-use environment with good coverage of a multi-modal mobility network can significantly promote active transportation and public transit use. However, we also find that ultra-dense, centralized developments can lead to increased travel time and increased vehicle use in the urban periphery. Our modeling and analysis method provides a simplified and effective way to assess urban design and planning scenarios from different mobility perspectives and facilitates data-driven, mobility-aware urban design and planning that can help identify better solutions more quickly.
Case report: Migraine resolution post bilateral subthalamic deep brain stimulation
Authors: Almuwais Ahmed , Lagrand Tjerk J , Lehn Alexander C
Published: February 2023

Background:

Chronic migraine can be challenging to treat and despite recent advances in treatment, there are cases that do not respond to current available pharmacological therapies.

Case:

We report a case of a 64-year-old male with a long history of chronic migraine who developed severe tremor-dominant Parkinson’s disease.

Conclusion:

After implantation of subthalamic deep brain stimulation (DBS), he reported not only benefit for his parkinsonian symptoms, but also a complete remission of his migraine attacks.
Effects of a Pretend Play Intervention on Health-Related Quality of Life in Children With Cancer: A Swedish–German Study
Authors: Witt Stefanie , Quitmann Julia , Höglund Anna T. , Russ Sandra , Kaman Anne , Escherich Gabriele , Frygner-Holm Sara
Published: February 2023

Background: Cancer diagnosis can lead to massive physical, emotional, and social burdens on children and their families. Although children have the right to be informed and participate in their care, research shows that children's views are often not considered in care situations. Thus, it is essential to strengthen children's communication and self-efficacy (SE) to convey desires and needs. The present study explores whether a play intervention is associated with improved health-related quality of life (HrQoL) and SE for communication in care situations. We hypothesize that HrQoL and SE for communication will increase from the beginning to after the pretend play intervention. Methods: Children with cancer from Germany and Sweden were enrolled. The pretend play intervention consisted of six to 10 play sessions. A heterogenic selection of questionnaires was used to measure children's HrQoL and SE before the first pretend play session and after the last play intervention. Results: Nineteen families were included in the presented analyses, including 14 self-reports of children and 19 proxy reports of parents. We found improvements in child-reported communication, and emotional and psychosocial well-being using generic and cancer-specific HrQoL measurements. Further, children's SE in care situations improved during the play intervention. Parents also reported minor improvements in the physical dimensions in both generic and chronic‐generic HrQoL, along with improvements in independence. Discussion: Overall, the cancer-specific pretend play intervention offers young children with cancer a secure environment and can contribute to their well-being, and communication skills, during or after cancer treatment.
The Expanding Role of Sonography in the Clinical Practice of Modern Obstetrics and Gynecology: A Clinical Perspective
Authors: Levine Elliot M. , Fernandez Carlos M.
Published: February 2023

A list of gynecologic diagnoses is provided, which shows the use of sonography in significantly assisting the practice of modern clinical gynecology. The clinical value of this technology to assist in formulating diagnoses for the presenting patients is discussed. Sonography has become a necessary tool for today’s practice of gynecology, and women’s health, in general.
Scope of Practice of Sonographers Across the United States: A Survey Study
Authors: Pessin Yosefa J.
Published: February 2023

Objective:

The purpose of this study was to determine the current scope of practice of sonographers in the United States and ascertain if sonographers’ daily responsibilities align with the Society of Diagnostic Medical Sonography’s (SDMS) Sonographer’s Scope of Practice and Clinical Standards.

Materials and Methods:

A survey was disseminated to SDMS members and clinical sonographers with at least 5 years experience. The survey addressed demographics, education, certification, specialties practiced, job title, work environment, and scope of practice.

Results:

Of the 613 sonographers who responded, 90% were female and 10% male; the most common age group was 55–64 (36.7%). Most sonographers had a Bachelor’s or Associate’s degree. Eighty-three percent of respondents were White, 5.4% Hispanic, Latino, or Spanish origin, 3% Black or African American, and 3% Asian. While 63% of sonographers have read the SDMS Scope of Practice, 52% reported they perform tasks not included or addressed, in their job description. Many teach sonography in the workplace and provide oral and/or written preliminary impressions and diagnoses.

