bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding clinical spectrum of PAICS deficiency: Comprehensive analysis of two sibling cases
Authors: Zikanova Marie , Weng Wen-Chin , Skopova Vaclava , Barešová Veronika , Liu Yao-Lin , Hsueh Hsueh-Wen , Chien Yin-Hsiu , Hwu Wuh-Liang , Souckova Olga , Hnizda Ales , Kmoch Stanislav , Lee Ni-Chung
Published: August 2024

De novo synthesis of purines (DNPS) is a biochemical pathway that provides the purine bases for synthesis of essential biomolecules such as nucleic acids, energy transfer molecules, signaling molecules and various cofactors. Inborn errors of DNPS enzymes present with a wide spectrum of neurodevelopmental and neuromuscular abnormalities and accumulation of characteristic metabolic intermediates of the DNPS in body fluids and tissues. In this study, we present the second case of PAICS deficiency due to bi-allelic variants of PAICS gene encoding for a missense p.Ser179Pro and truncated p.Arg403Ter forms of the PAICS proteins. Two affected individuals were born at term after an uncomplicated pregnancy and delivery and presented later in life with progressive cerebral atrophy, epileptic encephalopathy, psychomotor retardation, and retinopathy. Plasma and urinary concentrations of dephosphorylated substrates of PAICS, AIr and CAIr were elevated, though, in skin fibroblasts they remained undetectable. Both variants affect structural domains in SAICARs catalytic site and the oligomerization interface. In silico modelling predicted negative effects on PAICS oligomerization, enzyme stability and enzymatic activity. Consistent with these findings, affected skin fibroblast were devoid of PAICS protein and enzyme activity. This was accompanied by alterations in contents of other DNPS proteins, which had co-localized in granular structures that are characteristic of purinosome formation. Our observation expands the clinical spectrum of PAICS deficiency from recurrent abortions and fatal neonatal form to later onset neurodevelopmental disorders. The rarity of this condition may be based on poor clinical recognition and limited access to specialized laboratory tests diagnostic for PAICS deficiency.
Effects of temperature experienced across life stages on morphology and flight behavior of painted lady butterflies (Vanessa cardui)
Authors: Mesler Sarah P. , Mabry Karen E.
Published: August 2024

Background: With ongoing anthropogenic climate change, there is increasing interest in how organisms are affected by higher temperatures, including how animals respond behaviorally to increasing temperatures. Movement behavior is especially relevant here, as the ability of a species to shift its range is implicitly dependent upon movement capacity and motivation. Temperature may influence movement behavior of ectotherms both directly, through an increase in body temperature, and indirectly, through temperature-dependent effects on physiological and morphological traits that can influence movement.
Methods: Here, we investigate the influence of ambient temperature during two life stages, larval and adult, on body size and movement behavior of the painted lady butterfly (Vanessa cardui). We reared painted ladies to emergence at either a “low” (24 °C) or “high” (28 °C) temperature. At eclosion, we assessed flight behavior in an arena test, with half of the adults emerging from each rearing treatment tested at either the “low” or “high” temperature. We had a total of four treatment groups: the control (reared and tested at 24 °C), a consistently high temperature (reared and tested at 28 °C), and two treatments in which butterflies experienced flight tests at a temperature either higher or lower than the one at which they were reared. We measured adult body size, including wingspan, and determined flight speed, distance, and duration from video recordings.
Results: Adult butterflies that experienced the higher temperature during development were larger. We documented an interaction effect of rearing x testing temperature on flight behavior: unexpectedly, the fastest butterflies were those who experienced a change in temperature, whether an increase or decrease, between rearing and testing.
Conclusions: Individuals that experienced matching thermal environments flew more slowly, but for more time and covering more distance. Overall, the influence of body size per se on flight was minimal. We conclude that the potential role of “matching” thermal environments across life stages has been underinvestigated with regard to how organisms may respond to warming conditions.
Adapting Health Revenue Cycle Management Best Practices among Public or Private Healthcare providers in Saudi Arabia: A Pilot Study
Authors: Yafi Ola Al , Albabtain Monirah A. , Arafat Amr , Jassas Abdullatif Bin
Published: August 2024

The literature lacks evidence of scoring systems in health revenue cycle management (HRCM) assessment in Saudi Arabia. We established a gap analysis scoring system to classify healthcare providers' HRCM readiness. This pilot study aimed to assess the rate of adapting health revenue cycle management best practices among public or private healthcare providers in Saudi Arabia. This pilot study included ten healthcare providers in Saudi Arabia. The providers were assessed during the period from August 2022 to May 2023. HRCM components were assessed are contract management, pre-service, time-of-service, and post-service. Contract management and pre-service assessment found that all of the healthcare providers had missed some or most of sub-major functions. For Time-of-service, all healthcare providers required comprehensive gap analysis, and establishment of policies and procedures. Post-service was assessed in seven healthcare providers while absent in three. All healthcare providers required training and activation of reporting protocol and KPIs. Overall assessment revealed that one HCP had a low classification, seven had a moderate classification, and two had a high classification. All healthcare providers have a part that can be enhanced by training, comprehensive gap analysis, policies and procedures, ongoing monitoring, patient satisfaction research and developing health information systems.
The changes of serum uric acid and total cholesterol are associated with the severity of Crohn's disease：A cross-sectional study
Authors: Ni Jinchun , Tang Yunna , Hu Yiqun , Liu Lupeng , Lin Yumei , Ouyang Hui , Xie Chenxi
Published: August 2024

