Restricted Options Research Articles

Utilization of 3D printing modeling techniques in the simulation instruction of ultrasound-guided puncture procedures on scoliotic spines of spinal muscular atrophy

BackgroundPuncture training with simulation models has emerged as a critical method for transmitting puncture skills, improving success rates, and minimizing injuries. Yet, obstacles such as proper material for ultrasound guidance, restricted options of 3D printing resources, and available substances to simulate human skin and muscle still hinder the production of simulation models that closely replicate clinical practice. This study aimed to develop a selective laser melting (SLM), 3D-printed simulation model that replicated the spine and skin contours of patients with spinal scoliosis.MethodsThe 3D models of the scoliotic spines were developed from 3D reconstructions of high-resolution, computed tomography images from patients with spinal scoliosis, while the models of the skin to the bone structure were constructed based on the 3D reconstructions of the skin contours. SLM technology was used to print 3D models of the patients’ spines. Gelatin casting was implemented to simulate the patients’ skin and muscle tissues and to meet ultrasound anatomical requirements. Practical puncture training, which closely resembles clinical puncture practice, was then carried out to validate the effectiveness of the model. Improvements in proficiency and confidence in performing ultrasound-guided punctures after the simulation-model training were evaluated using the paired sample t test.ResultsThis research utilized 3D digital modeling, SLM 3D printing technology, and gelatin casting to establish simulation models of patients’ spines and skin contours impacted by spinal scoliosis. The use of medical grade stainless steel material for modeling the spine and gelatin for skin and muscle tissues ensured the model had superior ultrasound anatomical properties. After the simulation training session, participants’ proficiency and confidence in both ultrasound-assisted positioning and real-time guided puncture showed significant improvement, demonstrating the effectiveness of the simulation training model.ConclusionsThe simulation model closely mimicked real clinical situations and was an effective training tool for medical professionals. Furthermore, these findings demonstrated the potential of 3D printing technology in developing simulation models that closely replicate real-world clinical scenarios and may have significant implications for medical education and training.

Pancreatic cancer subtyping - the keystone of precision treatment.

In recent years, the incidence and mortality rates of pancreatic cancer have been rising, posing a severe threat to human health. Tumor heterogeneity remains a critical barrier to advancing diagnosis and treatment efforts. The lack of specific early symptoms, limited early diagnostic methods, high biological complexity, and restricted therapeutic options contribute to the poor outcomes and prognosis of pancreatic cancer. Therefore, there is an urgent need to explore the different subtypes in-depth and develop personalized therapeutic strategies tailored to each subtype. Increasing evidence highlights the pivotal role of molecular subtyping in treating pancreatic cancer. This review focuses on recent advancements in classifying molecular subtypes and therapeutic approaches, discussed from the perspectives of gene mutations, genomics, transcriptomics, proteomics, metabolomics, and immunomics.

Cryptococcal meningitis resistant to Fluconazole treatment: a case report

Justification: Cryptococcal meningitis is the second most common opportunistic infection in AIDS patients and is associated with high mortality rates. The antifungal agents proven effective in treating cryptococcosis include amphotericin B, fluconazole, and flucytosine. The prevalence of Cryptococcus spp. resistance to fluconazole varies by region and population. Case Report: Here, we report a fatal case of fluconazole-resistant cryptococcal meningitis in an immunosuppressed adult with AIDS. Severe liver dysfunction hindered effective treatment, while fluconazole resistance further restricted therapeutic options. Conclusions: Cryptococcal meningitis remains a major cause of morbidity and mortality worldwide, especially among AIDS patients. Early and appropriate antifungal treatment is crucial for improving outcomes. The growing concern over Cryptococcus spp. resistance to fluconazole remains poorly understood, highlighting the need for further studies to optimize early treatment strategies.

Fifth Metacarpal Neck Fractures: Less Is More.

