bluuebunny/crossref_metadata_2025 huggingface dataset:
Critical Mixed Methods: The Imperative for Critical Inquiry and Reflexivity in Research
Authors: Hernández-Johnson Mónica J. , Bendixen Lisa D.
Published: November 2024

Mixed methods research (MMR) combines qualitative and quantitative approaches, enabling researchers to achieve a more comprehensive and nuanced understanding of social phenomena. This integration is crucial because it allows for a richer exploration of complex issues and has evolved to incorporate social justice work. However, there are also concerns that the use of MMR is merely a token of recognition when working with “emic perspectives” as places of higher education favor post-positivist assumptions rooted in neoliberal agendas limited by impact measures constraining qualitative methods to the margins of academia. In light of these considerations, this work seeks to offer a practical guide to critical inquiry within the context of MMR. Critical mixed methods research (CMMR) deviates from the traditional MMR research process by using critical inquiry and self-reflection in every step, informed by critical theories, lenses, and constructs. Additionally, it offers practical recommendations to equip and support researchers to conduct rigorous, ethically informed, and transformative research, especially when working with underrepresented groups who face systemic barriers to opportunities, resources, and representation. Depending on the economic, socio-political, or geographic context, these groups can include racial/ethnic minorities, non-native language speakers, people with disabilities, immigrants and refugees, religious minorities, and so forth. Before introducing the critical mixed methods research (CMMR) guiding framework, it is imperative to delve into some of the critical advancements that have shaped this field.
Perovskite layered materials with A2B2O7 structures for high-temperature sensor applications – A comparative study
Authors: Sivagnanapalani P , Panda P K
Published: November 2024

Perovskite layered materials with A2B2O7 structure such as Ca2Nb2O7, Sr2Nb2O7, Nd2Ti2O7, La2Ti2O7, Sm2Ti2O7 and Pr2Ti2O7 possess very high Curie temperature (Tc > 1000°C). The above materials in powder form were synthesised using mixed oxide method by calcining well-mixed constituent powders between 1000°C and 1300°C for 2 h. Circular disc samples of 12 mm diameter were prepared and sintered at 1200–1450°C, with a soaking duration of 2 h. The sintered density, X-ray diffractometer, scanning electron microscope and electrical resistivity were measured for all samples. The samples experience a linear decrease in electrical resistivity from 1013 to 105 Ω.cm as temperature increases between 100 and 900°C. In this paper, a comparative study on electrical resistivity for the above materials was carried out to determine their suitability for sensing applications at high temperatures.
Assessment of hemodynamic parameters by PiCCO and PAC in patients treated with the Impella CP
Authors: Schmitt Dominik , Schneider Andreas , Lengenfelder Björn , Wagner Martin , Patschan Daniel , Sasko Benjamin , Ertl Georg , Frantz Stefan , Ritter Oliver , Weismann Dirk
Published: November 2024

In 28 patients supported by an Impella pump (Impella CP, Abiomed Inc.®, Danvers, MA), hemodynamic measurements by PiCCO (PULSION Medical Systems SE®, Feldkirchen, Germany) and pulmonary artery catheter (PAC or Swan-Ganz Catheter; Edwards Lifescience®, Unterschleissheim, Germany) were compared. There was a significant positive correlation of cardiac output (CO; r2 = 0.917, p < 0.001), systemic vascular resistance index (SVRI; r2 = 0.904, p < 0.001), stroke volume index (SI; r2 = 0.909, p < 0.001) and left ventricular work index (LCWI; r2 = 0.689, p < 0.001) in PiCCO and PAC measurements under Impella CP support. We conclude, that in patients with left-ventricular Impella support, hemodynamics may be assessentd by PiCCO or PAC.
A novel surgical technique for direct fixation of bony mallet finger with K-wires
Authors: Zhang HuaiBao , Du ShengHu , Zhu JunYi
Published: November 2024

We present a novel surgical technique for avoiding joint surface injury by directly immobilizing the bone mass fracture fragment with K-wires sparing the joint.
Association between carpal tunnel syndrome and shoulder pain: a case–control study
Authors: Akrivos Vasileios S , Koutalos Antonios A , Varitimidis Sokratis E
Published: November 2024

We investigated the prevalence of shoulder pain around the scapular spine in patients with carpal tunnel syndrome and in the general population. In those with carpal tunnel syndrome, 63% reported shoulder pain, against 5% in the control group.

Level of evidence: III
Clinical course for pancreatic necrosis and pancreatic pseudocysts due to severe acute or chronic pancreatitis
Authors: Fusco Stefano , Hanke Greta M. , Büringer Karsten , Minn Lisa , Blumenstock Gunnar , Schempf Ulrike , Götz Martin , Malek Nisar P. , Wichmann Dörte , Werner Christoph R.
Published: November 2024

Background:

The acute and chronic pancreatitis (CP) can lead to severe complications like walled-off necrosis, large symptomatic pseudocyst or multiorgan failure. The treatment of these complications is multivariate and can differ from conservative, symptomatic treatment or minimal-invasive, endoscopic transgastral stenting to transgastral necrosectomy.

Objectives:

This study aims to analyse the clinical course for patients that develop local complications of severe pancreatitis.

Design:

This is a retrospective observational single-centre study on 46 patients with severe pancreatitis.

