bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geographic accessibility to public dental practices in the Jazan region of Saudi Arabia
Authors: Shubayr Mosa Ali , Kruger Estie , Tennant Marc 
Published: June 2022

Abstract
Background
It is impossible to attain good general health without maintaining oral health and this becomes problematic when dental services are located far from the population that needs to utilise them. This study aimed to assess the geographic accessibility of dental clinics located in public primary healthcare clinics (PHCs) and hospitals in the Jazan region of Saudi Arabia and how long it takes to reach them by car and on foot.

Methods
The location of clinics and hospitals, maps of road systems, and the governorates' borders (administrative areas) within the Jazan region were downloaded using the QGIS mapping tool. The time taken to travel to the clinics and hospitals, either by driving or walking, was assessed. If the time was 30 min or less, residents in the area were classified as ‘serviced’. It was more than 30 min, they were ‘underserved’.

Results
Only 31% of Jazan residents were found to live in a serviced area if they drove to clinics and hospitals. Residents of Jazan's seven mountainous governorates were more likely to require services. Only 40% could drive less than 30 min to a primary health dental clinic. Only 19% of people could walk to a hospital in less than 30 min. Only two governorates had a majority of residents who lived in serviced areas.

Conclusion
The study demonstrates an accessibility issue, as many Jazan inhabitants must drive or walk for an extended period (> 30 min) to reach a healthcare facility, whether a primary health care centre or a hospital. This issue may result in many people not receiving necessary health care, compromising their oral health status. Additional research is needed to identify public, private and other health facilities in the region and the prevalence of oral disease.
Knowledge, perception, and clinical experiences on molar incisor hypomineralization amongst Portuguese dentists
Authors: Delgado Rita Maria , Botelho João , Machado Vanessa , Mendes José João , Lopes Luísa Bandeira 
Published: June 2022

Abstract
Aim
Molar incisor hypomineralization (MIH) is a prevalent oral health condition whose knowledge by dentists is key to the best clinical outcome. This study aimed to evaluate the knowledge, perceptions and clinical experiences of MIH among Portuguese dentists.

Methods
A cross-sectional structured questionnaire was distributed nationally through a web-based survey platform. Data concerning demographic variables, years of experience, dental specialty, MIH prevalence, diagnosis, severity, training demands and clinical management of MIH were collected. We calculated a knowledge score (KS), and compared data between Pediatric Dentists (PDs), General Dental Practitioners (GDPs) and other dental specialties (ODS).

Results
Overall, 2.2% of Portuguese dentists (n = 257) answered the questionnaire. Most participants reported having identified MIH in their practice (82.5%), with PD reporting the prevalence appeared to have increased, and practically all (91.7%) considered it a public health problem. Resin composite was often the used material to restore MIH teeth (56.0%), however PDs indicated glass ionomer cements as the preferred and preformed crowns a better option. The average KS on MIH was 41.3 (± 5.7), with GDPs having a similar score than PDs. Most respondents (94.9%) reported a lack of information about MIH and were willing to receive appropriate clinical training.

Conclusions
The average knowledge on MIH was considered low among Portuguese dentists. Respondents perceived an increased incidence of MIH, despite the lack of prevalence data in Portugal. The material of choice was Glass Ionomer and performed crowns, by PDs, while GDPs and ODS reported poor confidence to manage MIH. These results may serve future programs to increase knowledge, perceptions and clinical experiences towards MIH.
Opportunities and challenges for advance care planning in strongly religious family-centric societies: a Focus group study of Indonesian cancer-care professionals
Authors: Martina Diah , Kustanti Christina Yeni , Dewantari Rahajeng , Sutandyo Noorwati , Putranto Rudi , Shatri Hamzah , Effendy Christantie , van der Heide Agnes , Rietjens Judith A. C. , van der Rijt Carin 
Published: June 2022

Abstract
Background
Most studies on advance care planning in Asia originate in high-income Asian countries. Indonesia is a middle-income Asian country characterized by its religious devoutness and strong family ties. This study aims to explore the perspectives and experiences of Indonesian healthcare professionals on advance care planning for cancer patients.

Methods
Focus-group discussions were conducted in July and August 2019 and were analysed using thematic content analysis enhanced by dual coding and exploration of divergent views. Purposive sampling of physicians and nurses actively engaged in cancer care in a national cancer centre and a national general hospital.

