bluuebunny/crossref_metadata_2025 huggingface dataset:
Rationale and design of the SPRING trail: effectivity and safety of Pfo closuRe vs medIcine in alleviatiNg migraine, a multicenter, randomized and open-label trail
Authors: Zi-yang Yang , Hezhi Li , Dongling Luo , Ximeng Wang , Caojin Zhang ,   for the SPRING Investigators, Weibin Chen , Tao Guo , Tongtao Cui , Zhanhang Wang , Zhaojun Xiong , Hanhua Gao , Junxing Lai , Jie Yuan , Jianying Chen , Xiaodong Wang , Wei Liu , Hongwei Zhang , Gangcheng Zhang , Xuan Zheng , Qunshan Shen , Xiaobin Chen , Dujiang Xie , Wenqi Zhang , Zhongchao Wang , Wenbin Wei , Yang Zhou , Wei Zhang
Published: April 2024

Background

Migraine is a leading cause of disability worldwide. Several retrospective studies have suggested that the closure of the Patent Foramen Ovale (PFO) may provide relief from migraines. However, three randomized controlled trials did not meet their primary endpoints regarding migraine cessation, reduction in monthly migraine days, and responder rates.

Methods

The SPRING study is a multicenter, prospective, randomized, and open-label trial designed to compare the effectiveness and safety of PFO closure versus medication in the relief of migraines. The primary endpoint is the total cessation of migraines, as recorded in patient headache diaries during the follow-up period. Additional diagnostic tools include echocardiography with agitated saline contrast, transcranial Doppler, and routine laboratory measurements.

Conclusion

The SPRING trial aims to assess the effectiveness and safety of PFO closure versus medication in mitigating migraines in real-world settings. (Clinical Trails ID: NCT04946734).
Impact of climate-induced floods and typhoons on geriatric disabling health among older Chinese and Filipinos: a cross-country systematic review
Authors: Balikuddembe Joseph Kimuli , Zheng Yafang , Prisno Don Eliseo Lucero , Stodden Robert
Published: April 2024

Background

Apart from both China and the Philippines continuing to be exposed to and affected by different climate-induced hazards, in particular floods and typhoons, they are also reported to be witnessing rapid ageing populations of 60 years and older. As such, this systematic review synthesized the existing evidence about the impacts aggravated by floods and typhoons on the geriatric disabling health of older Chinese and Filipinos, respectively.

Methods

Four (4) electronic databases were systematically searched to identify eligible studies published between 2000 and early 2023. This process had to confirm the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA), as well as the standard protocol registered with PROSPERO (CRD42023420549).

Results

Out of 317 and 216 initial records retrieved for China and the Philippines, respectively, 27 (China) and 25 (Philippines) studies were eligible for final review. The disabling conditions they reported to affect the health of older adults were grouped into 4 categories: cognitive and intellectual, physical, chronic and terminal illnesses, and mental and psychological, with the latter identified as the most prevalent condition to affect older Chinese and Filipinos. On a sub-category level, posttraumatic stress disorder (PTSD) was the most common condition reported in 27 flood-related studies in China, while injuries and wounds prevailed in the Philippines, according to 25 typhoon-related studies.

Conclusion

The increasing occurrence of extreme climate hazards, especially floods and typhoons in China and the Philippines, respectively, impacted the health of their older adults with various disabling effects or conditions. Therefore, this calls for appropriate geriatric-informed interventions in the context of climate change and rapidly ageing settings beyond China and the Philippines to others that are also prone to floods and typhoons.
Streptococcus intermedius causing primary bacterial ventriculitis in a patient with severe periodontitis - a case report
Authors: Allonen Satu , Aittoniemi Janne , Vuorialho Matti , Närhi Lassi , Panula Kari , Vuento Risto , Honkaniemi Jari
Published: April 2024

Background

Streptococcus intermedius is a member of the S. anginosus group and is part of the normal oral microbiota. It can cause pyogenic infections in various organs, primarily in the head and neck area, including brain abscesses and meningitis. However, ventriculitis due to periodontitis has not been reported previously.

Case presentation

A 64-year-old male was admitted to the hospital with a headache, fever and later imbalance, blurred vision, and general slowness. Neurological examination revealed nuchal rigidity and general clumsiness. Meningitis was suspected, and the patient was treated with dexamethasone, ceftriaxone and acyclovir. A brain computer tomography (CT) scan was normal, and cerebrospinal fluid (CSF) Gram staining and bacterial cultures remained negative, so the antibacterial treatment was discontinued. Nine days after admission, the patient’s condition deteriorated. The antibacterial treatment was restarted, and a brain magnetic resonance imaging revealed ventriculitis. A subsequent CT scan showed hydrocephalus, so a ventriculostomy was performed. In CSF Gram staining, chains of gram-positive cocci were observed. Bacterial cultures remained negative, but a bacterial PCR detected Streptococcus intermedius. An orthopantomography revealed advanced periodontal destruction in several teeth and periapical abscesses, which were subsequently operated on. The patient was discharged in good condition after one month.