Background: More serological indicators with convenient and sensitive characteristics are needed in clinical practice to help determine the severity of Crohn's disease (CD).
Methods: One hundred and forty-one CD patients and ten health volunteers were included in this retrospective study. The serum urid acid (SUA) and indicators related to lipid metabolism were detected within one week before endoscopic and CT enterography (CTE) examinations. Patients were divided into groups according to CDAI（Crohn's disease activity index）scores.
Results: Patients were divided into two groups, and no patients with severe CD were included in the study. SUA values were increased in CD patients when compared to that of control group(p=0.033). The values of TC, apo A1, HDL-C and LDL-C were decreased in CD patients(p<0.05). The TC and LDL-C values were decreased in moderate CD group when compared to that of mild/remission group (p<0.01). Lower SUA and TC were independent risk factors for serious disease (for SUA, OR=2.319, 95%CI 1.067-5.041, p=0.034, for TC, OR=5.231, 95% CI 2.180-12.552, p<0.001). Both SUA and TC were correlated to CDAI scores negatively(p<0.05), and TC was also correlated to CRP negatively (r=-0.250, p=0.003). The sensitivity of TC and SUA was fine in distinguishing patients with moderate CD.
Conclusions: For CD patients, SUA and TC levels were associated with clinical activity. Detection of the two serum indicators may be conducive to screening serious disease.
HMGB-1 as a predictor of massive transfusion protocol activation in major trauma: a prospective observational study
Authors: Frelich Michal , Bebej Marek , Pavlíček Jan , Burša Filip , Vodička Vojtěch , Švagera Zdeněk , Kondé Adéla , Jor Ondřej , Sklienka Peter
Published: August 2024

Background
Massive bleeding causes approximately 50% of deaths in patients with major trauma. Most patients die within 6 hours of injury, which is preventable in at least 10% of cases. For these patients, early activation of the massive transfusion protocol (MTP) is a critical survival factor. With severe trauma, high-mobility group box 1 (HMGB-1, i.e., amphoterin) is released into the blood, and its levels correlate with the development of a systemic inflammatory response, traumatic coagulopathy, and fibrinolysis. Previous work has shown that higher levels of HMGB-1 are associated with a higher use of red blood cell transfusions. We conducted a single-center, prospective, observational study to assess the value of admission HMGB-1 levels in predicting activation of MTP in the emergency department.
Methods
From July 11, 2019, to April 23, 2022, a total of 104 consecutive adult patients with severe trauma (injury severity score > 16) were enrolled. A blood sample was taken at admission, and HMGB-1 was measured. MTP activation in the emergency department was recorded in the study documentation. The total amount of blood products and fibrinogen administered to patients within 6 hours of admission was monitored.
Results
Among those patients with massive bleeding requiring MTP activation, we found significantly higher levels of HMGB-1 compared to patients without MTP activation (median [interquartile range]: 84.3 µg/L [34.2–145.9] vs. 21.1 µg/L [15.7–30.4]; p < 0.001). HMGB-1 level showed good performance in predicting MTP activation, with an area under the curve of 0.84 (95% CI 0.75–0.93) and a cut-off value of 30.55 µg/L. HMGB-1 levels correlated significantly with the number of red blood cell units (rs [95% CI] 0.46 [0.28–0.61]; p < 0.001), units of fresh frozen plasma (rs 0.46 [0.27–0.61]; p < 0.001), platelets (rs 0.48 [0.30–0.62]; p < 0.001), and fibrinogen (rs 0.48 [0.32–0.62]; p < 0.001) administered in the first 6 hours after hospital admission.
Conclusions
Admission HMGB-1 levels reliably predict MTP activation in the emergency department and correlate with the amount of blood products and fibrinogen administered during the first 6 hours of hemorrhagic shock resuscitation.
Trial registration
NCT03986736 Registration date: June 4, 2019
Pharmacokinetics-pharmacodynamics of first line antitubercular drugs: A comparative study in tuberculosis patients with and without concomitant diabetes mellitus
Authors: Mondal Sourav , Roy Vandana , Meshram Girish Gulab , Khanna Ashwani , Velpandian Thirumurthy , Garg Sandeep
Published: August 2024

Purpose
To observe the variability in the plasma concentrations and pharmacokinetic-pharmacodynamic (PK-PD) profile of first-line antitubercular drugs in pulmonary tuberculosis (TB) patients with and without diabetes mellitus (DM).
Methods
Newly diagnosed pulmonary TB patients aged 18–60 with or without DM were included in the study. Group I (n = 20) included patients with TB, whereas Group II (n = 20) contained patients with TB and DM. After 2 weeks of therapy, plasma concentrations and other PK-PD parameters were determined. The improvement in clinical features, X-ray findings, sputum conversion and adverse drug reactions (ADRs) were measured after 2 months of ATT.
Results
Isoniazid displayed non-significantly higher plasma concentrations in diabetic patients, along with a significantly (P < 0.05) longer elimination half-life (t1/2). Rifampicin plasma concentration at 4, 8, and 12 h were significantly (P < 0.05) lower and it displayed significantly (P < 0.05) lower area under curves (AUC0 − 12 and AUC0−∞), shorter t1/2, higher clearance (Cl) and a lower AUC0−∞/MIC ratio in diabetic patients. Pyrazinamide and ethambutol showed non-significantly higher plasma concentrations, AUC0 − 12, AUC0−∞, and t1/2 in diabetic patients. The improvement in clinical features, X-ray findings, sputum conversion, and ADRs were comparable in both the groups.
Conclusions
The presence of DM in TB patients affects the PK-PD parameters of isoniazid, rifampicin, pyrazinamide and ethambutol variably in the Indian population. Studies in a larger number of patients are required to further elucidate the role of DM on the PK-PD profile of first-line antitubercular drugs and treatment outcomes in TB patients with concomitant DM.
Trial registration number
CTRI/2021/08/035578 dated 11/08/2021.
Understanding the multidimensional structure of poverty in Argentine households
Authors: Pizarro Adrián Maximiliano Moneta
Published: August 2024