Methods:

In this retrospective single-centre study, 46 out of 474 inpatients from January 2014 to December 2020, who were treated because of an acute or CP, developed acute pancreatitis complications and could be included. We analysed and compared the clinical course of different treatments (lumen apposing metal stents, transgastral double pigtail stent, endoscopic retrograde cholangiopancreatography, operation, conservative treatment) and different complications (walled-off necrosis (WON), pancreatic pseudocyst (PPC)).

Results:

Forty-six patients developed an acute complication due to severe pancreatitis. Twenty-seven patients developed a WON, while 19 patients suffered from PPC. 48% of the whole cohort had an alcoholic aetiology of pancreatitis. 78% were treated with antibiotics, 48% suffered from infected pancreatitis and 22% needed intensive care treatment. WON patients more often had a longer hospitalization of more than 21 days. PPC patients were correlated with an alcoholic aetiology, whereas WON patients were inversely correlated with an alcoholic aetiology. Increased lactate dehydrogenase, lipase, and C-reactive protein levels as well as leucocyte count could be associated with a higher probability to exhibit a WON instead of another local complication. The mortality rate was low with 7% in our study.

Conclusion:

WON and PPC differ in certain patients and laboratory characteristics such as aetiology, elevated laboratory values, antibiotic treatment or the duration of hospitalization. Invasive treatment is not required in all severe pancreatitis cases.
Enhancing Equity in Gifted Education: A Critical Content Analysis of Identifying Emergent Bilinguals in North Texas
Authors: Shen Yuyang , Sankofa Nicole , Mun Rachel U.
Published: November 2024

This study employs critical content analysis to investigate school districts’ identification process of gifted Emergent Bilinguals (EBLs) in North Texas. Despite the diverse population and significant presence of EBLs in Texas, this group is notably underrepresented in gifted programs. In order to uncover the inequities for gifted EBLs, this study examined 156 school districts’ websites in North Texas (Regions 10 and 11) to gather data. A thematic analysis approach was used to create a research-based rubric with 18 criteria for effectively identifying gifted EBLs. By specifically evaluating the random samples (34 school districts) and the commonly used identification tools in North Texas, three themes emerged from the content analysis: (a) selection process, (b) assessment, and (c) standardized assessment tools. These themes highlighted both effective practices and inequities in the identification process. The study concludes by offering recommendations for improving and creating a more equitable identification for gifted EBLs.
Progress and Trends on Delphinidin During 1993-2023: A Bibliometric Analysis
Authors: Yu Xiaoping , Jiang Hongjie , Wang Mengping , Yang Jingcheng , Zhang Zhen
Published: November 2024

Anthocyanins are bioflavonoids soluble in water. Delphinidin, an active monomer within anthocyanidins, possesses anti-inflammatory, antioxidant, and anti-tumor properties, among others. In recent years, substantial advancements have been achieved in delphinidin research. However, to date, no scholarly work has employed bibliometric analyses on delphinidin studies. This study aims to assess the progress of delphinidin research through bibliometric methods. The Web of Science (WoS) database was utilized to retrieve delphinidin-related literature from 1993 to 2023. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and R Studio. A total of 1586 articles were selected. China leads in the number of publications; the University of Porto is the most prolific institution; Food Chemistry is the journal with the greatest number of published articles; the most cited local literature is by TANAKA Y. The three most frequently occurring keywords are “anthocyanins” “identification” and “expression”. This study conducts a thorough bibliometric analysis of literature pertaining to delphinidin, serving as a foundational reference for future research into delphinidin.
The Role of Delayed Imaging at MRI in Rare Non-enhancing Prostate Cancer Brain Metastases: A Case Report
Authors: Parillo Marco , Santucci Domiziana , Stiffi Massimo , Faiella Eliodoro , Beomonte Zobel Bruno , Mallio Carlo Augusto
Published: November 2024

Brain metastases in prostate cancer are rare (<2% of cases). In magnetic resonance imaging, nearly all brain metastases exhibit contrast-enhancement, which may be affected by the time elapsed since the administration of the contrast agent. We discuss a case where the brain metastases in a patient with prostate cancer do not show a clear contrast-enhancement on magnetic resonance imaging using a standard brain metastases protocol. It also emphasizes the usefulness of delayed imaging in identifying blood–brain barrier damage. We present the case of a 69-year-old man diagnosed with prostate adenocarcinoma, currently in castration-resistant phase (last value of serum prostate-specific antigen: 45.1 ng/mL) with bone, mediastinal and inguinal lymph nodes, pulmonary, and hepatic metastases. In a contrast-enhanced whole-body computed tomography examination, the appearance of intra-axial brain lesions suspicious for metastases was documented. The subsequent contrast-enhanced brain magnetic resonance imaging showed the presence of 5 intra-axial lesions consistent with brain metastases. These lesions exhibited hyperintense signals in T2-fluid-attenuated inversion recovery images; after contrast agent administration, a ring-like contrast-enhancement was more clearly visible in T1-weighted images acquired later (about 15 minutes after contrast agent administration) than in those acquired earlier (about 5-7 minutes after contrast agent administration). In conclusion, for oncological subjects with multiple brain lesions lacking obvious contrast-enhancement using a standard magnetic resonance imaging protocol, we suggest acquiring late images. These might allow for the detection of even minimal post-contrast impregnation, improving confidence in the diagnosis of brain metastases.
Abnormal cochlear enhancement in Norrie disease
Authors: Barkovich Emil Jernstedt , Ferraciolli Suely Fazio , Jaimes Camilo
Published: November 2024