Results
We included 16 physicians and 16 nurses. These participants were open to the idea of advance care planning. We further identified four aspects of this planning that the participants considered to be important: 1) the family’s role in medical decision-making; 2) sensitivity to communication norms; 3) patients’ and families’ religious beliefs regarding the control and sanctity of life; and 4) the availability of a support system for advance care planning (healthcare professionals’ education and training, public education, resource allocation, and formal regulation). Participants believed that, although family hierarchical structure and certain religious beliefs may complicate patients’ engagement in advance care planning, a considerate approach to involving family and patients’ religious perspectives in advance care planning may actually facilitate their engagement in it.

Conclusion
Indonesian healthcare professionals believed that, for culturally congruent advance care planning in Indonesia, it was essential to respect the cultural aspects of collectivism, communication norms, and patients’ religious beliefs.
Probiotics and their beneficial effects on alcohol-induced liver injury in a rat model: the role of fecal microbiota
Authors: Chayanupatkul Maneerat , Somanawat Kanjana , Chuaypen Natthaya , Klaikeaw Naruemon , Wanpiyarat Natcha , Siriviriyakul Prasong , Tumwasorn Somying , Werawatganon Duangporn 
Published: June 2022

Abstract
Background
Current therapies for alcohol-induced liver injury are of limited efficacy and associated with significant side effects. With the proposed pathophysiology of alcohol-induced liver injury to be related to deranged gut microbiota, we hypothesized that probiotics would have beneficial effects in attenuating alcohol-induced liver injury.

Methods
Twenty-four male Sprague-Dawley rats were divided into 4 groups: control group, alcohol group, Lactobacillus plantarum group, and mixed-strain probiotics group. After 4 weeks, all rats were sacrificed, and blood samples were analyzed for ALT, lipopolysaccharide level (LPS), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Liver tissues were processed for histopathology, malondialdehyde (MDA) level and immunohistochemistry for toll-like receptors 4 (TLR-4). Stool samples were collected, and 16S rRNA sequencing was used to analyze the fecal microbiota.

Results
Liver histopathology showed the presence of significant hepatocyte ballooning in the alcohol group as compared with the control group, and the treatment with L. plantarum or mixed-strain probiotics alleviated these changes. Significant elevation of serum ALT, LPS, IL-6, and TNF-α, hepatic MDA levels, and hepatic TLR-4 expression were observed in alcohol-fed rats as compared with control rats. The administration of L. plantarum or mixed-strain probiotics restored these changes to the levels of control rats. The relative abundance of fecal bacteria at genus level showed a significant reduction in Allobaculum, Romboutsia, Bifidobacterium, and Akkermansia in the alcohol group as compared with the control group. In probiotics-treated rats, significant increases in Allobaculum and Bifidobacterium were observed, while the relative abundance of Romboutsia and Akkermansia was unchanged compared to the alcohol group. A reduction in alpha diversity was observed in alcohol-treated rats, whereas the improvement was noted after probiotic treatment.

Conclusions
The treatment with Lactobacillus, whether as single-, or mixed-strain probiotics, was beneficial in reducing the severity of alcohol-induced liver injury likely through the increase in beneficial bacteria, and the reduction of inflammatory responses, and oxidative stress.
Fabrication of methylene blue-loaded ovalbumin/polypyrrole nanoparticles for enhanced phototherapy-triggered antitumour immune activation
Authors: Xu Xiao , Mao Huafen , Wu Yunchao , Liu Suwan , Liu Jingjin , Li Qianzhe , Yang Mengyu , Zhu Jinqian , Zou Shengqiang , Du Fengyi 
Published: June 2022

Abstract
Background
Phototherapy-triggered immunogenic cell death (ICD) rarely elicits a robust antitumour immune response, partially due to low antigen exposure and inefficient antigen presentation. To address these issues, we developed novel methylene blue-loaded ovalbumin/polypyrrole nanoparticles (MB@OVA/PPY NPs) via oxidative polymerization and π–π stacking interactions.

