bluuebunny/crossref_metadata_2025 huggingface dataset:
EVs from cells at the early stages of chondrogenesis delivered by injectable SIS dECM promote cartilage regeneration
Authors: Zhu Weilai , Shi Jiaying , Weng Bowen , Zhou Zhenger , Mao Xufeng , Pan Senhao , Peng Jing , Zhang Chi , Mao Haijiao , Li Mei , Zhao Jiyuan
Published: August 2024

Articular cartilage defect therapy is still dissatisfactory in clinic. Direct cell implantation faces challenges, such as tumorigenicity, immunogenicity, and uncontrollability. Extracellular vesicles (EVs) based cell-free therapy becomes a promising alternative approach for cartilage regeneration. Even though, EVs from different cells exhibit heterogeneous characteristics and effects. The aim of the study was to discover the functions of EVs from the cells during chondrogenesis timeline on cartilage regeneration. Here, bone marrow mesenchymal stem cells (BMSCs)-EVs, juvenile chondrocytes-EVs, and adult chondrocytes-EVs were used to represent the EVs at different differentiation stages, and fibroblast-EVs as surrounding signals were also joined to compare. Fibroblasts-EVs showed the worst effect on chondrogenesis. While juvenile chondrocyte-EVs and adult chondrocyte-EVs showed comparable effect on chondrogenic differentiation as BMSCs-EVs, BMSCs-EVs showed the best effect on cell proliferation and migration. Moreover, the amount of EVs secreted from BMSCs were much more than that from chondrocytes. An injectable decellularized extracellular matrix (dECM) hydrogel from small intestinal submucosa (SIS) was fabricated as the EVs delivery platform with natural matrix microenvironment. In a rat model, BMSCs-EVs loaded SIS hydrogel was injected into the articular cartilage defects and significantly enhanced cartilage regeneration in vivo. Furthermore, protein proteomics revealed BMSCs-EVs specifically upregulated multiple metabolic and biosynthetic processes, which might be the potential mechanism. Thus, injectable SIS hydrogel loaded with BMSCs-EVs might be a promising therapeutic way for articular cartilage defect.
Differences in the relationship between pain and anxiety in total knee and hip arthroplasty: a longitudinal cross‐lagged analysis mediated by depression and pain catastrophizing
Authors: Paredes Ana Cristina , Costa Patrício , Costa Márcia , Oliveira Patrícia , Varanda Pedro , Almeida Armando , Pinto Patrícia R
Published: August 2024

Acute postsurgical pain (APSP) is an important risk factor for pain chronification, with reports of being more intense after total knee arthroplasty (TKA) than after total hip arthroplasty (THA). Psychological variables have been associated with differences in postsurgical pain experience. This study aimed to analyse the longitudinal reciprocal association between pain and anxiety levels in patients undergoing TKA or THA, to investigate the moderator role of the type of surgery and to explore psychological mediators in the anxiety – pain association.

Patients undergoing TKA ( n = 120) or THA ( n = 109) were evaluated before surgery and in the acute postsurgical period (48 h postsurgery). Presurgical assessment comprised sociodemographic, pain-related and psychological variables (anxiety, depression, pain catastrophizing, self-efficacy, optimism and satisfaction with life). Postsurgical assessment focused on pain frequency, pain intensity and anxiety. Longitudinal associations were explored using cross-lagged panel models that included the indirect effect paths through possible mediators (pain catastrophizing and depression). Multigroup analyses compared TKA and THA.

In the global sample, higher APSP was predicted by higher presurgical pain and worse presurgical anxiety. Multigroup analyses revealed that worse APSP was predicted by higher presurgical anxiety in patients undergoing TKA and by higher presurgical pain in patients undergoing THA. Furthermore, there was a positive significant indirect effect of pain catastrophizing, but not depressive symptoms, in the relationship between presurgical anxiety and APSP in THA. Anxiety and APSP are differently interrelated in TKA and THA. Psychological characteristics could be managed before surgery to favour better APSP control and potentially prevent pain chronification after total joint arthroplasty.
Ear buddies: A moderated mediation model of the effect of mobility on parasocial relationships with podcast hosts
Authors: Scherer Hailey , Cohen Elizabeth L.
Published: August 2024

The affordances of different media technologies can affect how users develop parasocial relationships with the media figures they encounter on those devices. This study examined the relationship between mobility and parasocial relationships with podcast hosts. Participants from Amazon Mechanical Turk ( n = 165) responded to a survey on a memorable podcast listening experience. The results revealed a conditional indirect effect of mobility on parasocial relationship strength through narrative transportation. Media multitasking moderated this effect. Specifically, there was a positive effect of mobility on transportation that increased incrementally at moderate and high levels of multitasking.
Dialysis disequilibrium syndrome: A case report
Authors: Benabdelouahab Nada , Ziati Kawtar , Oualili Latifa , Ssouni Oussama , Dendane Tarek , Zeggwagh Amine Ali , Abidi Khalid
Published: August 2024

