bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI-based navigated cryosurgery of extra-abdominal desmoid tumors using skin fiducial markers: a case series of 15 cases
Authors: Segal Ortal , Benady Amit , Pickholz Eliana , Ovadia Joshua E. , Druckmann Ido , Dadia Solomon , Rath Ehud , Albagli Assaf , Efrima Ben
Published: December 2023

Background

Precision surgery is becoming increasingly important in the field of Orthopaedic Oncology. Image-guided percutaneous cryosurgery (CRA) has emerged as a valid treatment modality for extra-abdominal desmoid tumors (EDTs). To date, most CRA procedures use CT-based guidance which fails to properly characterize tumor segments. Computer-guided MRI navigation can address this issue however, the lack of a fixed landmark for registration remains a challenge. Successful CRA correlates directly with precision approaches facilitated by intraoperative imaging guidance. This is the first study that attempts to assess the feasibility and efficacy of a novel approach of using skin fiducial markers to overcome the challenge of a MRI-based navigation CRA for symptomatic or progressive EDTs.

Methods

In this retrospective study conducted between 2018 and 2020, 11 patients at a single center with symptomatic or progressive EDTs were treated with CRA using intraoperative MRI navigation. Fifteen cryosurgery procedures were performed, each adhering to a personalized pre-operative plan. Total tumor size, viable and non-viable portions pre- and post-operation, and SF-36 questionnaire evaluating subjective health were recorded.

Results

All CRAs demonstrated 100% adherence to the predetermined plan. Overall, tumor size decreased Median= -56.9% [-25.6, -72.4]) with a reduction in viable tissue, (Median= -80.4% [-53.3, -95.2]). Four patients required additional CRAs. Only one patient’s tumor did not reduce in size. One patient suffered from local muscle necrosis. Pre-operation, the average physical and mental scores 41.6 [29.4, 43] and 26.3 [17.6, 40.9] respectively. Post-operation, the average physical and mental scores were 53.4[38, 59.7] and 38 [31.2, 52.7] respectively.

Conclusion

These findings provide an early indication of the feasibility and efficacy of performing percutaneous cryosurgery using skin fiducial marker registration for MRI-computed navigation to treat EDTs safely. Larger cohorts and multicenter evaluations are needed to determine the efficacy of this technique.
Shape-memory sawtooth-arm embracing clamp used in complex femoral revision hip arthroplasty for stem stability: average 9-year follow-up study
Authors: Hu Yi , Xu Zhengquan , Qiao Hua , Kong Keyu , Li Huiwu , Zhang Jingwei
Published: December 2023

Background

Nickel-Titanium shape-memory sawtooth-arm embracing clamps (SSECs) have been used in revision total hip arthroplasties (rTHAs) to protect stem stability. This study was to introduce this technique and report its mid to long-term clinical and radiographic outcomes.

Methods

We retrospectively reviewed all patients implanted with SSECs in our department from January 2008 to December 2015. 41 patients (41 hips) were finally included. Radiographs and Harris hip scores (HHS) were collected. Radiographs were blindly analyzed for evidence of loosening, subsidence and stress shielding. HHS were compared to previous records by student’s t tests. The average follow-up period was 9.3 years.

Results

All stems were stably fixed with no signs of loosening. The mean stem subsidence was 0.9 mm (range, 0 to 3 mm). Only one patient (2.4%) demonstrated the fourth degree of stress shielding, with the others none or minor bone resorption. The mean HHS at the final follow-up was 84.2 (range, 81 to 91), which was improved from 17.4 (range, 0 to 37) before surgery. No implant failures or re-revisions occurred. Dislocation occurred in 1 case during the follow-up period.

Conclusions

The SSEC protected stem fixation and achieved favorable clinical and radiographic outcomes in this 9-year follow-up study. It offered an additional extramedullary fixation option for surgeons to choose from in treating complex femoral revision arthroplasties.
Artichoke (Cynara scolymus L.) water extract alleviates palmitate-induced insulin resistance in HepG2 hepatocytes via the activation of IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling pathway
Authors: Deng Aihua , Wang Yun , Huang Kerui , Xie Peng , Mo Ping , Liu Fengying , Chen Jun , Chen Kaiyi , Wang Yun , Xiao Bing
Published: December 2023

Background

Artichoke (Cynara scolymus L.) is a typical element of a traditional Mediterranean diet and has potential health advantages for insulin resistance (IR) and type 2 diabetes mellitus (T2DM). This study aims to evaluate the effect and underlying mechanism of artichoke water extract (AWE) on palmitate (PA)-induced IR in human hepatocellular carcinoma (HepG2) cells.

Methods

The effect of AWE on cell viability was determined using CCK8 assay. Cellular glucose uptake, glucose consumption, glucose production, and glycogen content were assessed after AWE treatment. The gene expression and protein levels were examined by real-time polymerase chain reaction (qRT-PCR) and western blotting.

Results

The results showed that AWE dose-dependently increased cell viability in IR HepG2 cells (P < 0.01). AWE treatment significantly promoted glucose uptake and consumption, decreased glucose production, and increased the cellular glycogen content in IR HepG2 cells (P < 0.01). Mechanistically, AWE elevated the phosphorylation and total protein levels of major insulin signaling molecules in IR HepG2 cells, which resulted in a decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and the inhibition of glycogen synthase (GS) phosphorylation in IR HepG2 cells. Furthermore, the protective effect of AWE on IR HepG2 cells might be ascribed to the inhibition of the endoplasmic reticulum (ER) stress.