Norrie disease (ND) is a rare x-linked disease with retinal and cochlear vascular abnormalities. Clinically, it is characterized by congenital blindness and progressive sensorineural hearing loss during adolescence. We present images of a 3 year old child with ND and normal hearing demonstrating bilateral cochlear enhancement on brain MRI, a finding which has not been previously reported. ND mouse models show progressive degeneration of the endolymph-producing stria vascularis (SV); we hypothesize that these changes allow gadolinium leakage into the endolymph. Our images indicate that cochlear enhancement precedes changes in hearing and suggest that temporal bone/internal auditory canal MR imaging should be considered in the evaluation of ND. Future studies are needed to characterize the temporal evolution of this cochlear enhancement and how it corresponds with hearing loss. Mouse models suggest that it may be a transient phenomenon and diminish as the SV degenerates further. As ND gene therapy trials approach clinical use, cochlear enhancement could aid candidate selection and provide insight into treatment effect.
Linking phenotype with obstructive sleep apnoea severity: A cross-sectional cephalometric and polysomnographic study of obstructive sleep apnoea patients
Authors: Hor Jocelyn KL , Yow Mimi , Wong Hung Chew , Toh Song Tar
Published: November 2024

Background

Cephalometric features have been identified as phenotypic traits of individuals with obstructive sleep apnoea (OSA). However, few studies have investigated how cephalometric parameters varied with OSA severity, especially in the Asian population.

Objectives

The aim of this study was to investigate the relationship between cephalometric parameters and severity of OSA in the Southeast Asian Chinese population. A novel cephalometric measurement, length of soft palate below the functional occlusal plane, was also studied.

Methods

In this retrospective cross-sectional study of 113 Southeast Asian Chinese patients with OSA diagnosed by overnight polysomnography, the association of cephalometric parameters with the apnoea-hypopnoea index (AHI) was evaluated, controlling for age, gender and body mass index (BMI). STROBE guidelines were used in this study.

Results

Positive association was found between age and AHI (Median Regression Coefficient = 0.26; 95% CI 0.07 to 0.44; p = 0.006). The distance of hyoid bone to mandibular plane was positively associated with AHI (Median Regression Coefficient = 0.58; 95% CI 0.05 to 1.11; p = 0.032), but the correlation did not reach statistical significance after Bonferroni correction ( p = 0.64) or adjustment for age, gender and BMI ( p = 0.106). Median regression analyses revealed a statistically significant negative correlation between facial axis angle and AHI (Median Regression Coefficient = −0.53; 95% CI - 1.04 to −0.01; p = 0.046), after adjusting for age, gender and BMI.

Conclusion

This study indicated that AHI was positively associated with age and negatively associated with facial axis angle.
Parental technoference and the impact on familial relationships
Authors: Gahler Heather
Published: November 2024

Mobile technologies can become sources of interference that interrupt everyday family life. This concept, dubbed technoference, underlies the current study on how technological intrusions influence the parent–child relationship. This study of U.S. co-parents in families of preschool- and kindergarten-aged children examines the extent to which such interruptions are perceived to have negative consequences on the relationships that co-parents have with their children. The study found that the more the participant perceived the other co-parent as allowing technology to interfere during parent–child time together, the more likely the participant was to rate their co-parent's parent–child relationship quality negatively. Additional studies are needed to understand the young child's view of their parents' media use and how it impacts on their relationships.
Brentuximab-Induced Acute Interstitial Nephritis: A Case Report
Authors: Patterson Matthew , Dokouhaki Pouneh , Dumaine Chance S. , MacKay Rebecca , Tai Davina J.
Published: November 2024

Brentuximab vedotin is a combination monoclonal antibody to anti-CD30 conjugated to the anti-tubulin agent monomethyl auristatin E. It is approved for the treatment of mycosis fungoides, Hodgkin’s lymphoma, and systemic anaplastic large cell lymphoma. Brentuximab has been associated with a number of potential adverse reactions; however, reports of renal complications are rare. A 73-year-old male with mycosis fungoides was admitted to hospital with acute kidney injury following his third cycle of brentuximab. The patient’s serum creatinine (SCr) was 122 µmol/L with an estimated glomerular filtration rate (eGFR) of 58 mL/min/1.73 m2 at baseline. Following brentuximab, his SCr peaked at 1073 µmol/L over a 4-week period. Acute interstitial nephritis (AIN) was diagnosed after other causes of acute kidney injury were ruled out and subsequently confirmed on kidney biopsy. The patient was started on prednisone 50 mg daily. This was continued for 3 weeks, followed by a 5-week taper. The patient’s SCr decreased to 156 µmol/L by completion of the prednisone taper. He was not rechallenged with brentuximab. A kidney biopsy confirmed AIN in keeping with injury from an immune checkpoint inhibitor (ICI). However, brentuximab is not an ICI. The AIN from ICIs typically has tubulointerstitial inflammatory infiltrate comprised of T lymphocytes such as the case presented here. Therefore, this represents both a novel histopathologic finding in AIN from a non-ICI medication and a rare complication of brentuximab, previously only presented in abstract form.
Professional Autonomy in Nursing: A Concept Analysis
Authors: Mrayyan Majd T. , Abu Khait Abdallah , Rababa Mohammad , Algunmeeyn Abdullah , Al-Rawashdeh Sami , AL-Atiyyat Nijmeh , Rababa Majdi , Abu Saraya Ahmed , Al-Rjoub Saleem
Published: November 2024