The dialysis disequilibrium syndrome is a severe, but rare complication that can occur during or after hemodialysis. It primarily arises from an osmotic gradient, between the plasma and the brain, resulting from the rapidity of the dialysis. This gradient leads to the development of cerebral edema and an increase in intracranial pressure, manifesting as various neurological symptoms. Although this syndrome carries risks of morbidity and mortality, it can be prevented by identifying high-risk patients, implementing preventive measures, and ensuring early detection and prompt management of dialysis disequilibrium syndrome. We present a case of dialysis disequilibrium syndrome in a 59-year-old woman, to raise awareness of this uncommon entity. This review focuses on the discussion of clinical features, and prevention of dialysis disequilibrium syndrome, with a particular emphasis on understanding its pathophysiology, as it significantly influences preventive and management approaches.
A case report of metastatic esophageal squamous cell carcinoma during pregnancy
Authors: Shaikh Bisma , Alam Muhammad Taha , Samad Shahzaib , Danishwar Mahmood
Published: August 2024

Esophageal cancer is extremely rare in pregnant women, accounting for only 0.07%–0.1% of all malignant neoplasms in pregnancy. It is rapidly progressive in nature and requires timely intervention. Our literature search yielded six case reports of esophageal cancers in pregnancy thus far. We herein report the case of a 30-year-old female, presenting at 32 weeks of gestation with complaints of hoarseness, dysphagia, and weight loss. The biopsy taken from within the esophagus, using an endoscope during an upper endoscopy procedure confirmed the diagnosis of squamous cell carcinoma of esophagus and Positron emission tomography-computed tomography revealed metastasis to parathyroid region. She was confirmed with metastatic squamous cell cancer positive for cytokeratin 5/6 and cytokeratin P40 immunohistochemistry. The Positron emission tomography-computed tomography of the chest showed a large hypermetabolic soft tissue mass in the mid-esophagus with significant proximal dilation. The head-and-neck computed tomography scan represented a necrotic nodal mass in the neck and circumferential mural thickening involving the mid-esophagus resulting in the proximal dilation confirming the primary tumor site. Two weeks after the delivery, the patient started a chemotherapy regimen consisting of nine cycles of Carboplatin and Paclitaxel. Postchemotherapeutic computed tomography showed remonstration of lesion in the thyroid gland and middle part of the esophagus. Thus, in pregnant patients with new onset hoarseness, dysphagia, or substantial weight loss, clinicians should keep esophageal cancer as part of their differentials. A thorough history, detailed physical examination, and imaging should be performed to determine esophageal cancer, as it can advance swiftly and has a poor prognosis if left untreated.
Case report: ATM A1159T mutation in malignant peritoneal mesothelioma may be associated with tumor recurrence
Authors: Li Ying , Yang Jintao , Zheng Bei , Yan Na , Yang Wenjuan , Xie Xinling , Xu Guoshu , Zhang Meiling
Published: August 2024

Malignant peritoneal mesothelioma is an exceedingly rare malignant tumor. Herein, we present a case of malignant peritoneal mesothelioma in a 59-year-old Chinese female patient who was stable after treatment for multiple relapses. Imaging revealed massive ascites and an irregular thickening of the peritoneal mesangium. Laparoscopic biopsy revealed heterogeneous cell nests in the parietal peritoneal fibrous tissue, which were confirmed by immunohistochemical staining for Calretinin, WT-1, and D2-40. In terms of genetic screening, BAP1, CSF1R, and other key driver gene variants closely related to malignant peritoneal mesothelioma have been explored in tumor tissues. Notably, CARD11 driver mutation was first found in all malignant peritoneal mesothelioma patients, and ATM A1159T gene mutation found in recurrent focal tissue may be associated with recurrent tumor recurrence.
Postoperative multimodal rehabilitation for spontaneous smile restoration in severe Moebius syndrome: A case report and a short literature review
Authors: Salah Sana , Belhaj Maaouia Chaima , Toulgui Emna , Kalai Amine , Ben Salah Frih Zohra , Ben Saad Helmi
Published: August 2024

Moebius syndrome (MS) is a rare congenital disorder characterized by bilateral facial paralysis, significantly impacting an individual’s ability to convey emotions. The lengthening temporalis myoplasty (LTM) surgery is a crucial palliative intervention that can restore the smile in patients with MS by transferring the functional temporalis muscle to the paralyzed facial commissure. However, successful outcomes are closely tied to postoperative functional rehabilitation. This case report details the experience of a 29-year-old woman with severe MS who underwent LTM surgery followed by a comprehensive rehabilitation program. Over a period of 12 months, the patient achieved a spontaneous and symmetrical smile through a three-stage rehabilitation program focused on mandibular, voluntary, and spontaneous smile recovery. Speech therapy and psychological support were also integral components. This case underscores the importance of adopting a holistic approach to ensure successful and enduring outcomes from smile restoration surgery in patients with MS.
Case report—unveiling a case of hemoglobin D-Punjab variant with iron deficiency anemia in Sindh (Pakistan)
Authors: Jawed Inshal , Alam Mohammad Omer , Fatima Fasiha Bakhtawar , Johar Syeda Alisha , Shah Syed Adil Mir
Published: August 2024

