bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombospondin-2 acts as a bridge between tumor extracellular matrix and immune infiltration in pancreatic and stomach adenocarcinomas: an integrative pan-cancer analysis
Authors: Liao Xingchen , Wang Wei , Yu Baoping , Tan Shiyun 
Published: June 2022

Abstract
Background
Thrombospondin-2 (THBS2) is a versatile glycoprotein that regulates numerous biological functions, including the apoptosis-proliferation balance in endothelial cells, and it has been linked to tumor angiogenesis. However, the exact role of THBS2 in human cancer remains unknown. This study aimed to determine THBS2 expression in a pan-cancer analysis and its association with pan-cancer prognosis and to further identify its possible roles in tumor immunity and the extracellular matrix (ECM).

Methods
Data on THBS2 expression in cancers and normal tissues were downloaded from the Genotype-Tissue Expression portal and UCSC Xena visual exploration tool and analyzed using the ONCOMINE database, Perl programming language, and Gene Expression Profiling and Interactive Analyses vision 2 webserver. In addition, survival prognosis was analyzed using the survival, survminer, limma, and forestplot packages in R v. 4.0.3.Immune and matrix components were also analyzed using R v. 4.0.3. Most importantly, we partially validated the role and mechanism of THBS2 in pancreatic and gastric cancers in vitro using PANC1 and BGC-823 cell lines.

Results
THBS2 was significantly overexpressed in 17 of the 33 investigated cancers and linked to a poor prognosis in pan-cancer survival analysis. High THBS2 expression was an independent unfavorable prognostic factor in kidney renal papillary cell, mesothelioma, and stomach and pancreatic adenocarcinomas. Immune infiltration and THBS2 expression were also related. THBS2 expression has been linked to immune and stromal scores and immune checkpoint markers in various cancers. The protein–protein interaction network revealed that THBS2 is associated with multiple ECM and immune proteins. THBS2 knockdown decreased the expression of CD47 and matrix metallopeptidase 2 (MMP-2) as well as the proliferation, migration, and invasion of PANC1 and BGC-823 cells in vitro.

Conclusions
Our findings suggested that THBS2 might promote cancer progression by remodeling the tumor microenvironment, affecting CD47-mediated signaling pathways, activating the pro-tumor functions of a disintegrin and metalloproteinase with thrombospondin motifs, and enhancing MMP-2 expression. Furthermore, it functions as a bridge between the ECM and immune infiltration in cancer and serves as a potential prognostic biomarker for several cancers, especially pancreatic and gastric adenocarcinomas.
Recent advances in mRNA-LNP therapeutics: immunological and pharmacological aspects
Authors: Kiaie Seyed Hossein , Majidi Zolbanin Naime , Ahmadi Armin , Bagherifar Rafieh , Valizadeh Hadi , Kashanchi Fatah , Jafari Reza 
Published: June 2022

AbstractIn the last decade, the development of messenger RNA (mRNA) therapeutics by lipid nanoparticles (LNP) leads to facilitate clinical trial recruitment, which improves the efficacy of treatment modality to a large extent. Although mRNA-LNP vaccine platforms for the COVID-19 pandemic demonstrated high efficiency, safety and adverse effects challenges due to the uncontrolled immune responses and inappropriate pharmacological interventions could limit this tremendous efficacy. The current study reveals the interplay of immune responses with LNP compositions and characterization and clarifies the interaction of mRNA-LNP therapeutics with dendritic, macrophages, neutrophile cells, and complement. Then, pharmacological profiles for mRNA-LNP delivery, including pharmacokinetics and cellular trafficking, were discussed in detail in cancer types and infectious diseases. This review study opens a new and vital landscape to improve multidisciplinary therapeutics on mRNA-LNP through modulation of immunopharmacological responses in clinical trials.Graphical Abstract
Study on the morphological characteristics and rotational alignment axis of placement plane of the tibial component in total knee arthroplasty for hemophilia-related knee arthritis
Authors: Feng Ru , Zhong Qigang , Zheng Liujie , Ye Houlong , Luo Dasheng , Ding Mingyang , Pang Nanyu , Li Jiale , Yao Yunfeng 
Published: June 2022

