bluuebunny/crossref_metadata_2025_split huggingface dataset:
A low bleeding risk thrombolytic agent: citPA5
Authors: Chen Shanli , Fang Sudan , Zhou Yang , Huang Zhiwei , Yu Shujuan , Chen Dan , Wang Zhiyou , Xu Yanyan , Liu Peiwen , Li Yongkun , Lin Wei , Jiang Longguang , Yuan Cai , Huang Mingdong 
Published: March 2024

Abstract

Aims
Alteplase is a cornerstone thrombolytic agent in clinical practice but presents a potential bleeding risk. Stroke patients need pre-screening to exclude haemorrhagic stroke before using alteplase. In this study, we develop a new thrombolytic agent citPA5, characterized by an enhanced safety profile and minimal bleeding tendency.

Methods and results
A clot lysis agent, named citPA5, is developed based on rtPA with point mutations to completely suppress its proteolytic activity in the absence of fibrin. In the presence of fibrin, citPA5 exhibited significantly higher fibrinolytic activity (a 15.8-fold increase of kcat/Km). Furthermore, citPA5 showed resistance to endogenous fibrinolysis inhibitor, PAI-1, resulting in enhanced potency. In a series of safety evaluation experiments, including thrombelastography assay, mice tail bleeding assay, and a murine intracerebral haemorrhage (ICH) model, citPA5 did not cause systemic bleeding or worsen ICH compared with alteplase. This highlights the low risk of bleeding associated with citPA5. Finally, we found that citPA5 effectively improved cerebral blood flow and reduced infarct volume in a carotid embolism-induced stroke model.

Conclusion
This clot lysis agent, citPA5, not only exhibits a low risk of bleeding but also demonstrates highly effective thrombolysis capabilities. As a result, citPA5 shows great potential for administration prior to the classification of stroke types, making it possible for use in ambulances at the onset of stroke when symptoms are identified. The findings presented in this study also suggest that this strategy could be applied to develop a new generation of fibrinolytic drugs that offer greater safety and specificity in targeting fibrin.
International Lawyers in Post-Soviet Eurasia: Decoding the Divisibility
Authors: Simonyan Artur 
Published: March 2024

Abstract
This article examines the epistemic community of post-Soviet Eurasian international lawyers who interact, publish, teach and practise international law, predominantly in Russia and in Russian, forming a Russia-centred divisible college. By decoding the unknown group, the article presents its defining characteristics, including the link between membership in a Russia-centred epistemic community and the members’ potential Russlandversteher (Russia-apologist) behaviour. Analysing how post-Soviet Eurasian international lawyers act within different social arrangements (legal education, academic publication and practice of law), the article demonstrates how and to what extent such divisibility is symbolized in their political actorship.
Are day-flying moths more specialized in larval dietary breadth?—a test of the “Salient Aroma Hypothesis” in a predominantly nocturnal clade
Authors: Seifert Carlo L , Strutzenberger Patrick , Fiedler Konrad 
Published: March 2024

Abstract
Although diurnality is widespread across Lepidoptera and has evolved many times independently, its causes and ecological implications are yet poorly understood. The “Salient Aroma Hypothesis” (SAH) postulates that diurnal insect herbivores are overall more specialized in dietary breadth than species active at night. It is furthermore assumed that diurnality evolved more frequently in species that live in cooler environments. Using European geometrid moths as a model group, we tested whether diurnal activity in adults is associated with an increased larval dietary breadth as predicted by the SAH. We further investigated whether species that exclusively occur in colder regions or whose flight period is restricted to cool seasons are more likely to exhibit a diurnal flight activity. Contrary to expectation, we found no consistent differences in larval dietary breadth between diurnal and nocturnal species, and thus no support for the SAH. Diurnal activity occurred more frequently in species restricted to cold regions but not in species restricted to cool seasons. We conclude that diurnality could serve as an advantageous adaptation in cold environments, depending on further factors such as resource availability or predation pressure, but has no immediate consequences for larval dietary breadth.
Predicting Increased Incidence of Common Antibiotic-Resistant and Antibiotic-Associated Pathogens Using Ensemble Species Distribution Modeling
Authors: Brough Siqi C , Caddell Luke , Liou Raymond J , Patil Advait , De Leo Giulio , Forrester Joseph D 
Published: March 2024

