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Introduction: Pregnancy increases the risk of periodontitis due to the increase in progesterone and estrogen. Moreover, periodontitis during pregnancy is associated with development of pregnancy and birth related complications. The aim of this study is to determine, whether periodontal treatment during pregnancy can reduce systemic inflammation and lower the risk of adverse pregnancy and birth related outcomes. Methods and analysis: The PROBE study is a non-randomized controlled intervention study conducted among 600 pregnant women with periodontitis. The women will be recruited among all pregnant women at two Danish hospitals in Region Zealand during their nuchal translucency scan and will subsequently be screened for periodontitis. The intervention group includes 300 pregnant women, who will be offered state-of-the-art periodontal treatment during pregnancy. The control group includes additional 300 pregnant women, who will be offered periodontal treatment after giving birth. Outcome measures include periodontal measures, inflammatory, hormonal and glycaemic markers as well as the prevalence of preterm birth risk, low birth weight and risk markers of gestational diabetes mellitus (GDM) and preeclampsia that will be collected from all screened women and further during pregnancy week 20 and pregnancy week 35 for women enrolled in the intervention. Ethics and dissemination: The study's findings will be published in peer reviewed journals and disseminated at national and international conferences and through social media. The PROBE study is designed to provide important new knowledge as to whether periodontal treatment during pregnancy can reduce the prevalence of complications related to pregnancy and birth. Clinical trials registration: The study was registered on clinicaltrials.gov (NCT06110143). [ABSTRACT FROM AUTHOR]

Introduction: Reports of consensus conferences are usually valued less than reports of clinical trials even when rigorous methodology is used. However, limited data are available comparing the impact of these 2 methods of shaping clinical practice. Objective: Compare the publication impact of consensus conferences and clinical trials. Methods: Consensus publications from the Acute Disease Quality Initiative (ADQI) from 2002 through 2017 were identified and classified by subject matter. Randomized trials were identified in the same publication year and subject in journals, starting with the highest impact factor. Both publication types were matched, and total citations were determined for each using Google Scholar. A secondary analysis compared total costs for each publication type. Results and Conclusions: Seventeen ADQI consensus conference reports and 17 randomized trials were identified. ADQI reports received a similar number of citations per paper (median, interquartile range) compared to randomized trials (132, 54–228; vs. 159, 60–340, p = ns). Similarly, 10 (58.8%) ADQI reports and 10 randomized trials were cited >100 times. On average, ADQI reports appeared in journals with lower impact factors compared to clinical trials (5.4 ± 4.6 vs. 25.4 ± 27.1; p < 0.01). The median cost per citation (USD 2017) for ADQI reports was USD 606.01 compared to almost twice this figure, USD 1,182.59, for clinical trials on the same topics (p = 0.09). Despite being published in lower impact factor journals, consensus reports on topics in critical care nephrology, received similar citations to randomized controlled trials published the same year. [ABSTRACT FROM AUTHOR]

Background and Objectives: Given the fact that randomized controlled clinical trials are more valid than other research methods to determine the therapeutic effects of treatment, proper design and accurate reporting is of particular importance. This study was conducted with the aim of evaluating the quality of writing the title and abstract of randomized clinical trials of Iranian medical universities journals in 2016 using the Consolidated Standards of Reporting Trials (CONSORT) checklist. Materials and Methods: In this descriptive study, information gathering through internet search was limited to Persian language journals affiliated to the medical universities of the country. Based on the CONSORT checklist, which contains 18 questions, all randomly controlled clinical trials, consisting of 262 papers published in these magazines in 2016, were reviewed. Statistical analysis was performed using descriptive statistics and Chi-square and Fisher’s exact tests. Results: Only 34 (13%) of the articles refered to “randomized” word in the title of the article. Regarding the proportion of cases observed in the articles, based on the gender of the author, only two "mentioning the place of data collection" (p=0.009) and "mentioning clinical trial registration number" (p=0.020) and based on the scientific rank two cases, namely, “mentioning the full details of the responsible author” (p=0.002) and "mentioning the randomized method" (p=0.039) were significantly different. Conclusion: The need to follow CONSORT criteria and eliminate the deficiencies mentioned for conducting these studies in the country seems necessary. Therefore, it is recommended to the authors to use the CONSORT clinical checklist while writing randomized controlled clinical trials. [ABSTRACT FROM AUTHOR]

The amount of grey literature and 'softer' intelligence from social media or websites is vast. Given the long lead‐times of producing high‐quality peer‐reviewed health information, this is causing a demand for new ways to provide prompt input for secondary research. To our knowledge, this is the first review of automated data extraction methods or tools for health‐related grey literature and soft data, with a focus on (semi)automating horizon scans, health technology assessments (HTA), evidence maps, or other literature reviews. We searched six databases to cover both health‐ and computer‐science literature. After deduplication, 10% of the search results were screened by two reviewers, the remainder was single‐screened up to an estimated 95% sensitivity; screening was stopped early after screening an additional 1000 results with no new includes. All full texts were retrieved, screened, and extracted by a single reviewer and 10% were checked in duplicate. We included 84 papers covering automation for health‐related social media, internet fora, news, patents, government agencies and charities, or trial registers. From each paper, we extracted data about important functionalities for users of the tool or method; information about the level of support and reliability; and about practical challenges and research gaps. Poor availability of code, data, and usable tools leads to low transparency regarding performance and duplication of work. Financial implications, scalability, integration into downstream workflows, and meaningful evaluations should be carefully planned before starting to develop a tool, given the vast amounts of data and opportunities those tools offer to expedite research. [ABSTRACT FROM AUTHOR]

Despite the introduction of targeted vaccines and screening protocols, locally advanced cervical cancer represents a median proportion of 37% among all cervical carcinomas. Compared to early stages, it presents significantly lower cure rates, with a 5-year disease-free survival rate of 68% and a 5-year overall survival rate of 74%. According to current guidelines, definitive radiotherapy with concomitant chemotherapy represents the gold standard for locally advanced cervical cancer treatment. However, a significant number of patients relapse and die from metastatic disease. The aim of this narrative review is to examine the recent advancements in treating locally advanced cervical cancer, exploring new frontiers in therapeutic approaches. The PubMed database and clinical trial registries were searched to identify relevant articles published on locally advanced cervical cancer treatment up to March 2024, mainly focusing on papers published in the last decade. Abstracts presented at major international congresses that bring relevant evidence were included. Progress achieved in refining radiotherapy techniques, recent evidence regarding neoadjuvant treatment preceding surgery or concurrent chemoradiotherapy, and key findings concerning adjuvant treatment are thoroughly explored. Furthermore, a comprehensive review of prominent phase II and phase III trials examining the integration of immune checkpoint inhibitors is conducted, analyzing the various contexts in which they are applied. In light of the new evidence that has emerged in recent years and is discussed in this article, the appropriate selection of the most suitable therapeutic approach for each patient remains a complex but crucial issue. [ABSTRACT FROM AUTHOR]

Background: Stroke survivors with aphasia want to improve their everyday talking (discourse). In current UK practice, 90% of speech and language therapists believe discourse assessment and treatment is part of their role but are hampered by barriers in resources, time and expertise. There is a clinical need for well-articulated discourse assessment and treatments. LUNA is a multi-level treatment targeting words, sentences and discourse macrostructure in personal stories that addresses this clinical need. Objectives: This study aimed to assess the feasibility and acceptability of LUNA trial procedures in a randomised waitlist-controlled trial; and to evaluate preliminary efficacy. Methods: This paper reports a phase II, waitlist-controlled, proof-of-concept feasibility trial. Participants with chronic aphasia (n = 28) were recruited from the community and randomised to an Immediate (n = 14) or Delayed (n = 14) group. LUNA treatment was delivered twice weekly for 10 weeks via the videoconferencing technology, Zoom. Feasibility was assessed in terms of participant recruitment and retention, adherence, missing data, and treatment fidelity. Preliminary treatment efficacy was assessed in terms of between group differences in outcome measures relating to discourse, language, and psychosocial state. Results: The remote LUNA trial was feasible: 85% of those eligible consented to the trial; trial retention was 86%; 87% of treatment sessions were delivered as scheduled, and 79% of participants completed 80%+ of the treatment programme; data was missing only for participants who withdrew; treatment fidelity was high at 92% adherence; and only one clinical outcome measure demonstrated ceiling effects. ANCOVA analysis of the clinical outcome measures revealed group differences with medium and large effect sizes, indicating, improvements in the production of words, sentences, discourse macrostructure, overall language functioning (WAB-R), and psychosocial state (VAMS) following LUNA treatment. For most outcomes measured, similar treatment benefits were suggested in a secondary, non-parametric analysis. Conclusions: Large-scale evaluation of the clinical efficacy and cost-effectiveness of LUNA is warranted and supported by these findings. Trial registration: Clinical trials registration: NCT05847023 (clinical trials.gov). [ABSTRACT FROM AUTHOR]

The article presents reporting the results of a clinical trial across multiple papers. Topics discussed include the trial was prospectively registered on the clinicaltrials.gov registry and the protocol published in BMC public health; and according to the trial registry entry, the primary outcome was ‘Mediterranean diet compliance' which is discrepant with the protocol where the authors state the ‘first objective of the study is increase physical activity.