Hemoglobin D variations are a group of hemoglobinopathies caused by mutations in the genes that control the synthesis of new globin chains. Hemoglobin D-Punjab is the most prevalent but frequently asymptomatic, it can occasionally cause mild to moderate hemolytic anemia, making diagnosis difficult and raising the risk of misdiagnosis. This article discusses a rare instance of a seventeen-year-old male in Sindh, Pakistan with iron deficiency anemia who was later found to have the Punjab variation of the hemoglobin D. The patient had signs of weakness, exhaustion, and shortness of breath, which were initially alleviated by iron supplementation but eventually became refractory. Hemoglobin electrophoresis demonstrated the distinctive hypochromic, microcytic red blood cell shape, and laboratory tests verified the presence of the Hemoglobin D-Punjab feature. The instance emphasizes how crucial it is to distinguish Hemoglobin D-Punjab from other anemias in order to guarantee proper care. This case underscores the importance of recognizing hemoglobin D-Punjab trait, to provide appropriate genetic counseling and ensure the patient’s well-being. Increased awareness among healthcare professionals regarding the diverse spectrum of hemoglobinopathies is essential for accurate diagnosis and management.
Pregnancy outcome in a patient with end-stage kidney disease treated with an intensive automated peritoneal dialysis regimen: A case report
Authors: Henao-Sierra Jorge E , Alza-Arcila Lyzinhawer , Echeverry Esteban , Peralta Pérez Jocelyn Juceth , Tanaka Takegami Mayumi , Quiroz Alfaro Alejandro José
Published: August 2024

Pregnant women with end-stage kidney disease who undergo peritoneal dialysis have lower pregnancy rates and higher obstetric risk than their peers undergoing hemodialysis. Although there has been some improvement in pregnancy rates and outcomes due to the intensification of dialysis prescriptions, there is currently a lack of guidelines for optimizing peritoneal dialysis regimens for pregnant women with end-stage kidney disease. Besides, there is limited data available regarding pregnancy outcomes in women with end-stage kidney disease undergoing peritoneal dialysis. We report the case of a 23-year-old Hispanic woman with end-stage kidney disease caused by focal and segmental glomerulosclerosis. She became pregnant while undergoing successful treatment with an intensified automated peritoneal dialysis regimen. The patient gave birth to a live female preterm infant weighing 938 g during the 28th week of her pregnancy. The baby required neonatal intensive care due to prematurity, extremely low birth weight, and respiratory distress syndrome.
Gender stereotypes and petty corruption among street-level bureaucrats: Evidence from a conjoint experiment
Authors: Carreras Miguel , Vera Sofia , Visconti Giancarlo
Published: August 2024

Do female public servants receive a stronger negative public reaction from being involved in corruption than their male counterparts? While there are good theoretical reasons to suggest they do, the empirical evidence on this question to date, which primarily focuses on elected officials, remains inconclusive. To shed new light on this matter, we investigate a larger but hitherto understudied group: street-level bureaucrats. Using a conjoint experiment conducted in Paraguay, one of the most corrupt countries in Latin America, we evaluate public preferences for corrupt versus non-corrupt bureaucrats. Contrary to existing theories of gender and corruption, our results suggest there is no significant difference in how citizens react to male and female corrupt bureaucrats.
Importance of Visual Health for a Safe Driving: A Citations Network Analysis
Authors: Sánchez-Tena Miguel Ángel , Martinez-Perez Clara , Rocha-Rocha Laura , Villa-Collar Cesar , Alvarez-Peregrina Cristina
Published: August 2024

Nowadays, due to the increase in traffic accidents, research has emphasized the importance of vision in driving. This research aims to study the relationships between publications and their corresponding authors and identify the different research areas on vision and safe driving that have awakened interest in researchers. Web of Science was the database utilized for searching publications from the first paper published (1957) to December 2021, selecting the keywords: driv*, safety, and vision. The publications’ analysis was made using the CitNetExplorer, VOSviewer, and CiteSpace software. A total of 3,777 publications and 3,887 citation networks were found. In 2019, there was a total of 391 publications and 15 citation networks. The most cited publication was “Older Drivers and Cataract: Driving Habits and Crash Risk” published by Owsley et al. in 1999, with 76 as citation index. By the clustering function, five groups were found that cover the main research areas in this field: ocular movements, detection systems, road safety, and age. The citation network offers both, a quantitative and qualitative analysis of the main articles. Being a multidisciplinary field of study, current research emphasizes the importance of eye movements while driving, the visual impairment in elderly drivers, and the new video-based detection systems.
How Citizen Entrepreneurship Works
Authors: Langfermann Judith
Published: August 2024

Citizen Entrepreneurship (CE) is a promising approach to tackle global challenges such as climate change, poverty and social inequality, but also local problems. This paper explores how CE projects empower citizens to actively engage in their communities, focus on local needs and promote sustainable solutions. In doing so, theoretical frameworks such as Ostrom’s commons theory, innovation as a social good and Sen and Nussbaum’s capabilities approach provide insights into the foundations of CE. Methods for engaging citizens encompass a spectrum from participatory research approaches to leveraging digital platforms, thereby promoting collaboration and facilitating the exchange of knowledge among a diverse array of community stakeholders. CE promises to strengthen the resilience and well-being of communities by effectively addressing both local societal needs and global challenges.
How wars don’t end: A response to Gerard Toal’s analysis of ceasefire negotiations in Ukraine
Authors: Anghel Veronica
Published: August 2024