A question of great interest for the design of multidimensional poverty measures is whether they should include a monetary poverty indicator. One of the most common arguments for keeping income poverty separate from non-monetary poverty is that they reflect different dimensions of the phenomenon. This paper explores the multidimensional structure of poverty in Argentina and investigate whether monetary poverty should be considered as another indicator of multidimensional poverty using generalized structural equation modeling (GSEM) methods. Using categorical data from a household survey, a generalized confirmatory factor analysis model (GCFA) and a GSEM with a second order factor are analyzed. The GCFA model postulates the traditional assumption that monetary poverty is just another dimension of poverty, while the GSEM supports the hypothesis that monetary poverty is a cause of non-monetary poverty. The results show that the data fit well in both cases, but that it is more plausible to consider that the non-monetary factors are indicators of a higher order dimension and that this non-monetary poverty, as a whole, is explained by monetary poverty. Finally, the implications of these results for the design of multidimensional poverty indicators in Argentina are discussed.
JEL Classification: C38, I32
Automated detection of Kaposi sarcoma-associated herpesvirus infected cells in immunohistochemical images of skin biopsies
Authors: Hussain Iftak , Boza Juan , Lukande Robert , Ayanga Racheal , Semeere Aggrey , Cesarman Ethel , Martin Jeffrey , Maurer Toby , Erickson David
Published: August 2024

Immunohistochemical (IHC) staining for the antigen of Kaposi sarcoma-associated herpesvirus (KSHV), latency-associated nuclear antigen (LANA), is helpful in diagnosing Kaposi sarcoma (KS). A challenge, however, lies in distinguishing anti-LANA-positive cells from morphologically similar brown counterparts. In this work, we demonstrate a framework for automated localization and quantification of LANA positivity in whole slide images (WSI) of skin biopsies, leveraging weakly supervised multiple instance learning (MIL) while reducing false positive predictions by introducing a novel morphology-based slide aggregation method. Our framework generates interpretable heatmaps, offering insights into precise anti-LANA-positive cell localization within WSIs and a quantitative value for the percentage of positive tiles, which may assist with histological subtyping. We trained and tested our framework with an anti-LANA-stained KS pathology dataset prepared by pathologists in the United States from skin biopsies of KS-suspected patients investigated in Uganda. We achieved an area under the receiver operating characteristic curve (AUC) of 0.99 with a sensitivity and specificity of 98.15% and 96.00% in predicting anti-LANA-positive WSIs in a test dataset. We believe that the framework can provide promise for automated detection of LANA in skin biopsies, which may be especially impactful in resource-limited areas that lack trained pathologists.
Decreased Expression of hsa-miR-142-3p and hsa-miR-155-5p in Patients with Common Variable Immunodeficiency and Involvement of Their Target Genes and Biological Pathways
Authors: Ranjbarnejad Tayebeh , Gholaminejad Alieh , Sherkat Roya , Salehi Mansoor , Sharifi Mohammadreza
Published: August 2024

Background
Common variable immunodeficiency (CVID) is a heterogeneous disorder, and its pathogenesis is often unknown. Monogenic mutations have not been identified in the majority of CVID patients and the pathogenesis process is often unknown. Epigenetic modifications may be involved in unresolved patients. MiR-142 and miR-155 were identified as immune system modulators and are dysregulated in autoimmune and inflammatory diseases.
Methods
We assessed hsa-miR-142-3p and hsa-miR-155-5p expression in CVID patients and identified experimentally validated targets of these miRNAs. We constructed a protein‒protein interaction (PPI) network from the common targets of two miRNAs and determined the hub genes. The expression of the hub genes was investigated in the GEO datasets. Gene Ontology (GO) and pathway enrichment analysis were performed for the target genes.
Results
hsa-miR-142-3p and hsa-miR-155-5p expression was significantly reduced in CVID patients. Evaluation of the PPI network revealed several hub genes in which pathogenic mutations have been reported in PIDs/CVID, and other hub genes directly contribute to immune responses and the pathophysiology of PIDs. Expression analysis of the hub genes revealed that some of them were significantly dysregulated in CVID patients. Pathway enrichment analysis indicated the involvement of the FoxO-mediated signaling pathway, TGF-β receptor complex, and VEGFR2-mediated vascular permeability.
Conclusion
Considering the dysregulation of hsa-miR-142-3p and hsa-miR-155-5p in CVID and the known role of their target genes in the immune system, their involvement in the pathogenesis of CVID can be suggested.
The Prevalence and Factors Affecting Lower Urinary Tract Symptoms in Young Female University Students
Authors: ŞEN Mehmet Ali , AK Eda YAKIT , AYDIN Abdulkadir
Published: August 2024