Thyroid disease classification plays a crucial role in early diagnosis and effective treatment of thyroid disorders. Machine learning (ML) techniques have demonstrated remarkable potential in this domain, offering accurate and efficient diagnostic tools. Most of the real-life datasets have imbalanced characteristics that hamper the overall performance of the classifiers. Existing data balancing techniques process the whole dataset at a time that sometimes causes overfitting and underfitting. However, the complexity of some ML models, often referred to as "black boxes," raises concerns about their interpretability and clinical applicability. This paper presents a comprehensive study focused on the analysis and interpretability of various ML models for classifying thyroid diseases. In our work, we first applied a new data-balancing mechanism using a clustering technique and then analyzed the performance of different ML algorithms. To address the interpretability challenge, we explored techniques for model explanation and feature importance analysis using eXplainable Artificial Intelligence (XAI) tools globally as well as locally. Finally, the XAI results are validated with the domain experts. Experimental results have shown that our proposed mechanism is efficient in diagnosing thyroid disease and can explain the models effectively. The findings can contribute to bridging the gap between adopting advanced ML techniques and the clinical requirements of transparency and accountability in diagnostic decision-making. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer (EC) is the most common gynecological malignancy in both Europe and the USA. Approximately 3–5% of cases occur in women of reproductive age. Fertility-sparing treatment (FST) options are available, but very limited evidence regarding grade 2 (G2) ECs exists in the current literature. This systematic review aimed to comprehensively evaluate reproductive and oncologic outcomes among young women diagnosed with stage IA or G2EC disease who underwent FST. Methods: A comprehensive search of the literature was carried out on the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), the Health Technology Assessment Database, and Web of Science. Only original studies that reported the oncologic and reproductive outcomes of patients with stage IA and G2EC tumors who underwent FST were considered eligible for inclusion in this systematic review (CRD42023484892). Studies describing only the FST for endometrial hyperplasia or G1 EC were excluded. Results: Twenty-two papers that met the abovementioned inclusion criteria were included in the present systematic review. Preliminary analysis suggested encouraging oncologic and reproductive outcomes after FST. Conclusions: The FST approach may represent a feasible and safe option for women of childbearing age diagnosed with G2EC. Despite these promising findings, cautious interpretation is warranted due to inherent limitations, including heterogeneity in study designs and potential biases. Further research with standardized methodologies and larger sample sizes is imperative for obtaining more robust conclusions. [ABSTRACT FROM AUTHOR]

Non-timely reporting, selective reporting, or non-reporting of clinical trial results are prevalent and serious issues. WHO mandates that summary results be available in registries within 12 months of study completion and published in full text within 24 months. However, only a limited number of clinical trials in infectious diseases, including those done during the COVID-19 pandemic, have their results posted on ClinicalTrials.gov. An analysis of 50 trials of eight antiviral drugs tested against COVID-19 with a completion date of at least 2 years ago revealed that only 18% had their results published in the registry, with 40% not publishing any results. Non-timely and non-reporting practices undermine patient participation and are ethically unacceptable. Strategies should include obligatory reporting of summary results within 12 months in clinical trial registries, with progress towards peer-reviewed publication within 24 months indicated. Timely publication of research papers should be encouraged through an automated flagging mechanism in clinical trial registries that draws attention to the status of results reporting, such as a green tick for trials that have reported summary results within 12 months and a red tick in case of failure to do so. We propose the inclusion of mandatory clinical trial reporting standards in the International Conference on Harmonization Good Clinical Practice guidelines, which should prohibit sponsor contract clauses that restrict reporting (referred to as gag clauses) and require timely reporting of results as part of the ethics committees' clearance process for clinical trial protocols. [ABSTRACT FROM AUTHOR]

Background: When performing nail surgery, clinicians must choose from a multitude of procedures and variations within each procedure. Much has been published to guide this decision making, but there are a lack of up to date robust systematic reviews to assess the totality of this evidence. Methods: Five databases (MEDLINE, Embase, CINAHL, Web of Science and CENTRAL) and two registers (Clinicaltrials.gov and ISRCTN) were searched to January 2022 for randomised trials evaluating the effects of a surgical intervention(s) for ingrown toenails. Two independent reviewers screened records, extracted data, assessed risk of bias and certainty of evidence. Data on co-primary outcomes of symptom relief and symptomatic regrowth were presented in our first paper. This paper presents data for the secondary outcomes and further discussion. Results: Of 3,928 records identified, 36 randomised trials were included in the systematic review. Healing time appears to be reduced with shorter application of phenol. A reduced healing time was also apparent was with the addition of curettage, although this may also increase the risk of post-operative bleeding and pain. Post operative bleeding was also reportedly lower in people who received local anaesthetic with epinephrine but no tourniquet. Use of phenol with nail bed excision may decrease the risk of infection. Lower pain scores were reported when using partial matrixectomy and surgical interventions with phenol. Shorter duration of pain was reported with phenolisation and wedge resection. Participant satisfaction was high overall. Conclusion: This second paper reports secondary outcomes from a robust systematic review of randomised trials on surgical treatment of ingrown toenails. Despite the large volume of clinical trials conducted on the topic, few clinical conclusions can be drawn due to the poor quality of these studies. Further high-quality clinical trials are needed to answer fundamental questions in the surgical treatment of ingrown toenails. [ABSTRACT FROM AUTHOR]

Background: When performing nail surgery, clinicians must choose from a multitude of procedures and variations within each procedure. Much has been published to guide this decision making, but there are a lack of up to date robust systematic reviews to assess the totality of this evidence. Methods: Five databases (MEDLINE, Embase, CINAHL, Web of Science and CENTRAL) and two registers (Clinicaltrials.gov and ISRCTN) were searched to January 2022 for randomised trials evaluating the effects of a surgical intervention(s) for ingrown toenails. Two independent reviewers screened records, extracted data, assessed risk of bias and certainty of evidence. Data on co-primary outcomes of symptom relief and symptomatic regrowth were presented in our first paper. This paper presents data for the secondary outcomes and further discussion. Results: Of 3,928 records identified, 36 randomised trials were included in the systematic review. Healing time appears to be reduced with shorter application of phenol. A reduced healing time was also apparent was with the addition of curettage, although this may also increase the risk of post-operative bleeding and pain. Post operative bleeding was also reportedly lower in people who received local anaesthetic with epinephrine but no tourniquet. Use of phenol with nail bed excision may decrease the risk of infection. Lower pain scores were reported when using partial matrixectomy and surgical interventions with phenol. Shorter duration of pain was reported with phenolisation and wedge resection. Participant satisfaction was high overall. Conclusion: This second paper reports secondary outcomes from a robust systematic review of randomised trials on surgical treatment of ingrown toenails. Despite the large volume of clinical trials conducted on the topic, few clinical conclusions can be drawn due to the poor quality of these studies. Further high-quality clinical trials are needed to answer fundamental questions in the surgical treatment of ingrown toenails. [ABSTRACT FROM AUTHOR]

