bluuebunny/crossref_metadata_2025_split huggingface dataset:
Senna occidentalis (L.) Link root extract inhibits Plasmodium growth in vitro and in mice
Authors: Mogaka Simeon , Molu Halkano , Kagasi Esther , Ogila Kenneth , Waihenya Rebeccah , Onditi Faith , Ozwara Hastings 
Published: March 2023

Abstract
Background
Senna occidentalis (L.) Link has been used worldwide in traditional treatment of many diseases and conditions including snakebite. In Kenya, a decoction from the plant roots taken orally, is used as a cure for malaria. Several studies have demonstrated that extracts from the plant possess antiplasmodial activity, in vitro. However, the safety and curative potency of the plant root against established malaria infection is yet to be scientifically validated, in vivo. On the other hand, there are reports on variation in bioactivity of extracts obtained from this plant species, depending on the plant part used and place of origin among other factors. In this study, we demonstrated the antiplasmodial activity of Senna occidentalis roots extract in vitro, and in mice.

Methods
Methanol, ethyl acetate, chloroform, hexane and water extracts of S. occidentalis root were tested for in vitro antiplasmodial activity against Plasmodium falciparum, strain 3D7. Cytotoxicity of the most active solvent extracts was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the curative potency in Plasmodium berghei infected mice evaluated by Rane’s test.

Results
All of the solvent extracts tested in this study inhibited the propagation of P. falciparum, strain 3D7, in vitro, with polar extracts being more active than non-polar ones. Methanolic extracts had the highest activity (IC50 = 1.76) while hexane extract displayed the lowest activity (IC50 = 18.47). At the tested concentrations, methanolic and aqueous extracts exhibited high selectivity index against P. falciparum strain 3D7 (SI > 10) in the cytotoxicity assay. Further, the extracts significantly suppressed the propagation of P. berghei parasites (P < 0.05) in vivo and increased the survival time of the infected mice (P < 0.0001).

Conclusions
Senna occidentalis (L.) Link root extract inhibits the propagation of malaria parasites in vitro and in BALB/c mice.
Biases in bioethics: a narrative review
Authors: Hofmann Bjørn 
Published: March 2023

AbstractGiven that biases can distort bioethics work, it has received surprisingly little and fragmented attention compared to in other fields of research. This article provides an overview of potentially relevant biases in bioethics, such as cognitive biases, affective biases, imperatives, and moral biases. Special attention is given to moral biases, which are discussed in terms of (1) Framings, (2) Moral theory bias, (3) Analysis bias, (4) Argumentation bias, and (5) Decision bias. While the overview is not exhaustive and the taxonomy by no means is absolute, it provides initial guidance with respect to assessing the relevance of various biases for specific kinds of bioethics work. One reason why we should identify and address biases in bioethics is that it can help us assess and improve the quality of bioethics work.
Novel, thalidomide-like, non-cereblon binding drug tetrafluorobornylphthalimide mitigates inflammation and brain injury
Authors: Lecca Daniela , Hsueh Shih-Chang , Luo Weiming , Tweedie David , Kim Dong Seok , Baig Abdul Mannan , Vargesson Neil , Kim Yu Kyung , Hwang Inho , Kim Sun , Hoffer Barry J. , Chiang Yung-Hsiao , Greig Nigel H. 
Published: March 2023

Abstract
Background
Quelling microglial-induced excessive neuroinflammation is a potential treatment strategy across neurological disorders, including traumatic brain injury (TBI), and can be achieved by thalidomide-like drugs albeit this approved drug class is compromised by potential teratogenicity. Tetrafluorobornylphthalimide (TFBP) and tetrafluoronorbornylphthalimide (TFNBP) were generated to retain the core phthalimide structure of thalidomide immunomodulatory imide drug (IMiD) class. However, the classical glutarimide ring was replaced by a bridged ring structure. TFBP/TFNBP were hence designed to retain beneficial anti-inflammatory properties of IMiDs but, importantly, hinder cereblon binding that underlies the adverse action of thalidomide-like drugs.

Methods
TFBP/TFNBP were synthesized and evaluated for cereblon binding and anti-inflammatory actions in human and rodent cell cultures. Teratogenic potential was assessed in chicken embryos, and in vivo anti-inflammatory actions in rodents challenged with either lipopolysaccharide (LPS) or controlled cortical impact (CCI) moderate traumatic brain injury (TBI). Molecular modeling was performed to provide insight into drug/cereblon binding interactions.