Conclusions

Poor dental health can lead to life-threatening infections in the central nervous system, even in a completely healthy individual. Primary bacterial ventriculitis is a diagnostic challenge, which may result in delayed treatment and increased mortality.
Feasibility of a novel eHealth intervention for Parkinson’s disease targeting motor-cognitive function in the home
Authors: Sedhed Jenny , Johansson Hanna , Andersson Nina , Åkesson Elisabet , Kalbe Elke , Franzén Erika , Leavy Breiffni
Published: April 2024

Background

Parkinson’s disease (PD) drastically affects motor and cognitive function, but evidence shows that motor-cognitive training improves disease symptoms. Motor-cognitive training in the home is scarcely investigated and eHealth methods can provide continual support for PD self-management. Feasibility testing is however required.

Objective

To assess the feasibility (i) Recruitment capability (ii) Acceptability and Suitability (iii) Demand and Safety of a home-based motor-cognitive eHealth exercise intervention in PD.

Methods

The 10-week intervention was delivered using the ExorLive® application and exercises were individually adapted and systematically progressed and targeted functional strength, cardiovascular fitness, flexibility, and motor-cognitive function. People with mild-to moderate PD were assessed before and after the intervention regarding; gait performance in single and dual-task conditions; functional mobility; dual-task performance; balance performance; physical activity level; health related quality of life and perceived balance confidence and walking ability; global cognition and executive function. Feasibility outcomes were continuously measured using a home-exercise diary and contact with a physiotherapist. Changes from pre- and post-intervention are reported descriptively.

Results

Fifteen participants (mean age 68.5 years) commenced and 14 completed the 10-week intervention. In relation to interventionAcceptability, 64% of the motor sessions and 52% of motor-cognitive sessions were rated as “enjoyable”. ConcerningSuitability, the average level of exertion (Borg RPE scale) was light (11–12). Adherence was high, with 86% of all (420) sessions reported as completed. No falls or other adverse events occurred in conjunction with the intervention.

Conclusions

This motor-cognitive eHealth home exercise intervention for PD was safe and feasible in terms of Recruitment capability, Acceptability, Safety and Demand. The intensity of physical challenge needs to be increased before testing in an efficacy trial.

Trial registration

This trial is registered at Clinicaltrials.gov (NCT05027620).
Predictors of successful trial of labor after cesarean section (TOLAC) in women with one prior transverse cesarean section at Tertiary Hospitals in northwest Ethiopia: a multicenter study
Authors: Tegegne Gizachew Aynalem , Rade Bayew Kelkay , Yismaw Ayenew Engida , Taye Worku , Mengistie Berihun Agegn
Published: April 2024

Background

Trials of labor after cesarean section is the preferred strategy to decrease the cesarean delivery rate and reducing complications associated with multiple cesarean sections. The success rate of trials of labor after cesarean section and associated factors have not been well documented in Ethiopia. Hence, this study was aimed to determine the success rate and factors associated with the trial of labor after one cesarean section in five Comprehensive Specialized Hospitals located in northwest Ethiopia.

Methods

An institutional-based cross-sectional study was conducted among 437 women who came for the trial of labor from December 1, 2021, to March 30, 2022. All women who fulfilled the eligibility criteria were included to this study. Data was collected using structured and pre-tested questionnaire. Then, the data was entered into Epi Data 4.6 software and exported to SPSS version 26 for analysis. To identify the variables influencing the outcome variable, bivariable and multivariable logistic regression analyses were conducted. The model’s fitness was checked using the Hosmer-Lemeshow goodness of fit test, and an adjusted odds ratio with a 95% confidence interval was used to declare the predictors that are significantly associated with TOLAC.

Results

The success rate of the trial of labor after one cesarean section was 56.3% (95% CI, 51.3%, 61.2%). Maternal age ≥ 35 years (AOR: 3.3, 95% CI 1.2, 9.3), the fetal station at admission ≤ zero (AOR: 5. 6, 95% CI 3.3, 9.5), vaginal delivery before cesarean section (AOR: 1.9, 95% CI 1.2, 3.2), and successful vaginal birth after cesarean delivery (AOR 2.2, 95% CI 1.2, 4.1) were found to have a significant association with the success rate of trial of labor after cesarean section.

Conclusions

In this study, the success rate of the trial of labor after a cesarean section was low as compared to the ACOG guideline and other studies in different countries. Therefore, the clinicians ought to offer counsel during antenatal and intrapartum period, encourage the women to make informed decision on the mode of delivery, and the practitioners need to follow fetal and maternal conditions strictly to minimize adverse birth outcomes.
Examining provider practice-level disparities in delivery outcomes among patients with a history of Cesarean Delivery
Authors: McCarthy Lily , Tavella Nicola F , Wetzler Sara , Ardente Lily , Chadwick Molly , Paul Dexter , Sabet Nikki , Stern Toni , Bianco Angela
Published: April 2024

Background

Choosing whether to pursue a trial of labor after cesarean (TOLAC) or scheduled repeat cesarean delivery (SRCD) requires prenatal assessment of risks and benefits. Providers and patients play a central role in this process. However, the influence of provider-associated characteristics on delivery methods remains unclear. We hypothesized that different provider practice groups have different obstetric outcomes in patients with one prior cesarean delivery (CD).