Patient engagement is currently considered the cornerstone of a revolution in healthcare for its positive impact on health outcomes, health behaviors and healthcare costs. Patient engagement is focused on personalized care to consumers through providing knowledge, skills and confidence. Mobile health (mHealth) applications are an innovative means to facilitate patient engagement. Nevertheless, the extent to which the current mHealth applications are designed to engage patients in managing their chronic diseases is unclear. This paper aims to identify the Persuasive System Design (PSD) features present in current mHealth applications that increased the engagement of patients with chronic diseases. This review also aims to identify patient engagement-related outcomes of these features. This paper conducted a systematic literature review and meta-analysis to find relevant studies published from all years up to 2020 through six databases: PubMed, Scopus, Web of Science, Cinahl plus with full text, MEDLINE with full text, and Cochrane Library (Central register of controlled trials). The database search returned 4939 articles; after applying the inclusion and exclusion criteria, the number of included articles for the final review was 13. A qualitative content analysis was performed to identify PSD model features and their patient engagement-related outcomes. The quality assessment has been done through the Cochrane Risk of Bias tool for RCTs. The systematic literature review and meta-analysis identified eleven PSD features that can increase patient engagement through using mHealth applications. The identified PSD features have been shown to have various patient engagement-related outcomes. Behavior Change Techniques (BCTs) were combined with the identified PSD features. This paper identified persuasive features of mHealth application design that influence the engagement of patients with chronic diseases toward changing their behavior. The impact of these features is also analyzed in this review. The results show that an mHealth technology-mediated patient engagement model is needed. [ABSTRACT FROM AUTHOR]

Background: The new European Medicines Agency (EMA) Clinical Trials Information System (CTIS), based on the Clinical Trials Regulation (CTR EU 536/2014), came into full effect on 31 January 2022 and was intended to provide an easier, more streamlined approach to the registration of clinical trials taking place in Europe. Using the experience gained on the new regulatory framework from three multi-national European clinical research studies of outbreak-prone infectious diseases, this article describes the advantages and shortcomings of the new clinical trial submission procedure. Methods: We report the time to approval, size of the application dossier, and number of requests for information (RFIs) for each study. We also explore the experience of each study within the regulatory framework and its use of CTIS to document the real-world, practical consequences of the system on individual studies. The study assesses the experience of three multi-country studies conducted in Europe working within the EU and non-EU regulatory environments. Results: While the time to regulatory and ethical approval has improved since the implementation of the new regulation, the timelines for approvals are still unacceptably slow, particularly for studies being conducted in the context of an evolving outbreak. Within the new regulatory approval procedure, there is evidence of conflicting application requirements, increased document burden, barriers to submitting important modifications, and debilitating technical hurdles. Conclusions: CTIS promised to lower the administrative bar, but unfortunately this has not been achieved. There are challenges that need to be urgently confronted and addressed for international research collaborators to effectively manage health crises in the future. While the value of multi-national outbreak research is clear, the limitations and delays imposed by the system, which raise challenging ethical questions about the regulation, are prejudicial to all clinical research, especially publicly funded academic studies. This report is relevant to both regulators and clinical researchers. It is hoped that these findings can help improve pan-European clinical trials, especially for the purpose of epidemic preparedness and response. Trial registration: This paper references experiences gained during management of three pan-European trials: EU-SolidAct's Bari-SolidAct (CT No. 2022-500385-99-00 - 15 March 2022) and AXL-SolidAct (CT No. 2022-500363-12-00 - 19 April 2022), and MOSAIC (CT No. 2022-501132-42-00 - 22 June 2022). [ABSTRACT FROM AUTHOR]

The Letter to the Galatians is a polemical correspondence about the course of gospel mission that is at stake in the view of the apostle Paul. When Paul represents his own contacts with the Jerusalem church, he defends "our freedom which we have in Christ Jesus" (Gal 2:4). In his aim to focus on the unity of all in Christ, Paul even goes at lengths to state that there is no difference between slave and free (Gal 3:28), while polemically associating both a former state of unbelievers (Gal 4:8) and the emphasis by missionary opponents on circumcision and the covenant of the law (Gal 4:12–31) with bondage and slavery. Yet, what did freedom (ἐλευθερία, Gal 2:4) and its opposite, slavery (δουλεία, Gal 4:24, 5:1), exactly mean in the ancient world in which Paul and his readers lived and communicated? Jews, Greeks, and Romans did not necessarily mean the same by these terms, nor did freedom necessarily mean exactly the same as modern conceptions of the term. This paper aims to contextualize Paul's imagery with a view to biblical traditions, early Jewish notions of freedom, and Graeco-Roman registers of discourse, taking into account historical, literary, linguistic, and rhetorical-critical contexts of interpretation and revisiting the language of freedom and slavery with a view to insights from linguistic anthropology. The paper then revisits the Pauline position of "freedom in Christ" in relation to previous hypotheses of Paul's gospel mission. [ABSTRACT FROM AUTHOR]

Background: To systematically summarize and categorize the Chinese herbal medicine in the domestic traditional Chinese medicine (TCM) literature on type 2 diabetes mellitus (T2DM), in this paper, we mine traditional Chinese medicine data for relationships and provide for future practitioners and researchers. Methods: Taking randomized controlled trials on the treatment of T2DM in TCM as the research theme, we searched for full-text literature in three major clinical databases, including CNKI, Wan Fang, and VIP, published between 1990 and 2020. We then conducted frequency statistics, cluster analysis, association rules extraction, and principal component analysis based on a corpus of medical academic words extracted from 1116 research articles. Results: The most frequently used is Astragali Radix, and the most commonly used two-herb combination in T2DM treatment consisted of Coptidis Rhizoma and Moutan Cortex. Moutan Cortex, Alismatis Rhizoma, and Dioscoreae Rhizoma were the most frequently used three-herb combination. We found a "lung" and "liver" and "kidney" model and confirmed the value of classical meridian tropism theory and pattern identification. The treatment is mainly to fill deficiency and clear heat and consider water infiltration, dampness, blood circulation, and silt. Conclusion: This study provides an in-depth perspective on the TCM medication rules for T2DM and offers practitioners and researchers valuable information about the current status and frontier trends of TCM research on T2DM in terms of diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: This paper examines the events and conditions that led to the creation of the International Clinical Trials Registry Platform (ICTRP) in 2006 by the World Health Organization (WHO), and how the WHO addressed the issue of transparency in global pharmaceutical research. Using historical textual analysis, I trace the scientific debates that advocated for the establishment of official clinical trial registries in medical journals, and the sequence of actions following the GSK Paxil scandal in 2004, identifying the major ethical and scientific arguments that led to the involvement of the WHO as a key actor in trial registration in the context of the Big Pharma business model. Results: Through the questions "Why register?" and "Why registries?" as a roadmap, I examine the issues of publication bias and selective reporting by the industry, scrutinizing two ways in which the practice of publication bias damaged transparency in industry-sponsored research. The first involved ethical concerns regarding human subject exploitation and concealing of negative results. The second addresses the deterioration of the certainty of evidence due to incomplete access to trials results. By reviewing the series of events that occurred between 2004 and 2006 –between the Paxil scandal and the launch of the ICTRP—, I analyze the actions taken by the different actors involved: (1) the International Committee of Medical Journal Editors (ICMJE) and the creation of the Ottawa Group; (2) the WHO, beginning with the Ministerial Summit on Health Research held in November of 2004, and (3) the responses of the pharmaceutical industry and specifically GSK to the call for transparency and trial registration. Conclusions: The history of trial registration through the ICTRP as a dataveillance apparatus shows the difficulty of regulating a health enterprise turned into a global business. Moreover, it shows the challenges of globalization and how easier and faster it is to globalize business compared to good practices, raising the question of why it has been so hard to undo these trends. Indeed, the history of the movement for trial registration is not a history of regulation success, or at least not yet. [ABSTRACT FROM AUTHOR]

Pharmacovigilance studies based on spontaneous reporting systems use disproportionality analysis methods to identify drug‐event combinations with higher‐than‐expected reporting. Enhanced reporting is deemed as a proxy for a detected signal and is used to generate drug safety hypotheses, which can then be tested in pharmacoepidemiologic studies or randomized controlled trials. Higher‐than‐expected reporting means that the reporting rate of a drug‐event combination of interest is disproportionately higher than the rate in a specific comparator or reference set. Currently, it is unclear which comparator is the most appropriate for use in pharmacovigilance. Moreover, it is also unclear how the selection of a comparator may affect the directionality of the various reporting and other biases. This paper reviews commonly used comparators chosen for signal detection studies (active comparator, class‐exclusion comparator, and full data reference set). We give an overview of the advantages and disadvantages of each method based on examples from the literature. We also touch upon the challenges related to the derivation of general recommendations for the selection of comparators when mining spontaneous reports for pharmacovigilance. [ABSTRACT FROM AUTHOR]