Fifth metacarpal neck fractures are common injuries of the hand. There is a lack of consensus regarding the optimal treatment for these injuries, with a variety of treatment modalities available. We provide an updated literature review of randomized controlled trials comparing clinical and functional outcomes of operative versus nonoperative management of these injuries. A literature search in the PubMed/MEDLINE database was conducted. Inclusion criteria were as follows: (1) the study was a primary study written in English, (2) the study compared treatment options for fifth metacarpal neck fractures, and (3) the study was a randomized controlled trial. Relevant studies were then reviewed in entirety, and the results were tabulated for further comparison. Thirteen studies were identified and included for analysis. Operative management does not seem to offer a significant improvement in long-term outcomes. The majority of included studies compared nonoperative management approaches, ranging from buddy taping to more restrictive immobilization such as forearm-based ulnar gutter splints. In general, these studies demonstrate comparable outcomes with respect to pain, range of motion, and patient satisfaction. When operative management is pursued, intramedullary nailing may result in superior outcomes relative to transverse pinning. Many fifth metacarpal neck fractures can be successfully treated nonoperatively. Among nonoperative management options, nonoperative approaches seem to yield comparable results to more restrictive immobilization options. A thorough understanding of a patient's goals and expectations can help guide physicians and patients in selecting the best management option.

Role of Radiomics-based Multiomics Panel in the Microenvironment and Prognosis of Hepatocellular Carcinoma.

Role of Radiomics-based Multiomics Panel in the Microenvironment and Prognosis of Hepatocellular Carcinoma.

Monopedal robot branch-to-branch leaping and landing inspired by squirrel balance control.

Locomotors traversing arboreal environments must often leap across large gaps to land on small-diameter supports. Balancing these dynamic landings is challenging because of high incident momentum, restricted foothold options, and reduced capacity to produce reaction torques on narrow supports. We hypothesized that leg length control to enhance branch reaction control authority would markedly expand the range of successful landing conditions, drawing on the same powerful leg actuation required for leaping. Exploring this balance strategy, the monopedal robot Salto-1P demonstrates branch-to-branch leaps, including some upright balanced landings, despite negligible grasping torque. We also compared this landing strategy with the landings of squirrels, which similarly lack the grip strength found in other arboreal species. We demonstrate that greater radial force control reduces the inertial body torque and/or grasping torque at the support required to balance a given landing. Adding simple radial force balance control strategies to conventional balance controllers greatly expands potential landing conditions, increasing the range of initial angular momentum that can be balanced by 230 and 470% across ranges of landing angles for low-order models of the robot and squirrel, respectively.

An evaluation of an initiative to routinely ask about restrictive practices in a community learning disability service

PurposeThere is a high prevalence of individuals with intellectual disabilities experiencing restrictive practices in the community. A quality improvement initiative instructed clinicians in community intellectual disability services to routinely ask about restrictive practices that were in place for service users in the community. This paper aims to summarise an audit, re-audit and service evaluation of this initiative.Design/methodology/approachAn initial audit and re-audit measured the extent to which clinicians routinely asked about restrictive practices. A focus group then explored clinicians’ perceptions and barriers to having these conversations.FindingsClinicians routinely asked about the presence of restrictive practices in 51% of cases at the time of the first audit, and in 12% of cases at re-audit, although this was from a much larger sample size. Following this finding, a focus group with clinicians identified key barriers: fear of initiating difficult conversations, ambiguity in discerning the least restrictive option, difficulties navigating legal frameworks during transition to adult services and existing workload pressures.Practical implicationsFindings highlighted how early discussions and planning around restrictive practices are imperative for smoother transitions into adulthood. To address barriers in recording such information, the community learning disability service in question has established an area to record restrictive practices on the electronic patient record.Originality/valueTo the best of the authors’ knowledge, this is the first study addressing routine enquiries around restrictive practices for individuals with intellectual disabilities in community settings.