Conclusion

We conclude that AWE may improve glucose metabolism by regulating IRS1/PI3K/AKT/FoxO1 and GSK-3β signaling associated with the inhibition of ER stress in IR HepG2 cells induced by PA.
Ammidin ameliorates myocardial hypoxia/reoxygenation injury by inhibiting the ACSL4/AMPK/mTOR-mediated ferroptosis pathway
Authors: Han Yue , Yuan Hui , Li Fengxiang , Yuan Yueying , Zheng Xuezhi , Zhang Xudong , Sun Jian
Published: December 2023

Objective

The aim of the present study was to investigate the therapeutic effect of ammidin on hypoxia/reoxygenation (H/R) injury in primary neonatal rat cardiomyocytes by observing the role of ferroptosis in the process of H/R injury, and to verify its target and regulatory signaling pathways.

Methods

The network pharmacology analysis was used to predict the biological processes, core targets and related signaling pathways of Angelica dahurica in the treatment of ferroptosis. Cell viability was assessed using live cell imaging and cell counting kit-8. Lactate dehydrogenase (LDH), reactive oxygen species (ROS) production, and malondialdehyde (MDA), superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) content were determined to assess the level of ferroptosis. Western blotting was performed to measure protein expression.

Results

Network pharmacology predicted that Acyl-CoA synthetase long chain family member 4 (ACSL4) was highly associated with myocardial H/R injury in the intersection of Angelica dahurica and ferroptosis. The top three active components of Angelica dahurica were found to be mandenol, alloisoimperatorin and ammidin, among which ammidin was found to have the strongest binding to the target proteins of the ACSL4/AMPK/mTOR pathway. H/R reduced the viability of cardiomyocytes, while the inhibition of ferroptosis by ferrostatin-1 alleviated the H/R-induced inhibition of cardiomyocyte viability. This was evidenced by the increased cell viability, SOD release, MMP level and glutathione peroxidase 4 (GPX4) protein expression, as well as the decreased LDH and MDA release and ROS production and ACSL4 protein expression (P < 0.05). To verify the existence of ferroptosis in myocardial hypoxia/reoxygenation injury. In addition, ammidin increased cell viability and GPX4 protein expression (P < 0.05), decreased ROS generation, and MDA and MTT expression (P < 0.05), then inhibited ferroptosis, and finally alleviated myocardial H/R injury by regulating the ACSL4/AMPK signaling pathway.

Conclusions

Network pharmacology was used to predict the correlation between ammidin and ferroptosis following myocardial H/R injury. It was demonstrated that ammidin may regulate ferroptosis by inhibiting the ACSL4/AMPK/mTOR signaling pathway and reduce H/R injury in cardiomyocytes.
Development of a low-cost congenital abdominal wall defect simulator (wall-go) for undergraduate medical education: a validation study
Authors: Medeiros Gabriel Araújo , Gualberto Igor José Nogueira , da Silva Carlos Henrique Nascimento Domingue , Diniz Ana Maria Bicudo , de Santana Jan Beatriz Felinto , Volpe Fábio Perecin , Gadde Rahul , Mazzo Alessandra , de Oliveira Rodrigo Cardoso , Sbragia Lourenço
Published: December 2023

Background

Congenital Anomalies were responsible for 303,000 deaths in the neonatal period, according to the WHO, they are among the world’s top 20 causes of morbidity and mortality. Expensive simulators demonstrate several diseases, but few are related to congenital anomalies. This study aims to develop, validate, and evaluate low-cost simulator models (WALL-GO) of the most common abdominal wall defects, gastroschisis, and omphalocele, to enable diagnosis through an accessible tool with study value and amenable to replication.

Methods

Market research was conducted to find materials to build low-cost models. The researchers built the model and underwent validation assessment of the selected experts who scored five or more in the adapted Fehring criteria. The experts were assessed through a 5-point Likert scale to 7 statements (S1-7). Statements were assigned values according to relevance in face and transfer validities. Concomitantly, the model was also evaluated by students from 1st to 5th year with the same instruments. Content Validity Indexes (CVIs) were considered validated between groups with concordance greater than 90%. Text feedback was also collected. Each statement was subjected to Fisher’s Exact Test.

Results

Gastroschisis and omphalocele model costs were US $15 and US $27, respectively. In total, there were 105 simulator evaluators. 15 experts were selected. Of the 90 students, there were 16 (1st year), 22 (2nd), 16 (3rd), 22 (4th), and 14 (5th). Students and experts obtained CVI = 96.4% and 94.6%, respectively. The CVIs of each statement were not significantly different between groups (p < 0,05).

Conclusions

The WALL-GO models are suitable for use and replicable at a manufacturable low cost. Mannequins with abdominal wall defects are helpful in learning to diagnose and can be applied in teaching and training health professionals in developing and low-income countries.
The effect of health literacy intervention on adherence to medication of uncontrolled hypertensive patients using the M-health
Authors: Karami Maryam , Ashtarian Hossein , Rajati Mojgan , Hamzeh Behrooz , Rajati Fatemeh
Published: December 2023

Background

Given that patients’ medication adherence is regarded as the major part of disease control and improving health literacy can be effective in promoting adherence to healthy behaviors, the present study aimed to investigate the effect of health literacy intervention based on the medication adherence among uncontrolled hypertensive patients using mobile health (M-health).

