Objective: Our study aimed to compare the posterior interposition technique against the posterolateral transosseous technique in the same cadaver specimens. Methods: Computer and cadaver models of 2 fixation techniques were developed. The computer model was constructed to analyze bone volume removed during implant placement and the bony surface area available for fusion. The cadaver model included quasi-static multidirectional bending flexibility and dynamic fatigue loading. Relative motions between the sacrum and ilium were measured intact, after joint destabilization, after fixation with direct-posterior and posterolateral techniques, and after 18,500 cycles of fatigue loading. Relative positions between each implant and the sacrum and ilium were measured after fixation and fatigue loading to ascertain the quality of the bone-implant interface. The 2 techniques were randomized to the left and right sacroiliac joints of the same cadavers. Results: The posterior interposition technique removed less bone volume and facilitated a larger surface area available for bony fusion. Posterior interposition significantly reduced the nutation/counternutation motion of the sacroiliac joint (42% ± 8%) and reduced it more than the posterolateral transosseous technique (14% ± 4%). Upon fatigue loading, the posterior interposition implant maintained the bone-implant interface across all specimens, while the posterolateral transosseous implant migrated or subsided in 20%–50% of specimens. Conclusion Posterior interposition fixation of the sacroiliac joint reduces joint motion. The amount of fixation from the posterior technique is superior and more durable than the amount of fixation achieved by the posterolateral technique.

Objective: There is increased use of 3-dimensional (3D)-printing for manufacturing of interbody cages to create microscale surface features that promote bone formation. Those features may be vulnerable to abrasion and/or delamination during cage impaction. Our objective was to quantify loss of mass and changes in surface topography of 3D-printed titanium interbody cages due to surgical impaction. Methods: Eight surfaces of four 3D-printed titanium modular interbody fusion cages were tested. The cages were impacted into the Sawbones model with compression preload of either 200N or 400N using a guided 1-lb (0.45 kg) drop weight. Mass and surface roughness parameters of each endplate were recorded and compared for differences. Results: Significant weight loss was observed for the superior endplate group and for both 200N and 400N preloads. For pooled data comparison, significant postimpaction decreases were observed for mean roughness, root-mean-squared roughness, mean roughness depth, and total height of roughness profile. No significant differences were observed for profile skewness and kurtosis. There were significant changes in almost all roughness parameters in the anterior region of the cage postimpaction with significant changes in 2 out of 6 parameters in the middle, posterior, and central regions postimpaction. Conclusion Three-dimensional-printed titanium interbody fusion cages underwent loss of mass and alteration in surface topography during benchtop testing replicating physiologic conditions. There was an endplate- and region-specific postimpaction change in roughness parameters. The anterior surface experienced the largest change in surface parameters postimpaction. Our results have implications for future cage design and pre-approval testing of 3D-printed implants.

Objectives: This study aimed to describe and compare health-related quality of life (QoL) as measured by the World Health Organization Quality of Life–BREF (WHOQoL-BREF) and the EuroQol-5 Dimensions (EQ-5D) among the Malaysian population, examining differences by sociodemographic characteristics including age, income, sex, ethnicity, educational level, and occupation. Methods: This cross-sectional study used data from 19,402 individuals collected as part of a health and demographic surveillance system survey conducted in the Segamat district of Malaysia in 2018–2019. Descriptive statistics and measures of central tendency were produced.Differences in QoL among demographic sub-groups were examined using the t-test and analysisof variance, while the correlations between the WHOQoL-BREF and EQ-5D were evaluated usingPearson correlation coefficients. Results: Based on complete case analysis (n = 19,129), the average scores for the 4 WHOQoLBREF domains were 28.2 (physical), 24.1 (psychological), 12.0 (social relationships), and 30.4 (environment). The percentages of participants not in full health for each EQ-5D dimension were 12.8% (mobility), 3.1% (self-care), 6.9% (usual activities), 20.9% (pain/discomfort), and 6.8% (anxiety/depression). Correlations between the 4 WHOQoL-BREF domains and the 5 EQ-5D dimensions were relatively weak, ranging from –0.06 (social relationships with self-care and pain/discomfort; p < 0.001) to –0.42 (physical with mobility; p < 0.001). Conclusion Although health-related QoL as measured by the WHOQoL-BREF and the EQ-5D are correlated, these 2 measures should not be considered interchangeable. The choice betweenthem should be guided by the specific research questions and the intended use of the data.

OBJECTIVES: To explore potential keywords, research clusters, collaborative pattern, and research trends in the field of medical technology management (MTM) through bibliometric analysis, providing insights for researchers, policy makers, and hospital administrators. METHODS: A retrieval formula was applied to the title, abstract, and keywords in the Web of Science (WoS) Core Collection, along with system-recommended terms, to identify articles on MTM. A total of 181 articles published between 1974 and 2022 were retained for quantitative analysis. The global trend of research output; total citations, average citations, and H-index; and bibliographic coupling, co-authorship, and keyword co-occurrence were analyzed using VOSviewer. RESULTS: The number of articles on MTM has been steadily increasing year by year. The focus of research has shifted from addressing basic medical needs to prioritizing emergency response and medical information security. The United States, Italy, and the United Kingdom emerged as the main contributors, with the United States leading in both volume of publications (60 articles) and academic impact (H-index = 21). Authors from the United Kingdom and the United States led the way in cross-border cooperation. The top five institutions, ranked by total link strength among cross-institutional authors, were primarily located in Canada and Spain. CONCLUSIONS The field of MTM has experienced stable growth over the past three decades (1993-2022). The shift of research focus has prompted a heightened emphasis on protecting patient privacy and ensuring the security of medical data. Future research should emphasize interdisciplinary and professional collaboration, as well as international cooperation and open sharing of knowledge.
Bibliometrics ; Humans ; Biomedical Technology

OBJECTIVES

The purpose of this study was to develop a strategic plan using organizational development (OD) for the College of Allied Medical Professions (CAMP) to guide its management in facilitating its growth. This specific college in the study had faced various challenges due to changes such as a change in leadership and the occurrence of the global COVID-19 pandemic. This research assessed the different aspects of CAMP and proposed strategies for continuous improvement and adaptation to changes, whether internal or external.