Abstract
The Centers for Disease Control estimates antibiotic-associated pathogens result in 2.8 million infections and 38 000 deaths annually in the United States. This study applies species distribution modeling to elucidate the impact of environmental determinants of human infectious disease in an era of rapid global change. We modeled methicillin-resistant Staphylococcus aureus and Clostridioides difficile using 31 publicly accessible bioclimatic, health care, and sociodemographic variables. Ensemble models were created from 8 unique statistical and machine learning algorithms. Using International Classification of Diseases, 10th edition codes, we identified 305 528 diagnoses of methicillin-resistant S. aureus and 203 001 diagnoses of C. difficile presence. Three environmental factors—average maximum temperature, specific humidity, and agricultural land density—emerged as major predictors of increased methicillin-resistant S. aureus and C. difficile presence; variables representing health care availability were less important. Species distribution modeling may be a powerful tool for identifying areas at increased risk for disease presence and have important implications for disease surveillance systems.
Antileishmanial Activity of Cathelicidin and its Modulation by Leishmania donovani in a cAMP Response Element Modulator-Dependent Manner in Infection
Authors: Roy Shalini , Roy Souravi , Banerjee Madhurima , Madbhagat Pratibha , Chande Ajit , Ukil Anindita 
Published: March 2024

Abstract
Concerns regarding toxicity and resistance of current drugs in visceral leishmaniasis have been reported. Antimicrobial peptides are considered to be promising candidates and among them human cathelicidin hCAP18/LL-37 showed significant parasite killing on drug-sensitive and resistant Leishmania promastigotes, in addition to its apoptosis-inducing role. Administration of hCAP18/LL-37 to infected macrophages also decreased parasite survival and increased the host favorable cytokine interleukin 12. However, 1,25-dihydroxyvitamin D3 (vitamin D3)-induced endogenous hCAP18/LL-37 production was hampered in infected THP-1 cells. Infection also suppressed the vitamin D3 receptor (VDR), transcription factor of hCAP18/LL-37. cAMP response element modulator (CREM), the repressor of VDR, was induced in infection, resulting in suppression of both VDR and cathelicidin expression. PGE2/cAMP/PKA axis was found to regulate CREM induction during infection and silencing CREM in infected cells and BALB/c mice led to decreased parasite survival. This study documents the antileishmanial potential of cathelicidin and further identifies CREM as a repressor of cathelicidin in Leishmania infection.
Strategies for tailoring functional microbial synthetic communities
Authors: Jing Jiayi , Garbeva Paolina , Raaijmakers Jos M , Medema Marnix H 
Published: March 2024

Abstract
Natural ecosystems harbor a huge reservoir of taxonomically diverse microbes that are important for plant growth and health. The vast diversity of soil microorganisms and their complex interactions make it challenging to pinpoint the main players important for the life support functions microbes can provide to plants, including enhanced tolerance to (a)biotic stress factors. Designing simplified microbial synthetic communities (SynComs) helps reduce this complexity to unravel the molecular and chemical basis and interplay of specific microbiome functions. While SynComs have been successfully employed to dissect microbial interactions or reproduce microbiome-associated phenotypes, the assembly and reconstitution of these communities have often been based on generic abundance patterns or taxonomic identities and co-occurrences but have only rarely been informed by functional traits. Here, we review recent studies on designing functional SynComs to reveal common principles and discuss multidimensional approaches for community design. We propose a strategy for tailoring the design of functional SynComs based on integration of high-throughput experimental assays with microbial strains and computational genomic analyses of their functional capabilities.
Patient Experience of Women With Dense Breasts Undergoing Screening Contrast-Enhanced Mammography
Authors: Miller Matthew M , Mayorov Shanna , Ganti Ramapriya , Nguyen Jonathan V , Rochman Carrie M , Caley Matthew , Jahjah Jessie , Repich Kathy , Patrie James T , Anderson Roger T , Harvey Jennifer A , Rooney Timothy B 
Published: March 2024

Abstract

Objective
We investigated patient experience with screening contrast-enhanced mammography (CEM) to determine whether a general population of women with dense breasts would accept CEM in a screening setting.