Gerard Toal’s analysis of Ukraine and its allies’ hesitation to accept Russia’s peace terms, presented in ‘The Territorial Taboo: Explaining the Public Aversion to Negotiations in the Ukraine War Support Coalition’, attributes this reluctance to ‘commitment problems’ and ‘biases’. However, this explanation oversimplifies the issue. Achieving a stable post-agreement order necessitates Western resolve to provide security guarantees for Ukraine and a cohesive strategy regarding Russia’s role in the new global order. Toal’s suggestion of transferring occupied territories to end the war would enable Russia to further its goal of undermining Ukrainian sovereignty and bolster Putin’s dictatorship. This outcome contradicts NATO’s Strategic Concept, prolongs Ukrainian suffering, and perpetuates European security uncertainty. Furthermore, it would require a post-war narrative in which Ukrainians accept defeat and abandon their European aspirations. The resistance to Russia’s proposed settlement stems not from narrative taboos, but from a rational demand for a better resolution where unprovoked aggressors who want to upend international law through pre-modern lawlessness do not win the day.
Geographical storylines and the Russian invasion of Ukraine: Narrative power and narrative taboos, a (difficult) conversation
Authors: Bialasiewicz Luiza
Published: August 2024

How does the Russo-Ukrainian war end? On what territorial terms? Who – and where – has the right to decide on negotiations towards a settlement? These are all deeply geographical questions, and geographical storylines have been powerfully deployed in analyses of the conflict since the start of the full-scale Russian invasion of Ukraine in February 2022. In this conversation forum, we bring together a provocative article by Gerard Toal identifying what he terms a ‘territorial taboo’ espoused by discursive communities in both the US and Europe: a set of geographical storylines that, Toal suggests, render impossible any negotiated end to the war. To respond to Toal’s argument, we have reached out to three expert commentators on the topic: international relations scholar Kseniya Oksamytna, historian Michael Kimmage, and political scientist Veronica Anghel.
Dysuria and Vaginal Pain, Unusual Manifestations of B-acute Lymphoblastic Lymphoma
Authors: Mitra Ananya Datta , Mitra Anupam , Chung Jong H , Betts Elham Vali
Published: August 2024

Urinary symptoms are one of the most common reasons for emergency visits in females of pediatric age group and can be associated with various conditions like infections (most common), sexual trauma and rarely neoplastic processes. Here, we report a case of a 7-year-old female who presented in the emergency multiple times with the complaints of urinary symptoms and vaginal pain and was empirically treated with antibiotics and antifungals without symptomatic improvement. Her blood tests, physical examination during this time remained unrevealing. She was then transferred to our institution on her third emergency visit for further evaluation. On imaging studies, she was noted to have expansile lesions on her vertebral body at the L4 and T6 levels with compressive myelopathy with multiple bone and soft tissue lesions throughout her lower extremities. Patient developed saddle anesthesia requiring emergent decompression and biopsy of the epidural mass with the final pathology coming back as B-lymphoblastic leukemia/lymphoma. B-ALL/B-LBL is the most common pediatric hematologic malignancy and usually presents with fever, hepatosplenomegaly, lymphadenopathy, bone pain and bleeding. Occasionally, atypical presentations like bone and joint pain, osteoporosis, palpable paravertebral mass have been described. However, this is the first case report to describe a very unusual and unfamiliar presentation of this disease causing significant diagnostic difficulty resulting in delayed treatment. This case report can aid as a reminder that unusual pain or any nonspecific manifestations in pediatric patients, refractory to common treatment should be investigated with extreme diligence not to miss this neoplastic process.
Methadone Take-Home Policies and Associated Mortality: Permitting versus Non-Permitting States
Authors: Harris Rebecca Arden
Published: August 2024

To mitigate COVID-19 exposure risks in methadone clinics, the Substance Abuse and Mental Health Services Administration (SAMHSA) issued a temporary modification of regulations in March 2020 to permit, with state concurrence, extended take-home methadone doses. The modification allowed for up to 28 days of take-home methadone for stable patients and 14 days for those less stable. Using both interrupted time series and difference-in-differences methods, this study examined the association between the policy change and fatal methadone overdoses, comparing states that permitted the expansion of take-home doses with states that did not. The findings suggest the pandemic emergency take-home policy did not increase methadone-involved mortality.
Mechanical properties of branch and stem wood for two Mediterranean cultivars of olive tree
Authors: Mammoliti Angelo , Cataldo Maria Francesca , Papandrea Salvatore Francesco , Proto Andrea Rosario
Published: August 2024