AbstractBackgroundAbnormal epiphyseal growth plate development of the proximal tibia in hemophilia patients leads to notable morphological changes in the mature knee joint. This study aimed to compare the morphological characteristics of tibial component placement cut surface in patients with hemophilic arthritis (HA) and osteoarthritis (OA) and to determine the tibial component rotational alignment axis’ best position for HA patients.MethodsPreoperative computed tomography scans of 40 OA and 40 HA patients who underwent total knee arthroplasty were evaluated using a three-dimensional (3D) software. The tibial component’s placement morphological parameters were measured. The tibial component’s rotational mismatch angles were evaluated, and the most appropriate 0°AP axis position for HA patients was investigated.ResultsIn the two groups, the morphology was significantly different in some of the parameters (p < 0.05). The tibial component rotational mismatch angles were significantly different between both groups (p < 0.05). The medial 9.26° of the medial 1/3 of the patellar tendon was the point through which 0°AP axis passed for the HA patients. Similarly, the medial 13.02° of the medial 1/3 of the tibial tubercle was also the point through which the 0°AP axis passed.ConclusionsThe ratio of the anteroposterior length to the geometric transverse length of the placement section of the tibial component in HA patients was smaller than that in OA patients. The medial 9.26° of the medial 1/3 of the patellar tendon or the medial 13.02° of the medial 1/3 of the tibial tubercle seem to be an ideal reference position of the rotational alignment axis of the tibial component for HA patients.
Downregulation of CDK5 signaling in the dorsal striatum alters striatal microcircuits implicating the association of pathologies with circadian behavior in mice
Authors: Zhou Hu , Zhang Jingxin , Shi Huaxiang , Li Pengfei , Sui Xin , Wang Yongan , Wang Liyun 
Published: June 2022

AbstractDysfunction of striatal dopaminergic circuits has been implicated in motor impairment and Parkinson’s disease (PD)-related circadian perturbations that may represent an early prodromal marker of PD. Cyclin-dependent kinase 5 (CDK5) negatively regulates dopamine signaling in the striatum, suggesting a critical role of CDK5 in circadian and sleep disorders. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing to produce mice with a dorsal striatum (DS)-specific knockdown (KD) of theCdk5gene (referred to as DS-CDK5-KD mice) and investigate its role in vivo. DS-CDK5-KD mice exhibited deficits in locomotor activity and disturbances in activity/rest behavior. Additionally, Golgi staining of neurons in the DS revealed that CDK5 deletion reduced dendrite length and the number of functional synapses, which was confirmed by significant downregulation of MAP2, PSD-95, and synapsin I. Correlated with this, DS-CDK5-KD mice displayed reduced phosphorylation of Tau at Thr181. Furthermore, whole-cell patch-clamp recordings of green fluorescent protein-tagged neurons in the striatum of DS-CDK5-KD mice revealed a decreased frequency of spontaneous inhibitory postsynaptic currents and altered excitatory/inhibitory synaptic balance. Notably, anterograde labeling showed that CDK5 KD in the DS disrupted long-range projections to the secondary motor cortex, dorsal and ventral thalamic nuclei, and basolateral amygdala, which are involved in the regulation of motor and circadian rhythms in the brain. These findings support a critical role of CDK5 in the DS in maintaining the striatal neural circuitry underlying motor functions and activity/rest associated with circadian rhythms that are perturbed in neurodegenerative disorders.
Specific Learning Disorders and Eating Disorders: an Italian retrospective study
Authors: Aruta Salvatore Ferdinando , Pruccoli Jacopo , Bandini Nicole , Rucci Paola , Parmeggiani Antonia 
Published: June 2022

Abstract
Background
Although Anorexia Nervosa (AN) patients show dysfunctional behaviour in information processing, visual and verbal memory performance, and different cognitive fields, regardless of their BMI, the literature on the correlations between Eating Disorders (ED) and Neurodevelopmental Disorders (NDD) does not provide conclusive data. Rather than a consequence of the mental disorder, cognitive dysfunctions may be a risk factor for AN.