Methods

This was a retrospective cohort study of deliveries between April 29, 2015 – April 29, 2020. Subjects were divided into three cohorts: SRCD, successful VBAC, and unsuccessful VBAC (patients who chose TOLAC but had a CD). Disparities were reviewed between five different obstetric provider practice groups, determined from a breakdown of different providers delivering at the study site during the study period. Proportional differences were examined using Chi-squared tests and logistic regression models.

Results

1,439 deliveries were included in the study. There were significant proportional disparities between patients in the different groups. Specifically, patients from Group D were significantly more likely to undergo successful VBAC, while patients seeing a provider from Group A were more likely to deliver by SRCD. In our multivariate analysis of successful versus unsuccessful VBAC, patients from Group D had greater odds ratios of successful VBAC compared to Group A. Patients delivered by Group E had a significantly lower odds ratio of successful VBAC.

Conclusion

This study suggests an association between provider practice groups and delivery outcomes among patients with one prior CD. These data contribute to a growing body of literature around patient choice in pregnancy and the interplay of patients and providers. These findings help to guide future investigations to improve outcomes among patients with a history of CD.
One Health communication channels: a qualitative case study of swine influenza in Canada in 2020
Authors: Denis-Robichaud José , Hindmarch Suzanne , Nswal Nancy N. , Mutabazi Jean Claude , D’Astous Mireille , Gangbè Marcellin , Osborn Andrea , Zarowsky Christina , Rees Erin E. , Carabin Hélène
Published: April 2024

Background

With increased attention to the importance of integrating the One Health approach into zoonotic disease surveillance and response, a greater understanding of the mechanisms to support effective communication and information sharing across animal and human health sectors is needed. The objectives of this qualitative case study were to describe the communication channels used between human and animal health stakeholders and to identify the elements that have enabled the integration of the One Health approach.

Methods

We combined documentary research with interviews with fifteen stakeholders to map the communication channels used in human and swine influenza surveillance in Alberta, Canada, as well as in the response to a human case of H1N2v in 2020. A thematic analysis of the interviews was also used to identify the barriers and facilitators to communication among stakeholders from the animal and human health sectors.

Results

When a human case of swine influenza emerged, the response led by the provincial Chief Medical Officer of Health involved players at various levels of government and in the human and animal health sectors. The collaboration of public and animal health laboratories and of the swine sector, in addition to the information available through the surveillance systems in place, was swift and effective. Elements identified as enabling smooth communication between the human and animal health systems included preexisting relationships between the various stakeholders, a relationship of trust between them (e.g., the swine sector and their perception of government structures), the presence of stakeholders acting as permanent liaisons between the ministries of health and agriculture, and stakeholders' understanding of the importance of the One Health approach.

Conclusions

Information flows through formal and informal channels and both structural and relational features that can support rapid and effective communication in infectious disease surveillance and outbreak response.
The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats
Authors: Anwar Mai M. , Laila Ibrahim M. Ibrahim
Published: April 2024

Background

Vortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.

Methods

The experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.

Results

Interestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.

Conclusion

Thus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.
Developing a questionnaire to evaluate an automated audit & feedback intervention: a Rand-modified Delphi method
Authors: Van den Wyngaert Ine , Van Pottelbergh Gijs , Coteur Kristien , Vaes Bert , Van den Bulck Steve
Published: April 2024

Background

Audit and feedback (A&F) is a widely used implementation strategy to evaluate and improve medical practice. The optimal design of an A&F system is uncertain and structured process evaluations are currently lacking. This study aimed to develop and validate a questionnaire to evaluate the use of automated A&F systems.

Methods

Based on the Clinical Performance Feedback Intervention Theory (CP-FIT) and the REFLECT-52 (REassessing audit & Feedback interventions: a tooL for Evaluating Compliance with suggested besT practices) evaluation tool a questionnaire was designed for the purpose of evaluating automated A&F systems. A Rand-modified Delphi method was used to develop the process evaluation and obtain validation. Fourteen experts from different domains in primary care consented to participate and individually scored the questions on a 9-point Likert scale. Afterwards, the questions were discussed in a consensus meeting. After approval, the final questionnaire was compiled.

Results

A 34-question questionnaire composed of 57 items was developed and presented to the expert panel. The consensus meeting resulted in a selection of 31 questions, subdivided into 43 items. A final list of 30 questions consisting of 42 items was obtained.

Conclusion

A questionnaire consisting of 30 questions was drawn up for the assessment and improvement of automated A&F systems, based on CP-FIT and REFLECT-52 theory and approved by experts. Next steps will be piloting and implementation of the questionnaire.
Characterization of oral microbiota in 6–8-month-old small breed dogs
Authors: Morita Masahiro , Nambu Takayuki , Yamasaki Ryota , Nagai-Yoshioka Yoshie , Inoue Maki , Nishihara Tatsuji , Okinaga Toshinori , Ariyoshi Wataru
Published: April 2024

Background

Periodontitis is the most common oral disease in dogs, and its progression and severity are influenced by risk factors, such as age and body size. Recent studies have assessed the canine oral microbiota in relation to different stages of periodontitis and niches within the oral cavity. However, knowledge of the bacterial composition at different ages and body sizes, especially in puppies, is limited. This study aimed to characterize the oral microbiota in the healthy gingiva of small breed puppies using next-generation sequencing. Additionally, we assessed the impact of dental care practices and the presence of retained deciduous teeth on the oral microbiota.