There is currently a strong interest in wood and the demand for this material is expected to grow significantly worldwide. Consequently, market demand for wood from fruit orchards is growing as an additional source of supply. For these reasons, several studies were conducted to evaluate the properties of wood derived by orchard pruning or dismantling. Despite the abundance of raw materials from pruning, the mechanical properties of olive wood have not been studied completely by the scientific community, so the woody material obtained is usually considered waste or firewood. In fact, there is still a lack of knowledge about olive wood characteristics and considering the valuable role of olive species in the Mediterranean area, the current study aimed to determine and compare the physical and mechanical properties of branches and stem wood of two olive tree cultivars, “Sinopolese” and “Ottobratica”, to provide information on this wood species. These two olive cultivars are commonly cultivated in the Calabria region (Southern Italy) for the extraction of oil from drupes, but large masses of wood are derived from their pruning. For the choice of parts, the stem was considered to become a branch when, above each branch intersection, it changed in diameter and direction of growth. The branches with a diameter lower than 20 cm were excluded. The tests conducted for this purpose were: Roughness profile; Impact wave; Vibrational analysis; Static modulus of elasticity; Bending strength; Abrasion resistance; Static hardness; Footprints; Compression strength; Screw withdrawal resistance parallel to grain; Screw withdrawal resistance perpendicular to grain. A MANOVA analysis was conducted between the Cultivar-Tree part and the physical and mechanical properties. The results showed some differences between the two cultivars principally related to mechanical properties such as moduli of elasticity and rupture, footprint, compression strength, and screw withdrawal resistances, where in general, the “Sinopolese” cultivar showed higher values than the “Ottobratica”. Between the tree parts (stem and branches) within the same cultivars, branches demonstrated higher results in the majority of the tests, but highlighting statistical differences only in terms of static modulus of elasticity, bending strength, static hardness and screw withdrawal resistances depending on the cultivar. This result suggests that the branch wood, with its characteristics, could be valorized in the commercial utilization representing a valid opportunity for the local rural economy, even considering the conspicuous amount of wood obtained from olive pruning activity. Expanding knowledge about olive wood in terms of physical and mechanical characteristics could increase its use in multiple sectors and ensure a more aware use of the application of the wood resources by supporting the decision on its best end use.
PTBP1 knockdown impairs autophagy flux and inhibits gastric cancer progression through TXNIP-mediated oxidative stress
Authors: Wang Shimin , Wang Xiaolin , Qin Changhong , Liang Ce , Li Wei , Ran Ai , Ma Qiang , Pan Xiaojuan , Yang Feifei , Ren Junwu , Huang Bo , Liu Yuying , Zhang Yuying , Li Haiping , Ning Hao , Jiang Yan , Xiao Bin
Published: August 2024

Background

Gastric cancer (GC) is a prevalent malignant tumor, and the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) has been identified as a crucial factor in various tumor types. Moreover, abnormal autophagy levels have been shown to significantly impact tumorigenesis and progression. Despite this, the precise regulatory mechanism of PTBP1 in autophagy regulation in GC remains poorly understood.

Methods

To assess the expression of PTBP1 in GC, we employed a comprehensive approach utilizing western blot, real-time quantitative polymerase chain reaction (RT–qPCR), and bioinformatics analysis. To further identify the downstream target genes that bind to PTBP1 in GC cells, we utilized RNA immunoprecipitation coupled with sequencing (si-PTBP1 RNA-seq). To evaluate the impact of PTBP1 on gastric carcinogenesis, we conducted CCK-8 assays, colony formation assays, and GC xenograft mouse model assays. Additionally, we utilized a transmission electron microscope, immunofluorescence, flow cytometry, western blot, RT–qPCR, and GC xenograft mouse model experiments to elucidate the specific mechanism underlying PTBP1’s regulation of autophagy in GC.

Results

Our findings indicated that PTBP1 was significantly overexpressed in GC tissues compared with adjacent normal tissues. Silencing PTBP1 resulted in abnormal accumulation of autophagosomes, thereby inhibiting GC cell viability both in vitro and in vivo. Mechanistically, interference with PTBP1 promoted the stability of thioredoxin-interacting protein (TXNIP) mRNA, leading to increased TXNIP-mediated oxidative stress. Consequently, this impaired lysosomal function, ultimately resulting in blockage of autophagic flux. Furthermore, our results suggested that interference with PTBP1 enhanced the antitumor effects of chloroquine, both in vitro and in vivo.

Conclusion

PTBP1 knockdown impairs GC progression by directly binding to TXNIP mRNA and promoting its expression. Based on these results, PTBP1 emerges as a promising therapeutic target for GC.

Graphical Abstract
Comparison of serum prostate specific antigen (PSA), soluble E-cadherin (sE-cad), and inosine monophosphate dehydrogenase-2 (IMPDH-2) as aggressive prostate cancer predictors
Authors: Umar Ahmed Mohammed , Mungadi Ismaila Arzika , Agwu Ngwobia Peter , Abdulwahab-Ahmed Abdullah , Muhammad Abubakar Sadiq , Khalid Abdullahi
Published: August 2024

Background

This study aimed to compare serum prostate specific antigen (PSA), Soluble E-cadherin (sE-cad), and Inosine Monophosphate Dehydrogenase-2 in predicting prostate cancer aggressiveness by determining their correlations with Gleason score and International Society of Urological Pathology (ISUP) Grade Groups.

Methods

This was a hospital-based descriptive quantitative cross-sectional study whereby we enrolled 48 newly diagnosed prostate adenocarcinoma patients in the study. Their serum was analysed for PSA, sE-cad, and IMPDH-2. Pearson correlation coefficient was used to test the correlation between the serum sE-cad and Gleason score while Spearman rho correlation coefficient was used for PSA and IMPDH-2. The correlation coefficient (r) was graded as very weak (< 0.3), weak (0.3–0.4), moderate (0.5–0.6), or strong (≥ 0.7), while the magnitude was determined by calculating the coefficient of determination for the respective analysis (R2). The correlation between the biomarkers and the ISUP Grade groups was determined using the Kendall tau correlation coefficient (τ). All levels of statistical significance were set at p < 0.05.