Methods
Our retrospective study investigates the prevalence of Specific Learning Disorder (SLD) among patients with ED. We considered 262 patients being treated at the Emilia Romagna Feeding and Eating Disorders Outpatient Service in Bologna, Italy. We compared the results with the Italian reference values, according to the most recent data provided by the Italian Ministry of Education.

Results
We found that 25 patients out of 262 (9.54%) presented a comorbid diagnosis of SLD. This SLD prevalence is higher than the Italian reference values (4.9% in the school year 2018/19, p < 0.001). Comorbidity with SLD was significantly more frequent in males. A diagnosis of SLD was not associated with a higher frequency of any specific ED diagnosis or with psychiatric comorbidity in general. Positive family history for SLD was not significantly associated with either a positive family history for ED or a diagnosis of SLD.

Conclusions
This is the first Italian study to investigate the prevalence of SLD in ED patients during childhood and adolescence. Our data support previous research documenting that neuropsychological deficit could lead to the development of ED.
NSAIDs in sciatica (NIS): study protocol for an investigator-initiated multicentre, randomized placebo-controlled trial of naproxen in patients with sciatica
Authors: Grøvle Lars , Hasvik Eivind , Holst Rene , Haugen Anne Julsrud 
Published: June 2022

Abstract
Background
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to treat sciatica, despite insufficient evidence from placebo-controlled trials. NSAIDs may cause serious side effects; hence, there is a strong need to clarify their potential beneficial effects in patients with sciatica.

Methods
This is a multicentre, randomized, placebo-controlled, parallel-group superiority trial. Participants will be recruited among sciatica patients referred to outpatient clinics at hospitals in Norway who have radiating pain below the knee with a severity score of ≥ 4 on a 0–10 numeric rating scale and clinical signs of nerve root or spinal nerve involvement. The intervention consists of oral naproxen 500 mg or placebo twice daily for 10 days. Participants will report the outcomes and adverse events daily using an electronic case report form. The primary endpoint is change in leg pain intensity from baseline to day 10 based on daily observations. The secondary outcomes are back pain intensity, disability, sciatica symptom severity, rescue medication (paracetamol) consumption, opioid use, ability to work or study, 30% and 50% improvement in leg pain, and global perceived change of sciatica/back problem. The outcomes will be analysed using mixed effects models for repeated measurements. The total duration of follow-up is 12 (± 2) days.

Discussion
This trial aims to evaluate the benefits of naproxen, a non-selective NSAID, in patients with sciatica. No important differences in efficacy have been demonstrated between different NSAIDs in the management of musculoskeletal disorders; hence, the results of this trial will likely be applicable to other NSAIDs.

Trial registration
ClinicalTrials.gov NCT03347929. Registered on November 20, 2017.
Navigation programs relevant for African American men with prostate cancer: a scoping review protocol
Authors: Palmer Nynikka R. , Smith Ashley Nicole , Campbell Brittany A. , Andemeskel Ghilamichael , Tahir Peggy , Felder Tisha M. , Cicerelli Barbara 
Published: June 2022

AbstractBackgroundThe excess incidence and mortality due to prostate cancer that impacts African American men constitutes the largest of all cancer disparities. Patient navigation is a patient-centered healthcare system intervention to eliminate barriers to timely, high-quality care across the cancer continuum and improves health outcomes among vulnerable patients. However, little is known regarding the extent to which navigation programs include cultural humility to address prostate cancer disparities among African American men. We present a scoping review protocol of an in-depth examination of navigation programs in prostate cancer care—including navigation activities/procedures, training, and management—with a special focus on cultural context and humility for African American men to achieve health equity.MethodsWe will conduct comprehensive searches of the literature in PubMed, Embase, Web of Science, and CINAHL Complete, using keywords and index terms (Mesh and Emtree) within the three main themes: prostate cancer, patient navigation, and African American men. We will also conduct a search of the gray literature, hand-searching, and reviewing references of included papers and conference abstracts. In a two-phase approach, two authors will independently screen titles and abstracts, and full-text based on inclusion/exclusion criteria. All study designs will be included that present detailed data about the elements of navigation programs, including intervention content, navigator training, and/or management. Data will be extracted from included studies, and review findings will be synthesized and summarized.DiscussionA scoping review focused on cultural humility in patient navigation within the context of eliminating disparities in PCa care among African American men does not yet exist. This review will synthesize existing evidence of patient navigation programs for African American prostate cancer patients and the inclusion of cultural humility. Results will inform the development and implementation of future programs to meet the unique needs of vulnerable prostate cancer patients in safety net settings.Systematic review registrationPROSPERO 2021CRD42021221412
Economic burden of antibiotic-not-susceptible isolates in uncomplicated urinary tract infection: Analysis of a US integrated delivery network database
Authors: Shafrin Jason , Marijam Alen , Joshi Ashish V. , Mitrani-Gold Fanny S. , Everson Katie , Tuly Rifat , Rosenquist Peter , Gillam Michael , Ruiz Maria Elena 
Published: June 2022