Results
The as-prepared MB@OVA/PPY NPs with outstanding photothermal conversion efficiency (38%) and photodynamic properties were readily internalized into the cytoplasm and accumulated in the lysosomes and mitochondria. Upon 808 nm and 660 nm laser irradiation, the MB@OVA/PPY NPs not only ablated tumour cells by inducing local hyperthermia but also damaged residual tumour cells by generating a large amount of reactive oxygen species (ROS), finally triggering the release of many damage-associated molecular patterns (DAMPs). Moreover, the MB@OVA/PPY NPs synergized with DAMPs to promote the maturation and improve the antigen presentation ability of DCs in vitro and in vivo.

Conclusions
This work reported a PPY NPs-based nanoplatform to encapsulate the therepeutic proteins and absorb the functional molecules for combination therapy of tumours. The results demonstrated that the prepared MB@OVA/PPY NPs could be used as effective nanotherapeutic agents to eliminate solid tumours and trigger a powerful antitumour immune response.
Potential biomarkers of spinal dural arteriovenous fistula: C4BPA and C1QA
Authors: Wang Yinqing , Ma Yongjie , Yang Chengbin , Huang Xiahe , Yang Kun , Lan Fei , Fu Jingxuan , Song Zihao , Tian An , Feng Yueshan , Tu Tianqi , Li Haifeng , Hong Tao , Wang Yingchun , Zhang Hongqi 
Published: June 2022

Abstract
Background and purpose
A major challenge in spinal dural arteriovenous fistula (SDAVF) is timely diagnosis, but no specific predictive biomarkers are known.

Methods
In the discovery cohort (case, n = 8 vs. control, n = 8), we used cerebrospinal fluid (CSF) and paired plasma samples to identify differentially expressed proteins by label-free quantitative proteomics. Further bioinformatics enrichment analyses were performed to screen target proteins. Finally, it was validated by ELISA in two of the new cohorts (case, n = 17 vs. control, n = 9), and univariate analysis, simple linear regression, and receiver operator characteristic (ROC) curve analysis were performed to evaluate the diagnostic potential.

Results
In the discovery cohort, the most overexpressed proteins were APOB and C4BPA in CSF samples of patients. The GO/KEGG enrichment analysis indicated that the upregulated proteins were mainly involved in the acute inflammatory response and complement activation. Hub-gene analysis revealed that APP might be the key protein in the molecular interaction network. In the validation cohort, C4BPA and C1QA were significantly overexpressed in the CSF of patients, averaging 3046.9 ng/ml and 2167.2 ng/ml, respectively. Simple linear regression demonstrated that levels of C1QA and C4 were positively correlated with total protein in CSF (R2 = 0.8021, p = 0.0005; R2 = 0.7447, p = 0.0013). The areas under the ROC curves of C4BPA and C1QA were 0.86 and 1.00, respectively.

Conclusions
This study was the first to identify C4BPA and C1QA as potential biomarkers for the diagnosis of SDAVF and revealed that complement pathway activation might be one of the molecular mechanisms for venous hypertension myelopathy.
Repression of HIV-1 reactivation mediated by CRISPR/dCas9-KRAB in lymphoid and myeloid cell models
Authors: da Costa Lendel Correia , Bomfim Larissa Maciel , Dittz Uilla Victoria Torres , Velozo Camila de Almeida , da Cunha Rodrigo Delvecchio , Tanuri Amilcar 
Published: June 2022

Abstract
Background
Despite antiretroviral treatment efficacy, it does not lead to the complete eradication of HIV infection. Consequently, reactivation of the virus from latently infected cell reservoirs is a major challenge toward cure efforts. Two strategies targeting viral latency are currently under investigation: the “shock and kill” and the “block and lock.” The “Block and Lock” methodology aims to control HIV-1 latency reactivation, promoting a functional cure. We utilized the CRISPR/dCas9-KRAB platform, which was initially developed to suppress cellular genes transcription, to block drug-induced HIV-1 reactivation in latently infected T cells and myeloid cells.

Results
We identified a set of five sgRNAs targeting the HIV-1 proviral genome (LTR1-LTR5), having the lowest nominated off-target activity, and transduced them into the latently infected lymphoid (J-Lat 10.6) and myeloid (U1) cell lines. One of the sgRNAs (LTR5), which binds specifically in the HIV-1 LTR NFκB binding site, was able to promote robust repression of HIV-1 reactivation in latently infected T cells stimulated with Phorbol 12-Myristate 13-Acetate (PMA) and Ingenol B (IngB), both potent protein kinase C (PKC) stimulators. Reactivation with HDAC inhibitors, such as SAHA and Panobinostat, showed the same strong inhibition of reactivation. Additionally, we observed a hundred times reduction of HIV-1 RNA expression levels in the latently infected myeloid cell line, U1 induced with IngB.