Results

The mean age of the subjects was 69.4 years. The Means of serum PSA, sE-cad, and IMPDH-2 were 47.2 ng/ml, 136.5 ng/ml, and 89.8 pg/ml respectively. Serum PSA weakly correlated with both Gleason score (r = 0.3, p = 0.04) and ISUP grade groups (τ = 0.3, p = 0.02). The magnitude was 0.097. Similarly, serum sE-cad correlated weakly with both Gleason scores (r = 0.4, p = 0.01), and ISUP Grade Groups (τ = 0.3, p = 0.005). The magnitude was 0.134. However, serum IMPDH-2 neither correlated with Gleason score (r = 0.03, p = 0.86) nor ISUP Grade Groups (τ = 0.004, p = 0.97). Serum sE-cad did not outperform both IMPDH-2 (p = 0.91) or PSA (p = 0.23) in predicting the Gleason score.

Conclusions

Serum sE-cad best predicted aggressive prostate cancer but did not statistically outperform serum PSA or IMPDH-2. Hence, neither of the three are reliable predictors of aggressive prostate cancer.
A long way from Frome: improving connections between patients, local services and communities to reduce emergency admissions
Authors: Withers Kathleen , Pardy Karen , Topham Lynne , Lee Rachel , Ghanghro Amir , Cryer Hazel , Williams Huw
Published: August 2024

Background

Low socio-economic status can lead to poor patient outcomes, exacerbated by lack of integration between health and social care and there is a demand for developing new models of working.

Aim

To improve connections between patients, local services and their communities to reduce unscheduled admissions.

Design and setting

A primary care cluster with areas of high deprivation, consisting of 11 general practices serving over 74,000 people.

Method

A multi-disciplinary team with representatives from healthcare, local council and the third sector was formed to provide support for people with complex or social needs. A discharge liaison hub contacted patients following hospital discharge offering support, while cluster pharmacists led medicine reviews. Wellbeing Connectors were commissioned to act as a link to local wellbeing and social resources. Advance Care Planning was implemented to support personalised decision making.

Results

Unscheduled admissions in the over 75 age group decreased following the changes, equating to over 800 avoided monthly referrals to assessment units for the cluster. Over 2,500 patients have been reviewed by the MDT since its inception with referrals to social prescribing groups, physiotherapy and mental health teams; these patients are 20% less likely to contact their GP after their case is discussed. An improved sense of wellbeing was reported by 80% of patients supported by wellbeing connectors. Staff feel better able to meet patient needs and reported an increased joy in working.

Conclusion

Improved integration between health, social care and third sector has led to a reduction in admissions, improved patient wellbeing and has improved job satisfaction amongst staff.
Mapping the evidence on dementia care pathways – A scoping review
Authors: Saragosa Marianne , MacEachern Evan , Chiu Mary , Weylie Sean , Schneider Krista , Maloney Elaine R , Holland Jordanne , Kuluski Kerry , Orchanian-Cheff Ani , Nelson Michelle LA
Published: August 2024

Background

One way of standardizing practice and improving patient safety is by introducing clinical care pathways; however, such pathways are typically geared towards assisting clinicians and healthcare organizations with evidence-based practice. Many dementia care pathways exist with no agreed-upon version of a care pathway and with little data on experiences about their use or outcomes. The objectives of the review were: (1) to identify the dementia care pathway’s purpose, methods used to deploy the pathway, and expected user types; (2) to identify the care pathway’s core components, expected outcomes, and implications for persons with dementia and their care partners; and (3) determine the extent of involvement by persons with dementia and/or their care partners in developing, implementing, and evaluating the care pathways.

Methods

We systematically searched six literature databases for published literature in the English language in September 2023 utilizing Arskey and O’Malley’s scoping review framework.

Results

The findings from the dementia care pathways (n = 13) demonstrated assistance in dementia diagnostic and management practices for clinicians and offered structured care processes in clinical settings. For this reason, these pathways emphasized assessment and interventional post-diagnostic support, with less emphasis on community-based integrated dementia care.

Conclusion

Future dementia care pathway development can seek the involvement of persons with dementia and care partners in designing, implementing and evaluating such pathways, ensuring that outcome measures properly reflect the impact on persons with lived dementia experience and their care partners.
Age at separation, residential mobility, and depressive symptoms among twins in late adolescence and young adulthood: a FinnTwin12 cohort study
Authors: Wang Zhiyang , Whipp Alyce M. , Heinonen-Guzejev Marja , Kaprio Jaakko
Published: August 2024

Background

Separating with close siblings and leaving the parental home at an early age represents a major life event for an adolescent (reflected by age at separation in a twin pair) and may predispose them to poor mental health. This study aims to examine the association of age at separation and residential mobility on depressive symptoms in late adolescence and young adulthood and to explore possible underlying genetic effects.

Methods

Residential mobility consisted of the number and total distance of moves before age 17. Based on 3071 twins from the FinnTwin12 cohort, we used linear regression to assess the association of age at separation and residential mobility with General Behavior Inventory (GBI) scores at age 17 and in young adulthood. A higher GBI score indicated more depressive symptoms occurred. Then, the mixed model for repeated measures (MMRM) was used to visualize the scores’ trajectory and test the associations, controlling for "baseline" state. Twin analyses with a bivariate cross-lagged path model were performed between the difference in GBI scores, between cotwins, and separation status for the potential genetic influence.