Results

In this study, plaque samples were collected from the gingival margin of 20 small breed puppies (age, 6.9 ± 0.6 months). The plaque samples were subjected to next-generation sequencing targeting the V3-V4 region of the 16 S rRNA. The microbiota of the plaque samples was composed mostly of gram-negative bacteria, primarily Proteobacteria (54.12%), Bacteroidetes (28.79%), and Fusobacteria (5.11%). Moraxella sp. COT-017, Capnocytophaga cynodegmi COT-254, and Bergeyella zoohelcum COT-186 were abundant in the oral cavity of the puppies. In contrast, Neisseria animaloris were not detected. The high abundance of Pasteurellaceae suggests that this genus is characteristic of the oral microbiota in puppies. Dental care practices and the presence of retained deciduous teeth showed no effects on the oral microbiota.

Conclusions

In this study, many bacterial species previously reported to be detected in the normal oral cavity of adult dogs were also detected in 6–8-month-old small breed dogs. On the other hand, some bacterial species were not detected at all, while others were detected in high abundance. These data indicate that the oral microbiota of 6–8-month-old small breed dogs is in the process of maturating in to the adult microbiota and may also have characteristics of the small dog oral microbiota.
Repressive H3K27me3 drives hyperglycemia-induced oxidative and inflammatory transcriptional programs in human endothelium
Authors: Sánchez-Ceinos Julia , Hussain Shafaat , Khan Abdul Waheed , Zhang Liang , Almahmeed Wael , Pernow John , Cosentino Francesco
Published: April 2024

Background

Histone modifications play a critical role in chromatin remodelling and regulate gene expression in health and disease. Histone methyltransferases EZH1, EZH2, and demethylases UTX, JMJD3, and UTY catalyse trimethylation of lysine 27 on histone H3 (H3K27me3). This study was designed to investigate whether H3K27me3 triggers hyperglycemia-induced oxidative and inflammatory transcriptional programs in the endothelium.

Methods

We studied human aortic endothelial cells exposed to high glucose (HAEC) or isolated from individuals with diabetes (D-HAEC). RT-qPCR, immunoblotting, chromatin immunoprecipitation (ChIP-qPCR), and confocal microscopy were performed to investigate the role of H3K27me3. We determined superoxide anion (O2−) production by ESR spectroscopy, NF-κB binding activity, and monocyte adhesion. Silencing/overexpression and pharmacological inhibition of chromatin modifying enzymes were used to modulate H3K27me3 levels. Furthermore, isometric tension studies and immunohistochemistry were performed in aorta from wild-type and db/db mice.

Results

Incubation of HAEC to high glucose showed that upregulation of EZH2 coupled to reduced demethylase UTX and JMJD3 was responsible for the increased H3K27me3. ChIP-qPCR revealed that repressive H3K27me3 binding to superoxide dismutase and transcription factor JunD promoters is involved in glucose-induced O2− generation. Indeed, loss of JunD transcriptional inhibition favours NOX4 expression. Furthermore, H3K27me3-driven oxidative stress increased NF-κB p65 activity and downstream inflammatory genes. Interestingly, EZH2 inhibitor GSK126 rescued these endothelial derangements by reducing H3K27me3. We also found that H3K27me3 epigenetic signature alters transcriptional programs in D-HAEC and aortas from db/db mice.

Conclusions

EZH2-mediated H3K27me3 represents a key epigenetic driver of hyperglycemia-induced endothelial dysfunction. Targeting EZH2 may attenuate oxidative stress and inflammation and, hence, prevent vascular disease in diabetes.

Graphical Abstract
Functional CRISPR screens in T cells reveal new opportunities for cancer immunotherapies
Authors: Xiang Minghua , Li Huayi , Zhan Yuanyuan , Ma Ding , Gao Qinglei , Fang Yong
Published: April 2024

T cells are fundamental components in tumour immunity and cancer immunotherapies, which have made immense strides and revolutionized cancer treatment paradigm. However, recent studies delineate the predicament of T cell dysregulation in tumour microenvironment and the compromised efficacy of cancer immunotherapies. CRISPR screens enable unbiased interrogation of gene function in T cells and have revealed functional determinators, genetic regulatory networks, and intercellular interactions in T cell life cycle, thereby providing opportunities to revamp cancer immunotherapies. In this review, we briefly described the central roles of T cells in successful cancer immunotherapies, comprehensively summarised the studies of CRISPR screens in T cells, elaborated resultant master genes that control T cell activation, proliferation, fate determination, effector function, and exhaustion, and highlighted genes (BATF, PRDM1, and TOX) and signalling cascades (JAK-STAT and NF-κB pathways) that extensively engage in multiple branches of T cell responses. In conclusion, this review bridged the gap between discovering element genes to a specific process of T cell activities and apprehending these genes in the global T cell life cycle, deepened the understanding of T cell biology in tumour immunity, and outlined CRISPR screens resources that might facilitate the development and implementation of cancer immunotherapies in the clinic.
Effect of melatonin on developmental competence, mitochondrial distribution, and intensity of fresh and vitrified/thawed in vitro matured buffalo oocytes
Authors: Kandil Omaima Mohamed , Rahman Samar Mahfouz Abd El , Ali Rania S. , Ismail Esraa Aly , Ibrahim Nehad M.
Published: April 2024