Conclusion
Taken together, our results show that the KRAB fused CRISPR/dCas9 system can robustly prevent the HIV-1 latency reactivation process, mediated by PMA or IngB and SAHA or Panobinostat, both in myeloid and lymphoid HIV-1 latently infected cells. In addition, we demonstrated that KRAB repressor protein is crucial to reactivation resistance phenotype, and we have identified some useful hotspots sequences in HIV-1 LTR for the design sgRNAs.
Patient tilt improves efficacy of CO2 field-flooding in minimally invasive cardiac surgery
Authors: Vandenberghe Stijn , Singjeli Geni , Demertzis Stefanos 
Published: June 2022

AbstractObjectiveSpace limitations during minimally invasive cardiac surgery impede consistent use of CO2field-flooding. We compared different gas delivery methods, flow rates and the effect of patient inclination.MethodsA gastight model of MICS surgery with internal organs and right thoracotomy wound was created from a mannequin and equipped with a CO2concentration sensor in the left ventricle. Maximum achievable CO2concentration was compared for gas delivery via three commercial CO2diffusors (CarbonMini, Temed, Andocor) and also via a trocar with side port. Gas flow rates of 1, 3, 5 and 8 L per minute were tested. The model was placed either in supine position or with 20° oblique tilt. A simplified transparent model was also created and placed in an optical test bench to evaluate the gas cloud motions via real-time visualization.ResultsThe trocar consistently achieved higher CO2concentrations inside the left ventricle. At 1 l/min, approximately 2.5 min were needed to fill the supine model to its maximum CO2concentration, which was limited to a range of 48–82% in the left ventricle. At higher flow rates, filling time and concentration were significantly improved. In a tilted model, all devices and all flow rates generated on average 99% CO2in the ventricle. Imaging revealed constant gas exchange via the main incision, with CO2outflow via bottom and air inflow via the top of the incision.ConclusionsCO2field flooding in minimally invasive cardiac surgery is highly effective if the patient is tilted. Else a flow rate of 5 l/min is recommended to achieve the same protection.
Innominate artery direct cannulation provides brain protection during total arch replacement for acute type A aortic dissection
Authors: Kong Xiang , Ruan Peng , Yu Jiquan , Jiang Hui , Chu Tianshu , Ge Jianjun 
Published: June 2022

Abstract
Background
This study aimed to investigate the safety of direct innominate arterial (IA) cannulation using a pediatric arterial cannula to establish selective antegrade cerebral perfusion (ACP) during total arch replacement (TAR) for acute Stanford type A aortic dissection (ATAAD).

Methods
This retrospective study included patients with ATAAD who underwent TAR with the frozen elephant trunk (FET) technique between October 2020 and November 2021. Patients treated with direct IA cannulation using a pediatric arterial cannula for selective anterograde cerebral perfusion were included in the study.

Results
Of the 29 patients, 24 (82.8%) were male. The average age was 50.9 ± 9.47 years. Proximal repair included aortic root plasty (27 patients, [93.1%]) and Bentall surgery (2 patients, [6.9%]). Perioperative mortality and stroke rates were 3.4% and 6.9%, respectively. The mean lowest core temperature was 23.8 ± 0.74 °C and the mean ACP time was 25 ± 6.4 min. The aortic cross-clamp and cardiopulmonary bypass times were 141 ± 28 and 202 ± 29 min, respectively. There were no cases of IA injuries.

