bluuebunny/crossref_metadata_2025 huggingface dataset:
Intimate partner violence and its associations among HIV-infected MSM with new drug abuse in Jinan, China
Authors: Yu Yong , Cai Huiling , Chen Xi , Xiao Fuqun , Qin Keke , Li Jiahong
Published: December 2023

Background

Intimate Partner Violence (IPV) is prevalent among HIV-infected men who have sex with men (MSM), with well-established risk factors and adverse outcomes. However, there is a lack of comprehensive investigation of both upstream risk factors and downstream adverse outcomes among HIV-infected MSM in a Chinese context. This study aimed to examine IPV and its associations among a Chinese sample of HIV-infected MSM.

Methods

A cross-sectional study was conducted among 294 HIV-infected MSM in Jinan City from June to December 2020. All data were collected through an online questionnaire, which included IPV, sexual risk behavior, antiretroviral therapy (ART) adherence, depression, anxiety, and suicidal ideation. Chi-square tests and multivariate logistic regressions were performed to examine risk factors and adverse outcomes of IPV.

Results

Of the 294 HIV-infected MSM, 71.1% experienced any IPV, including control (37.1%), threat of public identity (30.6%), emotional violence (25.2%), security threat (18.4%), and physical violence (13.9%). The prevalence of sexual risk behavior, good ART adherence, depression, anxiety, and suicidal ideation was 55.1%, 53.4%, 48.3%, 32.3%, and 65.0%, respectively. Abuse of methamphetamine (METH) (aOR:2.79; 95%CI:1.43 ~ 5.45), capsule 0 or stimulating liquid (aOR:2.68; 95%CI:1.31 ~ 5.47), Magu (aOR:3.16; 95%CI:1.51 ~ 6.60), and other new drugs (aOR:2.87; 95%CI:1.52 ~ 5.43), disclosing HIV infection to partners (aOR:2.03; 95%CI:1.10 ~ 3.78), and gay sexual orientation (aOR = 3.32; 95%CI: 1.82 ~ 6.05) were significantly correlated with the experience of IPV. In addition, IPV was significantly associated with sexual risk behavior (aOR = 2.02; 95%CI:1.16 ~ 3.53), ART adherence (aOR = 2.63; 95%CI:1.46 ~ 4.74), depression (aOR = 3.83; 95%CI:2.09 ~ 7.02), anxiety (aOR = 2.27; 95%CI:1.19 ~ 4.35), and suicidal ideation (aOR = 3.78; 95%CI:2.11 ~ 6.80).

Conclusions

IPV is prevalent among HIV-infected MSM and is associated with poor behavioral and mental health, highlighting more efforts are needed to address this issue. The finding that new drug abuse, HIV disclosure, and gay sexual orientation are associated with increased risk of IPV provides essential insights for the development of comprehensive and targeted IPV prevention and intervention programs in the future.
A comparative analysis of suture-augmented and standard hamstring autograft single-bundle ACL reconstruction outcomes: short-term functional benefits without long-term impact
Authors: Tavakoli Darestani Reza , Afzal Sina , Pourmojarab Ali , Baroutkoub Mojtaba , Sayyadi Shahram , Barati Hasan
Published: December 2023

Background

Augmentation of the biologic graft with nonabsorbable suture material during anterior cruciate ligament reconstruction (ACLR) is a relatively new technique to enhance its biomechanical properties and add additional support to the critical process of healing. We aimed to compare the short-term functional patient-reported outcome measures (PROMs) and complication rates of patients treated with either standard single-bundle four-strand hamstring ACLR or added suture augmentation (SA).

Methods

Patients undergoing arthroscopic ACLR between February 2015-January 2017 and in the standard ACLR group, and between February 2017-September 2019 in the SA-ACLR group operated by adding a no.5 FiberWire® (Arthrex, Naples, FL, USA) braided suture to the hamstring autograft, were retrospectively reviewed and the PROMs were compared. Patients were followed up for a 24-month period and PROMs were assessed by the International Knee Documentation Committee (IKDC) Subjective Knee Form and Tegner-Lysholm knee score. Patients’ demographic and clinical characteristics, and postoperative complications including graft retear requiring revision surgery, deep vein thrombois, and surgical site infection were recorded and analyzed.

Results

We included 79 patients with mean age of 31.6 ± 8.3 years in the standard ACLR group, and 90 patients with mean oge of 30.5 ± 7.6 in the SA-ACLR group. There was no statistically significant difference between the two groups in terms of age, sex, body mass index, and medical comorbidities. The values of the IKDC scores increased to 75.8 ± 18.9 in the standard ACLR group, and 85.6 ± 12.6 in the SA-ACLR group, 24 months after the operation (P < 0.05). The 24-month postoperative Tegner-Lysholm scores escalated to 79.3 ± 21.0 in the standard ACLR group and 91.0 ± 13.7 in the SA-ACLR group (P < 0.05). Four (5.1%) patients in the standard ACLR group and 4 (4.4%) in the SA-ACLR group experienced graft retear requiring revision surgery (P > 0.05). Incidence of surgical site infection and deep vein thrombosis showed no significant differences between the two groups, 24 months after ACLR.