Background: In livestock breeding, oocyte cryopreservation is crucial for preserving and transferring superior genetic traits. This study was conducted to examine the additional effect of melatonin to maturation and vitrification media on the in vitro developmental capacity, mitochondrial distribution, and intensity of buffalo oocytes. The study involved obtaining ovaries from a slaughterhouse and conducting two phases. In the first phase, high-quality oocytes were incubated in a maturation medium with or without 10−9M melatonin for 22 h (at 38.5°C in 5% CO2). Matured oocytes were fertilized in vitro and cultured in SOF media for seven days. In the second phase, vitrified in vitro matured oocytes were stored in vitrified media (basic media (BM) containing a combination of cryoprotectants (20% Ethyl Glycol and 20% Dimethyl sulfoxide), with or without melatonin, and then stored in liquid nitrogen. Normal vitrified/thawed oocytes were fertilized in vitro and cultured as described. Finally, the matured oocytes from the fresh and vitrified/thawed groups, both with and without melatonin, were stained using DAPI and Mitotracker red to detect their viability (nuclear maturation), mitochondrial intensity, and distribution using a confocal microscope. The study found that adding 10−9M melatonin to the maturation media significantly increased maturation (85.47%), fertilization rate (84.21%)cleavage (89.58%), and transferable embryo (48.83%) rates compared to the group without melatonin (69.85%,79.88%, 75.55%, and 37.25% respectively). Besides that, the addition of melatonin to the vitrification media improved the recovery rate of normal oocytes (83.75%), as well as the cleavage (61.80%) and transferable embryo (27.00%) rates when compared to the vitrified TCM group (67.46%, 51.40%, and 17.00%, respectively). The diffuse mitochondrial distribution was higher in fresh with melatonin (TCM + Mel) (80%) and vitrified with melatonin (VS2 + Mel groups) (76.70%), Furthermore, within the same group, while the mitochondrial intensity was higher in the TCM + Mel group (1698.60) than other group. In conclusion, Melatonin supplementation improves the developmental competence and mitochondrial distribution in buffalo oocytes in both cases(in vitro maturation and vitrification).
Right ventricular myocardial edema leading to severe heart failure after open heart surgery – possible effect of high-dose corticosteroid therapy
Authors: Jeppesen Karoline Korsholm , Riber Lars Peter , Dahl Jordi Sanchez
Published: April 2024

Background

Cardiopulmonary bypass induces a systemic inflammatory response and alterations in fluid homeostasis, resulting in generalized tissue edema. Additionally, ischemia-reperfusion injury following cardioplegic arrest presumably prompts organ-specific myocardial edema.

Case presentation

The case report presents a 75-year-old Caucasian male diagnosed with aortic dissection, Stanford type A, who underwent complicated open-heart surgery. Postoperatively, the patient developed excessive myocardial edema, particularly affecting the right ventricle myocardium to an extent where the right ventricle surpassed the sternal rim, making it impossible to close the sternum. Ischemia was ruled out by performing coronary angiography, demonstrating well-calibrated coronary arteries. Transoesophageal echocardiography showed a restrictive right ventricle with free-wall thickness of 30 mm, severely reduced right ventricle systolic function and a volume-depleted left ventricle consistent with right ventricular heart failure due to right ventricular edema. The patient presented with unstable haemodynamics despite use of inotropes and continuation of open sternotomy. In an attempt to reduce myocardial edema, the patient was started on corticosteroid treatment despite of ongoing mediastinitis. Corticosteroid treatment reduced myocardial edema and enabled the closure of sternum on the 44th postoperative day.

Conclusions

The case report addresses the clinical relevance of corticosteroid treatment in selective cases of intractable haemodynamically significant postoperative myocardial edema.
The clinical trial activation process: a case study of an Italian public hospital
Authors: Pelazza Carolina , Betti Marta , Marengo Francesca , Roveta Annalisa , Maconi Antonio
Published: April 2024

Background/aims

In order to make the centers more attractive to trial sponsors, in recent years, some research institutions around the world have pursued projects to reorganize the pathway of trial activation, developing new organizational models to improve the activation process and reduce its times.

This study aims at analyzing and reorganizing the start-up phase of trials conducted at the Research and Innovation Department (DAIRI) of the Public Hospital of Alessandria (Italy).

Methods

A project was carried out to reorganize the trial authorization process at DAIRI by involving the three facilities responsible for this pathway: clinical trial center (CTC), ethics committee secretariat (ESC), and administrative coordination (AC).

Lean Thinking methodology was used with the A3 report tool, and the analysis was carried out by monitoring specific key performance indicators, derived from variables representing highlights of the trials’ activation pathway.

The project involved phases of analysis, implementation of identified countermeasures, and monitoring of timelines in eight 4-month periods.

The overall mean and median values of studies activation times were calculated as well as the average times for each facility involved in the process.

Results

In this study, 298 studies both sponsored by research associations and industry with both observational and interventional study design were monitored.

The mean trial activation time was reduced from 218 days before the project to 56 days in the last period monitored.