Conclusion:

There are regional differences in scope of practice and gender differences in place of employment and job title. Sonographers reported to practice within the SDMS parameters. The guidelines can be expanded to include educating health professionals in sonography and having an increased role in providing diagnoses.
The NFIA-ETO2 fusion blocks erythroid maturation and induces pure erythroid leukemia in cooperation with mutant TP53
Authors: Piqué-Borràs Maria-Riera , Jevtic Zivojin , Otzen Bagger Frederik , Seguin Jonathan , Sivalingam Rathick , Bezerra Matheus Filgueira , Louwaige Amber , Juge Sabine , Nellas Ioannis , Ivanek Robert , Tzankov Alexandar , Moll Ute , Cantillo Oriano Valerio , Schulz-Heddergott Ramona , Fagnan Alexandre , Mercher Thomas , Schwaller Juerg
Published: February 2023

The NFIA-ETO2 fusion is the product of a t(1;16)(p31;q24) chromosomal translocation so far exclusively found in pediatric patients with pure erythroid leukemia (PEL). To address the role for the pathogenesis of the disease, we expressed the NFIA-ETO2 fusion in murine erythroblasts. We observed that NFIA-ETO2 significantly increased proliferation and impaired erythroid differentiation of murine erythroleuemia (MEL) cells and of primary fetal liver-derived erythroblasts. However, NFIA-ETO2-expressing erythroblasts acquired neither aberrant in vitro clonogenic activity nor disease-inducing potential upon transplantation into irradiated syngenic mice. In contrast, in the presence of one of the most prevalent erythroleukemia-associated mutations, TP53R248Q, expression of NFIA-ETO2 resulted in aberrant clonogenic activity, and induced a fully penetrant transplantable PEL-like disease in mice. Molecular studies support that NFIA-ETO2 interferes with erythroid differentiation by preferentially binding and repressing erythroid genes that contain NFI binding sites and/or are decorated by ETO2, resulting in a activity shift from GATA- to ETS-motif-containing target genes. In contrast, TP53R248Q does not affect erythroid differentiation but provides self-renewal and survival potential, mostly via downregulation of known TP53 targets. Collectively, our work indicates that NFIA-ETO2 initiates PEL by suppressing gene expression programs of terminal erythroid differentiation and cooperates with TP53 mutation to induce erythroleukemia.
Recombinant factor VIII Fc fusion protein for first-time immune tolerance induction: final results of the verITI-8 study
Authors: Malec Lynn , Van Damme An , Chan Anthony K. C. , Spasova Mariya , Jain Nisha , Sensinger Charlotte , Dumont Jennifer , Lethagen Stefan , Carcao Manuel , Peyvandi Flora
Published: February 2023

Inhibitor development remains a major challenge in factor VIII (FVIII) replacement therapy. verITI-8 is the first prospective study of a recombinant FVIII Fc fusion protein (rFVIIIFc; efmoroctocog alfa) for first-time immune tolerance induction (ITI) in males with severe hemophilia A and high-titer inhibitors (historical peak ≥5 Bethesda units [BU]/mL). In this single-arm, open-label, multicenter study, screening was followed by ITI (rFVIIIFc 200 IU/kg per day until tolerization or maximum of 48 weeks). Those who achieved ITI success entered a tapering period, returning to standard prophylaxis, and then entered follow-up. Primary end point was time to tolerization with rFVIIIFc defined by inhibitor titer <0.6 BU/mL, incremental recovery (IR) ≥66% of expected IR (IR ≥1.32 IU/dL per IU/kg), and half-life (t½) ≥7 hours within 48 weeks. Sixteen patients received ≥1 rFVIIIFc dose. Twelve (75%), 11 (69%), and 10 patients (63%), respectively, achieved negative inhibitor titers, an IR ≥66%, and a t½ ≥7 hours (ie, tolerance) within 48 weeks. Median times in weeks to achieve these markers of success were 7.4 (interquartile range [IQR], 2.2-17.8), 6.8 (IQR, 5.4-22.4), and 11.7 (IQR, 9.8-26.2), respectively. All patients experienced ≥1 treatment-emergent adverse event (TEAE), and 1 reported ≥1 related TEAE (injection site pain). Nine patients experienced ≥1 treatment-emergent serious AE. No thrombotic events, discontinuations because of AEs, or deaths were reported during the study. As the first extended half-life rFVIII with prospective data in ITI, rFVIIIFc offered short time to tolerization with durable responses in almost two-thirds of patients and was well tolerated. This trial was registered at www.clinicaltrials.gov as #NCT03093480.
Penetrating gunshot wounds to the penis: a case report of combat patient injured in the war in Ukraine
Authors: Golovko Sergiy , Gybalo Rostislav , Lurin Igor , Taraban Igor , Kobirnichenko Artem , Ganiuk Vitalii , Gorobeiko Maksym , Dinets Andrii
Published: February 2023

Background

The current war in Ukraine is associated with frequent applications of multiple-launch rocket systems and cruise missiles as well as other various high-energy weapons to cause severe injuries in military personnel including abdomen wounds, vascular injury, and limb amputations as well as genitourinary trauma. The aim of this report is to demonstrate a case of successful penile salvage by restoring its function in a combat patient with gunshot genitourinary trauma in conditions of an interrupted supply of medical equipment.