Methods

An interventional study with a quasi-experimental design, was conducted on 118 uncontrolled hypertensive patients. Participants were randomly divided into the intervention (n = 59) and control (n = 59) groups using blocked randomization. In the intervention group, a mobile health (M-health) program was designed using programmed instruction to improve patients’ health literacy over a period of 3 months. Data was collected by administering health literacy and medication adherence questionnaires to participants before and after the intervention. The analysis involved using the independent sample t-test to compare the variables before and after the study.

Results

Before the intervention, the total score of health literacy was 33.34 and 33.14 in the intervention and control groups, respectively. After the intervention, it increased to 40.36 and 34.20 in the intervention and control groups, respectively, which was statistically significant in the intervention group (p = 0.01). Moreover, the medication adherence score of the intervention group significantly increased after the intervention. Both systolic and diastolic blood pressure decreased in the intervention group. However, it should be noted that the decrease in systolic blood pressure by 148.98 was statistically significant, while the decrease observed in diastolic blood pressure in the intervention group was not statistically significant (p = 0.08).

Conclusion

The application of programmed instruction through M-Health has shown a positive effect on the health literacy of uncontrolled hypertensive patients. In addition to detecting and treating patients, it is important to prioritize the improvement of health literacy in terms of medication adherence and the adoption of healthy behaviors.
“It’s about time they taught us”: a qualitative study evaluating the barriers to finding and screening child contacts under five at risk for TB in Gauteng Province, South Africa from the provider and caregiver perspectives
Authors: Munedzimwe Fadzai , Chetty-Makkan C. M. , Mukora R. , Charalambous S. , Turner K. , Chihota V.
Published: December 2023

Background

Inadequate numbers of children under five years of age who are exposed to tuberculosis (TB) in the home (child contact) are initiated on TB preventive treatment (TPT) in South Africa. We assessed barriers of initiating isoniazid preventive therapy (IPT) in this age group.

Methods

We conducted a qualitative study at two primary health clinics in the Ekurhuleni district in Gauteng Province. Between April and July 2019, we enrolled facility managers, TB staff and parents or legal guardians of child contacts (caregivers) attending for care, at the two facilities. Semi-structured questionnaires, facility observations and in-depth interviews using a semi-structured interview guide were used to collect data. Findings from the semi-structured questionnaires with facility staff and facility observations were summarized. Thematic analysis with a deductive approach was used to analyse the data from the in-depth interviews with caregivers.

Results

Two facility managers took part in the study and were assisted to complete the semi-structured questionnaires by TB staff. Fifteen caregivers aged between 18 and 43 years were interviewed of which 13 (87%) were female. Facility managers and TB staff (facility staff) felt that even though caregivers knew of family members who were on TB treatment, they delayed bringing their children for TB screening and TPT. Facility staff perceived caregivers as not understanding the purpose and benefits of TB prevention strategies such as TPT. Caregivers expressed the desire for their children to be screened for TB. However, caregivers lacked knowledge on TB transmission and the value of TB prevention in children at high risk of infection.

Conclusion

While facility staff perceived caregivers to lack responsibility, caregivers expressed limited knowledge on the value of screening their children for TB as reasons for not accessing TB preventive services. Health education on TB transmission, screening, and TB prevention strategies at a community level, clinics, creches, schools and via media are important to achieve the global end TB goal of early detection and prevention of TB.
Improving hospital quality risk-adjustment models using interactions identified by hierarchical group lasso regularisation
Authors: Ray Monika , Zhao Sharon , Wang Sheng , Bohl Alex , Romano Patrick S.
Published: December 2023

Background

Risk-adjustment (RA) models are used to account for severity of illness in comparing patient outcomes across hospitals. Researchers specify covariates as main effects, but they often ignore interactions or use stratification to account for effect modification, despite limitations due to rare events and sparse data. Three Agency for Healthcare Research and Quality (AHRQ) hospital-level Quality Indicators currently use stratified models, but their variable performance and limited interpretability motivated the design of better models.

Methods

We analysed patient discharge de-identified data from 14 State Inpatient Databases, AHRQ Healthcare Cost and Utilization Project, California Department of Health Care Access and Information, and New York State Department of Health. We used hierarchical group lasso regularisation (HGLR) to identify first-order interactions in several AHRQ inpatient quality indicators (IQI) - IQI 09 (Pancreatic Resection Mortality Rate), IQI 11 (Abdominal Aortic Aneurysm Repair Mortality Rate), and Patient Safety Indicator 14 (Postoperative Wound Dehiscence Rate). These models were compared with stratum-specific and composite main effects models with covariates selected by least absolute shrinkage and selection operator (LASSO).