Methods
In this institutional review board–approved prospective study, patients with heterogeneous and extremely dense breasts on their mammogram were invited to undergo screening CEM and complete pre-CEM and post-CEM surveys. On the pre-CEM survey, patients were asked about their attitudes regarding supplemental screening in general. On the post-CEM survey, patients were asked about their experience undergoing screening CEM, including causes and severity of any discomfort and whether they would consider undergoing screening CEM again in the future or recommend it to a friend.

Results
One hundred sixty-three women were surveyed before and after screening CEM. Most patients, 97.5% (159/163), reported minimal or no unpleasantness associated with undergoing screening CEM. In addition, 91.4% (149/163) said they would probably or very likely undergo screening CEM in the future if it cost the same as a traditional screening mammogram, and 95.1% (155/163) said they would probably or very likely recommend screening CEM to a friend. Patients in this study, who were all willing to undergo CEM, more frequently reported a family history of breast cancer than a comparison cohort of women with dense breasts (58.2% vs 47.1%, P = .027).

Conclusion
Patients from a general population of women with dense breasts reported a positive experience undergoing screening CEM, suggesting screening CEM might be well received by this patient population, particularly if the cost was comparable with traditional screening mammography.
(O-01) PREDICTORS OF INTRACAVERNOSAL INJECTION THERAPY IN MEN WITH ERECTILE DYSFUNCTION
Authors: Moreno J , Khera M 
Published: March 2024

Abstract

Introduction & Objective
Oral phosphodiesterase type 5 inhibitors (PDE5i) and intracavernosal injections (ICI) are effective treatments for erectile dysfunction (ED). However, the risk factors associated with the transition from oral therapy to ICI use remain less established. We aimed to identify predictive factors contributing to the progression from oral PDE5i to ICI therapy.

Methods
Retrospective chart review was conducted on patients presenting with erectile dysfunction at our clinic. Patients initiating therapy before clinical documentation or without follow-up were excluded. Statistical analysis utilized chi-square test, two-tailed student's t-test, and multivariable logistic regression performed in R.

Results
Among 259 men treated for ED, 61% (158) reported subjective improvement with oral PDE5i therapy alone, while 18% (46) initiated ICI therapy. Table 1 summarizes demographic information and cardiovascular risk factors. Men progressing to ICI had higher rates of hypertension (54.3% vs. 28.4%, p=0.0015), type 2 diabetes mellitus (32.6% vs. 11.4%, p=0.0013), and a history of radical prostatectomy (26.1% vs. 3.8%, p&lt;0.001) compared to those satisfied with oral therapy. Significant predictors for ICI progression on multivariate analysis were history of radical prostatectomy (OR 19.4, [95% CI, 1.42-678.88]) and diabetes mellitus (OR 8.6, [95% CI, 1.36-76.49]). Two patients (4.3%) experienced priapism as a complication of ICI use. Among the patients using ICI, 54% (25/46) reported satisfaction with their erections.

Conclusions
Cardiovascular risk factors and a history of radical prostatectomy were more prevalent among patients progressing from oral therapy to ICI in our cohort. These findings may guide early counseling on ED treatment progression for patients with these predictive factors.

Financing
No conflict.
(O-02) WAVERING PATTERN OF ERECTION AS A CLINICAL MANIFESTATION OF DORSAL VENOUS LEAKS OF THE PENIS
Authors: Uribe J F 
Published: March 2024

Abstract

Objective
The present study wants to evaluate the frequency of sudden loss of erection in patients possibly affected by penile congenital dorsal venous leaks, using a structured questionnaire to identify the so-called wavering pattern of erection, to refine the diagnosis. and indicate the need for other diagnostic tests such as doppler ultrasound or CavernoCT to identify such leaks.

Materials and Methods
In a group of 60 patients with confirmed ultrasound diagnosis of penile dorsal venous leak, a structured questionnaire of five questions was systematically administered about situations that led to loss of erection, including the following 5 items: Changes in position, external distractions, change from feet to lying down or vice versa, condom use and loss of erection during masturbation. Patients with at least four positive items were considered to comply with the so-called hesitant pattern of erection.

Results
It was found that in this group with ultrasound leaks, 81.6% of the patients fulfilled at least 4/5 items of the questionnaire and 18.3% with 3 or less. The most frequent question answered positively was “Changes of position” (91.6%), followed by “External distractions” (86.6%), third “loss of erection during masturbation” (83.4%), fourth “changes from lying to standing or vice versa” (80%) and the fifth “loss of erection with condom use” (66.6%).