Case presentation

We describe a case of a 48-year-old male patient with a combined shrapnel gunshot wound to the penis with damage to the urethra and combined injury to the soft tissues of the left thigh. Several hours after the injury, the patient underwent primary surgical debridement of the left thigh, ligation of the great saphenous vein of the thigh, primary sutures on the penile urethra and navicular fossa, suturing of the rupture of the head and penis, drainage of the wound, catheterization of the bladder, and epicystostomy. An artificial erection was performed intraoperatively.

The urethral catheter was removed 3 weeks after urethral suturing (May 4, 2022). The epicystostomy was removed 5 months after the injury (August 4, 2022) and 2 days after the restoration of spontaneous urination. At the follow-up of 7 months after the injury, the patient has normal urination with minor urinary dribbling, sufficient erection, and ejaculation.

Conclusions

We have shown that in a case of gunshot wounds to the penis and hanging part of the urethra, even in the presence of combined severe purulent lesions of non-urological localizations, it is possible to perform a primary reconstruction of urogenital injuries using a primary urethral suture and applying a negative pressure device. Findings from this case report shed new light on the management of penile gunshot injury in ongoing warfare as well as provide evidence of the possibility to perform adequate management for penile injury in conditions of limited medical resources, violation of international humanitarian law, and under frequent strikes of high-energy weapons.
OsDPE2 Regulates Rice Panicle Morphogenesis by Modulating the Content of Starch
Authors: Zheng Yi , Fu Debao , Yang Zenan
Published: February 2023

Starch is a carbon sink for most plants, and its biological role changes with response to the environment and during plant development. Disproportionating Enzyme 2 (DPE2) is a 4-α-glycosyltransferase involved in starch degradation in plants at night. LAX1 plays a vital role in axillary meristem initiation in rice. Herein, results showed that Oryza sativa Disproportionating Enzyme 2 (OsDPE2) could rescue the mutant phenotype of lax1-6, LAX1 mutant. OsDPE2 encodes rice DPE2 located in the cytoplasm. In this study, OsDPE2 affected the vegetative plant development of rice via DPE2 enzyme. Additionally, OsDPE2 regulated the reproductive plant development of rice by modulating starch content in young panicles. Furthermore, haplotype OsDPE2(AQ) with higher DPE2 enzyme activity increased the panicle yield of rice. In summary, OsDPE2 can regulate vegetative and reproductive plant development of rice by modulating starch content. Furthermore, DPE2 activities of OsDPE2 haplotypes are associated with the panicle yield of rice. This study provides guidance for rice breeding to improve panicle yield traits.
SSELM-neg: spherical search-based extreme learning machine for drug–target interaction prediction
Authors: Hu Lingzhi , Fu Chengzhou , Ren Zhonglu , Cai Yongming , Yang Jin , Xu Siwen , Xu Wenhua , Tang Deyu
Published: February 2023

Background

The experimental verification of a drug discovery process is expensive and time-consuming. Therefore, efficiently and effectively identifying drug–target interactions (DTIs) has been the focus of research. At present, many machine learning algorithms are used for predicting DTIs. The key idea is to train the classifier using an existing DTI to predict a new or unknown DTI. However, there are various challenges, such as class imbalance and the parameter optimization of many classifiers, that need to be solved before an optimal DTI model is developed.

Methods

In this study, we propose a framework called SSELM-neg for DTI prediction, in which we use a screening approach to choose high-quality negative samples and a spherical search approach to optimize the parameters of the extreme learning machine.

Results

The results demonstrated that the proposed technique outperformed other state-of-the-art methods in 10-fold cross-validation experiments in terms of the area under the receiver operating characteristic curve (0.986, 0.993, 0.988, and 0.969) and AUPR (0.982, 0.991, 0.982, and 0.946) for the enzyme dataset, G-protein coupled receptor dataset, ion channel dataset, and nuclear receptor dataset, respectively.

Conclusion

The screening approach produced high-quality negative samples with the same number of positive samples, which solved the class imbalance problem. We optimized an extreme learning machine using a spherical search approach to identify DTIs. Therefore, our models performed better than other state-of-the-art methods.
Malaria and the incidence of COVID-19 in Africa: an ecological study
Authors: Habibzadeh Farrokh
Published: February 2023

Background

It has been shown that stimulation of innate immunity may provide temporary protection against a variety of infectious diseases. Malaria has been shown to induce a robust innate immune response. This study was conducted to test the hypothesis that if the cumulative number of cases diagnosed with COVID-19 per 100,000 population was correlated with the prevalence of malaria in African countries where both malaria and COVID-19 were prevalent.