Sulbactam for carbapenem-resistant Acinetobacter baumannii infections: a literature review.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is characterized as a critical priority pathogen with restricted therapeutic options. To date, the most effective antimicrobial treatment against this difficult-to-treat bacterial strain has not been established. Sulbactam is a β-lactamase inhibitor with intrinsic activity against this pathogen, however, as a β-lactam, it can be hydrolysed by β-lactamases produced by A. baumannii. High-dose, extended-infusion treatment with sulbactam can overcome this hydrolysis by β-lactamases and is considered an effective therapeutic strategy against CRAB. The aim of this review is to analyse primary and secondary research studies that compare sulbactam-based with other regimens, such as polymyxin-containing regimens, tigecycline-containing regimens and other antimicrobial combinations against CRAB infections, especially ventilator-associated pneumonia (VAP), hospital-acquired pneumonia (HAP) and bacteraemia. Our findings suggest that results are conflicting, mostly because of high heterogeneity among studies. However, in most studies, sulbactam-based regimens have demonstrated comparable, and in several studies more favourable results in contrast to other antimicrobial treatments with respect to clinical cure and mortality in CRAB-associated pneumonia, yet without reaching statistical significance in most cases. The auspicious novel β-lactam/β-lactamase inhibitor combination sulbactam/durlobactam is also discussed, although real-world clinical data regarding its efficacy in CRAB infections are still scarce. More randomized controlled trials comparing sulbactam-based with other regimens are warranted to determine the most effective antimicrobial combination against CRAB infections. Nevertheless, current data suggest that sulbactam could play a major role in this combination treatment.

RNA biosensors for detection of pancreatic cancer.

RNA biosensors for detection of pancreatic cancer.

Facile Preparation of Durable Multicolor Superhydrophobic Coatings for Concrete Protection

AbstractConcrete is extensively used in construction, roadways, and other engineering fields. However, its hydrophilic and porous structure renders it susceptible to oxidative corrosion, sand erosion, and acid rain when exposed to outdoor environments. Therefore, developing superhydrophobic coatings with superior waterproofing properties is a critical strategy to protect concrete. Nevertheless, existing superhydrophobic concrete coatings suffer from issues, such as poor durability, complex application processes, restricted color options, and difficulties in large‐scale production. Herein, a spraying method is developed that utilizes nano‐SiO2, epoxy resin, cetyltriethoxysilane, and iron oxide dyes to produce a robust, corrosion‐resistant, and multicolored superhydrophobic concrete coating with red, yellow, blue, and green colors. The produced coatings exhibit a water contact angle (CA) of 156° ± 1° and a sliding angle (SA) of 5° ± 1°. The hydrophobicity of the coatings arises from the synergistic effects of cetyltriethoxysilane, which provides low surface energy, and SiO2, which creates micro and nanoscale roughness on the coating surface. Meanwhile, the coating's robustness stems from the adhesive properties of epoxy resin and hydrogen‐bonding interactions between SiO2 and the concrete substrate. Thus, the developed superhydrophobic coating shows significant potential for extending the lifespan of concrete building facades, enhancing decorative and waterproofing features, and ensuring surface cleanliness.

Mechanisms, therapeutic strategies, and emerging therapeutic alternatives for carbapenem resistance in Gram-negative bacteria.

Carbapenem-resistant Gram-negative bacteria (CR-GNB) have experienced an alarming surge in prevalence in recent years, escalating into a critical global healthcare crisis. As carbapenems represent the last line of defense against such pathogens, infections caused by CR-GNB have become increasingly challenging to treat, given the restricted therapeutic options and heightened mortality risks. The discovery and development of alternative therapeutic strategies that present novel avenues against multi-drug-resistant organisms are gaining increased attention, presenting a pressing need for innovative solutions. Our comprehensive review delves into the multifaceted landscape of carbapenem resistance in Gram-negative bacteria in response to this urgent challenge. The scope of this review aims to provide an up-to-date and in-depth exploration regarding the mode of action of carbapenem and the resisting mechanisms of carbapenem in GNB. Additionally, it discusses the state of the art of some clinical therapies for the treatment ofinfections caused by CR-GNB. Moreover, it describes several combinational and alternative therapies to combat CR-GNB, including the computational approach of "molecular docking". In light of the conclusions of this review, we call for the implementation of these strategies to develop comprehensive approaches to mitigate carbapenem resistance in Gram-negative bacteria.

Can the new model of shared property rights promote better corporate financial performance in China?