Aim
The objective of this study was to assess the prevalence and risk factors associated with Lower Urinary Tract Symptoms (LUTS) among female university students.
Method
This cross-sectional survey study included 397 female university students aged 18 years and older. Participants completed self-administered questionnaires that assessed sociodemographic and lower urinary tract symptoms (LUTS) characteristics, as well as the Bristol Female Lower Urinary Tract Symptoms Scale (BFLUTS).
Results
The study found that the mean age of the students was 20.89 ± 4.02 years. Among the female students, 37% (n:147) did not experience urinary incontinence (UI), while 25.4% (n:101) experienced stress UI. The BFLUTS total score was low, with a mean of 9.63 ± 6.49. Risk factors associated with LUTS in female university students include smoking, presence of chronic disease and chronic constipation, cleaning from front to back after toileting, frequent urinary tract infections, poor toilet hygiene, enuresis as a child, and maternal history of urinary incontinence.
Conclusion
It has been determined that female university students experience a considerable level of lower urinary tract symptoms (LUTS). To prevent the development of negative symptoms in the future, it is important to identify the associated risk factors and increase knowledge and awareness of the problem.
Does supervised administration based on routine soil-transmitted helminth surveillance reduce hookworm infection in villagers in Eastern China? A pragmatic trial
Authors: Hu Danbiao , Gu Minxia , Xu Wenjie , Wang Bin , Yu Yijiang , Wang Xiaoxiao , Yu Kegen , Ruan Wei
Published: August 2024

Background: Despite significant progress has been made in China through decades to reduce the prevalence of hookworm, including deworming and surveillance, the burden of this disease is still heavy in mountainous regions. We conducted a community-based intervention trial in Ninghai, a mountainous coastal county in Southeastern China, to explore a more efficient method of tackling hookworm infection in economically developed but geographically isolated areas.
Methods: Six villages were selected for this trial. Considering of their historical prevalence and demographic similarity. three villages assigned to the intervention group and three to the control group. Control methods of intervention groups involved deworming medicine and health education, which was deliberately provided by well-trained healthcare staffs. In control sites, only health education was provided while parasitic survey, the result of parasitic survey was informed if the result was positive, but medicine needed to be purchased by the patient. Our primary metrics was hookworm prevalence in residents, determined by modified Kato-Katz method. The infection intensity was also presented by eggs per gram of faeces (EPG).
Results: The analysis included 1330 participants in control sites and 1270 participants in intervention sites. The relative reduction in hookworm prevalence was significant in the intervention sites (81.99%, 95% CI: 60.15-91.86) comparing to the control sites (51.84%, 3.34-76.01). The relative reduction in hookworm infection intensity was not significantly different between the intervention sites and control sites (64.83%, 95% CI：-237.18-96.33 vs. 77.23%, 95% CI:-94.33-97.33). However, the prevalence of light and moderate intensity group, the relative reduction in intervention groups were greater than that in control groups (light infection group: 83.34%, 95% CI:60.87-92.91 vs. 45.8%, 95%CI: -14.21-74.28; moderate infection group: 100% vs. 62.06%, 95%CI: -263.82-96.04).
Conclusions: Notable for its ease of implementation, cost-effectiveness, and high participant compliance, the program leverages the established rural STHs surveillance system in China to promptly administer medication among infected individuals. Its potential of replicating over the nationwide and referring as an attempt for global efforts underscores its significance in combatting hookworm infection efficiently and economically.
Reversal of endocrine resistance via N6AMT1-NEDD4L pathway-mediated p110α degradation
Authors: Cui Yukun , Ji Likeng , Chen Jiongyu , He Li-Fang , Zhang Fan , Deng Zihao , Lin Jiediao , Qi Zhaochang , Luo Xi , Giuliano Armando , Cui Xiaojiang , Lin Stanley Li
Published: August 2024

Approximately 70% of breast cancer (BC) cases are luminal-type (estrogen receptor-positive, ER+), suitable for endocrine therapy with tamoxifen as the most commonly used drug. However, about 30% of these patients develop tamoxifen resistance due to various mechanisms, primarily involving PI3K pathway activation through mutations or unknown pathways. Here, we discover, via bioinformatics analysis and clinical samples, that N6 adenine–specific DNA methyltransferase 1 (N6AMT1) is highly expressed in luminal breast cancer but downregulated in tamoxifen-resistant (TamR) BC cells. ChIP-qPCR and luciferase reporter assays showed that FOXA1 binds to the N6AMT1 and enhances transcription. In TamR models, FOXA1 and N6AMT1 are downregulated, increasing p110α protein levels (but not mRNA), phospho-AKT levels, and tamoxifen resistance. In vivo, N6AMT1 overexpression enhanced tamoxifen sensitivity, while knockdown reduced it; this sensitivity could be restored with the p110α inhibitor A66. Clinically, decreased N6AMT1 expression correlates with poor prognosis in luminal BC patients. In TamR BC organoids, combining tamoxifen with A66 further reduced growth compared to either treatment alone. Mechanistically, increased p110α levels result from inhibited degradation by E3 ubiquitin ligase NEDD4L. These findings suggest N6AMT1 as a potential luminal breast cancer biomarker and highlight the FOXA1-N6AMT1-NEDDL4-p110α pathway as a therapeutic target to sensitize cells to tamoxifen.
Spatial and temporal distribution of ticks and associated pathogens collected from pet dogs in Spain throughout one year
Authors: Estrada-Peña Agustín , Burgio Federica , Fernández-Ruiz Natalia
Published: August 2024