From the first to the last monitoring period, each facility involved achieved at least a halving of the average time required to carry out its activities in the clinical trials’ activation pathway (CTC: 55 days vs 23, ECS: 25 days vs 8, AC 29 days vs 10).

Average activation time for studies with agreement remains longer than those without agreement (100 days vs. 46).

Conclusions

The reorganization project emphasized the importance of having clinical and administrative staff specifically trained on the trial activation process.

This reorganization led to the development of a standard operating procedure and a tool to monitor the time (KPIs of the process) that can also be implemented in other clinical centers.
Histone deacetylases regulate organ-specific growth in a horned beetle
Authors: Hu Yonggang , Crabtree Jordan R. , Macagno Anna L. M. , Moczek Armin P.
Published: April 2024

Background

Nutrient availability is among the most widespread means by which environmental variability affects developmental outcomes. Because almost all cells within an individual organism share the same genome, structure-specific growth responses must result from changes in gene regulation. Earlier work suggested that histone deacetylases (HDACs) may serve as epigenetic regulators linking nutritional conditions to trait-specific development. Here we expand on this work by assessing the function of diverse HDACs in the structure-specific growth of both sex-shared and sex-specific traits including evolutionarily novel structures in the horned dung beetle Onthophagus taurus.

Results

We identified five HDAC members whose downregulation yielded highly variable mortality depending on which HDAC member was targeted. We then show that HDAC1, 3, and 4 operate in both a gene- and trait-specific manner in the regulation of nutrition-responsiveness of appendage size and shape. Specifically, HDAC 1, 3, or 4 knockdown diminished wing size similarly while leg development was differentially affected by RNAi targeting HDAC3 and HDAC4. In addition, depletion of HDAC3 transcript resulted in a more rounded shape of genitalia at the pupal stage and decreased the length of adult aedeagus across all body sizes. Most importantly, we find that HDAC3 and HDAC4 pattern the morphology and regulate the scaling of evolutionarily novel head and thoracic horns as a function of nutritional variation.

Conclusion

Collectively, our results suggest that both functional overlap and division of labor among HDAC members contribute to morphological diversification of both conventional and recently evolved appendages. More generally, our work raises the possibility that HDAC-mediated scaling relationships and their evolution may underpin morphological diversification within and across insect species broadly.
Impact of tree planting on household well-being: evidence from the central highlands of Vietnam
Authors: Dinh Hoang Huu , Basnet Shyam , Zuo Alec
Published: April 2024

Household land use decisions in the tropics have a wide range of outcomes and impacts on economic development, environmental conservation, and social development. This study seeks to contribute to this debate by examining the effects of tree planting on poverty alleviation and welfare improvement in Vietnam. We employ a combination of multinomial endogenous treatment effect and propensity score matching, using survey data collected from 239 households in 11 communes in Vietnam’s Central Highlands region. We find that households engaged in tree planting can increase their income and alleviate poverty compared to non-engaging households. Specifically, long-term cashew plantations provide early harvests and have proven to be a preferred crop for households dealing with immediate livelihood needs. However, short-term acacia timber crops contribute insignificantly to poverty reduction and may be more suitable for households with greater financial resources. The policy implication underscores the importance of interventions tailored to support impoverished households with urgent livelihood needs. Prioritizing immediate necessities is crucial before households can invest in long-term tree planting.
Toward a Robust Definition of Sport Sex
Authors: Handelsman David J
Published: April 2024

Elite individual sports in which success depends on power, speed, or endurance are conventionally divided into male and female events using traditional binary definitions of sex. Male puberty creates durable physical advantages due to the 20- to 30-fold increase in circulating testosterone producing a sustained uplift in men's muscle, bone, hemoglobin, and cardiorespiratory function resulting from male puberty and sustained during men's lives. These male physical advantages provide strong justification for a separate protected category of female events allowing women to achieve the fame and fortune from success they would be denied if competing against men. Recent wider social acceptance of transgender individuals, together with the less recognized involvement of intersex individuals, challenge and threaten to defeat the sex classifications for elite individual female events. This can create unfair advantages if seeking inclusion into elite female events of unmodified male-bodied athletes with female gender identity who have gained the physical advantages of male puberty. Based on reproductive physiology, this paper proposes a working definition of sport sex based primarily on an individual's experience of male puberty and can be applied to transgender and various XY intersex conditions. Consistent with the multidimensionality of biological sex (chromosomal, genetic, hormonal, anatomical sex), this definition may be viewed as a multistrand cable whose overall strength survives when any single strand weakens or fails, rather than as a unidimensional chain whose strength is only as good as its weakest link.
Cardiovascular-Kidney-Metabolic Syndrome: Association with Adverse Events After Major Noncardiac Surgery
Authors: Roth Sebastian , M’Pembele René , Matute Purificación , Kotfis Katarzyna , Larmann Jan , Lurati Buse Giovanna
Published: April 2024

BACKGROUND:

The American Heart Association (AHA) recently defined the cardiovascular-kidney-metabolic syndrome (CKM) as a new entity to address the complex interactions between heart, kidneys, and metabolism. The aim of this study was to assess the outcome impact of CKM syndrome in patients undergoing noncardiac surgery.