Results
TFBP/TFNBP reduced markers of inflammation in mouse macrophage-like RAW264.7 cell cultures and in rodents challenged with LPS, lowering proinflammatory cytokines. Binding studies demonstrated minimal interaction with cereblon, with no resulting degradation of teratogenicity-associated transcription factor SALL4 or of teratogenicity in chicken embryo assays. To evaluate the biological relevance of its anti-inflammatory actions, two doses of TFBP were administered to mice at 1 and 24 h post-injury following CCI TBI. Compared to vehicle treatment, TFBP reduced TBI lesion size together with TBI-induction of an activated microglial phenotype, as evaluated by immunohistochemistry 2-weeks post-injury. Behavioral evaluations at 1- and 2-weeks post-injury demonstrated TFBP provided more rapid recovery of TBI-induced motor coordination and balance impairments, versus vehicle treated mice.

Conclusion
TFBP and TFNBP represent a new class of thalidomide-like IMiDs that lower proinflammatory cytokine generation but lack binding to cereblon, the main teratogenicity-associated mechanism. This aspect makes TFBP and TFNBP potentially safer than classic IMiDs for clinical use. TFBP provides a strategy to mitigate excessive neuroinflammation associated with moderate severity TBI to, thereby, improve behavioral outcome measures and warrants further investigation in neurological disorders involving a neuroinflammatory component.

Graphical Abstract
Integrated malaria prevention in low- and middle-income countries: a systematic review
Authors: Musoke David , Atusingwize Edwinah , Namata Carol , Ndejjo Rawlance , Wanyenze Rhoda K. , Kamya Moses R. 
Published: March 2023

Abstract
Background
As many countries aim to eliminate malaria, use of comprehensive approaches targeting the mosquito vector and environment are needed. Integrated malaria prevention advocates the use of several malaria prevention measures holistically at households and in the community. The aim of this systematic review was to collate and summarize the impact of integrated malaria prevention in low- and middle-income countries on malaria burden.

Methods
Literature on integrated malaria prevention, defined as the use of two or more malaria prevention methods holistically, was searched from 1st January 2001 to 31st July 2021. The primary outcome variables were malaria incidence and prevalence, while the secondary outcome measures were human biting and entomological inoculation rates, and mosquito mortality.

Results
A total of 10,931 studies were identified by the search strategy. After screening, 57 articles were included in the review. Studies included cluster randomized controlled trials, longitudinal studies, programme evaluations, experimental hut/houses, and field trials. Various interventions were used, mainly combinations of two or three malaria prevention methods including insecticide-treated nets (ITNs), indoor residual spraying (IRS), topical repellents, insecticide sprays, microbial larvicides, and house improvements including screening, insecticide-treated wall hangings, and screening of eaves. The most common methods used in integrated malaria prevention were ITNs and IRS, followed by ITNs and topical repellents. There was reduced incidence and prevalence of malaria when multiple malaria prevention methods were used compared to single methods. Mosquito human biting and entomological inoculation rates were significantly reduced, and mosquito mortality increased in use of multiple methods compared to single interventions. However, a few studies showed mixed results or no benefits of using multiple methods to prevent malaria.

Conclusion
Use of multiple malaria prevention methods was effective in reducing malaria infection and mosquito density in comparison with single methods. Results from this systematic review can be used to inform future research, practice, policy and programming for malaria control in endemic countries.
“It’s just another tool on my toolbelt”: New York state law enforcement officer experiences administering naloxone
Authors: Lloyd Danielle , Rowe Kirsten , Leung Shu-Yin John , Pourtaher Elham , Gelberg Kitty 
Published: March 2023

Abstract
Background
Although naloxone is widely acknowledged as a life-saving intervention and a critical tool for first responders, there remains a need to explore how law enforcement officers have adapted to a shifting scope of work. Past research has focused mainly on officer training, their abilities to administer naloxone, and to a lesser extent on their experiences and interactions working with people who use drugs (PWUD).

Methods
A qualitative approach was used to explore officer perspectives and behaviors surrounding responses to incidents of suspected opioid overdose. Between the months of March and September 2017, semi-structured interviews were conducted with 38 officers from 17 counties across New York state (NYS).