Results

Compared to twins separated before age 17, twins who separated later had significantly lower GBI scores at age 17 and in young adulthood. In MMRM, separation at a later age and a higher number of moves were associated with a higher GBI score in young adulthood. A small genetic effect was detected wherein GBI within-pair differences at age 17 were associated with separation status before age 22 (coefficient: 0.01).

Conclusion

The study provides valid evidence about the influence of siblings and family on depressive symptoms in later adolescence and young adulthood while finding some evidence for a reverse direction effect. This suggests more caution in the interpretation of results. A strong association between residential mobility and depressive symptoms was affirmed, although further detailed research is needed.
Treatment patterns in patients with newly diagnosed COPD in the USA
Authors: Anzueto Antonio , Rogers Sheri , Donato Bonnie , Jones Beverly , Modi Kushal , Olopoenia Abisola , Wise Robert
Published: August 2024

Background

Prompt and effective management with maintenance therapy (single or dual bronchodilator therapy) is recommended after the initial diagnosis of chronic obstructive pulmonary disease (COPD) to maintain lung function and prevent exacerbations. Contrary to guideline-based recommendations, most patients are not prescribed maintenance treatment at initial diagnosis. The current study assessed the pharmacologic treatment patterns and outcomes of newly diagnosed patients with COPD in the USA.

Methods

This retrospective, noninterventional study used de-identified data from the Inovalon Insights’ database (Commercial, Medicaid Managed Care, and Medicare Advantage–insured individuals) between January 1, 2015, and December 31, 2021. The “patient journey” from initial diagnosis was followed over a 4-year period. The primary outcome measure was the number of moderate or severe exacerbations. Secondary outcome measures included the cumulative incidence of exacerbations, mean cumulative count of moderate and severe exacerbations, rates of moderate and severe exacerbations in patients who remained untreated after diagnosis in 12-month time periods for 4 years, sociodemographic and clinical characteristics, and pharmacologic treatment patterns.

Results

The cohort consisted of 238,158 newly diagnosed patients with COPD (female [52.9%]; mean age 63.8 years). The majority of patients with COPD had Medicaid as their primary insurance (46.2%). Overall, during the 4-year follow-up period, 32.9% of the patients had at least one moderate or severe exacerbation, and 25.8% and 13.8% experienced moderate and severe exacerbations, respectively. At diagnosis, 86.2% of the patients were untreated and most remained untreated by the end of the follow-up (63.8%). Most patients (62.0%) received long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) as their initial treatment at diagnosis, and LABA/ICS continued to be the most common initial treatment during the 4-year period (64.0% at year 1; 58.0% at year 4).

Conclusions

Most patients with COPD were not treated at initial diagnosis and remained untreated during follow-up. Our data highlight a lack of adherence to recommendations for clinical practice.
Deterioration of neuroimmune homeostasis in Alzheimer’s Disease patients who survive a COVID-19 infection
Authors: Villareal Jonathan A. B. , Bathe Tim , Hery Gabriela P. , Phillips Jennifer L. , Tsering Wangchen , Prokop Stefan
Published: August 2024

Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer’s disease (AD). With the emergence of SARS-CoV-2 (COVID-19) and the resultant pandemic, many individuals from the same aging population vulnerable to AD suffered a severe systemic infection with potentially unidentified long-term consequences for survivors. To study the impact of COVID-19 survival on the brain’s intrinsic immune system in a population also suffering from AD, we profiled post-mortem brain tissue from patients in the UF Neuromedicine Human Brain and Tissue Bank with a diagnosis of AD who survived a COVID-19 infection (COVID-AD) and contrasted our findings with AD patients who did not experience a COVID-19 infection, including a group of brain donors who passed away before arrival of SARS-CoV-2 in the United States. We assessed disease-relevant protein pathology and microglial and astrocytic markers by quantitative immunohistochemistry and supplemented these data with whole tissue gene expression analysis performed on the NanoString nCounter® platform. COVID-AD patients showed slightly elevated Aβ burden in the entorhinal, fusiform, and inferior temporal cortices compared to non-COVID-AD patients, while tau pathology burden did not differ between groups. Analysis of microglia revealed a significant loss of microglial homeostasis as well as exacerbated microgliosis in COVID-AD patients compared to non-COVID-AD patients in a brain region-dependent manner. Furthermore, COVID-AD patients showed reduced cortical astrocyte numbers, independent of functional subtype. Transcriptomic analysis supported these histological findings and, in addition, identified a dysregulation of oligodendrocyte and myelination pathways in the hippocampus of COVID-AD patients. In summary, our data demonstrate a profound impact of COVID-19 infection on neuroimmune and glial pathways in AD patients persisting for months post-infection, highlighting the importance of peripheral to central neuroimmune crosstalk in neurodegenerative diseases.
Transcriptomic analysis unveils bona fide molecular signatures of microglia under conditions of homeostasis and viral encephalitis
Authors: Mulenge Felix , Gern Olivia Luise , Busker Lena Mareike , Aringo Angela , Ghita Luca , Waltl Inken , Pavlou Andreas , Kalinke Ulrich
Published: August 2024