METHODS:

This is a secondary analysis of a prospective international cohort study including patients aged ≥45 years with increased cardiovascular risk undergoing noncardiac surgery. Main exposure was CKM syndrome according to the AHA definition. The primary end point was a composite of major adverse cardiovascular events (MACE) 30 days after surgery. Secondary end points included all-cause mortality and non-MACE complications (Clavien-Dindo class ≥3).

RESULTS:

This analysis included 14,634 patients (60.8% male, mean age = 72±8 years). MACE occurred in 308 patients (2.1%), and 335 patients (2.3%) died. MACE incidence by CKM stage was as follows: CKM 0: 5/367 = 1.4% (95% confidence interval [CI], 0.4%-3.2%); CKM 1: 3/367 = 0.8% (95% CI, 0.2%-2.4%); CKM 2: 102/7440 = 1.4% (95% CI, 1.1%-1.7%); CKM 3: 27/953 = 2.8% (95% CI, 1.9%-4.1%); CKM 4a: 164/5357 = 3.1% (95% CI, 2.6%-3.6%); CKM 4b: 7/150 = 4.7% (95% CI, 1.9%-9.4%). In multivariate logistic regression, CKM stage ≥3 was independently associated with MACE, mortality, and non-MACE complications, respectively (MACE: OR 2.26 [95% CI, 1.78-2.87]; mortality: OR 1.42 [95% CI: 1.13 -1.78]; non-MACE complications: OR 1.11 [95% CI: 1.03-1.20]).

CONCLUSION:

The newly defined CKM syndrome is associated with increased morbidity and mortality after non-cardiac surgery. Thus, cardiovascular, renal, and metabolic disorders should be regarded in mutual context in this setting.
Three-Dimensional Structure Light Robot-Assisted Frameless Stereotactic Brain Biopsy
Authors: Chen Jie , Cheng Xing , Huang Jiashang , Luo Pengren , Mao Deqiang , Yang Haifeng
Published: April 2024

BACKGROUND AND OBJECTIVES:

To assess the feasibility, accuracy, and safety of 3-dimensional (3D) structure light robot-assisted frameless stereotactic brain biopsy.

METHODS:

Five consecutive patients (3 males, 2 females) were included in this study. The patients' clinical, imaging, and histological data were analyzed, and all patients received a 3D structure light robot-assisted frameless stereotactic brain biopsy. The raw and/or analyzed data of the study are available from the corresponding author.

RESULTS:

The statistical results showed a mean age of 59.6 years (range 40-70 years), a mean target depth of 60.9 mm (range 53.5-65.8 mm), a mean radial error of 1.2 ± 0.7 mm (mean ± SD), a mean depth error of 0.7 ± 0.3 mm, and a mean absolute tip error of 1.5 ± 0.6 mm. The calculated Pearson product-moment correlation coefficient (r = 0.23) revealed no correlation between target depth and absolute tip error. All biopsy needles were placed in line with the planned trajectory successfully, and diagnostic specimens were harvested in all cases. Histopathological analysis revealed lymphoma (2 cases), lung adenocarcinoma (1 case), glioblastoma multiforme (1 case), and oligodendroglioma (1 case).

CONCLUSION:

Surface registration using the 3D structure light technique is fast and precise because of the achievable million-scale point cloud data of the head and face. 3D structure light robot-assisted frameless stereotactic brain biopsy is feasible, accurate, and safe.
Swimming-Induced Pulmonary Edema: Evaluation, Diagnosis, and Treatment
Authors: Steele Stephen , Brahmbhatt Sunny , Patel Devak
Published: April 2024

Swimming-induced pulmonary edema (SIPE) is a rare but life-threatening acute illness that can occur in otherwise healthy athletes and individuals. Also known as immersion pulmonary edema, SIPE presents in swimmers, snorkelers, and SCUBA divers. It occurs in persons under heavy exertion in cold water temperatures, leading to coughing, shortness of breath, and sometimes blood-tinged sputum. Under these conditions, there is increased pulmonary vascular pressure, which may ultimately lead to pulmonary edema. This article synthesizes the latest data on the prevalence, pathophysiology, etiology, risks, short- and long-term complications, and the efficacy of supportive medical treatment interventions.
Oxygen Straight to the Brain: An Overview of Hyperbaric Oxygen Therapy for a Variety of Brain Morbidities
Authors: Leighton Terrance , VanHorne Edgar , Parsons Dale
Published: April 2024

Hyperbaric oxygen therapy as a treatment for conditions like traumatic brain injury, posttraumatic stress disorder, and migraines would seem intuitive, given its effect on condition-related ischemia and inflammation. However, hyperbaric therapeutic impacts for these in acute and chronic, or prolonged symptoms are elusive. This narrative review of hyperbaric's utility provided in sections per disease renders first a review of conventional pathological mechanisms and then articulates hyperbaric treatment targets versus their respective impacts. Multiple challenges exist using hyperbaric oxygen therapy for each morbidity, even in tertiary and adjunctive treatments. An almost universal shortfall across studies includes a lack of consistent, appropriate patient selection criteria intersected with delivery timing of therapy to symptomatic target, necessary to provide a higher fidelity in treatment metrics. Further research into these respective conditions is needed along with a revisitation of hyperbaric oxygen therapy's application to their conventional pathological mechanisms, lending new perspective to their employment and efficacy.
The novel pre-rRNA detection workflow “Riboprobing” allows simple identification of undescribed RNA species.
Authors: Gerhalter Magdalena , Kofler Lisa , Zisser Gertrude , Merl-Pham Juliane , Hauck Stefanie M. , Bergler Helmut
Published: April 2024