Results
Analysis of in-depth interviews revealed that officers generally considered the additional responsibility of administering naloxone to have become “part of the job”. Many officers reported feeling as though they are expected to wear multiple hats, functioning as both law enforcement and medical personnel and at times juggling contradictory roles. Evolving views on drugs and drug use defined many interviews, as well as the recognition that a punitive approach to working with PWUD is not the solution, emphasizing the need for cohesive, community-wide support strategies. Notable differences in attitudes toward PWUD appeared to be influenced by an officer’s connection to someone who uses drugs and/or due to a background in emergency medical services.

Conclusion
Law enforcement officers in NYS are emerging as an integral part of the continuum of care for PWUD. Our findings are capturing a time of transition as more traditional approaches to law enforcement appear to be shifting toward those prioritizing prevention and diversion. Widespread adoption of naloxone administration by law enforcement officers in NYS is a powerful example of the successful integration of a public health intervention into police work.
The MRI-guided two adaptive brachytherapy fractions versus one adaptive brachytherapy fraction in one application for the cervical cancer: a retrospective study
Authors: Song Shanshan , Han Dongmei , Zhang Ning , Mao Zhuang , Guo Xin , Cheng Guanghui 
Published: March 2023

Abstract
Purpose
This study retrospectively compared the clinical and toxicity outcomes for the cervical cancer of the MRI-guided two adaptive brachytherapy (IGABT) fractions versus one IGABT fraction in one application.

Methods
One hundred and twenty patients with cervical cancer received external beam radiotherapy combined with or without concurrent chemotherapy, which was followed by the IGABT. The IGABT in 63 patients had one IGABT in each application (Arm 1), while in the other 57 patients, at least one treatment was two continuous IGABT every other day in one application (Arm 2). Clinical outcomes including overall survival (OS), cancer specific survival (CSS), progression free survival (PFS), local control (LC) were analyzed. Brachytherapy-related toxicities were evaluated, which included pain, dizziness, nausea/vomiting, fever/infection, blood loss during the removal of applicator and needles, the deep venous thrombosis, and other acute toxicities. The Common Terminology Criteria for Adverse Events (CTC-AE 5.0) was used to evaluate the incidence and severity of toxicities of the urinary system, lower digestive system, and reproduction system. Kaplan–Meier and the Log-rank test were used to analyze the clinical outcomes.

Results
The median follow-up time of the patients in Arm 1 and Arm 2 was 23.5 and 12.0 months, respectively. The overall treatment time was significantly shorter in Arm 2 than Arm 1 (60 vs. 64 d; P = 0.017). The OS, CSS, PFS, and LC in Arm1 and Arm 2 was 77.8% vs. 86.0% (P = 0.632), 77.8% vs. 87.7% (P = 0.821), 68.3% vs. 70.2% (P = 0.207), and 92.1% vs. 94.7% (P = 0.583), respectively. The highest NRS of the pain during brachytherapy waiting period (2.22 ± 1.84 vs. 3.02 ± 1.65; P < 0.001) and at the time of the removal of the applicator (4.69 ± 1.49 vs. 5.30 ± 1.18; P < 0.001) in the patients who received one hybrid intracavitary and interstitial brachytherapy (IC/ISBT) in one application and two continuous IC/ISBT every other day in one application were significantly different. So far four patients with grade 3 late toxicities have been reported.

Conclusions
The findings of this study demonstrated that the two continuous IGABT every other day in one application is a logistically applicable, safe, and effective treatment strategy that could shorten the overall treatment time and reduce the medical cost, comparing with the one IGABT in one application.
Sexual dimorphism in reactive oxygen species production and a role for integrin α1β1 in estrogen receptor α and β expression in articular cartilage
Authors: Black Alicia L. , Haskins James , Pozzi Ambra , Clark Andrea L. 
Published: March 2023

Abstract
Background
Osteoarthritis (OA) is a debilitating disease involving cartilage degradation. A need remains for the discovery of new molecular targets in cartilage for pharmaceutical intervention of OA. One potential target is integrin α1β1 that protects against OA when it is upregulated by chondrocytes early in the disease process. Integrin α1β1 offers this protection by dampening epidermal growth factor receptor (EGFR) signaling, and its effects are more robust in females compared to males. The aim of this study, therefore, was to measure the impact of itga1 on chondrocyte EGFR activity and downstream reactive oxygen species (ROS) production in male and female mice. Furthermore, chondrocyte expression of estrogen receptor (ER) α and ERβ was measured to investigate the mechanism for sexual dimorphism in the EGFR/integrin α1β1 signaling axis. We hypothesized that integrin α1β1 would decrease ROS production and pEGFR and 3-nitrotyrosine expression, with this effect being greater in females. We further hypothesized that chondrocyte expression of ERα and ERβ would be greater in females compared to males, with a greater effect seen in itga1-null compared to wild-type mice.