Microglia serve as a front-line defense against neuroinvasive viral infection, however, determination of their actual transcriptional profiles under conditions of health and disease is challenging. Here, we used various experimental approaches to delineate the transcriptional landscape of microglia during viral infection. Intriguingly, multiple activation genes were found to be artificially induced in sorted microglia and we demonstrated that shear stress encountered during cell sorting was one of the key inducers. Post-hoc analysis revealed that publicly available large-scale single-cell RNA sequencing datasets were significantly tainted by aberrant signatures that are associated with cell sorting. By exploiting the ribosomal tagging approach, we developed a strategy to enrich microglia-specific transcripts by comparing immunoprecipitated RNA with total RNA. Such enriched transcripts were instrumental in defining bona fide signatures of microglia under conditions of health and virus infection. These unified microglial signatures may serve as a benchmark to retrospectively assess ex vivo artefacts from available atlases. Leveraging the microglial translatome, we found enrichment of genes implicated in T-cell activation and cytokine production during the course of VSV infection. These data linked microglia with T-cell re-stimulation and further underscored that microglia are involved in shaping antiviral T-cell responses in the brain. Collectively, our study defines the transcriptional landscape of microglia under steady state and during viral encephalitis and highlights cellular interactions between microglia and T cells that contribute to the control of virus dissemination.
Design and performance analysis of low damage anti-skid crescent drills for bone drilling
Authors: Zhao Jing , Wu Di , Wu Xiaojie , Zhang Ziyang , Wen Zhiguo , Liu Sinan
Published: August 2024

Background

With orthopedic surgery increasing year on year, the main challenges in bone drilling are thermal damage, mechanical damage, and drill skid. The need for new orthopedic drills that improve the quality of surgery is becoming more and more urgent.

Methods

Here, we report the skidding mechanism of drills at a wide range of inclination angle and propose two crescent drills (CDTI and CDTII). The anti-skid performance and drilling damage of the crescent drills were analyzed for the first time. Inclined bone drilling experiments were carried out with crescent drills and twist drills and real-time drilling forces and temperatures were collected.

Results

The crescent drills are significantly better than the twist drill in terms of anti-skid, reducing skidding forces, thrust forces and temperature. The highest temperature is generated close to the upper surface of the workpiece rather than at the hole exit. Finally, the longer crescent edge with a small and negative polar angle increases the rake angle of the cutting edge and reduces thrust forces but increases skidding force and temperature. This study can promote the development of high-quality orthopedic surgery and the development of new bone drilling tools.

Conclusion

The crescent drills did not skid and caused little drilling damage. In comparison, the CDTI performs better in reducing the skidding force, while the CDTII performs better in reducing the thrust force.
A novel robotic surgical assistant for total knee arthroplasty has a learning curve ranging from 6 to 14 cases and exhibits high accuracy in tibial bone cuts
Authors: Thongpulsawad Nimit , Achawakulthep Chaiwat , Intiyanaravut Tawan
Published: August 2024

Background

The adoption of robot-assisted total knee arthroplasty (TKA) aims to enhance the precision of implant positioning and limb alignment. Despite its benefits, the adoption of such technology is often accompanied by an initial learning curve, which may result in increased operative times. This study sought to determine the learning curve for the ROSA (Robotic Surgical Assistant) Knee System (Zimmer Biomet) in performing TKA and to evaluate the accuracy of the system in executing bone cuts and angles as planned. The hypothesis of this study was that cumulative experience with this robotic system would lead to reduced operative times. Additionally, the ROSA system demonstrated reliability in terms of the accuracy and reproducibility of bone cuts.

Methods

In this retrospective observational study, we examined 110 medical records from 95 patients who underwent ROSA-assisted TKA performed by three surgeons. We employed the cumulative summation methodology to assess the learning curves related to operative time. Furthermore, we evaluated the accuracy of the ROSA Knee System in performing TKA by comparing planned versus validated values for femoral and tibial bone cuts and angles.

Results

The learning curve for the ROSA Knee System spanned 14, 14, and 6 cases for the respective surgeons, with operative times decreasing by 22 min upon reaching proficiency (70.8 vs. 48.9 min; p < 0.001). Significant discrepancies were observed between the average planned and validated cuts and angles for femoral bone cuts (0.4 degree ± 2.4 for femoral flexion, 0.1 degree ± 0.6 for femoral coronal alignment, 0.3 mm ± 1.2 for distal medial femoral resection, 1.4 mm ± 8.8 for distal lateral femoral resection) and hip–knee–ankle axis alignment (0.3 degree ± 1.9 )(p < 0.05) but not for tibial bone cuts. Differences between planned and validated measurements during the learning and proficiency phases were nonsignificant across all parameters, except for the femoral flexion angle (0.42 degree ± 0.8 vs. 0.44 degree ± 2.7) (p = 0.49).

Conclusion

The ROSA Knee System can be integrated into surgical workflows after a modest learning curve of 6 to 14 cases. The system demonstrated high accuracy and reproducibility, particularly for tibial bone cuts. Acknowledging the learning curve associated with new robot-assisted TKA technologies is vital for their effective implementation.