Results

HGLR identified clinically meaningful interactions for all models. Synergistic IQI 11 interactions, such as between hypertension and respiratory failure, suggest patients who merit special attention in perioperative care. Antagonistic IQI 11 interactions, such as between shock and chronic comorbidities, illustrate that naïve main effects models overestimate risk in key subpopulations. Interactions for PSI 14 suggest key subpopulations for whom the risk of wound dehiscence is similar between open and laparoscopic approaches, whereas laparoscopic approach is safer for other groups. Model performance was similar or superior for composite models with HGLR-selected features, compared to those with LASSO-selected features.

Conclusions

In this application to high-profile, high-stakes risk-adjustment models, HGLR selected interactions that maintained or improved model performance in populations with heterogeneous risk, while identifying clinically important interactions. The HGLR package is scalable to handle a large number of covariates and their interactions and is customisable to use multiple CPU cores to reduce analysis time. The HGLR method will allow scholars to avoid creating stratified models on sparse data, improve model calibration, and reduce bias. Future work involves testing using other combinations of risk factors, such as vital signs and laboratory values. Our study focuses on a real-world problem of considerable importance to hospitals and policy-makers who must use RA models for statutorily mandated public reporting and payment programmes.
Managing comorbidities in chronic kidney disease reduces utilization and costs
Authors: Li Yong , Barve Kanchan , Cockrell Meghan , Agarwal Amal , Casebeer Adrianne , Dixon Suzanne W. , Poonawalla Insiya
Published: December 2023

Background

Effective management of comorbid diabetes and hypertension in patients with chronic kidney disease (CKD) is important for optimal outcomes. However, little is known about this relationship from a health plan perspective. The objective of this study was to evaluate the association of effective management of comorbid diabetes and/or hypertension with healthcare resource utilization (HCRU) in patients with chronic kidney disease (CKD).

Methods

This retrospective cohort study used the Humana Research Database to identify patients with CKD Stage ≥ 3a in 2017. Eligible patients were enrolled in a Medicare Advantage Prescription Drug plan for ≥ 12 months before and after the index date (first observed evidence of CKD). Patients with end-stage renal disease, kidney transplant, or hospice election preindex were excluded. Recommended comorbid disease management included hemoglobin A1c monitoring; adherence to glucose-lowering, cardiovascular, and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker medications; and nephrologist/primary care provider (PCP) visits. HCRU was evaluated for 12 months postindex.

Results

The final cohort of 241,628 patients was 55% female and 77% White, with an average age of 75 years. Approximately 90% of patients had Stage 3 CKD. Half had both diabetes and hypertension, and most of the remaining half had hypertension without diabetes. Patients meeting the criteria for good disease management, compared with patients not meeting those criteria, were less likely to experience an inpatient hospitalization, by as much as 40% depending on the criterion and the comorbidities present, or an emergency department visit, by as much as 30%. Total monthly healthcare costs were as much as 17% lower.

Conclusions

Management of comorbid diabetes and hypertension in patients with CKD was associated with lower HCRU and costs. Care coordination programs targeting patients with CKD must give careful attention to glucose and blood pressure control.

Trial registration

Not applicable.
SARSCoV-2 antibody prevalence and titers in persons living with HIV cared for at a large tertiary reference center in Mexico City
Authors: Soto-Nava Maribel , Dávila-Conn Vanessa , Venancio-Rocha Juan P. , García-Esparza Pedro , Tapia-Trejo Daniela , Hernández-Juan Ramón , Zarza-Sánchez Eduardo , Murakami-Ogasawara Akio , Ávila-Ríos Santiago
Published: December 2023

Objective

To assess SARS-CoV-2 antibody prevalence and titers in people living with HIV (PLWHIV) on antiretroviral treatment (ART) enrolled at a tertiary reference hospital in Mexico.

Methods

Two plasma aliquots per person, used for HIV viral load follow-up between 01/2020 and 09/2021, were used to assess total anti-N and neutralizing SARS-CoV-2 antibodies. Sociodemographic, clinical, and SARS-CoV-2 exposure risk information were collected. The risk associated with SARS-CoV-2 exposure and associations with antibody titers were analyzed with logistic, Cox, and linear multivariable models.

Results

803 PLWHIV participated; 233 had detectable SARS-CoV-2 antibodies (prevalent cases), and 132 seroconverted (incident cases). Overall, the adjusted prevalence was 46.45%, with an incidence rate of 3.78 cases/100 person-months. Factors associated with prevalent cases included lower age, location (western zone of Mexico City and the neighboring Mexico State), use of public transport, attendance at meetings without social distancing, and higher CD4 + T cell counts (p < 0.05; multivariable logistic model). BNT162b2 vaccination reduced incident cases (Cox adjusted HR = 0.4; p = 0.013). Notably, previously infected and vaccinated individuals showed maximization of neutralizing activity (p < 0.001). No associations between SARS-CoV-2 neutralization and HIV-related variables (CD4 + T cell counts, viral load, number of years in viral suppression, ART regimen) were found in multivariable analysis.