Conclusion

SA-ACLR is associated with improved short-term functional PROMs compared to the standard hamstring ACLR. Although SA did not reduce the retear rate, and infection and DVT rates did not differ between study groups, superior improvement of PROMs in SA approach, leverages this method for ACLR.
A randomized phase II study of acyclovir for the prevention of chemotherapy-induced oral mucositis in patients undergoing autologous hematopoietic stem cell transplantation
Authors: Hong Junshik , Park Hee-Kyung , Chang Sung-Ho , Byun Ja Min , Shin Dong-Yeop , Koh Youngil , Yoon Sung-Soo , Choi Youngnim , Kim Inho
Published: December 2023

Objectives

To prove our hypothesis that acyclovir prophylaxis in autologous hematopoietic stem cell transplantation (AHSCT) recipients with hematologic malignancies (HM) reduces the incidence of chemotherapy-induced oral mucositis (CIOM) by inhibiting the intraoral HSV reactivation during the neutropenic period, we conducted a randomized phase II study of acyclovir for the prevention of CIOM in adult HSV sero-positive AHSCT recipients.

Methods

Patients were randomized to either the study group (acyclovir 400 mg PO bid until neutrophil engraftment) or the control group (no prophylaxis) and received AHSCT. Oral examination and sampling for HSV were performed at three timepoints of AHSCT.

Results

In 54 patients who were randomized (for intention-to-analysis), the incidence of CIOM was 16.0% (4/25 patients) and 58.6% (17/29 patients) in the study group and the control group, respectively (P = 0.001). In 49 patients who completed the study (for per-protocol analysis), the incidence of CIOM was 13.0% (3/23 patients) and 61.5% (16/26 patients) in the study group and the control group, respectively (P = 0.001). In addition, HSV-1 PCR positivity in the study group was significantly lower than that the control group (4.3% vs. 46.2%, P = 0.001). A strong association between the HSV-1 reactivation status and CIOM was reconfirmed.

Conclusions

Prophylactic use of oral acyclovir effectively reduced the incidence of CIOM in patients with HM who were undergoing AHSCT.

Trial registrations

This trial was registered at the Clinical Research Information Service in the Republic of Korea under the number KCT0003885 (registration date 03/05/2019).
Effectiveness of using 2D atlas and 3D PDF as a teaching tool in anatomy lectures in initial learners: a randomized controlled trial in a medical school
Authors: Eroğlu Fatma Sıla , Erkan Beyza , Koyuncu Sevil Buket , Komşal Zeynep Rumeysa , Çiçek Feray Ekin , Ülker Müşerref , Toklu Merve Ebrar , Atlan Melike , Kıyak Yavuz Selim , Kula Serdar , Coşkun Özlem , Budakoğlu Işıl İrem
Published: December 2023

Background

Anatomy is a crucial part of medical education, and there have been attempts to improve this field by utilizing various methods. With the advancement of technology, three-dimensional (3D) materials have gained popularity and become a matter of debate about their effectiveness compared to two-dimensional (2D) sources. This research aims to analyze the effectiveness of 3D PDFs compared to 2D atlases.

Methods

This study is a randomized controlled trial involving 87 Year-1 and Year-2 medical students at Gazi University Faculty of Medicine, Turkey. The study was conducted in two steps. In Step-1, students were randomized to watch lecture videos on liver anatomy and male genitalia anatomy supplemented with either a 3D PDF (intervention group) or 2D atlas (control group) images. Following the video lectures, a test (immediate test) was administered. In Step-2, the same test (delayed test) was administered 10 days after the immediate test. The test scores were compared between the intervention and control groups. In addition to the descriptive analyses, Chi-square and Mann-Whitney U tests were performed.

Results

In the immediate test, while there was no significant difference between the groups for the liver test (p > 0.05), 3D PDF group’s scores (Median = 24.50) was significantly higher than the 2D atlas group’s in the genitalia test (Median = 21.00), (p = 0.017). The effect size (Cohen’s d) was 0.57. In the delayed test, there was no significant difference between the groups in the liver and genitalia tests (p > 0.05). However, the effect size in the immediate genitalia test was 0.40. Year-1 students’ immediate test of genitalia performances were significantly higher in the 3D PDF group (Median = 24.00) than the 2D atlas group (Median = 19.00), (p = 0.016). The effect size was 0.76. Also, Year-1 students’ 3D PDF group (Median = 20.50) presented with significantly higher performance than the 2D atlas group (Median = 12.00), (p = 0.044) in the delayed test of genitalia, with the 0.63 effect size.