Scientific research and technological innovation are driving modern economies; however, a new form of property rights is required to compensate knowledge workers for their contributions. In 1994, the Science and Technology Bureau of Shenzhen, China implemented a policy to encourage scientists and engineers to develop innovative technologies that would provide them a share of the profits earned from their innovations. This created a new “shared property rights” system. China’s shared property model is so new that the conditions under which it can improve enterprise profits remain unclear. To answer this question, we obtained data from the China Stock Market and Accounting Research database for 904 Chinese enterprises that had implemented shared property rights for the first time between 2009 and 2021 and used a propensity score matching method and econometric models to evaluate their performance. The results indicated that shared property incentives improved corporate financial performance and that benefits increased gradually over time. The new approach showed a stronger positive effect than restricted stock options during the study period. The strength of the incentive was greater for core technical staff than for senior executives, suggesting that scientists, engineers, and computer programmers should be the targets of a shared property rights incentive program. To take full advantage of the new shared property rights institution, enterprise managers should set the implementation period at a reasonable length (5 to 10 years, based on our study results). Enterprises can also test two or more simultaneous approaches that account for the specific needs of each category of workers, based on a careful examination of their current situation and expected or desired future situations.

Perioperative complications and cervical malalignment requiring revision following cervical C3 laminectomy and C4-6 laminoplasty.

Perioperative complications and cervical malalignment requiring revision following cervical C3 laminectomy and C4-6 laminoplasty.

Efficacy and safety of surufatinib in unresectable or metastatic grade 3 pancreatic neuroendocrine tumors (NET G3): Real-world analysis.

657 Background: Currently, there is limited exploration regarding the treatment of NET G3, resulting in restricted treatment options. Therapeutics for NET G1/2 may serve as an alternative. Surufatinib, with its potent targeting of VEGFRs, FGFR1, and CSF-1R, not only exerts inhibitory effects on tumor angiogenesis but also modulates the immune microenvironment. Due to its demonstrated efficacy and manageable safety profile, it has secured approval for the treatment of G1/2 NETs. Methods: This is a multi-center real-world study that retrospectively analyzes the clinical data of pts with NET G3 who received surufatinib-based treatment from December 2021 to February 2024, aiming to assess its efficacy and safety. Eligible pts were unresectable or metastatic p-NET with ki-67>20%. The primary endpoint was PFS, with secondary endpoints were ORR, DCR, and safety. Results: As of September 2024, data from 37 pts were analyzed. The median age was 54 years (range: 32-80), with 59.5% male. The median Ki-67 index was 30% (range: 25-70%), and 94.6% of the cases were non-functional p-NETs, with 89.2% having liver metastases and 35.1% having bone metastases. In terms of prior treatments, 18.9%, 40.5%, and 40.5% of pts had received 0, 1, and ≥2 systemic therapies, respectively. Among them, 81.1% had previously undergone chemotherapy, 35.1% had received interventional therapy of liver metastases, and 13.5% with everolimus or anti-angiogenic agents. 48.6% pts had surufatinib-based combination treatment. The median PFS was 9.30 months (mo, 95% CI: 8.02–13.02), with an ORR of 21.6% and a DCR of 81.1%. First-line (1L) treatment showed a higher ORR (42.9% vs. 16.7%) and a trend of better PFS (9.67 vs. 9.04 mo, p=0.7) compared to ≥2L treatment. Combination therapy improved ORR (33.3% vs. 10.5%) with a similar PFS (9.30 vs. 9.44 mo, p=0.93) compared to surufatinib monotherapy. Liver metastases had limited impact on PFS (9.93 vs 9.30 mo, p=0.55). Common grade ≥3 adverse events included hypertension (8.1%), proteinuria (5.4%), and elevated bilirubin (5.4%). Conclusions: Surufatinib has demonstrated initial efficacy and manageable safety in pts with NET G3, providing a new treatment option for these pts. First-line therapy may be a favorable factor for improving PFS. To delve deeper into these findings, additional subgroup analyses, with a particular emphasis on pts with ep-NET G3 will be conducted in the future.