Conclusions

SARS-CoV-2 infection was associated with community risk rather than HIV-associated variables in PLWH on ART and clinical follow-up. Antibody neutralization activity in vaccinated participants was maximized with previous SARS-CoV-2 infection.
A review of foot-and-mouth disease in Ethiopia: epidemiological aspects, economic implications, and control strategies
Authors: Zewdie Girma , Akalu Mirtneh , Tolossa Wondwossen , Belay Hassen , Deresse Getaw , Zekarias Mariamawit , Tesfaye Yeneneh
Published: December 2023

Foot-and-mouth disease (FMD) is a contagious viral disease that affects the livelihoods and productivity of livestock farmers in endemic regions. It can infect various domestic and wild animals with cloven hooves and is caused by a virus belonging to the genus Aphthovirus and family Picornaviridae, which has seven different serotypes: A, O, C, SAT1, SAT2, SAT3, and Asia-1. This paper aims to provide a comprehensive overview of the molecular epidemiology, economic impact, diagnosis, and control measures of FMD in Ethiopia in comparison with the global situation. The genetic and antigenic diversity of FMD viruses requires a thorough understanding for developing and applying effective control strategies in endemic areas. FMD has direct and indirect economic consequences on animal production. In Ethiopia, FMD outbreaks have led to millions of USD losses due to the restriction or rejection of livestock products in the international market. Therefore, in endemic areas, disease control depends on vaccinations to prevent animals from developing clinical disease. However, in Ethiopia, due to the presence of diverse antigenic serotypes of FMD viruses, regular and extensive molecular investigation of new field isolates is necessary to perform vaccine-matching studies to evaluate the protective potential of the vaccine strain in the country.
CD146-positive adipose-derived stem cells subpopulation enriched by albumin magnetic sphere ameliorates knee osteoarthritis pain and promotes cartilage repair
Authors: Wu Lianghao , Zhang Xu , Yi Chengqing , Ren Hanru
Published: December 2023

Background

The use of adipose stem cell (ADSCs) subpopulations in cartilage repair remains poorly characterized. In this study, we constructed an albumin magnetic sphere with specific targeting of CD146 (CD146-AMs) for sorting a subpopulation of CD146-positive ADSCs (CD146 + ADSCs) and explored the role of CD146 + ADSCs on joint pain and cartilage repair in rats with knee osteoarthritis (KOA).

Methods

CD146-AMs were prepared and analyzed in materialistic characterization tests. Subpopulations of CD146 + ADSCs were sorted using CD146-AMs. Surface labeling, viability, and proliferation of a subpopulation of CD146 + ADSCs were evaluated in vitro. Molecular characterization of mRNA and protein expression profiles was analyzed by microarray. A rat KOA pain model was established by the iodoacetic acid method, and KOA pain and the promotion of cartilage repair were assessed after treatment with bilateral joint cavity injections of CD146 + ADSCs.

Results

The CD146-AMs prepared in this study had an average particle size of 242.63 ± 6.74 nm, an average potential of 33.82 ± 3.53 mv, and high CD146 targeting and low cytotoxicity. The positive rate of enriched CD146 + ADSCs was 98.21% and showed a high level of stem cell marker expression and good cell viability. Gene and protein expression profiles showed that CD146 + ADSCs have different cellular functions, especially in regulating inflammation. In the KOA model, low, medium and high concentrations of CD146 + ADSCs were able to improve KOA pain and promote cartilage repair in a concentration-dependent trend.

Conclusions

The CD146-AMs prepared in this study were able to safely and efficiently sort out the CD146 + ADSCs subpopulation. The subpopulation of CD146 + ADSCs has a unique molecular profile that ameliorates KOA pain and repairs cartilage damage in rats, providing a new idea for KOA treatment.
Correlation between ESR1 and APOE gene polymorphisms and risk of osteonecrosis of the femoral head: a case–control study
Authors: Wang Yuan , Ma Xiaoya , Guo Jinping , Li Yujie , Xiong Yuyan
Published: December 2023

Background

Osteonecrosis of the femoral head (ONFH) is a disease with a high disability rate, and genetic factors are closely related to its pathogenesis. This study aimed to investigate the possible correlation between ESR1 and APOE gene polymorphisms and the risk of ONFH.

Methods

In this case–control study, the potential association between three genetic variants (rs2982573 C < T, rs10872678 C < T, and rs9322332 A < C) of the ESR1 gene and two genetic variants (rs7259620 A < G and rs769446 C < T) of the APOE gene with the risk of ONFH was investigated. Correlations between gene polymorphisms and ONFH risk were assessed using logistic regression analysis, with calculation of odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The overall analysis demonstrated that rs9322332 in the ESR1 gene exhibited a correlation with a decreased risk of ONFH under the homozygous (AA vs.CC: OR = 0.69, 95% CI [0.53–0.90], p = 0.006), dominant (CA + AA vs. CC: OR = 0.70, 95% CI [0.54–0.90], p = 0.006), and additive (OR = 0.79, 95% CI [0.66–0.95], p = 0.013) models. The stratification analysis revealed that rs9322332 was linked to a lower risk of ONFH in subgroups characterized by individuals aged over 51 years and non-smokers. Nevertheless, there were no notable correlations found between ESR1 rs2982573 and rs10872678, as well as APOE rs7259620 and rs769446, with the risk of ONFH.