Ribosomes translate mRNA into proteins and are essential for every living organism. In eukaryotes both ribosomal subunits are rapidly assembled in a strict hierarchical order, starting in the nucleolus with transcription of a common precursor ribosomal RNA (pre-rRNA). This pre-rRNA encodes three of the four mature rRNAs which are formed by several, consecutive endonucleolytic and exonucleolytic processing steps. Historically, Northern Blots are used to analyze the variety of different pre-rRNA species, only allowing rough length estimations. Although this limitation can be overcome with Primer Extension, both approaches often use radioactivity and are time consuming and costly. Here we present “Riboprobing” a reverse transcription-based workflow extended by linker ligation for easy and fast detection and characterization of various pre-rRNA species and their 5` as well as 3` ends. Using standard molecular biology lab equipment, our technique allows reliable discrimination of pre-rRNA species not resolved by Northern Blotting (e.g.: 27SA2, 27SA3 and 27SB). The method can be successfully used for analysis of total cell extracts as well as purified pre-ribosomes for a straightforward evaluation of the impact of mutant gene versions or inhibitors. In the course of method development, we identified and characterized a hitherto undescribed aberrant pre-rRNA, arising from LiCl inhibition. This pre-rRNA fragment spans from processing site A1 to E, forming a small RNP that is lacking most early joining assembly factors. This finding expands our knowledge of how the cell deals with severe pre-rRNA processing defects and demonstrates the strict requirement for the 5’ETS for the assembly process.
Παθοφυσιολογικές μεταβολές ερυθροκυττάρων σε ασθενείς με διπλή ετεροζυγωτία β θαλασσαιμίας / δρεπανοκυτταρικής νόσου
Authors: Γιαννάκη Αιμιλία
Published: April 2024

Η Δρεπανοκυτταρική Νόσος (ΔΝ) συνιστά μία ετερογενή ασθένεια σε ότι αφορά τη σοβαρότητα των κλινικών εκδηλώσεων, πόσο δε μάλλον στην ετερόζυγη μορφή της, κατά τη συνύπαρξή της με τη β-θαλασσαμία. Σκοπός της παρούσης μελέτης ήταν η διαστρωμάτωση των βSβ+ δειγμάτων αίματος σε σχέση με τη σοβαρότητα των κλινικών εκδηλώσεων που παρουσίαζαν. Για το σκοπό αυτό, λήφθηκαν δείγματα αίματος από τριάντα δύο (32) ασθενείς με ΔΝ, τα οποία εξετάστηκαν για διάφορες παραμέτρους (αιμόσταση, φλεγμονή, οξειδοαναγωγική ισσοροπία), σε σχέση με υγιή άτομα (controls). Συμπληρωματικά, οι δρεπανοκυτταρικοί ασθενείς εκ των υστέρων (α) κατηγοριοποιήθηκαν βάσει της δόσης της L-γλουταμίνης που έλαβαν ως συμπλήρωμα διατροφής και (β) διαχωρίστηκαν σε δύο υποομάδες υψηλού και χαμηλού RDW. Η ομάδα των ασθενών παρουσίασε αναιμία, φλεγμονή και υψηλή πηκτικότητα. Χαρακτηριστικά, η χορήγηση μεγαλύτερης δόσης L-γλουταμίνης σχετίστηκε με χαμηλότερους δείκτες φλεγμονής και οξείδωσης (π.χ. ενεργές ρίζες οξυγόνου), καθώς και τροποποιημένο προφίλ της αιμόστασης. Σε αντίθεση, η ομάδα με το υψηλό RDW παρουσίασε αυξημένη αιμόλυση, υψηλότερους δείκτες φλεγμονής, στρεσογόνου ερυθροποίησης, καθώς και οξειδωτικών φαινομένων (π.χ. αιμοσφαιρίνη δεσμευμένη στη μεμβράνη). Επιπλέον, τα επίπεδα των παραμέτρων της αιμόστασης (π.χ. τα Δ-διμερή) βρέθηκαν σαφώς υψηλότερα, σε σχέση με την ομάδα των ασθενών χαμηλού RDW. Η συγχορήγηση υψηλών δόσεων L-γλουταμίνης μαζί με υδροξυουρία, φαίνεται ότι περιορίζει μερικά δρεπανοκυτταρικά χαρακτηριστικά, πιθανόν εξαιτίας της αντιοξειδωτικής ενίσχυσης. Επιπλέον, η ανισοκυττάρωση ενδέχεται να τροποποιεί τις διαδικασίες της αιμόστασης και την τάση για αιμόλυση. Αυτό έχει ως αποτέλεσμα την αναταραχή της οξειδοαναγωγικής και της προ-αντι-φλεγμονώδους ισορροπίας, δημιουργώντας έτσι ένα θετικό κύκλο ανάδρασης, μέσω της πρόκλησης στρεσογόνου ερυθροποίησης και επομένως, της παρουσίας ανάμεικτου ερυθροκυτταρικού πληθυσμού.