Professional autonomy is critical for nursing practice and professional development. A clear understanding of the professional autonomy concept and its applications in the real world is warranted. This paper clarified the “professional autonomy in nursing” concept using Walker and Avant’s method and the PRISMA flowchart and checklist to conduct the current analysis. Five electronic databases were searched: PubMed, ScienceDirect, ProQuest, Web of Science, and CINAHL Plus with Full Text. The search yielded 21 articles on “professional autonomy in nursing” between 2019 and 2023—however, six old articles related to measurement tools or instruments. The elements that characterize “professional autonomy in nursing” fall into four categories: shared leadership, professional skills, inter- and intra-professional collaboration, and a healthy work environment. Professional autonomy in nursing is defined as the professional nurse’s competency and innovative performance to determine independent or interdependently nursing activities while conserving accountability for decisions and reflecting advocacy and caring. The consequences of the concept are positive outcomes such as high patient satisfaction with provided care, nurses’ accountability, empowerment, a sense of self-efficacy, commitment to the profession, career, and organization, as well as high quality of work. The definitions and measurements of “professional autonomy in nursing” have developed over time, which mandates a continued study and analysis of this concept. It is essential to understand the multidimensional nature of the concept in order to offer professional development programs.
Middle Power Norm Entrepreneur: Indonesia’s Advocacy of the ASEAN Indo-Pacific Outlook
Authors: Putra Bama Andika , Cangara Abdul Razaq , Darwis
Published: November 2024

This article seeks to decipher Indonesia’s role as a norm entrepreneur for the norms of amity and cooperation in the Indo-Pacific region by employing the conceptual framework of the “norm life cycle” developed by Finnemore and Sikkink and Holbraad’s avail of regional initiatives for middle powers. It argues that in contrast to existing literature that construed Indonesia’s role in ASEAN as a form of leadership, Indonesia is merely introducing emerging norms that coincide with its administration’s national interests and priorities. Jokowi initially wielded the regional platform of ASEAN to echo the norm of amity and cooperation, which are introduced through motives of altruism, empathy, and emotional commitment. The norm continued to the norm cascade stage, as the norm became institutionalized in the form of ASEAN Outlook in the Indo-Pacific and provided “peer pressure among states” to eliminate initial opposition to the proposal. Lastly, this article argues that the emerging norm is internalized among ASEAN member states and critical regional actors that contributed to the geopolitical and geostrategic shifts in the Indo-Pacific.
Factors on medical clerkship students’ quality of life: A survey study
Authors: Astiarani Yunisa , Kristian Kevin , Ekaputra Anthony , Hardi Nicholas
Published: November 2024

Introduction:

Due to the higher demand for healthcare provision in Indonesia, increasing the number of medical schools in Indonesia was highly encouraged. Meanwhile, medical students were considered a susceptible population to a variety of issues that negatively impact their quality of life (QOL) in comparison to the general community.

Objectives:

The study aims to assess the QOL of Indonesian medical students during the clinical clerkship program (years 4–5) of their medical training while also exploring the association between the results and their ongoing rotation.

Methods:

The survey was conducted online to 311 students at a private medical school in Jakarta using the Indonesian version of WHOQOL-BREF. Participants’ characteristics, sleep duration, physical activity, and smoking history were also assessed to see if there was any association. Results: 82% of 311 registered clerkship students responded to the survey. In terms of overall QOL, being in a major department, 7–9 h of sleep duration, and owning a private vehicle increased the QOL.

Conclusion:

This study suggested that medical schools’ policies may consider sleep duration, travel time, transportation-related infrastructure, and social-related infrastructure to underpin students’ social relationships and, afterward, improve their QOL in intangible ways.
Comparison of Imaging Characteristics in Pediatric Patients With Trochlear Versus Medial Femoral Condyle Osteochondritis Dissecans
Authors: Tracey Olivia C. , Lijesen Emilie , Bram Joshua T. , Oji Nnaoma M. , Chipman Danielle E. , Fabricant Peter D. , Green Daniel W.
Published: November 2024

Background:

Although osteochondritis dissecans (OCD) lesions are well-described in the femoral condyles and have been associated with varus limb alignment, there is limited data on OCD lesions in the trochlea.

Purpose:

To compare the baseline imaging characteristics in pediatric patients with trochlear OCD with those with medial femoral condyle (MFC) OCD to understand whether measures of coronal plane alignment predispose to OCD development by anatomic location.

Study Design:

Cross-sectional study; Level of evidence, 3.