When a lien is established by entry in a specific public register (registry), it is a registered lien – a mortgage. According to the method of establishment, the right of lien, which is established by entry in the public register (registry), is called a mortgage. In modern real law insurance systems, an important place is occupied by lien law insurance, which allows the creditor, upon maturity of the claim, if it is not settled, to be settled from the value of the pledged thing, regardless of whether the thing at the time of settlement is owned by the pledge debtor or not. In this sense, the arrangement of lien insurance on things that are restricted in circulation for social, political and security reasons is particularly important. Thus, for weapons, a special regulation has determined the regime of legal circulation characterized by various restrictions, approvals and records of possession and ownership. Possession of weapons in the Republic of Croatia is governed by the Act on the Acquisition and Possession of Weapons by Citizens. However, the assumptions, effects and procedure for registration of a registered lien on weapons as movable property are governed by the Act on the Register of Court and Public Notary Security of Claims on Movable Property and Rights. In this regard, there are various registers in which different actual rights to weapons are registered, and which are kept by different state bodies. The paper analyses the actual legal significance (declaratory and constitutive) of the registration of weapons in various registers, the procedure and legal consequences of the registration. Open issues of establishment and transfer of lien rights, satisfaction of the lien creditor, right to possession and use of weapons as pledge are highlighted. The adequacy of the existing types of entries in the Register of Court and Public-Notary Security of Claims on Movable Property and Rights is analysed. The paper offers to provide guidelines and possible solutions for the regulation of these issues de lege ferenda that would meet the general, political and legal interests, as well as interests in private law of real rights holders on weapons. [ABSTRACT FROM AUTHOR]

A limited number of studies have directly examined the effects of liposomal encapsulated phytochemicals and their anti-obesity effects in adults. This study aimed to summarize the evidence on the effect of liposomal encapsulated phytochemicals and their role in regulating major pathways involved in the anti-obesity mechanism. A systematic search was performed using several search engines like Science Direct, Google Scholar, and other online journals, focusing on laboratory research, systematic reviews, clinical trials, and meta-analysis that focused on liposomal encapsulated phytochemicals with anti-obesity properties, and followed the preferred reporting terms for this systematic review. An initial search provided a result of 1810 articles, and 93 papers were selected after the inclusion and exclusion criteria. Very few studies have been conducted on the liposomal encapsulation of phytochemicals or its synergistic study to combat obesity; hence this review paves the way for future obesity research and is mainly helpful for the pediatric obesity population. Liposomal encapsulation of phytochemicals has improved the efficiency of freely administered phytochemicals. Targeted delivery improved drug utilization and regulated the anti-obesity pathways. PPARƔ is a major therapeutic target for obesity as it inhibits adipocyte differentiation and maintains energy homeostasis. [ABSTRACT FROM AUTHOR]

This paper outlines a range of factors associated with extradition and transnational online intellectual property offending by examining the Australian case of Hew Griffiths. In documenting key legal issues from available domestic and international verdicts examining this case, we show how broad legislative drafting in Australia works alongside the decision to initiate conspiracy charges to favour extradition. We also examine how Australian legal requirements that remove the presumption of bail for transnational fugitives limit the prospect of mounting a fair defence against extradition and during a foreign trial, and the limited direct impact of determinations by the United Nations Human Rights Committee on these national processes. We critically discuss the implications of these rulings in the Griffiths case in light of the evolving role of extradition law in a digital age and their implications on theories of criminal jurisdiction founded on the principle of extraterritoriality. [ABSTRACT FROM AUTHOR]

Up to 50% of autistic people experience co-occurring anxiety, which significantly impacts their quality of life. Consequently, developing new interventions (and/ or adapting existing ones) that improve anxiety has been indicated as a priority for clinical research and practice by the autistic community. Despite this, there are very few effective, evidence-based therapies available to autistic people that target anxiety; and those that are available (e.g., autism adapted Cognitive Behavioural Therapy; CBT) can be challenging to access. Thus, the current study will provide an early-stage proof of concept for the feasibility and acceptability of a novel app-based therapeutic approach that has been developed with, and adapted for, autistic people to support them in managing anxiety using UK National Institute for Health and Care Excellence (NICE) recommended adapted CBT approaches. This paper describes the design and methodology of an ethically approved (22/LO/0291) ongoing non-randomised pilot trial that aims to enrol approximately 100 participants aged ≥16-years with an existing autism diagnosis and mild-to-severe self-reported anxiety symptoms (trial registration NCT05302167). Participants will be invited to engage with a self-guided app-based intervention—'Molehill Mountain'. Primary (Generalised Anxiety Disorder Assessment, Hospital Anxiety and Depression Scale) and secondary outcomes (medication/ service use and Goal Attainment Scaling) will be assessed at baseline (Week 2 +/- 2), endpoint (Week 15 +/- 2) and three follow-ups (Weeks 24, 32 and 41 +/- 4). Participants will also be invited to complete an app acceptability survey/ interview at the study endpoint. Analyses will address: 1) app acceptability/ useability and feasibility (via survey/ interview and app usage data); and 2) target population, performance of outcome measures and ideal timing/ duration of intervention (via primary/ secondary outcome measures and survey/ interview)–with both objectives further informed by a dedicated stakeholder advisory group. The evidence from this study will inform the future optimisation and implementation of Molehill Mountain in a randomised-controlled trial, to provide a novel tool that can be accessed easily by autistic adults and may improve mental health outcomes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Femoroacetabular impingement syndrome is one of the main causes of hip pain, and there is a lack of research in the field of rehabilitation for femoroacetabular impingement syndrome in China. OBJECTIVE: To present the research trends and research hotspots in the field of femoroacetabular impingement syndrome rehabilitation based on the Web of Science and Citespace software in the form of scientific data combined with atlas and to analyze research prospects and propose future research directions. METHODS: Keywords regarding femoroacetabular impingement syndrome rehabilitation from 2012 to 2021 were searched in the Web of Science Core Collection, and the results were bibliometrically analyzed. Citespace software was then used to conduct visually analyze countries, institutions, authors, journals, keywords and co-cited references. Finally, research trends and hotspots in the past 10 years were summarized. RESULTS AND CONCLUSION: Femoroacetabular impingement syndrome rehabilitation has gradually attracted the attention of scholars and the number of publications and citations has increased yearly, with the United States taking the lead. Chinese scholars have published fewer papers in this field and only have cooperative relations with Australian and American scholars. China’s influence in this field needs to be improved. Keyword and literature co-citation burst analyses indicate that the research trends are gait function in patients with femoroacetabular impingement syndrome, clinical efficacy of non-surgical treatment/conservative treatment/physiotherapy for femoroacetabular impingement syndrome, and the efficacy of hip arthroscopy vs. non-surgical treatment. The high-frequency co-citations, high centrality and cluster analyses indicate that the research hotspots in this field are exploring the diagnosis of pain due to femoroacetabular impingement syndrome, the short-, medium-, and long-term clinical effects of non-surgical treatment vs. hip arthroscopy, the rehabilitation effect of physiotherapy, the applicability of self-report scales, the rehabilitation scheme of femoroacetabular impingement syndrome with cartilage injury or glenoid lip injury and paying attention to their rehabilitation process, preventing femoroacetabular impingement syndrome from progressing to osteoarthritis. Based on the analysis of relevant literature in the past 10 years, this review details the future research directions in this field, including explorations on the clinical efficacy of non-surgical/surgical treatment, the middle- and long-term efficacy of non-surgical treatment vs. surgical treatment, the concurrent loss of femoroacetabular impingement syndrome, and randomized controlled trials on the prognosis and rehabilitation of femoroacetabular impingement syndrome. [ABSTRACT FROM AUTHOR]