Conclusion

ESR1-rs9322332 is closely linked to a decreased risk of ONFH, thereby enhancing our understanding of the relationship between gene polymorphisms and ONFH.
SNHG17 alters anaerobic glycolysis by resetting phosphorylation modification of PGK1 to foster pro-tumor macrophage formation in pancreatic ductal adenocarcinoma
Authors: Lin Jiayu , Liu Yihao , Liu Pengyi , Qi Wenxin , Liu Jia , He Xingfeng , Liu Qian , Liu Zehua , Yin Jingxin , Lin Jiewei , Bao Haili , Lin Jianhong
Published: December 2023

Background

Within the tumor immune microenvironment (TME), tumor-associated macrophages (TAMs) are crucial in modulating polarization states to influence cancer development through metabolic reprogramming. While long non-coding RNAs (lncRNAs) have been shown to play a pivotal role in the progression of various cancers, the underlying mechanisms by which lncRNAs alter M2 polarization through macrophage metabolism remodeling remain unelucidated.

Methods

RNA sequencing was used to screen for differentially expressed lncRNAs in TAMs and normal tissue-resident macrophages (NTRMs) isolated from pancreatic ductal adenocarcinoma (PDAC) tissues, whilst RT-qPCR and FISH were employed to detect the expression level of SNHG17. Moreover, a series of in vivo and in vitro experiments were conducted to assess the functions of SNHG17 from TAMs in the polarization and glycolysis of M2-like macrophages and in the proliferation and metastasis of pancreatic cancer cells (PCs). Furthermore, Western blotting, RNA pull-down, mass spectrometry, RIP, and dual-luciferase assays were utilized to explore the underlying mechanism through which SNHG17 induces pro-tumor macrophage formation.

Results

SNHG17 was substantially enriched in TAMs and was positively correlated with a worse prognosis in PDAC. Meanwhile, functional assays determined that SNHG17 promoted the malignant progression of PCs by enhancing M2 macrophage polarization and anaerobic glycolysis. Mechanistically, SNHG17 could sponge miR-628-5p to release PGK1 mRNA and concurrently interact with the PGK1 protein, activating the pro-tumorigenic function of PGK1 by enhancing phosphorylation at the T168A site of PGK1 through ERK1/2 recruitment. Lastly, SNHG17 knockdown could reverse the polarization status of macrophages in PDAC.

Conclusions

The present study illustrated the essential role of SNHG17 and its molecular mechanism in TAMs derived from PDAC, indicating that SNHG17 might be a viable target for PDAC immunotherapy.
Beyond the exome: utility of long-read whole genome sequencing in exome-negative autosomal recessive diseases
Authors: AlAbdi Lama , Shamseldin Hanan E. , Khouj Ebtissal , Helaby Rana , Aljamal Bayan , Alqahtani Mashael , Almulhim Aisha , Hamid Halima , Hashem Mais O. , Abdulwahab Firdous , Abouyousef Omar , Jaafar Amal , Alshidi Tarfa , Al-Owain Mohammed , Alhashem Amal , Al Tala Saeed , Khan Arif O. , Mardawi Elham , Alkuraya Hisham , Faqeih Eissa , Afqi Manal , Alkhalifi Salwa , Rahbeeni Zuhair , Hagos Samya T. , Al-Ahmadi Wijdan , Nadeef Seba , Maddirevula Sateesh , Khabar Khalid S. A. , Putra Alexander , Angelov Angel , Park Changsook , Reyes-Ramos Ana M. , Umer Husen , Ullah Ikram , Driguez Patrick , Fukasawa Yoshinori , Cheung Ming Sin , Gallouzi Imed Eddine , Alkuraya Fowzan S.
Published: December 2023

Background

Long-read whole genome sequencing (lrWGS) has the potential to address the technical limitations of exome sequencing in ways not possible by short-read WGS. However, its utility in autosomal recessive Mendelian diseases is largely unknown.

Methods

In a cohort of 34 families in which the suspected autosomal recessive diseases remained undiagnosed by exome sequencing, lrWGS was performed on the Pacific Bioscience Sequel IIe platform.

Results

Likely causal variants were identified in 13 (38%) of the cohort. These include (1) a homozygous splicing SV in TYMS as a novel candidate gene for lethal neonatal lactic acidosis, (2) a homozygous non-coding SV that we propose impacts STK25 expression and causes a novel neurodevelopmental disorder, (3) a compound heterozygous SV in RP1L1 with complex inheritance pattern in a family with inherited retinal disease, (4) homozygous deep intronic variants in LEMD2 and SNAP91 as novel candidate genes for neurodevelopmental disorders in two families, and (5) a promoter SNV in SLC4A4 causing non-syndromic band keratopathy. Surprisingly, we also encountered causal variants that could have been identified by short-read exome sequencing in 7 families. The latter highlight scenarios that are especially challenging at the interpretation level.

Conclusions

Our data highlight the continued need to address the interpretation challenges in parallel with efforts to improve the sequencing technology itself. We propose a path forward for the implementation of lrWGS sequencing in the setting of autosomal recessive diseases in a way that maximizes its utility.
Multifocal gastrointestinal stromal tumor with osseous metaplasia: a case report
Authors: Al Saleem Maryam Abdullah , Khan Nida Mirzaman , ElSharkawy Tarek Mohammad
Published: December 2023

Background

Gastrointestinal stromal tumor is considered the most common mesenchymal neoplasm of the gastrointestinal tract. The majority of gastrointestinal stromal tumor cases are located in the stomach and usually affects older adults. Most of gastrointestinal stromal tumor cases are sporadic; however, few have a syndromic association, including Carney triad, Carney–Stratakis syndrome, familial gastrointestinal stromal tumor syndrome, and neurofibromatosis type 1.