Conclusion

3D PDF is more effective than 2D atlases in teaching anatomy, especially to initial learners. It is particularly useful for teaching complex anatomical structures, such as male genitalia, compared to the liver. Hence, it may be a valuable tool for medical teachers to utilize during lectures.
The application of artificial intelligence in health policy: a scoping review
Authors: Ramezani Maryam , Takian Amirhossein , Bakhtiari Ahad , Rabiee Hamid R. , Ghazanfari Sadegh , Mostafavi Hakimeh
Published: December 2023

Background

Policymakers require precise and in-time information to make informed decisions in complex environments such as health systems. Artificial intelligence (AI) is a novel approach that makes collecting and analyzing data in complex systems more accessible. This study highlights recent research on AI’s application and capabilities in health policymaking.

Methods

We searched PubMed, Scopus, and the Web of Science databases to find relevant studies from 2000 to 2023, using the keywords “artificial intelligence” and “policymaking.” We used Walt and Gilson’s policy triangle framework for charting the data.

Results

The results revealed that using AI in health policy paved the way for novel analyses and innovative solutions for intelligent decision-making and data collection, potentially enhancing policymaking capacities, particularly in the evaluation phase. It can also be employed to create innovative agendas with fewer political constraints and greater rationality, resulting in evidence-based policies. By creating new platforms and toolkits, AI also offers the chance to make judgments based on solid facts. The majority of the proposed AI solutions for health policy aim to improve decision-making rather than replace experts.

Conclusion

Numerous approaches exist for AI to influence the health policymaking process. Health systems can benefit from AI’s potential to foster the meaningful use of evidence-based policymaking.
Job satisfaction and regulation in the aged care sector: staff perspectives
Authors: Cameron Emilie , Noble Natasha , Bryant Jamie , Norton Grace , Allanson OAM Viv , Sanson-Fisher Rob
Published: December 2023

Background

The quality of care provided in residential aged care facilities is largely dependent on the job satisfaction of employees and the organisational framework and systems that they provide care in. This study aimed to explore aged care staff perceptions of job satisfaction, regulation of the sector and the Royal Commission into Aged Care Quality and Safety.

Methods

A cross-sectional survey conducted in 2019-early 2020 with staff employed in various roles at residential aged care services in Australia. The study specific survey collected views and experiences about working in the aged care sector as well as information about their role.

Results

A total of 167 aged care staff completed the survey of which 71% worked in a direct care role. Most participants indicated they thought they were doing a worthwhile and important job (98%), were proud to work in the sector (94%) and found the job personally rewarding (94%). However, participants also reported feeling emotionally drained by the work (37%) and fatigued by having to face a day of work (30%). 72% of participants felt the Royal Commission would lead to improvements in the care provided to residents.

Conclusion

Aged care staff have an overall positive feeling towards their work. Additional support including increasing skills to deliver high-quality care, creating a supportive work environment to reduce job stressors and changes to the way the sector is regulated, are likely to lead to improved care.
The triglyceride glucose index trajectory is associated with hypertension: a retrospective longitudinal cohort study
Authors: Xin Fengling , He Shuyou , Zhou Yu , Jia Xueni , Zhao Yulong , Zhao Hui
Published: December 2023

Background

Previous studies have found that the triglyceride glucose index (TyG index) trajectories are associated with cardiovascular diseases. However, the association between the patterns of TyG index trajectories and risk for hypertension has not been investigated. In a longitudinal general population, we aimed to identify distinct TyG index trajectories over 12 years and describe their association with incidence of hypertension.

Method

Of the 15,056 adults retrospectively recruited from the Physical Examination Center of the Second Affiliated Hospital of Dalian Medical University in northeast of China from 2011 to 2022. TyG index was calculated as ln (fasting TG [mg/dL] × FPG [mg/dL]/2) and the TyG index trajectories were developed using group-based trajectory modelling. Cox regression analysis was accomplished to assess the association between TyG index and incidence of hypertension.

Results

The median age of the population was 38 years, and 7352 (48.83%) of the participants were men. Three distinct TyG index trajectories were identified: “low increasing” (N = 7241), “moderate increasing” (N = 6448), and “high stable” (N = 1367). Using “low increasing” trajectory as a reference, “moderate increasing” and “high stable” trajectory were associated with increased risk of hypertension (HR = 2.45; 95% CI 2.25–2.67 and HR = 3.88; 95% CI 3.48–4.33). After adjusting for baseline sex, age, diabetes, smoking, systolic blood pressure, diastolic blood pressure, BMI, cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood glucose, triglyceride, urea, uric acid, and glomerular filtration rate, the HR were slightly attenuate in “moderate increasing” and “high stable” trajectories to 1.38 (95% CI 1.23–1.54) and 1.69 (95% CI 1.40–2.02) respectively. Meanwhile, similar results were observed in multiple sensitivity analyses. The HR of the “moderate increasing” and “high stable” trajectory groups were 2.63 (95% CI 2.30–3.00) and 4.66 (95% CI 3.66–5.93) in female, and 1.66 (95% CI 1.48–1.86) and 2.33 (95% CI 2.04–2.66) in male.