Introduction: Fibroblast activation protein (FAP) is highly overexpressed in stromal tissue of various cancers. While FAP has been recognized as a potential diagnostic or therapeutic cancer target for decades, the surge of radiolabeled FAP-targeting molecules has the potential to revolutionize its perspective. It is presently hypothesized that FAP targeted radioligand therapy (TRT) may become a novel treatment for various types of cancer. To date, several preclinical and case series have been reported on FAP TRT using varying compounds and showing effective and tolerant results in advanced cancer patients. Here, we review the current (pre)clinical data on FAP TRT and discuss its perspective towards broader clinical implementation. Methods: A PubMed search was performed to identify all FAP tracers used for TRT. Both preclinical and clinical studies were included if they reported on dosimetry, treatment response or adverse events. The last search was performed on July 22 2022. In addition, a database search was performed on clinical trial registries (date 15th of July 2022) to search for prospective trials on FAP TRT. Results: In total, 35 papers were identified that were related to FAP TRT. This resulted in the inclusion of the following tracers for review: FAPI-04, FAPI-46, FAP-2286, SA.FAP, ND-bisFAPI, PNT6555, TEFAPI-06/07, FAPI-C12/C16, and FSDD. Conclusion: To date, data was reported on more than 100 patients that were treated with different FAP targeted radionuclide therapies such as [177Lu]Lu-FAPI-04, [90Y]Y-FAPI-46, [177Lu]Lu-FAP-2286, [177Lu]Lu-DOTA.SA.FAPI and [177Lu]Lu-DOTAGA.(SA.FAPi)2. In these studies, FAP targeted radionuclide therapy has resulted in objective responses in difficult to treat end stage cancer patients with manageable adverse events. Although no prospective data is yet available, these early data encourages further research. [ABSTRACT FROM AUTHOR]

Simple Summary: Peritoneal metastases have a poor prognosis, and one potential treatment option is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). The specific role of HIPEC is still poorly defined. In this cross-sectional study, we systematically analyzed all HIPEC trials registered on ClinicalTrials.gov to identify current research areas and to provide a perspective on expected outcomes. Only 11% (n = 26) of HIPEC trials registered on ClinicalTrials.gov (n = 234) have been published. The registered trials are very heterogeneous regarding methodological approaches and study designs. Currently, research is being conducted on 20 different drugs. The most studied cancers in HIPEC trials are peritoneal metastatic colorectal tumors, gastric cancer, and ovarian cancer. Introduction: Over the past two decades, cytoreductive surgery and HIPEC has improved outcomes for selected patients with peritoneal metastasis from various origins. This is a cross-sectional study with descriptive analyses of HIPEC trials registered on ClinicalTrials.gov. This study aimed to characterize clinical trials on HIPEC registered on ClinicalTrials.gov with the primary objective of identifying a trial focus and to examine whether trial results were published. Methods: The search included trials registered from 1 January 2001 to 14 March 2022. We examined the associations of exposure variables and other trial features with two primary outcomes: therapeutic focus and results reporting. Results: In total, 234 clinical trials were identified; 26 (11%) were already published, and 15 (6%) trials have reported their results but have not been published as full papers. Among ongoing nonpublished trials, 81 (39%) were randomized, 30 (14%) were blinded, n = 39 (20%) were later phase trials (i.e., phases 3 and 4), n = 152 (73%) were from a single institution, and 91 (44%) had parallel groups. Most of the trials were recruiting at the time of this analysis (75, 36%), and 39 (20%) were completed but had yet to publish results. In total, 68% of the trials focused on treatment strategies, and 53% investigated the oncological outcome. The most studied neoplasms for HIPEC trials were peritoneally metastasized colorectal cancer (32%), gastric cancer (29%), and ovarian cancer (26%). Twenty different drugs were analyzed in these clinical trials. Conclusions: Many study results are awaited from ongoing HIPEC trials. Most HIPEC trials focused on gastric, colorectal, or ovarian cancer. Many clinical trials were identified involving multiple entities and chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Systematic reviews rank at the top of the evidence hierarchy. Concise writing implies drafting the systematic review article succinctly, i.e. using as few words to express as full an extent of the research effort as possible. Precise writing means drafting the text with accuracy especially with respect to the methodological and statistical aspects. The Abstract ought to be succinct and structured to allow for editors, peer reviewers and readers to get the gist of the key aspects of the systematic review with a quick read. The readership needs to be able to critically appraisal systematic reviews for their internal and external validity rapidly. The Abstract also needs to be standalone, representing an independent summary that can be fully understood without the need for reading the full paper. The standard structure of the main text of a scientific article called IMRaD (Introduction, Methods, Results and Discussion) applies equally to systematic reviews in the same way as it does to any other kinds of research manuscripts whether related to laboratory experiments or clinical trials. Restricting the word count limits to those imposed by journals may at first seem difficult, even unfair, to systematic reviewers. However, with the availability of online appendices to transparently and fully report the details of the methods, results and other aspects of the work undertaken allows for a succinct print or PDF article. Writing a shorter manuscript is more effortful than writing a longer report. This commentary is aimed at novice systematic reviewers to help them learn the written and unwritten writing rules in order to assist them in producing impactful publications to support evidence-based medicine. [ABSTRACT FROM AUTHOR]

Background: One of the recently documented modalities of fascial plane block is the erector spinae plane (ESP) block, which was first described for the treatment of chronic thoracic neuropathic pain and postoperative pain in thoracic surgery. Since then, the technique has been used for a wide variety of clinical scenarios, including cardiac surgery. Aim: Through a review of clinical trials, to synthesize and evaluate the use of ESP block in cardiac surgery. Method: This is an exploratory study, based on the method of literature review with evidence synthesis. The database chosen for the selection of papers was PUBMED, using the following search strategy: "erector spinae plane block" AND "cardiac surgery". Studies published in the last five years were evaluated, and any paper that discussed the proposed topic and was a clinical trial was initially included in the sample. Results: Eleven studies were identified that met the previously established search strategy. After reading the titles and abstracts, one text was excluded because it was a letter to the editor. Conclusion: For all papers evaluated, ESP block provided good analgesia and safety during and after cardiac surgical procedures, being superior to classic techniques such as thoracic epidural anesthesia (TEA) and intravenous analgesia with or without opiates. This data was also confirmed in pediatric surgeries. In addition, ESP block was responsible for the reduction of several adverse effects typical of the classical methods of analgesia mentioned, such as nausea, vomiting and longer periods of mechanical ventilation. Another interesting finding was the association of the technique with analgesia of the superficial parasternal intercostal plane and pectoral nerve block, which provided a reduction in the use of opiates, an increase in the satisfaction of patients undergoing ESP block and a decrease in pain scores. [ABSTRACT FROM AUTHOR]

Background Few studies have assessed participant safety in human challenge trials (HCTs). Key questions regarding HCTs include how risky such trials have been, how often adverse events (AEs) and serious adverse events (SAEs) occur, and whether risk mitigation measures have been effective. Methods A systematic search of PubMed and PubMed Central for articles reporting on results of HCTs published between 1980 and 2021 was performed and completed by 7 October 2021. Results Of 2838 articles screened, 276 were reviewed in full. A total of 15 046 challenged participants were described in 308 studies that met inclusion criteria; 286 (92.9%) of these studies reported mitigation measures used to minimize risk to the challenge population. Among 187 studies that reported on SAEs, 0.2% of participants experienced at least 1 challenge-related SAE. Among 94 studies that graded AEs by severity, challenge-related AEs graded "severe" were reported by between 5.6% and 15.8% of participants. AE data were provided as a range to account for unclear reporting. Eighty percent of studies published after 2010 were registered in a trials database. Conclusions HCTs are increasingly common and used for an expanding list of diseases. Although AEs occur, severe AEs and SAEs are rare. Reporting has improved over time, though not all papers provide a comprehensive report of relevant health impacts. We found very few severe symptoms or SAEs in studies that reported them, but many HCTs did not report relevant safety data. This study was preregistered on PROSPERO as CRD42021247218. [ABSTRACT FROM AUTHOR]

Background: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. Methods: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. Discussion: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. Trial registration: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772) [ABSTRACT FROM AUTHOR]