Background: Ticks feeding on pets represent a serious health risk because of the direct effects produced on hosts and as vectors of zoonotic pathogens. Human actions on the landscape, the presence/absence of wildlife, and the trend toward a less predictable and warmer climate are transforming the distribution of ticks on dogs. We investigated the faunal composition and the distribution of ticks in pet dogs across the biogeographical Spanish territory, including the Canary Islands.
Methods: Overall, 24 veterinary practices collaborated to randomly collect ticks from cats and dogs monthly (June 2021 to July 2022). Veterinary practices were selected according to the biogeographical regions of Spain, aiming not only for a spatial pattern, but for ecological preferences of the ticks. Ticks were morphologically identified, and the pathogens within individual ticks were identified by standard molecular methods. The owner’s postal code defined the area of residence.
Results: In total, 299 ticks belonging to 13 species, plus a few immature Hyalomma spp., were identified. Eleven specimens were damaged, preventing morphological identification. The dominant species were Rhipicephalus sanguineus s.l., Dermacentor reticulatus and Ixodes hexagonus. While R. sanguineus s.l. is prevalent throughout Spain, the other species appeared only in the northern (colder and wetter) regions of Spain. Ehrlichia sp., Babesia sp. and two strains of Rickettsia massiliae were found in the ticks, plus the anecdotal presence of Anaplasma ovis. There was a lack of correlation between some animal traits, including age and sex, with parasitism. Dogs spending most of their time in a garden or in fields had a propensity to be more parasitized. The most abundant tick species were consistently linked to biogeographical areas (with corresponding climatic conditions) in the target territory.
Conclusions: This survey of randomly sampled pet dogs showed a year-round tick infestation risk. The survey supports the widespread distribution of R. sanguineus s.l. and its winter activity in most of the Spanish territory. Other common species of ticks in Europe (like Ixodes ricinus) are less common in Spain. Mixed species infestations were never observed. These results underpin the need for year-round tick control on dogs even during the winter months.
Characterization of Cannabis Usage in Individuals with Non-Cancer Chronic Pain in the State of Maine Using the Behavioral Risk Factor Surveillance System (BRFSS)
Authors: Bordonaro Rachel , Bean Elizabeth N. , Cao Ling
Published: August 2024

Background
One in 3 Mainers experiences chronic pain. Maine legalized medical and recreational cannabis usage in 2009 and 2016, respectively. To assess marijuana usage in Mainers with chronic pain, we obtained data from Maine’s Behavioral Risk Factor Surveillance System (BRFSS), an annual anonymous survey, from 2017 to 2020. Maine’s BRFSS began asking frequency of marijuana usage in 2017, followed by ways of use and reasons for use starting in 2020.
Methods
We identified individuals with chronic pain as those that reported having a rheumatoid condition diagnosis, and controls as those who reported no such conditions. To focus on non-cancer chronic pain, we excluded individuals that had previous cancer diagnoses. For each of the three separate marijuana questions, we eliminated those that answered “don’t know/unsure” or “refused” for the question of interest or their sex. This resulted in 11,360 individuals in the pain group vs. 19,798 individuals in the control group. Data were stratified by sex and analyzed in Microsoft Excel and SigmaPlot.
Results
We observed an increase of high users (21–30/last 30 days) and reduction of non-users for both sexes from 2017 to 2020, which was significant in controls (p < 0.05). The average age of marijuana users was lower regardless of sex or pain status compared to non-users (p < 0.05). Regardless of pain status, although smoking was the most used consumption method, more males tended to smoke marijuana while more females tended to eat it (p < 0.01). Individuals with pain, regardless of sex, were more likely to respond, “use it some other way” (p < 0.01). Respondents of both sexes with chronic pain and females, regardless of pain status, reported more medicinal usage (p < 0.001).
Conclusions
Since the legalization of marijuana, Mainers have started to use it more frequently. High users are generally younger than non-users. Females and chronic pain sufferers are more likely to use marijuana for medicinal reasons, and in non-traditional ways. Further characterization is warranted as cannabis usage becomes more prevalent in individuals both with and without chronic pain.
Clinical Management and Treatment Outcomes of Prostatic Abscess in a Tertiary Care Center
Authors: Ngo Xuan Thai , Nguyen Hoai Phan , Ly Hoai Tam , Thai Minh Sam , Chau Quy Thuan , Hoang Khac Chuan , Thai Kinh Luan , Le Nhut Trung , Choi Se Young , Tiong Ho Yee , Nguyen Tuan Thanh
Published: August 2024