Methods

In this ecological study, the cumulative incidence of COVID-19 and the prevalence of malaria were compared in 53 African countries. A negative binomial regression analysis with the cumulative incidence of COVID-19 as the dependent variable, and the human development index (HDI) and the prevalence of malaria, as independent variables, were used.

Results

The mean cumulative incidence of COVID-19 was 522 cases per 100,000. Each 0.1 unit increase in HDI was associated with 2.4-fold (95% confidence interval 1.8–3.1) increase in the cumulative incidence of COVID-19. Prevalence of malaria was also independently associated with the cumulative incidence; each 10% increase in the prevalence was associated with 28% (10–41%) decrease in the cumulative incidence of COVID-19.

Conclusions

Malaria might protect people against SARS-CoV-2 through the stimulation of innate immunity. Stimulation of the innate immune system could be the first line of defense in the pandemic preparedness arsenal.
Gorham-Stout disease affecting the spine with cerebrospinal fluid leakage and Chiari-like tonsillar herniation: a rare case report and review of literature
Authors: Xing Qian-qian , Miao Meng , Zhang Qiao-wei , Wu Yue , He Fei-fang
Published: February 2023

Background

Gorham-Stout disease (GSD) is a very rare disorder characterized by massive osteolysis of poorly understood aetiology. The association between GSD involving the skull base and cerebrospinal fluid (CSF) leakage has been reported in the literature. However, few cases of CSF leakage and Chiari-like tonsillar herniation in GSD involving the spine have been reported.

Case presentation

We present the case of a 20-year-old man with GSD involving the thoracic and lumbar spine, which caused CSF leakage and Chiari-like tonsillar herniation. The patient underwent four spinal surgeries for osteolytic lesions of the spine over a 10-year period. Here, we discuss the possible aetiology of the development of CSF leakage. Epidural blood patch (EBP) was performed at the T11-T12 level to repair the CSF leakage. After EBP treatment, rebound intracranial hypertension (RIH) developed, and tonsillar herniation disappeared 2 months later.

Conclusions

GSD involving the spine with CSF leakage and Chiari-like tonsillar herniation is relatively rare. For patients who have undergone multiple spinal surgeries, minimally invasive treatment is an alternative treatment for CSF leakage. EBP can repair CSF leakage secondary to GSD and improve chronic brain sagging, with reversibility of Chiari-like malformations.
Multi-region sampling with paired sample sequencing analyses reveals sub-groups of patients with novel patient-specific dysregulation in Hepatocellular Carcinoma
Authors: Jeon Ah-Jung , Teo Yue-Yang , Sekar Karthik , Chong Shay Lee , Wu Lingyan , Chew Sin-Chi , Chen Jianbin , Kendarsari Raden Indah , Lai Hannah , Ling Wen Huan , Kaya Neslihan Arife , Lim Jia Qi , Ramasamy Adaikalavan , Oguz Gokce , Chung Alexander Yaw-Fui , Chan Chung Yip , Cheow Peng-Chung , Kam Juinn Huar , Madhavan Krishnakumar , Kow Alfred , Ganpathi Iyer Shridhar , Lim Tony Kiat Hon , Leow Wei-Qiang , Loong Shihleone , Loh Tracy Jiezhen , Wan Wei Keat , Soon Gwyneth Shook Ting , Pang Yin Huei , Yoong Boon Koon , Ong Diana Bee-Lan , Lim Jasmine , de Villa Vanessa H. , Cruz Rouchelle D.dela , Chanwat Rawisak , Thammasiri Jidapa , Bonney Glenn K. , Goh Brian K. P. , Tucker-Kellogg Greg , Foo Roger Sik Yin , Chow Pierce K. H.
Published: February 2023

Background

Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC).

Methods

Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients’ matched adjacent normal samples.

Results

Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate.

Discussion/conclusion

Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.
A variant of RAG1 gene identified in severe combined immunodeficiency: a case report
Authors: Zhang Xinping , Kang Xiayan , Yang Meiyu , Cai Zili , Song Yulei , Zhou Xiong , Cao Jianshe , Wang Chengjuan , Huang Kang , Peng Yani , He Jie , Xiao Zhenghui
Published: February 2023

Background

The recombination-activating gene 1 (RAG1) protein is essential for the V (variable)-D (diversity)-J (joining) recombination process. Mutations in RAG1 have been reported to be associated with several types of immune disorders. Typical clinical features driven by RAG1 variants include persistent infections, severe lymphopenia, and decreased immunoglobulin levels .