Materials and methods
Femoral and tibial cartilage of male and female, wild-type and itga1-null mice were processed for ex vivo confocal imaging of ROS, immunohistochemical analysis of 3-nitrotyrosine, or immunofluorescence of pEGFR and ERα and ERβ.

Results
We show that ROS-producing chondrocytes are more abundant in female itga1-null compared to wild-type mice ex vivo; however, itga1 had limited influence on the percent of chondrocytes stained positively for 3-nitrotyrosine or pEGFR in situ. In addition, we found that itga1 influenced ERα and ERβ expression in femoral cartilage from female mice, and that ERα and ERβ were coexpressed as well as colocalized in chondrocytes. Finally, we show sexual dimorphism in ROS and 3-nitrotyrosine production, but surprisingly not in pEGFR expression.

Conclusions
Together these data highlight sexual dimorphism in the EGFR/integrin α1β1 signaling axis and underline the need for further investigation into the role of ERs in this biological paradigm. Understanding the molecular mechanisms underlying the development of OA is essential for the development of individualized, sex-specific treatments in this age of personalized medicine.
Customized biofilm device for antibiofilm and antibacterial screening of newly developed nanostructured silver and zinc coatings
Authors: Ghezzi Daniele , Boi Marco , Sassoni Enrico , Valle Francesco , Giusto Elena , Boanini Elisa , Baldini Nicola , Cappelletti Martina , Graziani Gabriela 
Published: March 2023

Abstract
Background
Bacterial colonisation on implantable device surfaces is estimated to cause more than half of healthcare-associated infections. The application of inorganic coatings onto implantable devices limits/prevents microbial contaminations. However, reliable and high-throughput deposition technologies and experimental trials of metal coatings for biomedical applications are missing. Here, we propose the combination of the Ionized Jet Deposition (IJD) technology for metal-coating application, with the Calgary Biofilm Device (CBD) for high-throughput antibacterial and antibiofilm screening, to develop and screen novel metal-based coatings.

Results
The films are composed of nanosized spherical aggregates of metallic silver or zinc oxide with a homogeneous and highly rough surface topography. The antibacterial and antibiofilm activity of the coatings is related with the Gram staining, being Ag and Zn coatings more effective against gram-negative and gram-positive bacteria, respectively. The antibacterial/antibiofilm effect is proportional to the amount of metal deposited that influences the amount of metal ions released. The roughness also impacts the activity, mostly for Zn coatings. Antibiofilm properties are stronger on biofilms developing on the coating than on biofilms formed on uncoated substrates. This suggests a higher antibiofilm effect arising from the direct contact bacteria-coating than that associated with the metal ions release. Proof-of-concept of application to titanium alloys, representative of orthopaedic prostheses, confirmed the antibiofilm results, validating the approach. In addition, MTT tests show that the coatings are non-cytotoxic and ICP demonstrates that they have suitable release duration (> 7 days), suggesting the applicability of these new generation metal-based coatings for the functionalization of biomedical devices.

Conclusions
The combination of the Calgary Biofilm Device with the Ionized Jet Deposition technology proved to be an innovative and powerful tool that allows to monitor both the metal ions release and the surface topography of the films, which makes it suitable for the study of the antibacterial and antibiofilm activity of nanostructured materials. The results obtained with the CBD were validated with coatings on titanium alloys and extended by also considering the anti-adhesion properties and biocompatibility. In view of upcoming application in orthopaedics, these evaluations would be useful for the development of materials with pleiotropic antimicrobial mechanisms.