The study utilized frameworks such as the McKinsey 7-S Model, SOAR (Strengths, Opportunities, Aspirations, Results), and Appreciative Inquiry (AI). These frameworks would help evaluate the institution's internal and external environment and provide input for the possible milestones of the OD roadmap. Data was to be collected using surveys, focus group discussions (FGDs), and key informant interviews (KIIs) with faculty, staff, and other stakeholders.

The findings highlighted CAMP's commitment to academic excellence, interdisciplinary collaboration, and innovative research, among other things. The college's structure, resource allocation, and staff development also needed improvement. Certain strategies were identified in accordance with CAMP's identity, current status, and desired outcomes.

The finalized strategic plan, using the OD interventions, showcased the identified strategies to enhance research capacity, collaboration, communication, and well-being among the college's constituents. Long-term and short-term objectives were established to ensure resilience during leadership transitions and other changes throughout the college's lifetime.

During liver injury, intrahepatic macrophage compartment is augmented by circulating monocytes that infiltrate the liver driven by C-C motif chemokine ligand/C-C motif chemokine receptor (CCL/CCR) axis including CCL1‒CCR8 axis, thereby contributing to liver inflammation. Numerous small molecular receptor antagonists, including R243, have been developed for targeting CCR8; however, these agents face challenges in clinical translation, potentially attributed to their poor pharmacokinetic profiles, lack of target specificity, and potential adverse effects. In this study, we designed four CCR8 antagonizing peptides (AP8i-AP8iv) and performed molecular characterization in silico and therapeutic investigation in vitro and in vivo. Based on in silico docking, molecular dynamic simulation using homology build model and in-vitro (competitive) binding studies, AP8ii (YEWRFYHG) evidenced highly favorable and selective interactions at the CCR8-active site. AP8ii inhibited CCL1-driven chemotaxis and LPS/IFNγ-induced pro-inflammatory activation of monocytes-macrophages in vitro. In a CCl₄-induced acute liver injury mouse model, AP8ii treatment decreased intrahepatic infiltration of circulating monocytes. Moreover, AP8ii reduced liver inflammation, as indicated by decreased F4/80, IL6 and iNOS expression, diminished ALT levels, and attenuated fibrosis, as indicated by reduced collagen-I expression. In conclusion, we report a novel CCR8-antagonizing peptide that inhibited CCL1-driven intrahepatic monocytes infiltration and differentiation into pro-inflammatory phenotype, consequently ameliorating liver inflammation and fibrogenesis in an acute liver injury mouse model.

Somatostatin receptor 1 (SSTR1) is a crucial therapeutic target for various neuroendocrine and oncological disorders. Current SSTR1-targeted treatments, including the first-generation somatostatin analog lanreotide (Lan) and the second-generation analog pasireotide (Pas), show promise but encounter challenges related to selectivity and efficacy. This study presents high-resolution cryo-electron microscopy structures of SSTR1 complexed with Lan or Pas, revealing the distinct mechanisms of ligand-binding and activation. These structures illustrate unique conformational changes in the SSTR1 orthosteric pocket induced by each ligand, which are critical for receptor activation and ligand selectivity. Combined with the biochemical assays and molecular dynamics simulations, our results provide a comparative analysis of binding characteristics within the SSTR family, highlighting subtle differences in SSTR1 activation by Lan and Pas. These insights pave the way for designing next-generation therapies with enhanced efficacy and reduced side effects through improved receptor subtype selectivity.

G protein-coupled receptors (GPCRs) are significant drug targets, but their potential in cancer therapy remains underexplored. Conventional GPCR agonists or antagonists have shown limited effectiveness in cancer treatment, necessitating new GPCR-targeting strategies for more effective therapies. This study discovers that Yersinia pestis LcrV, a crucial linker protein for plague infection, acts as a biased agonist of a GPCR, the formyl peptide receptor 1 (FPR1). The LcrV protein induces unique conformational changes in FPR1, resulting in G proteins being activated in a distinctive state without subunit dissociation. This leads to a biased signaling profile characterized by cyclic adenosine monophosphate (cAMP) responses and β-arrestin2 recruitment, but not calcium mobilization. In FPR1-expressing triple-negative breast cancer (TNBC) cells, LcrV bi-directionally modulates intracellular signaling pathways, downregulating extracellular signal-regulated kinases (ERK1/2) and Akt pathways while upregulating Jun N-terminal kinase (JNK) and p38 pathways. This dual modulation results in cell cycle arrest and the inhibition of TNBC cell proliferation. In TNBC xenograft mouse models, long-term LcrV treatment inhibits tumor growth more effectively than a conventional FPR1 antagonist. Additionally, LcrV treatment reprograms tumor cells by reducing stemness-associated proteins OCT4 and c-MYC. Our findings highlight the potential of biased GPCR agonists as a novel GPCR-targeting strategy for cancer treatment.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.