Background
Prostatic abscess (PA) is an uncommon but serious urological emergency with a high mortality rate if not properly treated. It can lead to severe complications, including urosepsis and death. Diagnosing and treating PA remains challenging due to limited comparative studies on treatment modalities.
Objective
This study aims to characterize the clinical features and evaluate the treatment outcomes of prostatic abscesses treated at our center.
Methods
This retrospective study describes a case series of patients hospitalized with PA at our hospital from January 2017 to April 2020.
Results
Seventy-six cases of PA were confirmed using transrectal ultrasonography (TRUS), MRI, or CT scan. The mean age was 51.58 years (range 24 to 85). The most common predisposing factors were diabetes mellitus, urinary tract infections, and immunodeficiency. Presenting symptoms included lower urinary tract symptoms (67%), fever and chills (47%), and perineal pain (32%). Digital rectal examination revealed a severely tender prostate with areas of fluctuation in two-thirds of cases. Single abscess cavities were found in 36.84% of cases, while 63.16% had multiple cavities. Bacteria were isolated from urine, pus, and blood in 31.34%, 58.2%, and 19.6% of cases, respectively, with E. coli and Burkholderia pseudomallei being predominant pathogens. Mycobacterium tuberculosis was found in the pus of 4 out of 45 cases. Management included conservative treatment in 5 cases (6.58%) and surgical interventions in most cases: open cystostomy with abscess drainage (50%), TRUS-guided aspiration (15.79%), and transurethral resection deroofing (23.68%). Successful treatment was achieved in 93% of cases.
Conclusion
Prostatic abscess is a serious infection with high mortality. Early diagnosis, appropriate antibiotic therapy, and surgical intervention are crucial for successful treatment. Empirical antibiotic decisions should adhere to the guidelines of each medical facility.
Platelet Aggregation Test is Useful for Predicting Postprocedural Bleeding after Gastric Endoscopic Submucosal Dissection under Continuous Antiplatelet Agents
Authors: Hirata Shoichiro , Iwamuro Masaya , Takenaka Ryuta , Kawai Daisuke , Kagawa Daiki , Yamamoto Takashi , Ishida Masaya , Miyamoto Kazuya , Okamoto Yuki , Kumahara Kana , Takahara Masahiro , Hori Keisuke , Tsugeno Hirofumi , Fujiki Shigeatsu , Otsuka Motoyuki
Published: August 2024

Objectives:
This study aimed to assess the correlation between platelet aggregation levels measured using aggregometry and the incidence of postprocedural bleeding after endoscopic submucosal dissection (ESD) in patients with gastric neoplasms receiving antiplatelet agents.
Methods:
Between April 2013 and March 2020, 69 patients (47 men, 22 women) underwent gastric ESD for 82 lesions while continuously receiving antiplatelet agents. Platelet aggregation levels were assessed before ESD by using an aggregometer-based grading-type score (G-type score), reflecting the status of platelet aggregation.
Results:
Patients were administered single antiplatelet agents, such as aspirin (n = 32), cilostazol (n = 14), or thienopyridine derivatives (n = 10), while other patients received multiple antiplatelet agents (n = 13). En-bloc resection was achieved in all cases, and R0 resection was accomplished in 81 lesions (98.8%). Post-ESD bleeding was observed in nine patients. When the G-type score equal to or lower than 0 was determined as an indicator of post-ESD bleeding, the sensitivity was 100% and specificity was 28%. Multivariate analysis revealed that the G-type score equal to or lower than 0 and tumor diameter ≥ 35 mm were significant risk factors for predicting bleeding following gastric ESD.
Conclusions:
The platelet aggregation test is a promising marker for predicting the bleeding risk after gastric ESD in patients receiving antiplatelet agents.
Uniform impact on individual megakaryocytes is essential for efficient in vitro platelet production
Authors: Strassel Catherine , Dasgupta Andrei K Garzon , Pongerard Anais , Mallo Lea , Michel Anita , Lanza Francois , Boiron Olivier , Knapp Yannick
Published: August 2024

Different approaches are being developed to efficiently produce in vitro platelets from cultured megakaryocytes to meet the constant demand of platelet transfusion and serve for research purposes. Recent works have shown that turbulence and periodic stress can significantly enhance platelet yield. Here we have developed and characterized a platelet production device that takes in account these properties. This device is based on the Taylor-Couette reactor in which a suspension is confined and sheared between two concentric cylinders. We have demonstrated that such a system allows obtaining high number of in vitro platelets per megakaryocyte with native-like morphology and functional properties. Using the combination of in silico and in vitro techniques, we claimed that overall turbulent conditions are not sufficient for efficient platelet release, and highlighted the importance of the uniform impact of flow on each megakaryocyte, a property that must be taken into account along with general flow characteristics when designing platelet release bioreactors. In addition, we have demonstrated that our system can be scaled up to large volumes without loss of efficiency, a significant advantage for the industrialization of platelet culture. In conclusion, we have developed a platelet production device with a predictable and highly precise effect on each megakaryocyte.
Early prediction model of pyonephrosis caused by calculi based on imaging omics combined with clinical variables
Authors: Yan Yongchao , Liu Yunbo , Guo Yize , Li Bin , Li Yanjiang , Wang Xinning
Published: August 2024

Objective:
This retrospective aims to develop a comprehensive predictive model based on CT radiomic features and clinical parameters, facilitating early preoperative diagnosis of pyonephrosis.
Methods:
Clinical and radiological data from 311 patients treated for upper urinary tract stones with obstructive pyelohydronephrosis, between January 2018 and May 2023, were retrospectively collected. Univariate and multivariate logistic regression analyses were conducted on clinical data to identify independent risk factors for pyonephrosis. A clinical model was developed using logistic regression. The 3D Slicer software was employed to manually delineate the region of interest (ROI) in the preoperative CT images, corresponding to the area of pyelohydronephrosis, for feature extraction. The optimal radiomic features were selected to construct radiomic models and calculate the radiomic score (Radscore). Subsequently, a combined clinical-radiomic model—the nomogram—was established by integrating the Radscore with independent risk factors.
Results:
Univariate and multivariate logistic regression analyses identified cystatin C, Hounsfield Unit (HU) of Pyonephrosis, history of ipsilateral urological surgery, and positive urine culture as independent risk factors for pyonephrosis (P<0.05). Fourteen optimal radiomic features were selected from CT images to construct four radiomic models, with the Naive Bayes model demonstrating the best predictive performance in both training and validation sets. In the training set, the AUCs for the clinical model, radiomic model, and nomogram were 0.902, 0.939, and 0.991, respectively; in the validation set, they were 0.843, 0.874, and 0.959. Both calibration and decision curves showed good agreement between the predicted probabilities of the nomogram and the actual occurrences.
Conclusion:
The nomogram, constructed from CT radiomic features and clinical variables, provides an effective non-invasive predictive tool for pyonephrosis, surpassing both clinical and radiomic models.
High intensity in interspinous ligaments: a diagnostic sign of lumbar instability and back pain for degenerative lumbar spondylolisthesis
Authors: jiang Jiang , Chen min , Huang ding-an , Luo jun-jie , Han jian-bang , Hu min , Wang ying-feng
Published: August 2024