Methods:

This study retrospectively reviewed all pediatric patients (age ≤18 years) diagnosed with isolated trochlear OCD at a tertiary-care medical center from January 2016 to May 2023; all included patients had weight-bearing hip-to-ankle alignment radiographs. Hip-knee-ankle angle (HKA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), mechanical axis deviation (MAD), Caton-Deschamps Index (CDI), patellar tilt, and sulcus angle were measured on initial/preoperative anteroposterior and lateral knee radiographs. Tibial tubercle-trochlear groove (TT-TG) distance and OCD lesion size were measured on initial/preoperative magnetic resonance imaging sequences. Patients were 1 to 2 matched based on age (±2 years) and sex to a cohort with isolated MFC OCD.

Results:

A total of 18 extremities in 16 patients were included in the trochlear OCD cohort and matched to 36 extremities in the MFC OCD cohort. The mean age at the first clinical visit for all patients was 14.8 ± 1.5 years and did not differ significantly between the two groups ( P = .40). The extremities with trochlear OCD had significantly less varus HKA (1°± 2° vs −1°± 2°; P = .004) and MAD (4 ± 8 vs −3 ± 8 mm; P = .004) compared with the MFC cohort as well as lower mLDFA (86°± 2° vs 88°± 2°; P = .004). There were no differences in MPTA, CDI, patellar tilt, sulcus angle, TT-TG distance, or OCD lesion size between groups.

Conclusion:

Pediatric patients with trochlear OCD had statistically less varus coronal plane alignment compared with age- and sex-matched patients with MFC OCD, with the latter exhibiting more significant varus based on the HKA and MAD.
Who Says We Can’t: Collaborative and Cooperative Learning Through an Asynchronous Online Group Project
Authors: Liu Chin-Yen Alice
Published: November 2024

This article presents a comprehensive and practical formative activity aimed at bolstering students’ quantitative reasoning skills, specifically tailored for a Supply Chain & Operations Management course, within a collaborative group learning context facilitated by online platforms. While the focus is on Supply Chain & Operations Management, the outlined approach is versatile and can be seamlessly adapted to various subjects across online asynchronous courses that emphasize collaborative and cooperative group work. By offering a detailed framework for implementing group discussions and projects, this article significantly contributes to the pedagogical repertoire available to instructors striving to enrich student engagement, improve learning outcomes, and cultivate essential soft skills in online educational settings. Through this formative activity, students are not only equipped with enhanced quantitative reasoning abilities but also benefit from increased collaboration, critical thinking, and holistic skill development, thereby enhancing their overall educational experience.
Health Policies Within the Poverty Agendas of the Lula Da Silva and Rousseff Administrations: The Influence of the World Bank
Authors: Lazarini Welington Serra , Sodré Francis , Siqueira Carlos Eduardo
Published: November 2024

The anti-poverty agenda has been at the heart of the World Bank's discourse in recent decades. Social policies started to be identified as strategic for combating poverty and promoting development in poor countries. We analyzed the health policy recommendations made by the World Bank to Brazil in the Lula da Silva and Rousseff administrations from 2003 to 2014. Document analysis was used to explore the partnership contracts between the World Bank and Brazil, projects financed by the World Bank in Brazil, and the document “20 Years of Construction of the Health System in Brazil: An Analysis of the Unified Health System.” Content analysis of documents show that there was a predominance of projects focusing on reducing poverty, while social policies occupied a secondary place in the agenda. The World Bank approached states and municipalities expanding the spread of its state reform agenda, in addition to reinterpreting the structural framework of the Sistema Único de Saúde (SUS). We conclude that the Bank acted to limit the original principles of the SUS in favor of hegemonic interests of the current phase of capitalist accumulation.
TIMP1 regulates ferroptosis in osteoblasts by inhibiting TFRC ubiquitination: an in vitro and in vivo study
Authors: Peng Bo , Feng Zhiwei , Yang Ao , Liu Jinmin , He Jinwen , Xu Lihu , Tian Cong , Sheng Xiaoyun , Wang Yaobin , Chen Rongjin , Wang Xingwen , Ren Xiaojun , Geng Bin , Xia Yayi
Published: November 2024

Background

In clinical practice, alterations in the internal environment of type 2 diabetes can significantly affect bone quality. While the increased risk of fractures among diabetic patients is well-established, the precise mechanisms by which hyperglycemia influences bone quality remain largely unclear.

Methods

Western blotting, immunohistochemistry (IHC), and micro-CT were used to examine ferroptosis-related protein expression and bone morphology changes in the bone tissues of type 2 diabetic mice. The CCK8 assay determined the optimal conditions for inducing ferroptosis in osteoblasts by high glucose and high fat (HGHF). Ferroptosis phenotypes in osteoblasts were analyzed using flow cytometry, Western blotting, and two-photon laser confocal microscopy. Transcriptomic sequencing of the control and HGHF groups, followed by bioinformatic analysis, identified and validated key genes. TIMP1 was knocked down in osteoblasts to assess its impact on ferroptosis, while TFRC expression was inhibited and activated to verify the role of TIMP1 in regulating ferroptosis through TFRC. The therapeutic effect of TIMP1 inhibition on osteoporosis was evaluated in a type 2 diabetic mouse model.

Results

The expression of TIMP1 is increased in type 2 diabetic osteoporosis. In vitro, TIMP1 knockout inhibited ferroptosis in osteoblasts induced by high glucose and high fat (HGHF). However, overexpression of TFRC reversed the ferroptosis inhibition caused by TIMP1 knockout. Suppression of TIMP1 expression alleviated the progression of osteoporosis in type 2 diabetic mice. Mechanistic studies suggest that TIMP1 regulates HGHF-induced ferroptosis in osteoblasts through TFRC.