Conclusions

Elevated TyG index at baseline and long-term TyG index trajectories were associated with the risk of hypertension. Early identification of increasing TyG index could provide insights for preventing hypertension later in life.
Is intimate partner violence vertically transmitted among women in sub-Saharan Africa? Evidence from demographic health surveys between 2010 and 2019
Authors: Alawode Oluwatobi Abel , Bolarinwa Obasanjo Afolabi , Hajjar Julia Marie , Chukwudeh Stephen Okechukwu , Yaya Sanni
Published: December 2023

Background

Violence against women is a major human rights violation, and the continuous occurrence of this can have many implications for women’s social and health outcomes. The experience of violence from an intimate partner could be more intriguing, especially if such women experienced their mother’s intimate partner violence (IPV) issues. Thus, this study examined the vertical transmission of IPV among women in sub-Saharan Africa (SSA).

Methods

A total of 97,542 eligible women were drawn from 27 countries in SSA using a retrospective secondary dataset from Demographic Health Surveys conducted between 2010 and 2019. Multivariable analysis was employed to determine the association between the vertical transmission of IPV from mother to daughter and the covariates associated with IPV in SSA at p < 0.05.

Results

The results showed that 40% of the respondents had experienced lifetime IPV, whilst 25% of those women reported that their mothers experienced it in childhood in SSA. Country-specific variations showed the highest prevalence of IPV experienced in Sierra Leone (60%) and the lowest in Comoros (9%). Results from model 1 showed that women who reported that their mothers experienced IPV were found to be significantly more than two times more likely to have experienced any form of IPV compared to those whose mothers did not (aOR = 2.66; 95% CI: 2.59–2.74), after adjusting for cofounders in Model 2, the result still showed that women who reported that their mothers experienced IPV were found to be significantly more than two times more likely to have experienced any form of IPV compared to those whose mothers did not (aOR = 2.56; 95% CI: 2.48–2.63). On the other hand, women with higher-educated partners, women in rural areas, and those from female-headed households were less likely to experience IPV.

Conclusion

This study concluded that women whose mothers experienced IPV were more likely to have experienced IPV. Our study also identified that education, rural areas, and female-headed households were protective factors against experiencing IPV. To address the groups of women at higher risk for experiencing IPV, we recommend ensuring that girls complete their education to promote greater wealth and resources.
Lonidamine liposomes to enhance photodynamic and photothermal therapy of hepatocellular carcinoma by inhibiting glycolysis
Authors: Lei Lei , Dai Wenbin , Man Jiaping , Hu Haitao , Jin Qiao , Zhang Bo , Tang Zhe
Published: December 2023

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has great promise in the treatment of cancer. However, there are many obstacles that can restrict the therapeutic efficacy of phototherapy. The hypoxic tumor microenvironment can restrict the production of reactive oxygen species (ROS) in PDT. As for PTT, the thermotolerance of cancer cells may lead to ineffective PTT. In this study, IR780 and glycolysis inhibitor lonidamine (LND)-encapsulated liposomes are prepared for photodynamic and photothermal therapy of hepatocellular carcinoma. IR780 can be used as a photosensitizer and photothermal agent for simultaneous PDT and PTT after being irradiated with 808 nm laser. LND can reduce the oxygen consumption of cancer cells by inhibiting glycolysis, which will relieve tumor hypoxia and produce more ROS for PDT. On the other hand, energy supply can be blocked by LND-induced glycolysis inhibition, which will inhibit the production of heat shock proteins (HSPs), reduce the thermotolerance of tumor cells, and finally enhance the therapeutic efficacy of PTT. The enhanced PTT is studied by measuring intracellular HSPs, ATP level, and mitochondrial membrane potential. The antitumor effect of IR780 and LND co-loaded liposomes is extensively investigated by in vitro and in vivo experiments. This research provides an innovative strategy to simultaneously enhance the therapeutic efficacy of PDT and PTT by inhibiting glycolysis, which is promising for future creative approaches to cancer phototherapy.
Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells
Authors: Kundu Snehangshu , Nunes Luís , Adler Jeremy , Mathot Lucy , Stoimenov Ivaylo , Sjöblom Tobias
Published: December 2023

Background

Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We therefore integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1 mutations for functional studies to understand their contribution to cancer development and metastasis.

Methods

Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed with a bioinformatic pipeline to find 3D-mutated cluster pairs and hotspot mutations in EPH receptors. From these, 15 recurring EPHB1 mutations were stably expressed in colorectal cancer followed by confocal microscopy based in vitro compartmentalisation assays and phospho-proteome analysis.

Results

The 3D-protein structure-based bioinformatics analysis resulted in 63% EPHB1 mutants with compartmentalisation phenotypes vs 43% for hotspot mutations. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation.