Introduction: Tenofovir alafenamide (TAF) is approved for paediatric use in fixed‐dose combination tablets, but efficacy and safety data in children are limited. We conducted a systematic review on the efficacy/effectiveness and safety of TAF in infants, children and adolescents living with HIV. Methods: We searched MEDLINE, Embase, the Cochrane Library, clinical trial registries, reference lists and relevant conferences to identify literature published January 2009–March 2021. We included clinical trials and observational studies assessing the efficacy/effectiveness or safety of TAF through ≥6 months of treatment in participants aged 0–19 years. Results and discussion: Overall 3626 abstracts and 371 full papers were screened. Four single‐arm, innovator‐funded trials (341 participants) and a pooled analysis of those trials were identified. All four trials included treatment‐experienced and virally suppressed children or adolescents. One trial also included treatment‐naïve adolescents with baseline viral load >1000 copies/ml. The risk of bias was rated as low in one study and unclear in the other three owing to missing data on study design (all conference presentations). At 48 weeks, 92% (46/50) of treatment‐naïve participants were virally suppressed (one trial). Among treatment‐experienced participants with viral load at 48 weeks, 214 of 224 participants were virally suppressed. Across the studies, one grade 3/4 adverse event was considered drug‐related (intermediate uveitis). There were three discontinuations for adverse events (grade 2 anxiety and insomnia, grade 1 iridocyclitis [drug‐related] and grade 1 pulmonary tuberculosis [unrelated to treatment]). One accidental death occurred across the four studies. In the pooled analysis of 223 participants, the median change in bone mineral density z‐score (height‐ and age‐adjusted) from baseline to 48 weeks was −0.12 (interquartile range [IQR] −0.46, 0.17) to 0.05 (IQR not reported) for spine, and −0.09 (IQR −0.33, 0.07) to 0.09 (IQR not reported) for total body less head. Weight‐for‐age z‐scores increased by 0.25 from baseline to 48 weeks. Conclusions: Four single‐arm trials were identified in this systematic review, with initial evidence suggesting good viral suppression and no obvious safety concerns in children and adolescents on TAF‐containing regimens over 24–48 weeks. However, further comparative and longer‐term safety data are needed in children and adolescents, including on weight and metabolic changes. [ABSTRACT FROM AUTHOR]

This paper explores distinct usages of the response particle right in American versus British English conversation. The analysis shows that, in American English, right conveys the speaker's knowing stance and, in certain environments, the speaker's claim of primary knowledge. In contrast, in British English, right registers provided information as previously unknown, informative, and relevant to the current speaker's ongoing project. The analysis draws on large corpora of audio- and video-recorded ordinary and institutional interactions in British and American English. We use the methodology of Conversation Analysis to examine sequential environments in which right is used, its interactional import, and prosodic realizations. • The response particle right is used differently in US versus UK English interaction. • In US English, right coneys a knowing stance and sometimes epistemic authority. • In UK English, right registers information as previously unknown but informative. • Implications of these findings are discussed. • The study employs Conversation Analysis to examine diverse data corpora. [ABSTRACT FROM AUTHOR]

Background: Selective publication of studies has important scientific, ethical, and public health implications. Aim: We studied selective publication among mood disorder research protocols registered in the Clinical Trials Registry of India (CTRI) database. We also examined the frequency and nature of protocol deviations among the published articles. Methods: Using a systematic search strategy, we examined the publication status of all mood disorder-related research protocols registered in the CTRI database from inception till December 31, 2019. Logistic regression analysis was used to identify variables associated with selective publication. Results: Of 129 eligible protocols identified, only a third (n = 43, 33.3%) were published in literature; among those published, only 28 (21.7%) were placed in MEDLINE indexed journals. Protocol deviations were observed in more than half of the published papers (n = 25, 58.1%); many of these (41.9%) were related to sample size deviations, though, importantly, deviations in primary and secondary outcomes were also noted (16.2%). Retrospective registration of trials (odds ratio, 2.98, 95% confidence interval, 1.32--6.71) was significantly associated with publication; other variables, such as funding status or multicentric sampling, were not associated with eventual publication. Conclusions: Two out of three mood disorder research protocols registered in India do not translate into published research. These findings from a low- and middle-income country with limited spending on health care research and development represent wastage of resources and raise scientific and ethical concerns about unpublished data and futile patient participation in research. [ABSTRACT FROM AUTHOR]

Introduction: Previous analysis of registered clinical trials has found a number of protocols result in changes in the registered primary outcome measures. This investigation determined if reported primary outcomes in chiropractic-related clinical trials registered in clinicaltrials.gov match their published results. Additionally, we assessed secondary outcomes, publication status and whether raw data were posted to the registry. Methods: Clinicaltrials.gov was searched for chiropractic-related trials and having a completed status. If the study was published, outcome measures were compared between the clinicaltrials.gov entry and the published paper to assess for consistency. Results: Within clinicaltrials.gov 171 chiropracticrelated protocols were identified with 102 of those published (59.6% publication rate). Ninety-two of the published papers (90.2%) had agreement between their primary outcome and the entry on clinicaltrials.gov and 82 (80.4%) agreed with the secondary outcomes. Conclusion: A modest rate of agreement between clinicaltrails.gov entries and the published papers was found. While chiropractic-related clinical trials are fewer compared to medical trials, chiropractic-related research has a substantially better rate of primary and secondary outcome concordance with registered protocols. [ABSTRACT FROM AUTHOR]

Introduction: Unsafe abortion is the cause of a substantial number of maternal mortalities and morbidities globally, but specifically in low- and middle-income countries. Medical abortion methods provided by non-physicians may be a way to reduce the burden of unsafe abortions. Currently, only one systematic review comparing non-physicians with physicians for medical abortion exists. However, the review does not have any setting restrictions and newer evidence has since been published. Therefore, this review aims to evaluate the effectiveness, acceptability, and safety of first-trimester abortion managed by non-physicians compared with physicians in low- and middle-income countries.Material and Methods: The databases PubMed, Cochrane Library, Global Health Library, and EMBASE were searched using a structured search strategy. Further, the trial registries clinicaltrials.gov and The International Clinical Trial Registry Platform were searched for published and unpublished trials. Randomized controlled trials comparing provision of medical abortion by non-physicians with that by physicians in low- or middle-income countries were included. Risk of bias was assessed using the Cochrane Risk of Bias tool. Trials that reported effect estimates on the effectiveness of medical methods on complete abortion were included in the meta-analysis. The protocol was prospectively registered in the PROSPERO database, ID: CRD42020176811.Results: Six papers from four different randomized controlled trials with a total of 4021 participants were included. Two of the four included trials were assessed to have overall low risk of bias. Four papers had outcome data on complete abortion and were included in the meta-analyses. Medical management of first-trimester abortion and medical treatment of incomplete abortion were found to be equally effective when provided by a non-physician as when provided by a physician (risk ratio 1.00; 95% CI 0.99-1.01). Further, the treatment was equally safe, and women were equally satisfied when a non-physician provided the treatment compared with a physician.Conclusions: Provision of medical abortion or medical treatment for incomplete abortion in the first trimester is equally effective, safe, and acceptable when provided by non-physicians compared with physicians in low- and middle-income countries. We recommend that the task of providing medical abortion and medical treatment for incomplete abortion in low- and middle-income countries should be shared with non-physicians. [ABSTRACT FROM AUTHOR]

Objectives: To document how many pregnant women with COVID-19 reported in the literature had participated in randomised trials, what treatments they received outside such trials and compare the latter with evidence-based treatment recommendations.Study Design: A systematic review of observational studies.Methods: Two clinical trial registries were searched to identify COVID-19 trials open to pregnant women. Studies were then extracted from a regularly updated list of scientific case reports and case series of confirmed or suspected maternal COVID-19 in pregnancy to identify the number of women enrolled into a trial and the pharmaceutical treatments they received outside such trials.Results: 156 studies (case reports, case series and registries) reporting 43,185 pregnant women with COVID-19, after de-duplication. Of these 2,671 (6.2%) were potentially eligible for a randomised trial but only seven women (0.26%) were reported to have enrolled. For 2,839 women the papers included information on treatment received, 1515/2829 (54%) women had received ≥ 1 treatment and in total a COVID-19 pharmaceutical treatment was administered 1,296 times outside of a trial. In 566 (44%) cases the treatments administered to the pregnant women were not recommended by the National Institutes of Health (NIH) at the time of administration. Of 179 case reports of women with COVID 19 in pregnancy, 109/179 women received ≥ 1 COVID-19 pharmaceutical treatment and in total COVID-19 experimental pharmaceutical treatments were administered 274 times.Conclusion: During the early phase of the COVID-19 pandemic, pregnant women excluded from randomised trials did not avoid unproven or ineffective treatments. [ABSTRACT FROM AUTHOR]