Background: To investigate the clinical significance of high intensity in interspinous ligaments at the affected segment in degenerative lumbar spondylolisthesis (DLS), as well as to determine the most effective diagnostic modalities for evaluating segmental instability.
Methods: This study reviewed a consecutive series of patients with L4/5 DLS between July 2023 and December 2023. The enrolled patients were divided into two groups based on the presence or absence of high intensity signals in interspinous ligaments: the higher group ( Group H), and non-higher group (Group NH). Translational and angular motion was determined by using flexion and extension (FE) radiographs or an sitting lumbar lateral radiograph with a supine sagittal MR image (combined, S-MR). Five-repetition sit-to-stand test (5R-STS) were employed to evaluate patients objective functional impairment (OFI).
Results: Overall, 73 patients were enrolled in this study, and there were 22 (30.1%) patients in group H and 51(69.9%) patients in group NH, with an average age of 60.3 ± 8.1 years. The patients in Group H exhibited significantly longer 5R-STS times and serious OFI compared to those in Group NH. Compared to Group NH, Group H exhibited significantly higher SP in the sitting position (21.8% vs 16.7%; P < 0.001*), while no significant differences were observed in the upright, flexion, extension, and supine MRI positions (all P values > 0.05). In Group H,“instability” was recognized in 77.3 % of patients using S-MR versus 40.9 % patients using FE (P < 0.001); While in Group NH, no significant difference was observed in the incidence of“instability”between FE and s-MR (37.3% vs. 31.4%, P=0.53). Overall, a significantly higher incidence of instability was found in Group H compared to Group NH (77.3 % vs .37.3 %, P <0 .001*).
Conclusions.DLS with a high intensity within the interspinous ligaments is a distinct subgroup associated with segmental instability, the combination of 5R-STS and S-MR should be regarded as the most clinically relevant approach for assessing OFI and lumbar instability.
Aerobic Exercise and Cognitive Function in Chronic Severe Traumatic Brain Injury Survivors: A Within-Subject A-B-A Intervention Study
Authors: López Lidia Pérez , Coll-Andreu Margalida , Torras-Garcia Meritxell , Font-Farré Manel , Oviedo Guillermo R. , Ortis Lluis Capdevila , Guerra-Balic Myriam , Portell-Cortés Isabel , Costa-Miserachs David , Morris Timothy P.
Published: August 2024

Background
Following acute and sub-acute rehabilitation from severe traumatic brain injury (TBI), minimal to no efficacious interventions to treat ongoing cognitive deficits are available. Aerobic exercise is a non-invasive behavioral intervention with promise to treat cognitive deficits in TBI populations.
Methods
In this within-subject A-B-A study design, we incorporated 20-weeks of supervised aerobic exercise interventions delivered three times per week (Phase B) between participants typical rehabilitation schedules (Phases A). We further tested if participation in supervised aerobic exercise increased participants daily physical activity (PA) levels using waist-worn actigraphy.
Results
Five of six participants increased trail-making test part B by more than 10% pre-to-post phase B, with three of six making a clinically meaningful improvement (+ 1SD in normative scores). Linear mixed effects models showed a significant main effect of time at the group level with significant improvement in TMT-B pre-to-post exercise and no significant effect in other planned comparisons (pre-exercise to baseline nor follow-up to post-exercise) indicating that the addition of the intervention improved performance that was not due to practice effects. Statistically significant increases in daily moderate-to-vigorous PA were also seen during phase B compared to Phase A with three of six individuals making a significant behavior changes when analyzed at the individual level.
Conclusions
The addition of supervised aerobic exercise to typical rehabilitation strategies in chronic survivors of severe TBI can improve executive set shifting abilities and increase voluntary daily PA levels.
Trial Registration
ISRCTN17487462.
Peripheral CD4 (+) T Cell Immunity and Brain Microglial Activation Associated with Cognitive Heterogeneity in Aged Rats
Authors: Yu Lian , Liu Miao-Miao , Guan Mei-Qi , Wang Rui , Yang Xiao-Rong , Zhang Xiu-Min , Wei Jing-Jing , Wu Shu-Fen , Gu Hong , Fu Qiang , Guo Jun-Hong , Li Yan-Li
Published: August 2024