Conclusion

This study demonstrates that TIMP1 expression is increased during type 2 diabetic osteoporosis and that TIMP1 promotes ferroptosis in osteoblasts by regulating TFRC. These findings suggest that TIMP1 is a promising novel therapeutic target for type 2 diabetic osteoporosis.
Perinatal presentation of Klinefelter syndrome and variants: take-home lessons for the urologist
Authors: Frownfelter Matthew , Zekan David , Al-Omar Osama , Abdelhalim Ahmed
Published: November 2024

Background

Klinefelter syndrome (KS) is a sex chromosome disorder usually diagnosed in adulthood during work-up for infertility or hypogonadism. Perinatal diagnoses are uncommon.

Case presentation

We report two newborn cases of KS with associated hypospadias and bilateral cryptorchidism suspected on prenatal genetic testing triggered by ambiguous genital appearance on prenatal ultrasound. Management is presented and the relevant literature on the prenatal and prepubertal presentation and management of KS is summarized.

Conclusions

Klinefelter syndrome can be suspected prenatally in patients with increased nuchal translucency or ambiguous genitalia. Cell-free DNA can establish prenatal diagnosis with good sensitivity and specificity. Early diagnosis allows for early initiation of multidisciplinary care, focused counseling, lifestyle modification, early androgen replacement, and cryopreservation during late puberty or early adulthood. Testosterone treatment during infancy was linked to improved phenotypic features of KS and better cognitive and behavioral outcomes.
Qualitative exploration of 3D printing in Swedish healthcare: perceived effects and barriers
Authors: Sag Olivya Marben , Li Xiang , Åman Beatrice , Thor Andreas , Brantnell Anders
Published: November 2024

Background

Three-dimensional (3D) printing produces objects by adding layers of material rather than mechanically reducing material. This production technology has several advantages and has been used in various medical fields to, for instance, improve the planning of complicated operations, customize medical devices, and enhance medical education. However, few existing studies focus on the adoption and the aspects that could influence or hinder the adoption of 3D printing.

Objective

To describe the state of 3D printing in Sweden, explore the perceived effects of using 3D printing, and identify barriers to its adoption.

Methods

A qualitative study with respondents from seven life science regions (i.e., healthcare regions with university hospitals) in Sweden. Semi-structured interviews were employed, involving 19 interviews, including one group interview. The respondents were key informants in terms of 3D printing adoption. Data collection occurred between April and May 2022 and then between February and May 2023. Thematic analysis was applied to identify patterns and themes.

Results

All seven regions in Sweden used 3D printing, but none had an official adoption strategy. The most common applications were surgical planning and guides in clinical areas such as dentistry, orthopedics, and oral and maxillofacial surgery. Perceived effects of 3D printing included improved surgery, innovation, resource efficiency, and educational benefits. Barriers to adoption were categorized into organization, environment, and technology. Organizational barriers, such as high costs and lack of central decisions, were most prominent. Environmental barriers included a complex regulatory framework, uncertainty, and difficulty in interpreting regulations. Technological barriers were less frequent.

Conclusions

The study highlights the widespread use of 3D printing in Swedish healthcare, primarily in surgical planning. Perceived benefits included improved surgical precision, innovation, resource efficiency, and educational enhancements. Barriers, especially organizational and regulatory challenges, play a significant role in hindering widespread adoption. Policymakers need comprehensive guidance on 3D printing adoption, considering the expensive nature of technology investments. Future studies could explore adoption in specific clinical fields and investigate adoption in non-life science regions within and outside Sweden.
Screening the Global Health Priority Box against Plasmodium berghei liver stage parasites using an inexpensive luciferase detection protocol
Authors: Nguyen Gia-Bao , Cooper Caitlin A. , McWhorter Olivia , Sharma Ritu , Elliot Anne , Ruberto Anthony , Freitas Rafael , Pathak Ashutosh K. , Kyle Dennis E. , Maher Steven P.
Published: November 2024

Background

Malaria, a disease caused by parasites of the genus Plasmodium, continues to impact many regions globally. The rise in resistance to artemisinin-based anti-malarial drugs highlights the need for new treatments. Ideally, new anti-malarials will kill the asymptomatic liver stages as well as the symptomatic blood stages. While blood stage screening assays are routine and efficient, liver stage screening assays are more complex and costly. To decrease the cost of liver stage screening, a previously reported luciferase detection protocol requiring only common laboratory reagents was adapted for testing against luciferase-expressing Plasmodium berghei liver stage parasites.

Methods

After optimizing cell lysis conditions, the concentration of reagents, and the density of host hepatocytes (HepG2), the protocol was validated with 28 legacy anti-malarials to show this simple protocol produces a stable signal useful for obtaining quality small molecule potency data similar to that obtained from a high content imaging endpoint. The protocol was then used to screen the Global Health Priority Box (GHPB) and confirm the potency of hits in dose–response assays. Selectivity was determined using a galactose-based, 72 h HepG2 assay to avoid missing mitochondrial-toxic compounds due to the Crabtree effect. Receiver-operator characteristic plots were used to retroactively characterize the screens’ predictive value.