Conclusions
It is considered that the systematic performance of some key questions in patients under 40 years of age who consult for erectile dysfunction can guide an underlying diagnosis of congenital venous leaks that should be verified with adequate diagnostic images and whose use as a valid instrument requires verification additional.

Key words
erectile dysfunction, vasculogenic impotence, penile diseases, penile veins.

Financing
No conflict.
(O-10) CLINICAL PROFILE AND SATISFACTION LEVEL OF PATIENTS UNDERGOING PENILE PROSTHESIS IMPLANTATION AT PEDRO ERNESTO UNIVERSITY HOSPITAL (HUPE/UERJ) 2018-2022
Authors: Crelier G M , Bastos G B , Menezes M C , Vidal V A , Schiavini J L , Filho RdTF , Lara C M C , Junior H R J , Damião R 
Published: March 2024

Abstract

Introduction
Erectile dysfunction (ED) can significantly impact couples' sexual quality of life, with penile prosthesis implants often yielding satisfaction rates of up to 90%. This treatment remains underutilized, less than 5% of refractory ED patients to undergo this therapy. This study aims to assess the satisfaction levels of patients who have undergone penile prosthesis implantation and explore associated factors.

Methods
We reviewed 48 medical records of patients who underwent penile prosthesis implantation between 2018-2022 and administered satisfaction questionnaires 6 months after the procedure.

Results
93% expressed satisfaction post-surgery, with 66% reporting increased libido. Additionally, 83% noted ease in achieving penetration, 75% were content with the prosthesis size, and 95% stated willingness to undergo the surgery again. Common causes of sexual dysfunction were post-radical prostatectomy (45%), followed by diabetes mellitus (22%). Peyronie's disease was the etiology in 6% of cases, and priapism in 2%. The average age was 63 years (range: 27-80), with 20% being obese, 37% having diabetes mellitus, and 56% experiencing systemic arterial hypertension. Approximately 20% of procedures presented complications, surgical wound infection being the most common and prosthesis extrusion the most severe.

Discussion
Literature identifies predictors associated with satisfaction after penile prosthesis implantation, such as Peyronie's disease, BMI &gt; 30, post-radical prostatectomy, implant type, postoperative complications, and patient age; our study revealed that only 7% expressed dissatisfaction, primarily due to postoperative complications.

Conclusion
Penile prosthesis implantation proves to be a safe procedure with a high success rate and satisfaction level. Dissatisfaction primarily arises from postoperative complications, emphasizing the importance of offering this therapeutic option to patients with severe ED.

Financing
No conflict.
(O-15) SEXUALITY IN PATIENTS WITH ADVANCED PROSTATE CANCER: A REVIEW
Authors: Cabral Junior J B 
Published: March 2024

Abstract

Introduction
Androgen deprivation therapy (ADT) remains the gold standard in treatment of advanced prostate cancer (APC). Disease remission means improved quality of life, mental health, social interactions, in addition to pain reduction. However, most experience a significant drop in sexual desire, reduction in rigidity and duration of erections, and a decrease in the frequency of sexual intercourse.

Material and Methods
A review of literature on sexuality in patients with APC was carried out.

Results
The prevalence of sexual dysfunction (SD) in patientes with APC is higher. However, its treatment remains in the background, considering the priority given to oncological treatment. Assessing baseline sexual function before starting ADT, as well as monitoring changes that occur during treatment are important aspects to mitigate negative effects. Individualization of the therapeutic plan allows satisfactory erectile response with oral medications in up to 33% of patients, reaching 80% with the use of combined therapies, such as injections and vacuum devices. Intermittent ADT appears as an interesting option for selected groups of patients with APC, with biochemical recurrence and low-volume metastatic disease, allowing a recovery of sexual function in the intervals without treatment, although recovery of sexual function becomes less pronounced and treatment-free intervals become shorter over time.

Conclusions
The significant drop observed in sexual health still remains a major challenge in the management of patients with APC. Although physical and psychosocial variables may be involved in the etiology of SD, erectile function remains the main determinant of sexual satisfaction in men undergoing any treatment for prostate cancer. Despite emerging themes have been observed in the literature, such as sexual psychotherapy and the role of physical exercises in mitigating the negative effects of ADT, specific studies in this population are still needed.