Case presentation

Herein, we report a rare case of a 54-year-old Middle-Eastern female with multifocal gastrointestinal stromal tumor mixed type (epithelioid and spindle cell type) with osseous metaplasia. Fluoresce in situ hybridization analysis of platelet-derived growth factor receptor alpha revealed deletion in 42% of the tumor cells studied. Interestingly, next generation sequencing revealed platelet-derived growth factor receptor alpha exon 12 mutation (p.Y555C) and exon 14 mutation (p.N659Y).

Conclusions

In conclusion, osseous metaplasia in GIST is a very rare event and only few cases are reported in the literature. The number of reported cases is inadequate to confirm the pathogenesis and the prognosis.
COVISHIELD vaccine-induced thyroiditis: a case report
Authors: Sachin J. , Shukla Ravindra , Anil Abhishek , Saravanan Aswini , Santhyavu Sanjay , Varthya Shoban Babu , Ambwani Sneha , Singh Surjit
Published: December 2023

Background

The rapid development of coronavirus disease 2019 vaccines during the pandemic has left their long-term effects largely unknown. Instances of autoimmune and subacute thyroiditis showing features of autoimmune/inflammatory syndrome induced by adjuvants have been reported post-vaccination. This case report aims to highlight the autoimmune/inflammatory syndrome induced by adjuvants syndrome after coronavirus disease 2019 vaccination, drawing attention to a possible connection with thyroid dysfunction and urging for further thorough research.

Case presentation

We present a case of thyroiditis induced by the COVISHIELD vaccine in a 37-year-old Indian woman. An apparently normal and healthy adult woman developed neck pain and easy fatigability 2 weeks after the second dose of COVISHIELD, which gradually increased and was associated with irritability, decreased sleep, excessive sweating, tremor, palpitation, and weight loss. She presented to the outpatient department after 1 week of symptoms and was evaluated with laboratory tests and imaging. She was diagnosed with thyroiditis due to the coronavirus disease 2019 vaccine and was treated with propranolol.

Conclusion

This case report adds to the growing evidence of coronavirus disease 2019 vaccine-related thyroid issues. The development of thyroiditis is rare and underreported post-coronavirus disease 2019 vaccination; hence, research to evaluate the association of coronavirus disease 2019 vaccines with thyroid dysfunction needs to be done in the future.
Periodic dynamics of predator-prey system with Beddington–DeAngelis functional response and discontinuous harvesting
Authors: Wang Yingying , Xia Zhinan
Published: December 2023

This paper investigates a delayed predator-prey model with discontinuous harvesting and Beddington–DeAngelis functional response. Using the theory of differential inclusion theory, the existence of positive solutions in the sense of Filippov is discussed. Under reasonable assumptions and periodic disturbances, the existence of positive periodic solutions of the model is studied based on the theory of Mawhin’s coincidence degree. Finally, through numerical simulation, the correctness and feasibility of the conclusions are verified.
Estimating health state utilities in Duchenne muscular dystrophy using the health utilities index and EQ-5D-5L
Authors: Audhya Ivana F. , Szabo Shelagh M. , Bever Andrea , O’Sullivan Fiona , Malone Daniel C. , Feeny David , Neumann Peter , Iannaccone Susan T. , Jayasinghe P. , Gooch Katherine L.
Published: December 2023

Background

The progression of Duchenne muscular dystrophy (DMD) is characterized by loss of ambulation, respiratory insufficiency, cardiomyopathy, and early mortality. DMD profoundly impacts health-related quality-of-life (HRQoL). However, few health state utility data exist; published utilities tend to be derived from small samples for a limited number of health states and are often based on caregiver-reported patient health status. This study estimated utility values for varied clinical and functional health states in DMD, based on patient-reported health status.

Methods

Individuals with DMD in the US aged 12–40 years completed the EQ-5D (5-level) and Health Utilities Index (HUI) preference-based instruments. Based on responses to a clinical questionnaire, participants self-classified into functional health states according to level of lower and upper limb function, use of respiratory support, and presence of cardiomyopathy. Mean [standard deviation (SD)] utility and EQ-5D visual analogue scale (VAS) scores were estimated according to health state; and median (interquartile range) attribute levels calculated to understand which domains of health are most severely affected in DMD.

Results

Of 63 males with DMD, mean (SD) age was 19.8 (6.1) years and 11 (17.5%) were ambulatory. Mean (SD) utility values were 0.92 (0.08; HUI2), 0.84 (0.20; HUI3), and 0.84 (0.13; EQ-5D) for ambulatory patients without cardiomyopathy (n = 10). For non-ambulatory patients with moderately impaired upper limb function, night and daytime ventilation without cardiomyopathy, mean (SD) utilities were 0.49 (0.07) for the HUI2, 0.16 (0.15) for the HUI3 and 025 (0.14) for the EQ-5D. Mean (SD) VAS scores for the same health states were 91 (9) and 83 (21), respectively. In addition to impairments in mobility/ambulation, and self-care, attributes like usual activities and pain also showed notable effects of DMD.