Results

Optimal luciferase signal was achieved using a lower HepG2 seed density (5 × 103 cells/well of a 384-well microtitre plate) compared to many previously reported luciferase-based screens. While producing lower signal compared to a commercial alternative, this luciferase detection method was found much more stable, with a > 3 h half-life, and robust enough for producing dose–response plots with as few as 500 sporozoites/well. A screen of the GHPB resulted in 9 hits with selective activity against P. berghei liver schizonts, including MMV674132 which exhibited 30.2 nM potency. Retrospective analyses show excellent predictive value for both anti-malarial activity and cytotoxicity.

Conclusions

This method is suitable for high-throughput screening at a cost nearly 20-fold less than using commercial luciferase detection kits, thereby enabling larger liver stage anti-malarial screens and hit optimization make-test cycles. Further optimization of the hits detected using this protocol is ongoing.
Light at night exposure and risk of dementia conversion from mild cognitive impairment in a Northern Italy population
Authors: Filippini Tommaso , Costanzini Sofia , Chiari Annalisa , Urbano Teresa , Despini Francesca , Tondelli Manuela , Bedin Roberta , Zamboni Giovanna , Teggi Sergio , Vinceti Marco
Published: November 2024

Background

A few studies have suggested that light at night (LAN) exposure, i.e. lighting during night hours, may increase dementia risk. We evaluated such association in a cohort of subjects diagnosed with mild cognitive impairment (MCI).

Methods

We recruited study participants between 2008 and 2014 at the Cognitive Neurology Clinic of Modena Hospital, Northern Italy and followed them for conversion to dementia up to 2021. We collected their residential history and we assessed outdoor artificial LAN exposure at subjects’ residences using satellite imagery data available from the Visible Infrared Imaging Radiometer Suite (VIIRS) for the period 2014–2022. We assessed the relation between LAN exposure and cerebrospinal fluid biomarkers. We used a Cox-proportional hazards model to compute the hazard ratio (HR) of dementia with 95% confidence interval (CI) according to increasing LAN exposure through linear, categorical, and non-linear restricted-cubic spline models, adjusting by relevant confounders.

Results

Out of 53 recruited subjects, 34 converted to dementia of any type and 26 converted to Alzheimer’s dementia. Higher levels of LAN were positively associated with biomarkers of tau pathology, as well as with lower concentrations of amyloid β1−42 assessed at baseline. LAN exposure was positively associated with dementia conversion using linear regression model (HR 1.04, 95% CI 1.01–1.07 for 1-unit increase). Using as reference the lowest tertile, subjects at both intermediate and highest tertiles of LAN exposure showed increased risk of dementia conversion (HRs 2.53, 95% CI 0.99–6.50, and 3.61, 95% CI 1.34–9.74). In spline regression analysis, the risk linearly increased for conversion to both any dementia and Alzheimer’s dementia above 30 nW/cm2/sr of LAN exposure. Adding potential confounders including traffic-related particulate matter, smoking status, chronic diseases, and apolipoprotein E status to the multivariable model, or removing cases with dementia onset within the first year of follow-up did not substantially alter the results.

Conclusion

Our findings suggest that outdoor artificial LAN may increase dementia conversion, especially above 30 nW/cm2/sr, although the limited sample size suggests caution in the interpretation of the results, to be confirmed in larger investigations.
Myoelectric motor execution and sensory training to treat chronic pain and paralysis in a replanted arm: a case study
Authors: Kristoffersen Morten B. , Munoz-Novoa Maria , Buist Mirka , Emadeldin Mona , Reinholdt Carina , Ortiz-Catalan Max
Published: November 2024

Background

Following upper limb amputation, surgeries such as arm transplantation or replantation might be an option to restore function. After such surgeries, rehabilitation of the arm is needed. However, conventional rehabilitation is dependent on some volitional movement of the arm. If there is no or minimal movement of the arm, conventional rehabilitation might not be successful. The purpose of this study is to evaluate a novel combination of myoelectric motor execution (MME) and sensory training (ST) to reduce pain and improve upper limb function in a person with a highly impaired replanted arm.

Methods

The participant, a 72-year-old male, had his right arm replanted after a traumatic accident. No functional recovery was achieved following conventional rehabilitation and chronic neuropathic pain developed post-surgery. The participant then received 18 sessions of MME in which intended movements were decoded from the replanted arm’s myoelectric signals using machine learning and real-time feedback was provided on a screen. Nine sessions included ST using tactile grids where the participant discriminated different sensations.

Results

The participant regained active extension of the thumb (4 degrees) and regained active wrist movement (flex: 6 degrees, extend: 10 degrees), both of which had no active movement prior the MME interventions. He also perceived an increase in sensation in the thumb and fingers. Pain levels fluctuated throughout the study and no consistent change could be concluded.

Conclusion

MME is a novel virtual rehabilitation treatment which provides feedback using virtual limbs and serious games. MME combined with ST is a potential rehabilitation treatment for individuals with highly impaired arms and hands which might ameliorate chronic neuropathic pain.
Experiences of violence while in insecure migration status: a qualitative evidence synthesis
Authors: Innes Alexandria , Bunce Annie , Manzur Hannah , Lewis Natalia V.
Published: November 2024

Background

The global movement of people in the context of strict immigration laws and policies places significant numbers of people in insecure migration status worldwide. Insecure status leaves people without recourse to legal, governmental or social protection from violence and abuse. This review synthesized qualitative studies that reported how migrants associated physical and physically enforced sexual violence they experienced with their insecure migration status.