Conclusion
Direct IA cannulation using a pediatric arterial cannula is a simple, safe, and effective technique for establishing ACP during TAR with the FET technique for ATAAD and can avoid the potential complications of axillary artery cannulation.
Bilateral upper extremity motor priming (BUMP) plus task-specific training for severe, chronic upper limb hemiparesis: study protocol for a randomized clinical trial
Authors: Stoykov Mary Ellen , Biller Olivia M. , Wax Alexandra , King Erin , Schauer Jacob M. , Fogg Louis F. , Corcos Daniel M. 
Published: June 2022

AbstractBackgroundVarious priming techniques to enhance neuroplasticity have been examined in stroke rehabilitation research. Most priming techniques are costly and approved only for research. Here, we describe a priming technique that is cost-effective and has potential to significantly change clinical practice. Bilateral motor priming uses the Exsurgo priming device (Exsurgo Rehabilitation, Auckland, NZ) so that the less affected limb drives the more affected limb in bilateral symmetrical wrist flexion and extension. The aim of this study is to determine the effects of a 5-week protocol of bilateral motor priming in combination with task-specific training on motor impairment of the affected limb, bimanual motor function, and interhemispheric inhibition in moderate to severely impaired people with stroke.MethodsSeventy-six participants will be randomized to receive either 15, 2-h sessions, 3 times per week for 5 weeks (30 h of intervention) of bilateral motor priming and task-specific training (experimental group) or the same dose of control priming plus the task-specific training protocol. The experimental group performs bilateral symmetrical arm movements via the Exsurgo priming device which allows both wrists to move in rhythmic, symmetrical wrist flexion and extension for 15 min. The goal is one cycle (wrist flexion and wrist extension) per second. The control priming group receives transcutaneous electrical stimulation below sensory threshold for 15 min prior to the same 45 min of task-specific training. Outcome measures are collected at pre-intervention, post-intervention, and follow-up (8 weeks post-intervention). The primary outcome measure is the Fugl-Meyer Test of Upper Extremity Function. The secondary outcome is the Chedoke Arm and Hand Activity Index-Nine, an assessment of bimanual functional tasks.DiscussionTo date, there are only 6 studies documenting the efficacy of priming using bilateral movements, 4 of which are pilot or feasibility studies. This is the first large-scale clinical trial of bilateral priming plus task-specific training. We have previously completed a feasibility intervention study of bilateral motor priming plus task-specific training and have considerable experience using this protocol.Trial registrationClinicalTrials.govNCT03517657. Retrospectively registered on May 7, 2018.
Drugs and convalescent plasma therapy for COVID-19: a survey of the interventional clinical studies in Italy after 1 year of pandemic
Authors: Puopolo Maria , Morciano Cristina , Buoncervello Maria , De Nuccio Chiara , Potenza Rosa Luisa , Toschi Elena , Palmisano Lucia 
Published: June 2022

Abstract
Background
The 2019 novel coronavirus disease (COVID-19) pandemic has highlighted the importance of health research and fostered clinical research as never before. A huge number of clinical trials for potential COVID-19 interventions have been launched worldwide. Therefore, the effort of monitoring and characterizing the ongoing research portfolio of COVID-19 clinical trials has become crucial in order to fill evidence gaps that can arise, define research priorities and methodological issues, and eventually, formulate valuable recommendations for investigators and sponsors. The main purpose of the present work was to analyze the landscape of COVID-19 clinical research in Italy, by mapping and describing the characteristics of planned clinical trials investigating the role of drugs and convalescent plasma for treatment or prevention of COVID-19 disease.

Methods
During an 11-month period between May 2020 and April 2021, we performed a survey of the Italian COVID-19 clinical trials on therapeutic and prophylactic drugs and convalescent plasma. Clinical trials registered in the Italian Medicines Agency (AIFA) and ClinicalTrials.gov websites were regularly monitored. In the present paper, we report an analysis of study design characteristics and other trial features at 6 April 2021.

Results
Ninety-four clinical trials planned to be carried out in Italy were identified. Almost all of them (91%) had a therapeutic purpose; as for the study design, the majority of them adopted a parallel group (74%) and randomized (76%) design. Few of them were blinded (33%). Eight multiarm studies were identified, and two of them were multinational platform trials. Many therapeutic strategies were investigated, mostly following a drug repositioning therapeutic approach.

Conclusions
Our study describes the characteristics of COVID-19 clinical trials planned to be carried out in Italy over about 1 year of pandemic emergency.
High level quality clinical trials were identified, although some weaknesses in study design and replications of experimental interventions were observed, particularly in the early phase of the pandemic.
Our findings provide a critical view of the clinical research strategies adopted for COVID-19 in Italy during the early phase of the pandemic. Further actions could include monitoring and follow-up of trial results and publications and focus on non-pharmacological research areas.