Conclusions

In DMD, although a relationship between disease progression and HRQoL is observed, there is large variability in utility within functional health states, and across instruments. Utility values for less severe non-ambulatory health states described by level of upper limb function are novel. These utility values, derived based on direct patient feedback rather than from caregiver report, are relevant to individuals of varying functional statuses and augment scarce DMD-specific utility data.
Virtual, augmented, mixed, and extended reality interventions in healthcare: a systematic review of health economic evaluations and cost-effectiveness
Authors: Gómez Bergin Aislinn D. , Craven Michael P.
Published: December 2023

Introduction

Health economic evaluations are required to best understand the value of interventions to the health economy. As extended reality technologies (an umbrella term including virtual, augmented, and mixed reality) become cheaper and more accessible it is likely that they will be used more within healthcare.

Objective

The aim of this study was to systematically review common practices within health economic evaluations of extended reality interventions in healthcare and to discuss the methods, outcomes, and methodological quality to inform future HEEs.

Methods

MEDLINE, Embase, NHSEED, PubMed, and the ACM Digital Library were searched, and studies retrieved and screened. We extracted descriptions of the population, intervention, comparator, outcomes, context, costs, and economic evaluation data from studies that fit our criteria. We included studies that involved healthcare patients who were provided extended reality interventions versus standard care, other types of care, or another extended reality application within the same setting where the outcome included both health outcomes and health economic evaluations.

Results

The search identified 1,693 records in total, of which 1,271 were excluded after title and abstract screening. A total of 422 articles were retrieved and screened and the majority (n = 233) were excluded as they did not contain a health economic analysis or cost data. Fourteen articles were included in this review, all of which found that extended reality health interventions could provide cost savings. Our findings showed considerable heterogeneity between studies and a lack of clear descriptions of XR interventions, limiting their use within procurement.

Conclusion

Extended reality in healthcare has the potential to offer significant clinical benefits and research has shown it to be promising at delivering cost-savings. We make recommendations based on the findings of our review for future health economic analyses to help ensure that health economic analyses can support decision-makers in procuring these technologies.

Trial registration

PROSPERO 2022 CRD42022342110.
A Study Planning Exercise Associated with Decreased Distraction Levels among Introductory Biology Students
Authors: Walck-Shannon Elise M. , Rowell Shaina F. , Bednarski April E. , Barber Ashton M. , Yuan Grace J. , Frey Regina F.
Published: December 2023

This article describes how students incorporated distraction into their study plans. During planning, students formed an implementation intention (IF[obstacle], THEN[solution]) statement. Students who planned for distraction obstacles reported less distraction during studying than students who planned for other obstacles.
Improvements in Survival and Clinical Benefit With Gemcitabine as First-Line Therapy for Patients With Advanced Pancreas Cancer: A Randomized Trial
Authors: Burris H A , Moore M J , Andersen J , Green M R , Rothenberg M L , Modiano M R , Cripps M C , Portenoy R K , Storniolo A M , Tarassoff P , Nelson R , Dorr F A , Stephens C D , Von Hoff D D
Published: December 2023

PURPOSE

Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer.

PATIENTS AND METHODS

One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival.

RESULTS

Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated.

CONCLUSION

This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.
Proceedings of Societies
Authors: Lankester Dr.
Published: December 2023

Eighteen presents of books were announced, and the thanks of the Society returned to their respective donors.
OXPHOS capacity is diminished and the phosphorylation system inhibited during diapause in an extremophile, embryos of Artemia franciscana
Authors: Patil Yuvraj N. , Gnaiger Erich , Landry Alexander P. , Leno Zachary J. , Hand Steven C.
Published: December 2023

Diapause exhibited by embryos of Artemia franciscana is accompanied by severe arrest of respiration. A large fraction of this depression is attributable to downregulation of trehalose catabolism that ultimately restricts fuel to mitochondria. This study now extends knowledge on the mechanism by revealing metabolic depression is heightened by inhibitions within mitochondria. Compared with that in embryo lysates during post-diapause, oxidative phosphorylation (OXPHOS) capacity P is depressed during diapause when either NADH-linked substrates (pyruvate and malate) for electron transfer (electron transfer capacity, E) through respiratory Complex I or the Complex II substrate succinate are used. When pyruvate, malate and succinate were combined, respiratory inhibition by the phosphorylation system in diapause lysates was discovered as judged by P/E flux control ratios (two-way ANOVA; F1,24=38.78; P<0.0001). Inhibition was eliminated as the diapause extract was diluted (significant interaction term; F2,24=9.866; P=0.0007), consistent with the presence of a diffusible inhibitor. One candidate is long-chain acyl-CoA esters known to inhibit the adenine nucleotide translocator. Addition of oleoyl-CoA to post-diapause lysates markedly decreased the P/E ratio to 0.40±0.07 (mean±s.d.; P=0.002) compared with 0.79±0.11 without oleoyl-CoA. Oleoyl-CoA inhibits the phosphorylation system and may be responsible for the depressed P/E in lysates from diapause embryos. With isolated mitochondria, depression of P/E by oleoyl-CoA was fully reversed by addition of l-carnitine (control versus recovery with l-carnitine, P=0.338), which facilitates oleoyl-CoA transport into the matrix and elimination by β-oxidation. In conclusion, severe metabolic arrest during diapause promoted by restricting glycolytic carbon to mitochondria is reinforced by depression of OXPHOS capacity and the phosphorylation system.