Cognitive decline is a critical hallmark of brain aging. Although aging is a natural process, there is significant heterogeneity in cognition levels among individuals; however, the underlying mechanisms remain uncertain. In our study, we classified aged male Sprague-Dawley rats into aged cognition-unimpaired (AU) group and aged cognition-impaired (AI) group, by using an attentional set-shifting task. The transcriptome sequencing results of medial prefrontal cortex (mPFC) demonstrated significant differences in microglial activation and inflammatory response pathways between the two groups. Specifically, compared to AU rats, AI rats exhibited a greater presence of CD86-positive microglia and major histocompatibility complex class II (MHC-II)-positive microglia, along with elevated inflammatory molecules, in mPFC. Conversely, AI rats exhibited a reduction in the amount of microglia expressing CD200R and the anti-inflammatory molecules Arg-1 and TGF-β. Additionally, peripheral blood analysis of AI rats demonstrated elevated levels of Th17 and Th1 cells, along with proinflammatory molecules; however, decreased levels of Treg cells, along with anti-inflammatory molecules, were observed in AI rats. Our research suggested that peripheral Th17/Treg cells and central microglial activation were associated with cognitive heterogeneity in aged rats. This may provide a new target for healthy aging.
Stress Hyperglycemia ratio in the prediction of 1-year outcomes in patients with acute myocardial infarction: A retrospective large sample cohort study
Authors: Yan Ning , Wu Peng , Zhang Zhengjun , Wang Mohan , Ma Ali , Chen Dapeng , Jia Shaobin , Ma Xueping , Li Xiaocheng , Ma Juan
Published: August 2024

Background Stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is linked to the poor clinical outcomes in patients with coronary artery disease (CAD). Nonetheless, the exploration of SHR's relationship with the prognosis of Acute Myocardial Infarction (AMI) remains scant. Therefore, this study aims to elucidate the connection between SHR and the 1-year clinical outcomes following AMI through a large cohort design analysis. Methods In this retrospective study 4012 patients who were diagnosed with AMI were consecutively enrolled from General Hospital of Ningxia Medical University(2016–2019). These patients were stratified into three distinct groups according to the tertiles of the SHR: Group T1 (SHR < 0.90, n = 1337), Group T2 (0.90 ≤ SHR < 1.11, n = 1337), and Group T3 (SHR ≥ 1.11, n = 1338). All patients were clinically followed for 1-years to collect major adverse cardiovascular events (MACEs), which included all-cause death, nonfatal myocardial infarction (MI), rehospitalization for angina, rehospitalization for heart failure (RHF) and stroke. After controlling for different confounding factors, cox regression models and restricted quadratic splines were used to investigate the relationship between SHR and 1-years clinical outcomes. Results During a 1-year follow-up, a total of 229 all-cause mortalities were record, resulting in an all-cause mortality rate of 5.71% (n = 229). Additionally, 861 MACEs were recorded, yielding a MACE rate of 21.46%. After adjusting for covariates, SHR was found to be significantly associated with 1-year MACE [hazard ratio (HR) = 2.18; 95% confidence interval (CI) = 1.64–2.89; p < 0.001] and all-cause mortality (HR = 3.11; 95% CI = 1.77–5.46; P < 0.001) in patients with AMI, and the T3 group exhibited a higher risk of 1-year MACE (HR = 1.67; 95% CI = 1.34–2.09; p < 0.001) and all-cause mortality (HR = 1.67; 95% CI = 1.02–2.73; p = 0.042) compared with T1 group. A U-shaped association was observed between SHR and 1-year MACE as well as all-cause mortality, with inflection points of 0.87 for poor prognosis in both outcomes. Conclusion SHR is significantly and positively associated with one-year clinical outcomes in patients with AMI. Furthermore, there is a specific non-linear association between SHR and MACE and all-cause mortality (both inflection point 0.87). Interventions aimed at reducing SHR levels below 0.87 through medication management have the potential to significantly improve outcomes.
HDAC inhibitor SAHA resolved intermediate filament bundling and defective autophagy caused by the lack of sacsin in ARSACS.
Authors: Paré Alexandre M , Larochelle Nancy , Dvorak Ryan A. , Minotti Sandra , Atkinson Caitlin S. , Cheng-Boivin Zacharie , Gentil Benoit J.
Published: August 2024

Autosomal recessive spastic ataxia of the Charlevoix-Saguenay (ARSACS) is a progressive childhood-onset neurological disease caused by loss-of-function mutations in the SACS gene. This condition is characterized by cerebellar ataxia, peripheral neuropathy, and spastic plasticity. ARSACS patient-derived fibroblasts and mouse models lacking sacsin exhibit altered mitochondrial networks, intermediate filament bundling, dysregulated autophagic flux, and aberrant protein/organelle localization. Sacsin, a large multidomain protein, plays a critical role in chaperoning and protein homeostasis, particularly in neurons. Dysregulation of autophagy in ARSACS is evidenced by increased LC3 levels and defective lysosome-autophagosome fusion in the absence of sacsin. Recent omics approaches suggest sacsin’s involvement in cytoskeleton regulation, intracellular transport, calcium homeostasis, synaptic organization, and mitochondrial maintenance. This study aimed to explore the effects of histone deacetylase (HDAC) inhibitors on neurofilament (NF) protein acetylation and autophagic flux in ARSACS. NF proteins from Sacs-/- mice showed no significant acetylation differences compared to controls, though HDAC inhibitor SAHA resolved NF bundling. Purification and analysis of NF proteins confirmed high purity and minor acetylation differences at specific lysines (K214). Treatment with SAHA reduced NF bundling in Sacs-/- motor neurons and promoted lysosomal recruitment to autophagosomes in ARSACS patient-derived fibroblasts, indicating restored autophagic flux. These findings highlight the potential of HDAC inhibitors in resolving cytoskeletal abnormalities and improving autophagic processes in ARSACS, offering promising therapeutic avenues for this debilitating disorder. Further research is needed to elucidate the precise mechanisms underlying these effects and their implications for NF homeostasis and autophagy regulation in ARSACS.