Conclusions

This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations, uncovering EPHB1 mutation phenotypes and demonstrating the utility of protein structure-based mutation analysis in characterization of novel cancer genes.
The role of m6A epigenetic modifications in tumor coding and non-coding RNA processing
Authors: Wen Tongxuan , Li Tong , Xu Yeqiu , Zhang Yuanzhuang , Pan Hai , Wang Yong
Published: December 2023

Background

Epigenetic modifications of RNA significantly contribute to the regulatory processes in tumors and have, thus, received considerable attention. The m6A modification, known as N6-methyladenosine, is the predominant epigenetic alteration found in both eukaryotic mRNAs and ncRNAs.

Main body

m6A methylation modifications are dynamically reversible and are catalyzed, removed, and recognized by the complex of m6A methyltransferase (MTases), m6A demethylase, and m6A methyl recognition proteins (MRPs). Published evidence suggests that dysregulated m6A modification results in abnormal biological behavior of mature mRNA, leading to a variety of abnormal physiological processes, with profound implications for tumor development in particular.

Conclusion

Abnormal RNA processing due to dysregulation of m6A modification plays an important role in tumor pathogenesis and potential mechanisms of action. In this review, we comprehensively explored the mechanisms by which m6A modification regulates mRNA and ncRNA processing, focusing on their roles in tumors, and aiming to understand the important regulatory function of m6A modification, a key RNA epigenetic modification, in tumor cells, with a view to providing theoretical support for tumor diagnosis and treatment.
Inhaled nitric oxide suppresses neuroinflammation in experimental ischemic stroke
Authors: Sienel Rebecca I. , Mamrak Uta , Biller Janina , Roth Stefan , Zellner Andreas , Parakaw Tipparat , Khambata Rayomand S. , Liesz Arthur , Haffner Christof , Ahluwalia Amrita , Seker Burcu F. , Plesnila Nikolaus
Published: December 2023

Ischemic stroke is a major global health issue and characterized by acute vascular dysfunction and subsequent neuroinflammation. However, the relationship between these processes remains elusive. In the current study, we investigated whether alleviating vascular dysfunction by restoring vascular nitric oxide (NO) reduces post-stroke inflammation. Mice were subjected to experimental stroke and received inhaled NO (iNO; 50 ppm) after reperfusion. iNO normalized vascular cyclic guanosine monophosphate (cGMP) levels, reduced the elevated expression of intercellular adhesion molecule-1 (ICAM-1), and returned leukocyte adhesion to baseline levels. Reduction of vascular pathology significantly reduced the inflammatory cytokines interleukin-1β (Il-1β), interleukin-6 (Il-6), and tumor necrosis factor-α (TNF-α), within the brain parenchyma. These findings suggest that vascular dysfunction is responsible for leukocyte adhesion and that these processes drive parenchymal inflammation. Reversing vascular dysfunction may therefore emerge as a novel approach to diminish neuroinflammation after ischemic stroke and possibly other ischemic disorders.
The inter-link of ageing, cancer and immunity: findings from real-world retrospective study
Authors: Fu Xiaomin , Qin Peng , Li Fanghui , Zhu Huifang , You Hongqin , Zhang Yong , Xu Benling , Li Tiepeng , Zhang Fang , Han Lu , Zhao Lingdi , Ma Baozhen , Wang Zibing , Gao Quanli
Published: December 2023

Background

Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce.

Methods

In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software.

Results

Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05).

Conclusions

This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.
The oral sensory organs in Bathochordaeus stygius (Tunicata Appendicularia) are unique in structure and homologous to the coronal organ
Authors: Le Mai-Lee Van , Müller Lisa-Marie , Stach Thomas
Published: December 2023

Background

Appendicularia consists of approximately 70 purely marine species that belong to Tunicata the probable sister taxon to Craniota. Therefore, Appendicularia plays a pivotal role for our understanding of chordate evolution. In addition, appendicularians are an important part of the epipelagic marine plankton. Nevertheless, little is known about appendicularian species, especially from deeper water.

Results

Using µCT, scanning electron microscopy, and digital 3D-reconstruction techniques we describe three pairs of complex oral sensory organs in the mesopelagic appendicularian Bathochordaeus stygius. The oral sensory organs are situated at the anterior and lateral margin of the mouth and inside the mouth cavity. A single organ consists of 22–90 secondary receptor cells that project apical cilia through a narrow hole in the epidermis. The receptor cells are innervated by branches of the second brain nerve.