Graphical Abstract
DEPROMP Trial: the additive value of PSMA-PET/CT-guided biopsy for prostate cancer management in biopsy naïve men—study protocol for a randomized trial
Authors: Krausewitz P. , Bundschuh R. A. , Gaertner F. C. , Essler M. , Attenberger U. , Luetkens J. , Kristiansen G. , Muders M. , Ohlmann C-H. , Hauser S. , Ellinger J. , Ritter M. 
Published: March 2023

Abstract
Background
The primary objective is to determine the proportion of men with suspected prostate cancer (PCA) in whom the management plans are changed by additive gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) guided prostate biopsy (PET-TB) in combination with standard of care (SOC) using systematic (SB) and multiparametric magnetic resonance imaging-guided biopsy (MR-TB) compared with SOC alone. The major secondary objectives are to determine the additive value of the combined approach of SB + MR-TB + PET-TB (PET/MR-TB) for detecting clinically significant PCA (csPCA) compared to SOC; to determine sensitivity, specificity, positive and negative predictive value and diagnostic accuracy of imaging techniques, respective imaging classification systems, and each biopsy method; and to compare preoperatively defined tumor burden and biomarker expression and pathological tumor extent in prostate specimens.

Methods
The DEPROMP study is a prospective, open-label, interventional investigator-initiated trial. Risk stratification and management plans after PET/MR-TB are conducted randomized and blinded by different evaluation teams of experienced urologists based on histopathological analysis and imaging information: one including all results of the PET/MR-TB and one excluding the additional information gained by PSMA-PET/CT guided biopsy. The power calculation was centered on pilot data, and we will recruit up to 230 biopsy-naïve men who will undergo PET/MR-TB for suspected PCA. Conduct and reporting of MRI and PSMA-PET/CT will be performed in a blinded fashion.

Discussion
The DEPROMP Trial will be the first to evaluate the clinically relevant effects of the use of PSMA-PET/CT in patients with suspected PCA compared to current SOC. The study will provide prospective data to determine the diagnostic yields of additional PET-TB in men with suspected PCA and the impact on treatment plans in terms of intra- and intermodal changes. The results will allow a comparative analysis of risk stratification by each biopsy method, including a performance analysis of the corresponding rating systems. This will reveal potential intermethod and pre- and postoperative discordances of tumor stage and grading, providing the opportunity to critically assess the need for multiple biopsies.

Trial registration
German Clinical Study Register DRKS 00024134. Registered on 26 January 2021.
Efficacy of lotilaner against myiasis caused by Cochliomyia hominivorax (Diptera: Calliphoridae) in naturally infested dogs
Authors: do Vale Tássia Lopes , Costa Alcyjara Rego , Miranda Leandro Macedo , Silva Geovane Ferreira , Silva Naylene Carvalho Sales , Lima Tiago Barbalho , Chaves Daniel Praseres , Sager Heinz , Lasmar Pedro Veloso Facury , Costa–Junior Livio Martins 
Published: March 2023

Abstract
Background
The New World screwworm fly, Cochliomyia hominivorax, is widely distributed across South America. This parasitic insect is a significant cause of primary myiasis in animals, including dogs. There is an urgent need for a rapid and efficient treatment to improve the recovery of affected animals. In the present study we evaluated the potential of lotilaner for the treatment of myiasis caused by C. hominivorax larvae in naturally infested dogs. Lotilaner belongs to the isoxazoline class of chemical compounds and is marketed as Credelio™ for use against ticks and fleas in dogs and cats.

Methods
Eleven dogs with naturally acquired myiasis were enrolled in this study based on the severity of lesions and the number of identified larvae. All animals received a single oral administration of lotilaner at a minimum dose of 20.5 mg/kg body weight. After treatment, the number of expelled larvae, live or dead, was determined at 2, 6 and 24 h, and the larval expulsion rate, larvicidal effect and overall efficacy were calculated. After 24 h, the remaining larvae were removed, counted and identified. The lesions were cleaned, and palliative treatment was administered when necessary, according to the animal's health status.

Results
All larvae were identified as C. hominivorax. The larval expulsion rate was 80.5% and 93.0% at 2 and 6 h post-treatment, respectively. Lotilaner showed an overall efficacy of 100% at 24 h post-treatment.

Conclusions
Lotilaner demonstrated a rapid onset of action and a high efficacy against C. hominivorax. We therefore recommend lotilaner for the effective treatment of myiasis in dogs.

Graphical Abstract