N14 Patients and clinicians have different priorities when discussing pain in the IBD clinic

Abstract Background Pain affects approximately 70% of patients with inflammatory bowel disease (IBD), persisting for five or more years in nearly half, and significantly impacts their quality of life.1 However, surveys indicate it is not routinely discussed in the IBD clinic.1,2 Clinicians often focus on objective measures of IBD activity rather than on pain and its management, assuming that addressing disease-related factors will alleviate pain.3 Compounding this, patients find it hard to articulate their pain and may not report it because they believe that pain is not taken seriously by clinicians.4 This study aimed to identify communication barriers and opportunities for improvement by comparing clinicians' understanding and management of pain with reports of patients' lived experiences. Methods Semi-structured interviews with nurses and doctors (n=13), analysed alongside 83 pre-existing transcripts from nurses, doctors and patients in other IBD-pain studies using reflective thematic analysis, led to the identification of three primary themes. Results Clinicians reported that pain is a stronger indicator of complications in Crohn’s disease than in ulcerative colitis, leading them to ask about it more often in consultation with patients with Crohn’s disease. However, patients felt that pain inquiries were minimal in both conditions. Discrepancies between intentions and practices were noted, with clinicians showing empathy for pain but not following through on its management. The study revealed power imbalances in the clinician-patient relationship. Clinicians were perceived by patients as having the authority to make decisions and prioritise disease management. Limited time and restricted options for pain management exacerbated imbalances, leading some clinicians to default to secondary irritable bowel syndrome diagnoses when pain persisted during remission. Inadequate acknowledgment of pain contributed to patients feeling uncared for. Addressing pain in patients who do not complain posed challenges. Some patients refrained from reporting pain due to a need to remain positive, concerns about clinician busyness, or the hassle of additional tests. One clinician expressed not wanting to exacerbate the pain by drawing attention to it. However, avoiding discussion is likely counterproductive with some clinicians relating that educating patients on "normal" and "abnormal" symptoms could be effective, although time constraints posed challenges. Conclusion The study emphasises the importance of comprehensive pain evaluation and management, advocating for more open dialogues between clinicians and patients. Understanding the biological basis of pain and the role of dysregulated modulation in maintaining it may help bridge the gap in perspectives.

A cohort-based multi-omics identifies nuclear translocation of eIF5B /PD-L1/CD44 complex as the target to overcome Osimertinib resistance of ARID1A-deficient lung adenocarcinoma

BackgroundOsimertinib has emerged as a critical element in the treatment landscape following recent clinical trials. Further investigation into the mechanisms driving resistance to Osimertinib is necessary to address the restricted treatment options and survival advantages that are compromised by resistance in patients with EGFR-mutated lung adenocarcinoma (LUAD).MethodsSpatial transcriptomic and proteomic analyses were utilized to investigate the mechanisms of Osimertinib resistance. Co-IP, MS, RNA-seq, ChIP-seq, RIP-seq, and ATAC-seq were performed in cell lines to further explore the mechanism. To validate the findings, in vitro and in vivo molecular experiments were conducted.ResultsWe found that the ARID1A deficiency results in resistance to Osimertinib by hindering programmed cell death through the EZH2/PTEN/E2F1 axis. This altered axis influences PD-L1 transcription through E2F1-mediated promoter activation and PD-L1 translation via the MDM2/eIF5B/PD-L1 axis. Subsequently, ARID1A deficiency results in increased expression of eIF5B and Importin-β1, promoting PD-L1 nuclear-translocation. The nuclear PD-L1 (nPD-L1) interacts with CD44, leading to nPD-L1 complex formation, activation of the RASGEF1A promoter, initiation of the Ras pathway, and contributing to Osimertinib resistance. Targeting the transcription, translation and nuclear-translocation of PD-L1 using lipid nanoparticles (LNPs) overcomes ARID1A deficiency-induced resistance.ConclusionARID1A deficiency promotes PD-L1 nuclear translocation and induces Osimertinib resistance.