Conclusions

Based on position, morphology, and innervation we suggest that the oral sensory organs are homologues of the coronal organs in other tunicates. We discuss the hypothesized homology of coronal organs and the lateral line system of primary aquatic vertebrates. The complex oral sensory organs of B. stygius are unique in tunicates and could be adaptations to the more muffled environment of the mesopelagic.
Efficacy of recombinant H5 vaccines delivered in ovo or day of age in commercial broilers against the 2015 U.S. H5N2 clade 2.3.4.4c highly pathogenic avian Influenza virus
Authors: Kapczynski Darrell R. , Chrzastek Klaudia , Shanmugasundaram Revathi , Zsak Aniko , Segovia Karen , Sellers Holly , Suarez David L.
Published: December 2023

Background

Avian influenza is a highly contagious, agriculturally relevant disease that can severely affect the poultry industry and food supply. Eurasian-origin H5Nx highly pathogenic avian influenza viruses (HPAIV) (clade 2.3.4.4) have been circulating globally in wild birds with spill over into commercial poultry operations. The negative impact to commercial poultry renewed interest in the development of vaccines against these viruses to control outbreaks in the U.S.

Methods

The efficacy of three recombinant H5 vaccines delivered in ovo or day of age were evaluated in commercial broilers challenged with the 2015 U.S. H5N2 clade 2.3.4.4c HPAIV. The recombinant vaccines included an alphavirus RNA particle vaccine (RP-H5), an inactivated reverse genetics-derived (RG-H5) and recombinant HVT vaccine (rHVT-AI) expressing H5 hemagglutinin (HA) genes. In the first experiment, in ovo vaccination with RP-H5 or rHVT-AI was tested against HPAI challenge at 3 or 6 weeks of age. In a second experiment, broilers were vaccinated at 1 day of age with a dose of either 107 or 108 RP-H5, or RG-H5 (512 HA units (HAU) per dose).

Results

In experiment one, the RP-H5 provided no protection following in ovo application, and shedding titers were similar to sham vaccinated birds. However, when the RP-H5 was delivered in ovo with a boost at 3 weeks, 95% protection was demonstrated at 6 weeks of age. The rHVT-AI vaccine demonstrated 95 and 100% protection at 3 and 6 weeks of age, respectively, of challenged broilers with reduced virus shedding compared to sham vaccinated birds. Finally, when the RP-H5 and rHVT vaccines were co-administered at one day of age, 95% protection was demonstrated with challenge at either 3 or 6 weeks age. In the second experiment, the highest protection (92%) was observed in the 108 RP-H5 vaccinated group. Significant reductions (p < 0.05) in virus shedding were observed in groups of vaccinated birds that were protected from challenge. The RG-H5 provided 62% protection from challenge. In all groups of surviving birds, antibody titers increased following challenge.

Conclusions

Overall, these results demonstrated several strategies that could be considered to protected broiler chickens during a H5 HPAI challenge.
Optimizing COVID-19 treatment in immunocompromised patients: early combination therapy with remdesivir, nirmatrelvir/ritonavir and sotrovimab
Authors: Gentile Ivan , Foggia Maria , Silvitelli Maria , Sardanelli Alessia , Cattaneo Letizia , Viceconte Giulio
Published: December 2023

Background

Morbidity and mortality are higher in immunocompromised patients affected by COVID-19 than in the general population. Some authors have successfully used antiviral combination, but never in the early phase of the infection.

Methods

We conducted a retrospective cohort study to determine the efficacy and safety of the combination of two antivirals, with and without a monoclonal antibody (mAb), in both the early (within 10 days of symptoms) and in a later phase (after 10 days) of SARS-CoV-2 infection in immunocompromised patients admitted to our Facility.

Results

We treated 11 patients (seven in an early phase and four in a late phase of COVID-19) with 10 days of intravenous remdesivir plus five days of oral nirmatelvir/ritonavir, also combined with sotrovimab in 10/11 cases. Notably, all the “early” patients reached virological clearance at day 30 from the end of the therapy and were alive and well at follow-up, whereas the corresponding numbers in the “late” patients were 50% and 75%. Patients in the “late” group more frequently needed oxygen supplementation (p = 0.015) and steroid therapy (p = 0.045) during admission and reached higher COVID-19 severity (p = 0.017).

Discussion

The combination of antiviral and sotrovimab in the early phase of COVID-19 is well tolerated by immunocompromised patients and is associated with 100% of virological clearance. Patients treated later have lower response rates and higher disease severity, but whether therapy plays a causative role in such findings has yet to be determined.
Physical workload and cardiopulmonary parameters in relation to individual capacity of bulk waste workers – a cross-sectional field-study
Authors: Kraft Alexander Michael , Velasco Garrido Marcial , Herold Robert , Harth Volker , Preisser Alexandra Marita
Published: December 2023

Purpose

Waste collection is considered particularly heavy work, although no previous study has yet investigated the strain of bulk waste collection. The aim of this study is to determine the workload of bulk waste workers in practice.

Method

We conducted a cross-sectional field-study. Fourteen male volunteers from the bulk waste collection of the municipal sanitation department in Hamburg, Germany, were included. Performance was determined by cardiopulmonary exercise testing under laboratory conditions. During the shift, each worker was accompanied by a researcher, and heart rate (HR) was recorded under field conditions using an HR watch with a belt system. We examined mean HR, relative heart rate (RHR), relative aerobic strain (RAS), calculated oxygen uptake ($$\mathrm{\overset{.}{V}O}_2$$

V
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)  and individual ventilatory threshold 1 (VT1) as parameters of workload during their daily work.