Abstract
Background
Uncomplicated urinary tract infections (uUTIs) are one of the most common bacterial infections in the United States (US). Contemporary data are important for understanding the health economic impact of antimicrobial-resistant uUTIs. We compared the economic burden among patients with uUTI isolates susceptible or not-susceptible to the initial antibiotic prescription.

Methods
This retrospective cohort study utilized electronic health record data (1 July 2016–31 March 2020) from a large Mid-Atlantic US integrated delivery network database. Patients were females aged ≥ 12 years with a uUTI, who received oral antibiotic treatment and had ≥ 1 urine culture within ± 5 days of diagnosis. The primary outcome was the difference in healthcare resource use and costs (all-cause, urinary tract infection [UTI]-related) among patients with susceptible versus not-susceptible isolates during the 6 months after the index uUTI diagnosis. Secondary outcomes included: pharmacy costs, hospital admissions and emergency department visits, as well as the probability of uUTI progressing to complicated UTI (cUTI) between patients with susceptible and not-susceptible isolates. Patient outcomes were compared using 1:1 propensity score matching. Winsorized costs were adjusted to 2020 quarter 1 US dollars ($).

Results
A total of 2565 patients were eligible for analysis. The propensity score-matched sample comprised 2018 patients, with an average age of 44.0 and 41.0 years for the susceptible and not-susceptible populations, respectively. In the 6 months post-index uUTI event, patients with not-susceptible isolates had significantly more all-cause prescriptions orders (+ 1.41 [P = 0.001]), UTI-related prescriptions orders (+ 0.26 [P < 0.001]) and a higher probability of all-cause inpatient (+ 1.4% [P = 0.009]), outpatient (+ 6.1% [P = 0.006]), or UTI-related outpatient (+ 3.7% [P = 0.039]) encounters. Patients with a uUTI and an antibiotic-not-susceptible isolate were significantly more likely to progress to cUTI than those with susceptible isolates (odds ratio: 2.35 [confidence interval: 1.66–3.33; P < 0.001]). Over 6 months, patients with not-susceptible versus susceptible isolates had significantly higher all-cause costs (+ $426 [P = 0.031]) and UTI-related costs (+ $157 [P = 0.034]).

Conclusions
Patients with a uUTI caused by antibiotic-not-susceptible isolates had higher healthcare resource usage, costs, and increased likelihood of progressing to cUTI than those with antibiotic-susceptible isolates.
Prevalence of potential drug − drug interactions in the cardiothoracic intensive care unit patients in a Chinese tertiary care teaching hospital
Authors: Wang Haitao , Shi Haitao , Wang Na , Wang Yan , Zhang Li , Zhao Yujie , Xie Jiao 
Published: June 2022

Abstract
Background
With an increasing number of reviews describing clinically significant drug–drug interactions (DDIs), the scope and severity of interactions involving commonly used drugs in cardiothoracic intensive care units (CCUs) remain unclear. This study aims to identify risk factors and determine the incidence of potential DDIs in intensive care units.

Methods
DDIs were identified based on the profile of the prescribed drug and classified according to the Micromedex drug interaction database. Potential risk factors associated with DDIs have been identified.