The Application and Optimization Path of Supply Chain Finance in Financing for Small and Medium-Sized Enterprises

With the acceleration of economic globalization and market competitiveness, small and mediumsized businesses confront numerous problems in extending their business and capital operations. Supply chain finance, as an innovative financial service model, opens up new funding opportunities for small and medium-sized businesses. This article first examines the fundamental concepts and operational mechanisms of supply chain finance, then investigates its current application status and problems faced by small and medium-sized enterprises, and finally proposes a path to optimize supply chain finance services for small and medium-sized enterprises using financial technology to improve their financing efficiency and overall competitiveness. Supply chain finance has sparked widespread interest among businesses, particularly small and medium-sized businesses, due to its ability to effectively integrate upstream and downstream enterprise resources, reduce financing costs, shorten financing cycles, and improve capital utilization efficiency. Small and medium-sized businesses often encounter issues such as short finance cycles and restricted credit options. Supply chain finance may link core organizations with multi-level suppliers, providing more flexible and cost-effective financing alternatives for small and medium-sized businesses.

Event planner destination choice: A case study of Nashville

Site attributes and destination image play critical roles in the event planning process, significantly impacting the success of events. This study examines the influence of site selection factors and destination image on the decision-making process of event planners, with a focus on Nashville, TN in the US. This study adopted purposive and snowball sampling techniques to enhance triangulation in data collection. To ensure trustworthiness and credibility, the criteria for selecting interviewees are as follows: 1) currently employed in an event company, 2) possessing experience in selecting event sites, and 3) having planned events in Nashville. This study utilizes in-depth interviews with 15 participants, and the data were subjected to thematic analysis using NVivo12. Findings indicate that client demands and budget considerations are primary determinants in site selection, while secondary factors include AV, Wi-Fi, and F&B options. Concerning Nashville’s destination image, perceptions of high hotel room rates, limited event space for larger gatherings, and restricted date options emerge. These findings underscore a potential disparity between event planners’ perceptions and the actual destination image. Thus, Convention and Visitors Bureaus/Destination Marketing Organizations (CVBs/DMOs) should incorporate event planners’ perceptions of destination image alongside site attributes to enhance the destination’s appeal to event organizers.

Glucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth. Single and combinatorial treatments with both drugs at 5 µM concentration led to efficient cell cycle arrest, reduced expression of cyclins A and E, increased lipid storage in lysosomal compartments, accompanied by increased uptake of lysotracker, and elevated expression of the autophagy marker Lc3 II. Both drugs affected mitochondrial function, indicated by altered mitotracker uptake and impaired mitochondrial respiration. Aripiprazole in monotherapy, or even more pronounced in combination with Genz, also potentiated the effect of the cytostatic drugs sorafenib and doxorubicin on tumor cell- and tumor spheroid-growth inhibition. Targeting GCS with Genz with the parallel application of cationic amphiphilic drugs such as aripiprazole in combination with cytostatic drugs may thus represent a potent therapeutic approach in the treatment of HCC and potentially other cancer types.

Targeting Refractory Triple-Negative Breast Cancer with Sacituzumab Govitecan: A New Era in Precision Medicine.

Advanced triple-negative breast cancer (TNBC) has poorer outcomes due to its aggressive behavior and restricted therapeutic options. While therapies like checkpoint inhibitors and PARP inhibitors offer some benefits, chemotherapy remains ineffective beyond the first line of treatment. Antibody-drug conjugates (ADCs) like sacituzumab govitecan-hziy (SG) represent a significant advancement. SG combines SN-38, an irinotecan derivative, with a Trop-2-targeting antibody via a pH-sensitive linking moiety, achieving a good drug:antibody ratio. In a phase I-II study involving metastatic TNBC (mTNBC) individuals, SG achieved an overall response rate of 33.3% and a median response period of 7.7 months. The phase III ASCENT trial demonstrated SG's efficacy in relapsed or refractory TNBC, improving median progression-free survival and median overall survival compared to chemotherapy. Common side effects include neutropenia, nausea, and fatigue. This article highlights the clinical potential, pharmacokinetics, safety profile, and resistance mechanisms of SG along with key ongoing clinical trials, emphasizing its role in managing refractory mTNBC, especially in third-line therapy. The review also discusses current strategies for managing adverse reactions and sequencing ADC treatments in clinical practice, along with the predicted basis of resistance. The optimal sequencing of SG relative to other ADCs, such as trastuzumab deruxtecan or T-DXd, remains an evolving question, especially as newer agents with distinct mechanisms of action and safety profiles enter the field. Further research is essential to establish evidence-based strategies for sequencing SG and addressing disease progression post-ADC therapy.