Results

During the shift, HR was scaled: 102 bpm (SD 10.2), RHR: 36.9%, $$\mathrm{\overset{.}{V}O}_2$$

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: 1267 ml/min (SD 161), RAS: 49.4% (SD 9.3), and $$\mathrm{\overset{.}{V}O}_2$$

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 in relation to VT1: 75% (SD 18.5). There was no significant difference between oxygen consumption during the main task of lifting and carrying bulky waste and the individual $$\mathrm{\overset{.}{V}O}_2$$

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 at VT1.

Conclusion

Although the burden of the main task of lifting and carrying bulky waste is very high (at VT1 for more than 3 h), interruptions from other tasks or formal breaks spread the burden over the entire shift. The total workload exceeded most recommendations in the literature across the different work periods. However, the total burden remains below VT1, the only parameter that takes individual endurance performance into account. We recommend again VT1 as an individual upper limit for prolonged occupational work.
The potential roles of gossypol as anticancer agent: advances and future directions
Authors: Paunovic Danijela , Rajkovic Jovana , Novakovic Radmila , Grujic-Milanovic Jelica , Mekky Reham Hassan , Popa Dragos , Calina Daniela , Sharifi-Rad Javad
Published: December 2023

Gossypol, a polyphenolic aldehyde derived from cottonseed plants, has seen a transformation in its pharmaceutical application from a male contraceptive to a candidate for cancer therapy. This shift is supported by its recognized antitumor properties, which have prompted its investigation in the treatment of various cancers and related inflammatory conditions. This review synthesizes the current understanding of gossypol as an anticancer agent, focusing on its pharmacological mechanisms, strategies to enhance its clinical efficacy, and the status of ongoing clinical evaluations.

The methodological approach to this review involved a systematic search across several scientific databases including the National Center for Biotechnology Information (NCBI), PubMed/MedLine, Google Scholar, Scopus, and TRIP. Studies were meticulously chosen to cover various aspects of gossypol, from its chemical structure and natural sources to its pharmacokinetics and confirmed anticancer efficacy. Specific MeSH terms and keywords related to gossypol’s antineoplastic applications guided the search strategy.

Results from selected pharmacological studies indicate that gossypol inhibits the Bcl-2 family of anti-apoptotic proteins, promoting apoptosis in tumor cells. Clinical trials, particularly phase I and II, reveal gossypol’s promise as an anticancer agent, demonstrating efficacy and manageable toxicity profiles. The review identifies the development of gossypol derivatives and novel carriers as avenues to enhance therapeutic outcomes and mitigate adverse effects.

Conclusively, gossypol represents a promising anticancer agent with considerable therapeutic potential. However, further research is needed to refine gossypol-based therapies, explore combination treatments, and verify their effectiveness across cancer types. The ongoing clinical trials continue to support its potential, suggesting a future where gossypol could play a significant role in cancer treatment protocols.
Haematological reference intervals for pregnant Icelandic mares on pasture
Authors: Oddsdóttir Charlotta , Jónsdóttir Hanna Kristrún , Sturludóttir Erla
Published: December 2023

Background

Few studies have been conducted on haematological reference intervals (RIs) in Icelandic horses. Reference intervals have been published for Icelandic horses in Austria and a preliminary study in Iceland compared haematological values in riding horses to published RIs for other breeds as well as Icelandic horses abroad. Haematological parameters can vary greatly due to factors such as breed, gender, age, reproductive status, and training, as well as feeding, prior exercise and management method. Icelandic broodmares are kept on pasture under supervision throughout the year, with haylage provided during the winter, and it is therefore of interest to establish haematological reference intervals for pregnant broodmares in Iceland. The purpose of this study was to establish haematological RIs specific to Icelandic broodmares in the first months of pregnancy, kept on pasture. Blood samples from 183 mares, stabilised in EDTA were analysed using IDEXX ProCyte Dx and total protein was analysed in serum samples from 157 of the 183 mares, using IDEXX Catalyst One analyser. The RIs were established using the guidelines of the American Society for Veterinary Clinical Pathology.

Results

The RIs for red blood cell count, haematocrit and haemoglobin were higher in pasture-kept Icelandic mares in early pregnancy, most of which were lactating, than in pregnant mares of other breeds. This was also true for white blood cell count, as well as numbers of monocytes, eosinophils, and basophils, which in some instances might illustrate problems in the automated categorisation of some leukocytes.