Background: Research on clinical trials that employ stem cells to treat children's diseases is limited. The clinical trial registry database provides a unique window to us to get known about clinical trial researches with different statuses. However, few studies aimed to perform a comprehensive and thorough analysis of those registered trials in the aforementioned field based on ClinicalTrials.gov and the ICTRP portal site. Methods: Our study covered the clinical researches about stem cell therapy enrolling subjects aged under 18 years old registered on ClinicalTrials.gov and WHO ICTRP before May 18, 2021. A cross-sectional study was implemented to comprehensively describe and analyze the included trials that met the criteria. Results were available on ClinicalTrials.gov, and publications related to the included trials were identified. All analyses were performed utilizing the SPSS 25.0 software. Results: Eventually, 202 clinical trials were included and evaluated. The participant number of trials tended to be small; 71.3% were enrolled < 50. And 93.5% of the subjects were without gender restrictions. Till May 2020, 112 trials had been preliminary completed, of which only 39 trials had published papers or uploaded results. Most (73.6%) of 186 interventional trials were in phase 1 and phase 2, where 131 (70.4%) trials were conducted without masking, and 26.3% trials were randomized; 55.4% trials were performed single group assignment. Of 16 observational trials, case-only/series took up 37.5%. Hematopoietic stem cells (37.1%) and mesenchymal stem cells (36.1%) were mostly employed, while umbilical cord blood (UCB)-derived cells (24.3%) and bone marrow (BM)-derived cells (20.8%) were the major sources. Conclusions: This study provided an overall picture of utilizing stem cells for treatment and management of childhood diseases. Since clinical trials in this area are insufficient in quantity and quality, there is an urgent need of larger, better-designed trials. Increased investment in clinical research of stem cell treatment products should be carried out to achieve the transformation of results as soon as possible. Moreover, it is important to optimize the management of the registration platform and shorten the time it takes for research results to be published. [ABSTRACT FROM AUTHOR]

Background: Nasal High Flow (NHF) therapy delivers flows of heated humidified gases up to 60 LPM (litres per minute) via a nasal cannula. Particles of oral/nasal fluid released by patients undergoing NHF therapy may pose a cross-infection risk, which is a potential concern for treating COVID-19 patients. Methods: Liquid particles within the exhaled breath of healthy participants were measured with two protocols: (1) high speed camera imaging and counting exhaled particles under high magnification (6 participants) and (2) measuring the deposition of a chemical marker (riboflavin-5-monophosphate) at a distance of 100 and 500 mm on filter papers through which air was drawn (10 participants). The filter papers were assayed with HPLC. Breathing conditions tested included quiet (resting) breathing and vigorous breathing (which here means nasal snorting, voluntary coughing and voluntary sneezing). Unsupported (natural) breathing and NHF at 30 and 60 LPM were compared. Results: Imaging: During quiet breathing, no particles were recorded with unsupported breathing or 30 LPM NHF (detection limit for single particles 33 μm). Particles were detected from 2 of 6 participants at 60 LPM quiet breathing at approximately 10% of the rate caused by unsupported vigorous breathing. Unsupported vigorous breathing released the greatest numbers of particles. Vigorous breathing with NHF at 60 LPM, released half the number of particles compared to vigorous breathing without NHF. Chemical marker tests: No oral/nasal fluid was detected in quiet breathing without NHF (detection limit 0.28 μL/m3). In quiet breathing with NHF at 60 LPM, small quantities were detected in 4 out of 29 quiet breathing tests, not exceeding 17 μL/m3. Vigorous breathing released 200–1000 times more fluid than the quiet breathing with NHF. The quantities detected in vigorous breathing were similar whether using NHF or not. Conclusion: During quiet breathing, 60 LPM NHF therapy may cause oral/nasal fluid to be released as particles, at levels of tens of μL per cubic metre of air. Vigorous breathing (snort, cough or sneeze) releases 200 to 1000 times more oral/nasal fluid than quiet breathing (p < 0.001 with both imaging and chemical marker methods). During vigorous breathing, 60 LPM NHF therapy caused no statistically significant difference in the quantity of oral/nasal fluid released compared to unsupported breathing. NHF use does not increase the risk of dispersing infectious aerosols above the risk of unsupported vigorous breathing. Standard infection prevention and control measures should apply when dealing with a patient who has an acute respiratory infection, independent of which, if any, respiratory support is being used. Clinical trial registration: ACTRN12614000924651 [ABSTRACT FROM AUTHOR]

• Only 50% of the published trials were registered. • Unregistered trials may have collected other measures that remain unreported. • Many additional outcomes not appearing in trial registries were published. • Some reported positive findings are likely spurious due to unadjusted multiple comparisons. Sedentary behaviour research is a relatively new field, much of which has emerged since the widespread acceptance of clinical trial registration. The aim of this study was to investigate the trial registration and related issues in studies investigating the effect of frequent activity interruptions to prolonged sitting-time. Secondary analysis of a scoping review including systematic searches of databases and trial registries. We included experimental studies investigating the effects of frequent activity interruptions to prolonged sitting-time. We identified 32 trials published in 45 papers. Only 16 (50%) trials were registered, with all 16 trials being completed and published. Of the unregistered trials, we identified three (19%) for which similarities in the sample size and participant demographics across papers was suggestive of duplicate publication. Identification of potential duplicate publications was difficult for the remaining 13 (81%). Results from 53 (76%) of the 70 registered outcomes were published, but 11 (69%) registered trials reported results from additional outcomes not prospectively registered. A total of 46 different outcomes (out of 53 reported outcome measures, similar measures were collated) were reported across all trials, 31 (67%) of which were collected in ≤2 trials. We found direct evidence of trial registration issues in experimental trials of breaking up sitting-time. The lack of prospective registration of all trials, and the large number of outcomes measured per trial are key considerations for future research in this field. These issues are unlikely to be confined to the field of sedentary behaviour research. [ABSTRACT FROM AUTHOR]

Background: Surgical resection for Bismuth‐Corlette type IV (BC‐IV) hilar cholangiocarcinomas, also termed Klatskin tumours are technically challenging and were once considered unresectable tumours. Following advances in hepatobiliary imaging and surgical techniques, emerging evidence suggests that surgical resection is a viable avenue for long‐term survival. We aimed to identify factors affecting survival outcomes of hepatic resections for BC‐IV cholangiocarcinomas. Method: A systematic review was performed across multiple databases and several clinical trial registries. Two reviewers independently screened and selected papers that contained survival data on BC‐IV cholangiocarcinoma after hepatic resections. Results: Of 13 499 papers from our search result, 21 papers satisfied the inclusion criteria. The median post‐operative survival was 30.8 months. The average 1‐ and 5‐year post‐operative survivals were 61.6 and 33.3%, respectively. Predictors of long‐term survival included achievement of R0 margins, minimisation of operative time and reduction intra‐operative blood loss. Conclusion: Our analysis demonstrates improving post‐operative outcomes and survival in surgical resection of BC‐IV cholangiocarcinoma and suggests that radical surgical resection is a valid treatment option for the disease. [ABSTRACT FROM AUTHOR]