Results
A total of 3193 medication episodes were evaluated, and 680 DDIs (21.3%) were found. A total of 203 patients were recruited into the study, with an average of 3.4 DDIs per patient [95% confidence interval (3.2 − 3.6)]. A total of 84.2% of the patients experienced at least one DDI. Anticoagulant and antiplatelet agents were involved in 33.5% (228/680) of the potential drug − drug interactions in the CCU. Univariate analysis and multiple logistic regression analysis showed that the age of the patient and the number of medications prescribed were significantly correlated with the occurrence of DDIs. In multiple linear regression analysis, the number of DDIs had a significant correlation only with the number of prescription drugs.

Conclusions
A high prevalence of DDIs was observed, especially in intensive care units without pharmacist intervention and computerized drug monitoring systems, highlighting the need for active surveillance to prevent potential adverse events.
Study on space diversity and influencing factors of Tunpu settlement in central Guizhou Province of China
Authors: Ge Hongyi , Wang Zhitai , Bao Yu , Huang Zongsheng , Chen Xintong , Wu Bin , Qiao Yunwei 
Published: June 2022

Abstract
The Tunpu settlements are the historical product of the co-evolution development of the unique geographical and cultural environment of Guizhou and the military defense policies of Ming Dynasty (1368–1644 AD), which created products such as the station troops and station farms. In this study, taking 10 Tunpu settlements in central Guizhou as the research objects, the space diversity of the Tunpu settlement and its influencing factors were analyzed based on the theory and calculation method of plant community species diversity. The results showed that: (1) On the whole, the space α-diversities of the military Tunpu settlements and the commercial Tunpu settlements were relatively high, with strong spatial similarity, while the residential Tunpu settlements had a lower degree of space α-diversity and significant difference. The space α-diversity of different types of the Tunpu settlement presents a variety of changes from the core protected areas to coordinated control areas. (2) There was a significant correlation between the spatial network and spatial morphological indicators and space β-diversity among the Tunpu settlement, and the stepwise regression showed that spatial morphological indicators had a strong explanatory power for the space β-diversity among the Tunpu settlements. (3) The space diversities of the Tunpu settlements were affected by the multiple synergies of natural environment, policy support, social-economic factors and cultural customs. Among them, policy factors and cultural factors were the dominant factors in the space diversity characteristics of the Tunpu settlements. By analyzing the space diversity law and its driving factors of the Tunpu settlements, this study could provide an important scientific basis for the protection planning and management of traditional settlements.
The forgotten appearance of metastatic melanoma in the small bowel
Authors: Mendes Serrao Eva , Joslin Emily , McMorran Victoria , Hough Caroline , Palmer Cheryl , McDonald Sarah , Cargill Emma , Shaw Ashley S. , O’Carrigan Brent , Parkinson Christine A. , Corrie Pippa G. , Sadler Timothy J. 
Published: June 2022

Abstract
Background
Melanoma is the most aggressive form of skin cancer, with a tendency to metastasise to any organ of the human body. While the most common body organs affected include liver, lungs, brain and soft tissues, spread to the gastrointestinal tract is not uncommon. In the bowel, it can present with a multitude of imaging appearances, more rarely as an aneurysmal dilatation. This appearance is classically associated with lymphoma, but it has more rarely been associated with other forms of malignancy.

Case presentation
We report a case series of three patients with aneurysmal dilatation in the small bowel (SB) confirmed to be due to metastatic melanoma (MM). All patients had non-specific symptoms; most times being attributed initially to causes other than melanoma. On CT the identified aneurysmal SB dilatations were diagnosed as presumed lymphoma in all cases. In two cases, the aneurysmal dilatation was the first presentation of metastatic disease and in two of the cases more than one site of the gastrointestinal tract was concomitantly involved. All patients underwent surgical resection with histological confirmation of MM.

Conclusions
Recognition of unusual SB presentation of MM, such as aneurysmal SB dilatation, is important to expedite diagnosis, provide appropriate treatment, and consequently improve quality of life and likely survival of these patients. As the most common cancer to metastasise to the SB and as a known imaging mimicker, MM should remain in any radiologist’s differential diagnosis for SB lesions with aneurysmal dilatation.