Methods

We conducted a qualitative evidence synthesis of 31 studies published between 1 January 2000 and 31 May 2023, with data from Europe, North America, East Asia, South Asia, the Middle East and Africa. Our thematic synthesis produced 14 inductive descriptive codes, four descriptive themes and three analytical themes.

Results

We generated robust qualitative evidence showing that women experienced sexual violence while in transit or without status in a host state, and that they associated that violence with their insecure migration status. This was the case across the various geographic routes and destination countries. We found evidence that women associated intimate partner violence with lacking (legal) access to support because of their insecure migration status. We found evidence that women connected their unwillingness to leave violent circumstances, and therefore their prolonged or repeated exposure to violence, with a fear of immigration removal produced by their insecure migration status.

Conclusion

To protect people in insecure migration status from experiencing violence that they associated with their migration status, it’s necessary to ensure that the reporting of violence does not lead to immigration enforcement consequences for the victim.
A Natural History Study of Timothy Syndrome
Authors: Timothy Katherine W. , Bauer Rosemary , Larkin Kerry A. , Walsh Edward P. , Abrams Dominic J. , Gonzalez Corcia Cecilia , Valsamakis Alexandra , Pitt Geoffrey S. , Dick Ivy E. , Golden Andy
Published: November 2024

Background

Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C. Initially, Timothy syndrome was characterized by a cardiac presentation of long QT syndrome and syndactyly of the fingers and/or toes, all associated with the CACNA1C variant, Gly406Arg. However, subsequent identification of diverse variants in CACNA1C has expanded the clinical spectrum, revealing various cardiac and extra-cardiac manifestations. It remains underexplored whether individuals with the canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) exhibit overlapping symptoms. Moreover, case reports have indicated that some CACNA1C variants may produce a cardiac-selective form of Timothy syndrome often referred to as non-syndromic long QT type 8 or cardiac-only Timothy syndrome, however few reports follow up on these patients to confirm the cardiac selectivity of the phenotype over time.

Methods

A survey was administered to the parents of patients with Timothy syndrome, querying a broad range of symptoms and clinical features. Study participants were organized into 5 separate categories based on genotype and initial diagnosis, enabling comparison between groups of patients which have been described differentially in the literature.

Results

Our findings reveal that Timothy syndrome patients commonly exhibit both cardiac and extra-cardiac features, with long QT syndrome, neurodevelopmental impairments, hypoglycemia, and respiratory issues being frequently reported. Notably, the incidence of these features was similar across all patient categories, including those diagnosed with non-syndromic long QT type 8, suggesting that the ‘non-syndromic’ classification may be incomplete.

Conclusions

This study represents the first Natural History Study of Timothy syndrome, offering a comprehensive overview of the disease’s clinical manifestations. We demonstrate that both cardiac and extra-cardiac features are prevalent across all patient groups, underscoring the syndromic nature of CACNA1C variants. While the critical role of long QT syndrome and cardiac arrhythmias in Timothy syndrome has been well recognized, our findings indicate that hypoglycemia and respiratory dysfunction also pose significant life-threatening risks, emphasizing the need for comprehensive therapeutic management of affected individuals.
Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson’s and other related neurodegenerative diseases
Authors: Riaz Zainab , Richardson Gabriel S. , Jin Huajun , Zenitsky Gary , Anantharam Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G.
Published: November 2024

Nuclear pore complexes (NPCs) are embedded in the nuclear envelope and facilitate the exchange of macromolecules between the nucleus and cytoplasm in eukaryotic cells. The dysfunction of the NPC and nuclear transport plays a significant role in aging and the pathogenesis of various neurodegenerative diseases. Common features among these neurodegenerative diseases, including Parkinson’s disease (PD), encompass mitochondrial dysfunction, oxidative stress and the accumulation of insoluble protein aggregates in specific brain regions. The susceptibility of dopaminergic neurons to mitochondrial stress underscores the pivotal role of mitochondria in PD progression. Disruptions in mitochondrial-nuclear communication are exacerbated by aging and α-synuclein-induced oxidative stress in PD. The precise mechanisms underlying mitochondrial impairment-induced neurodegeneration in PD are still unclear. Evidence suggests that perturbations in dopaminergic neuronal nuclei are linked to PD-related neurodegeneration. These perturbations involve structural damage to the nuclear envelope and mislocalization of pivotal transcription factors, potentially driven by oxidative stress or α-synuclein pathology. The presence of protein aggregates, pathogenic mutations, and ongoing oxidative stress can exacerbate the dysfunction of NPCs, yet this mechanism remains understudied in the context of oxidative stress-induced PD. This review summarizes the link between mitochondrial dysfunction and dopaminergic neurodegeneration and outlines the current evidence for nuclear envelope and nuclear transport abnormalities in PD, particularly in oxidative stress. We highlight the potential role of nuclear pore and nucleocytoplasmic transport dysfunction in PD and stress the importance of systematically investigating NPC components in PD.