Case presentation

In this study, a 2-month-24-days-old infant with recurrent fever was admitted to our hospital with multiple infections and absence of T and B lymphocytes. The infant was diagnosed with severe combined immunodeficiency (SCID). A homozygous variation c.2147G>A (NM_000448.2: exonme2: c.2147G>A (p.Arg716Gln)) was identified in the RAG1 gene using whole-exome sequencing and Sanger sequencing. The predicted 3D structure of variant RAG1 indicated altered protein stability. Additionally, decreased expression of variant RAG1 gene was detected at both the mRNA and protein levels.

Conclusions

Our study identified a novel homozygous variant in RAG1 gene that causes SCID. This finding expands the variant spectrum of RAG1 in SCID and provides further evidence for the clinical diagnosis of SCID.
“He’s a little skinny and he’s a little wide.”: a mixed design investigation of American Indian student perceptions of healthy bodies
Authors: Cothran Donetta J. , Kulinna Pamela Hodges
Published: February 2023

Background

Childhood is a critical developmental time of wellness patterns, yet little is known about what children know and believe. Even less is known about non-majority cultures like American Indian youth. The purpose of this study was to explore American Indian students’ understandings of nutrition and physical activity.

Methods

This mixed methods study took place in 10 schools in an American Indian community in the Southwestern U.S. Ninety American Indian students in grades 3–12 (8–19 years old) were interviewed. The interview included an 8-point body size chart. Numerical data were analyzed via t-test statistics while a constant comparison process and analysis was used for the interview data.

Results

Students rated approximately 85% of students in Category 5 or smaller on the scale while placing 60% of adults at or above that size. There was a general trend of a larger body type for boys seen as healthy compared to that for girls. Students generally believed that their classmates were larger than the healthy body size.

For students, a healthy body was the result of compliance with “eat right and exercise” rules. They exhibited little understanding of nutrition or physical activity and there were few developmental differences in understanding. Health was a corporeal concept and violators of the eat right and exercise rules were seen as lazy.

Conclusions

Students held narrow and corporeal focused notions of health focused on simple rules. People who violated the rules were “lazy”, a concept that seemed to underlie multiple constructs and a finding that holds true in other investigations. Students also reported few adult role models, a topic that should be explored with expanded family groups to better represent the multi-generational (e.g. grandparents, uncles, aunts) family housing common in the community. The findings are limited to a single American Indian community and a mixed design of relatively small numbers. This addition to the literature from a non-majority cultural group expands our knowledge of student perspectives on health. These findings can be used to create more effective curricula and interventions. Schools need more effective, but also alternately framed approaches that promote broader views of health.
Hierarchical multiple regression investigating factors associated with depressive symptoms in the middle-aged and elderly undergoing haemodialysis
Authors: Chiou Chou-Ping , Bai Yu-Ling , Lai Liu-Yuan , Hsieh Hsiu-Chu , Chang Shin-Tsu
Published: February 2023

Background

Depressive moods are commonly seen in patients who receive haemodialysis. This can cause a lack of compliance in their treatment procedures and increase the rate of hospitalization. This study aimed to investigate the relationship between social support and degree of depression in middle-aged and elderly patients undergoing haemodialysis and the predictors of depressive symptoms.

Methods

A cross-sectional correlational study was designed with a structured questionnaire survey. Patients over 40 years of age were included from five haemodialysis centres. Measures embraced a demographic and clinical characteristics questionnaire, the Centre for Epidemiologic Studies Depression Scale, and the Personal Resource Questionnaire 2000. Statistical analysis was performed using hierarchical multiple regression analysis.

Results

A total of 179 patients over 40 years of age were included from five haemodialysis centres in the analysis. The mean CES-D score was 19.0(12.3); the majority of participants (60.3%) had a CES-D score ≥ 15, indicating likely depressive status. The mean PRQ2000 score was 75.7(15.9). The proportional mean of the PRQ2000 was 72.11%, indicating moderate social support for participants in this study. Data disclosed that marital status, number of comorbidities, exercise behaviour, and social support could significantly predict depressive symptoms; total explanatory variance was 31.3%.

Conclusion

Health care professionals should identify those at high risk of depressive symptoms when they provide care to the middle-aged and elderly patients undergoing haemodialysis. These findings may lead to greater insights into the nursing and rehabilitative care of patients treated by chronic maintenance haemodialysis.