Conclusions

As no RIs have been published for other pasture-kept Icelandic horses, future investigations should include other groups of pasture-kept Icelandic horses. Such an analysis might elucidate the effect of breed, management, and pregnancy on haematological values in pasture-kept Icelandic horses.
Pathophysiology of ion channels in amyotrophic lateral sclerosis
Authors: Stringer Robin N. , Weiss Norbert
Published: December 2023

Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion channels and alteration in neuronal excitability represent a hallmark of the disease, manifesting not only during the symptomatic period but also in the early pre-symptomatic stages. In this review, we delve into these alterations observed in ALS patients and preclinical disease models, and explore their consequences on neuronal activities. Furthermore, we discuss the potential of ion channels as therapeutic targets in the context of ALS.
Immunotheranostic target modules for imaging and navigation of UniCAR T-cells to strike FAP-expressing cells and the tumor microenvironment
Authors: Loureiro Liliana R. , Hoffmann Lydia , Neuber Christin , Rupp Luise , Arndt Claudia , Kegler Alexandra , Kubeil Manja , Hagemeyer Christoph E. , Stephan Holger , Schmitz Marc , Feldmann Anja , Bachmann Michael
Published: December 2023

Background

Chimeric antigen receptor (CAR) T-cells are a promising approach in cancer immunotherapy, particularly for treating hematologic malignancies. Yet, their effectiveness is limited when tackling solid tumors, where immune cell infiltration and immunosuppressive tumor microenvironments (TME) are major hurdles. Fibroblast activation protein (FAP) is highly expressed on cancer-associated fibroblasts (CAFs) and various tumor cells, playing an important role in tumor growth and immunosuppression. Aiming to modulate the TME with increased clinical safety and effectiveness, we developed novel small and size-extended immunotheranostic UniCAR target modules (TMs) targeting FAP.

Methods

The specific binding and functionality of the αFAP-scFv TM and the size-extended αFAP-IgG4 TM were assessed using 2D and 3D in vitro models as well as in vivo. Their specific tumor accumulation and diagnostic potential were evaluated using PET studies after functionalization with a chelator and suitable radionuclide.

Results

The αFAP-scFv and -IgG4 TMs effectively and specifically redirected UniCAR T-cells using 2D, 3D, and in vivo models. Moreover, a remarkably high and specific accumulation of radiolabeled FAP-targeting TMs at the tumor site of xenograft mouse models was observed.

Conclusions

These findings demonstrate that the novel αFAP TMs are promising immunotheranostic tools to foster cancer imaging and treatment, paving the way for a more convenient, individualized, and safer treatment of cancer patients.

Graphical Abstract
Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development
Authors: Jian Congcong , Wei Lingli , Wu Tong , Li Shilin , Wang Tingting , Chen Jianghua , Chang Shengjia , Zhang Jie , He Binhan , Wu Jianhong , Su Jiang , Zhu Jing , Wu Min , Zhang Yan , Zeng Fanxin
Published: December 2023

Objectives

Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis.

Methods

A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects.

Results

Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort.

Conclusions

These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
Neural EGFL-like 1, a craniosynostosis-related osteochondrogenic molecule, strikingly associates with neurodevelopmental pathologies
Authors: Li Chenshuang , Zheng Zhong , Ha Pin , Jiang Wenlu , Soo Chia , Ting Kang
Published: December 2023

Various craniofacial syndromes cause skeletal malformations and are accompanied by neurological abnormalities at different levels, leading to tremendous biomedical, financial, social, and psychological burdens. Accumulating evidence highlights the importance of identifying and characterizing the genetic basis that synchronously modulates musculoskeletal and neurobehavioral development and function. Particularly, previous studies from different groups have suggested that neural EGFL-like-1 (Nell-1), a well-established osteochondrogenic inducer whose biopotency was initially identified in the craniofacial tissues, may also play a vital role in the central nervous system, particularly regarding neurological disorder pathologies. To provide first-hand behavior evidence if Nell-1 also has a role in central nervous system abnormalities, we compared the Nell-1-haploinsufficient (Nell-1+/6R) mice with their wild-type counterparts regarding their repetitive, social communication, anxiety-related, locomotor, sensory processing-related, motor coordination, and Pavlovian learning and memory behaviors, as well as their hippocampus transcriptional profile. Interestingly, Nell-1+/6R mice demonstrated core autism spectrum disorder-like deficits, which could be corrected by Risperidone, an FDA-approved anti-autism, anti-bipolar medicine. Besides, transcriptomic analyses identified 269 differential expressed genes, as well as significantly shifted alternative splicing of ubiquitin B pseudogene Gm1821, in the Nell-1+/6R mouse hippocampus, which confirmed that Nell-1 plays a role in neurodevelopment. Therefore, the current study verifies that Nell-1 regulates neurological development and function for the first time. Moreover, this study opens new avenues for understanding and treating craniofacial patients suffering from skeletal deformities and behavior, memory, and cognition difficulties by uncovering a novel bone-brain-crosstalk network. Furthermore, the transcriptomic analysis provides the first insight into deciphering the mechanism of Nell-1 in neurodevelopment.