Financing
No conflict.
(O-21) MAJOR ADVERSE EFFECTS OF ANABOLIC STEROID USE IN TRANSGENDER MEN DURING GENDER-REAFFIRMING HORMONE THERAPY: A SYSTEMATIC REVIEW OF THE LITERATURE
Authors: Garcia S , Peña Rodríguez S , Fernandez Mantilla D , Diaz Ritter C 
Published: March 2024

Abstract

Objective
Gender-affirming hormone therapy for female-to-male transsexuals is based on testosterone administration. Testosterone therapy (TT) is associated with side effects such as arteriosclerosis and insulin resistance, among others. This review aims to synthesize the main findings in the literature regarding these adverse effects and identify gaps in knowledge that will guide future studies

Methodology
A systematic review of the literature was carried out with search strategies based on Mesh terms. The bibliographic databases PubMed, Embase, and SCOPUS were selected, and the following search algorithm was applied. We included clinical trials, meta-analyses, systematic reviews, and cohort studies. The articles were evaluated by three investigators, who initially reviewed the title and abstract and determined whether the article met the inclusion criteria. We followed the recommendations of the PRISMA statement for this process.

Results
The search provided a total of 93 articles (PubMed n = 61, Embase n = 2, Scopus n = 30). Four duplicates were eliminated. Finally, 22 articles met the inclusion criteria. Two studies found hematologic side effects of TT; 4 studies evidenced an increase of metabolic profile without any clinically significant side effects, 1 cohort showed an incidence of hepatic failure of 0.6% in the first year. 2 studies showed that TT was associated with endothelial disfunction and a proinflammatory state. 1 study showed an increase in body weight and lean mass and reduction in body fat. 3 studies showed that TT has no association with an increased risk of breast cancer. 1 study reported a high prevalence of acne with a highest value at 6 months post initiation of therapy.

Conclusions
The use of TT showed side effects on metabolic profile bases without clinically significant repercussions. Additionally, even after showing endothelial damage, no cardiovascular events were reported. Further studies are required about this topic.
Figure 1. Flowchart Selection of items according to PRISMA 2020.

Financing
No conflict.
(O-26) INITIAL EXPERIENCE IN IMPLEMENTING AN INTRACAVERNOSAL INJECTABLE THERAPY PROGRAM FOR THE TREATMENT OF ERECTILE DYSFUNCTION IN PATIENTS AT A PUBLIC HOSPITAL
Authors: Cabral Júnior J B , Souza Filho C A , Amorim G J A , Oliveira R A P , Ramos L A I A , Souza R C , Cavalcante F J C 
Published: March 2024

Abstract

Introduction
Intracavernous injectable therapy (IIT) has been considered a second-line therapy for the treatment of erectile dysfunction (ED) since the emergence of phosphodiesterase type 5 inhibitors (IPDE-5) for oral use in the late 1990s. The ease of access to IPDE-5, with increasingly accessible costs, in addition to the safety and efficacy with the use of these medications, caused IIT to fall into disuse for a good period. In turn, about 30% of men with ED do not respond satisfactorily to the oral use of IPDE-5, needing to resort to some other form of treatment.

Materials and Method
Patients with ED unresponsive to oral IPDE-5 were referred for IIT. Subsequently, they were submitted to a questionnaire to evaluate the results.

Results
Eight men answered the applied questionnaire. The mean age of patients was 61 years (44-75 years). All patients reported that their partner was aware of the treatment used, and 75% of patients reported the presence of some comorbidity. The response to the test was considered satisfactory in 75% of the patients, with full erection (EHS 4) in 37.5%, and partial erection with penetration (EHS 3) in 37.5%. Only one patient (12.5%) reported not having adapted to the proposed treatment, despite having a satisfactory erection. After a 12-month follow-up, only one patient (12.5%) continues to use IIT, 3 (37.5%) opted for penile prosthesis implantation, while the others chose not to adhere to any subsequent treatment. In 62.5% of patients there was no report of any side effect.

Conclusion
Despite high rates of efficacy and satisfaction reported in the literature, our initial experience showed a low rate of adherence to IIT. The team's lack of experience and difficulty in following up patients probably contributed to these results, revealing a need for better team training and patient guidance.

Financing
No conflict.