In emergency response and disaster rescue, unmanned aerial vehicles (UAVs) onboard thermal infrared (TIR) sensors are an essential means of acquiring ground information in the nighttime working environment. To enable field personnel to make better decisions based on TIR video streams returned from a UAV, the geographic information enhancement of TIR video streams is required. At present, it is difficult for low-cost UAVs to carry high-precision attitude sensors and thus obtain high-precision camera attitude information to meet the enhanced processing requirements of UAV TIR video streams. To this end, this paper proposes an improved Kalman filter algorithm to improve the geographic registration (geo-registration) accuracy by fusing the positioning and heading data from the dual-antenna real-time kinematic global positioning system (RTK-GPS) with onboard internal measurement unit (IMU) data. This method can yield high-precision position and attitude data in real time based on low-cost UAV hardware, based on which high-precision geo-registration results can be obtained. The computational complexity can be reduced compared with video stream feature tracking algorithms. Furthermore, the problem of unstable matching due to the low resolution and texture level of TIR video streams can be avoided. The experimental results prove that the proposed method can reduce the registration error by 66.15%, and significantly improve the geo-registration accuracy of UAV TIR video streams. Thus, it can strongly support the popularization and practicality of the application of augmented reality (AR) technology to low-cost UAV platforms. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic has driven an unprecedented level of global activity in drug discovery and clinical development for effective therapeutics targeting the coronavirus disease. There are currently 744 therapeutics being tested in 2879 clinical trials globally. Almost 90% of these clinical trials are focused on monotherapies. Combination therapies are the mainstay of antiviral therapeutics to increase the potency of the individual compounds and to combat the rapid evolution of resistance, although combination therapies have inherently complex clinical and regulatory development challenges. Increased understanding of the SARS‐CoV‐2 lifecycle and COVID‐19 pathology provides a scientific rationale for evaluating the effectiveness of different combinations. In this paper, we provide an overview of the current clinical trial landscape for combination therapeutics targeting COVID‐19 through weekly scanning of national and international clinical trial registries. Our analysis delves specifically into dual combination therapies in what can be defined as "pivotal clinical trials" (active, randomised, controlled and at least phase II), with a focus on new and repurposed therapeutic candidates that have shown positive signals and/or been granted authorisation for emergency use based on positive efficacy and safety data. [ABSTRACT FROM AUTHOR]

This article explores an interplay between process crash failures and concurrency. Namely, it aims at answering the question, "Is it possible to cope with more crash failures when some number of crashes occur before some predefined contention point happened?". These crashes are named λ-constrained crashes , where λ is the predefined contention point (known by the processes). Hence, this article considers two types of process crashes: λ -constrained crashes and classical crashes (which can occur at any time and are consequently called any-time crashes). Considering a system made up of n asynchronous processes communicating through atomic read/write registers, the article focuses on the design of two agreement-related algorithms. Assuming λ = n − 1 and no any-time failure, the first algorithm solves the consensus problem in the presence of one λ -constrained crash failure, thereby circumventing the well-known FLP impossibility result. The second algorithm considers k -set agreement for k ≥ 2. It is a k -set agreement algorithm such that λ = n − ℓ and ℓ ≥ k = m + f that works in the presence of up to (2 m + ℓ − k) λ -constrained crashes and (f − 1) any-time crashes, i.e., up to t = (2 m + ℓ − k) + (f − 1) process crashes. It follows that considering the timing of failures with respect to a predefined contention point enlarges the space of executions in which k -set agreement can be solved despite the combined effect of asynchrony, concurrency, and process crashes. The paper also presents agreement-related impossibility results for consensus and k -set agreement in the context of λ -constrained process crashes (with or without any-time crashes). [ABSTRACT FROM AUTHOR]

Goal. Stroke patients are usually accompanied by motor dysfunction, which greatly affects daily life. Electroacupuncture is a kind of nondrug therapy that can effectively improve motor function. However, the effect of electroacupuncture is hard to be measured immediately in clinic. This paper is aimed to reveal the instant changes in brain activity of three groups of stroke patients before, during, and after the electroacupuncture treatment by the EEG analysis in the alpha band and beta band. Methods. Seven different functional connectivity indicators including Pearson correlation coefficient, spectral coherence, mutual information, phase locking value, phase lag index, partial directed coherence, and directed transfer function were used to build the BCI-based brain network in stroke patients. Results and Conclusion. The results showed that the brain activity based on the alpha band of EEG decreased after the electroacupuncture treatment, while in the beta band of EEG, the brain activity decreased only in the first two groups. Significance. This method could be used to evaluate the effect of electroacupuncture instantly and quantitatively. The study will hopefully provide some neurophysiological evidence of the relationship between changes in brain activity and the effects of electroacupuncture. The study of BCI-based brain network changes in the alpha and beta bands before, during, and after electroacupuncture in stroke patients of different periods is helpful in adjusting and selecting the electroacupuncture regimens for different patients. The trial was registered on the Chinese clinical trial registry (ChiCTR2000036959). [ABSTRACT FROM AUTHOR]

Background: The advent of computer‐guided surgery removed the need for complex surgical interventions such as extensive flap elevations, second stage implant exposure, and complications usually associated with conventional protocols. Purpose (a) Analyze available literature reporting on applicability, accuracy, clinical outcome of flapless surgery with or without computer guidance. (b) Evaluate quality of studies, in terms of scientific level of evidence and ethical committee approval. Materials and methods: A PUBMED search was performed in July 2018. A first search was based on a general search string limited to "Dental Implants" and "flapless surgery." A second search focused on accuracy of computer‐guided surgery using search string "Surgery, Computer‐Assisted" or "guided surgery," and "Dental implants." The following inclusion criteria were applied: (a) studies in English; (b) human studies (excluding cadaver); (c) systematic reviews; (d) systematic reviews with meta‐analysis. Reviews not mentioning accuracy were excluded in search 2. Results: Nine reviews included in total. Implant survival ranged between 89% and 100%. Early surgical and prosthetic complications reported in 9.1% to 36.4% of reviewed papers. Tooth‐supported guides show more accuracy than bone or mucosa‐supported guides. Fully guided surgery yields higher accuracy, with lower values for horizontal coronal, horizontal apical and angular deviation (1.00, 1.23, and 3.13°mm, respectively) than those placed with half guided surgery (1.44, 1.91, and 4.30 mm, respectively). Thirty‐four of 71 human studies included in nine reviews, mentioned ethical committee approval or compliance with Declaration of Helsinki. Conclusions: Guided flapless surgery is comparable to free‐hand surgery in terms of implant survival, marginal bone remodeling, and peri‐implant variables. Clinicians advised to take care in all steps of the protocol, and include safety margins around virtually planned implants. Regarding compliance with research ethics, we should question whether scientific reports of clinical trials performed without an ethical umbrella are trustworthy. Compliance of ethics standards is imperative for submitted research papers. [ABSTRACT FROM AUTHOR]

The number of rheumatology journals, and papers related to this specialty, is expanding every day. Careful consideration for ethical aspects of such published work is mandatory for authors, readers, reviewers, editors, and all stakeholders. Recent instances of lack of appropriate research ethics committee overview, or participant consent for inclusion in the research study, or a case report, resulting in retractions, emphasize the need for greater awareness regarding these ethical aspects. Authors should strive to avoid redundancy, especially for review articles, both systematic and narrative. Clinical trial registration before commencing enrolment is mandatory as per contemporary norms. Transparent declaration of authorship contributions as well as appropriate attribution of authorship are recommended, since these may help avoid subsequent authorship conflicts. Authors, reviewers, and editors should disclose conflicts of interest, both financial and non-financial. Unbiased peer review is a critical part of editorial decision making; recent instances of peer review fraud have resulted in numerous retractions of scientific papers. Any reproduction of text, figures, or tables should be with due attribution to source, and after seeking permission of the copyright holder. Citations to published work should be relevant and diverse. Research assessment should rely on the assessment of quality of published work, rather than mere citation analyses. Authors should beware predatory, low-quality journals, and utilize social media channels to ethically promote their research with due consideration to privacy and copyright. Rheumatology societies should collaborate to develop guidelines for ethical research reporting, and educate young scientists regarding these principles. [ABSTRACT FROM AUTHOR]

• We report the development of the new disease registry: International SMA Registry. • The aim was to establish a system for collection of highly curated data. • The paper describes the development of the registry and its final version. • Over 800 patients have been collected since June 2018. • The registry will be of help in conducting studies on large cohort of patients. We report the development of a new disease registry on SMA as the result of a collaboration among three national networks in United States, Italy, and United Kingdom in partnership with a biotechnology company and with the support of advocacy groups. The aim of establishing a large collaborative registry within academic centers was to establish a structured but flexible system for collection of prospective, highly curated data that will deeply phenotype all patients with SMA and follow them longitudinally over several years. This paper describes the process leading to the development of the registry including the identification of the relevant data elements, the design of an electronic CRF with a shared data dictionary, the piloting of the first version and the definition of the final version. The registry will provide a central structure for conducting academic studies based on a much larger cohort of patients than those available in the individual networks. Due to the quality control of the data collected the registry can also be used for postmarketing purposes, allowing to share, in a transparent and controlled way, real-world data with pharmaceutical partners, drug regulatory agencies, and advocacy groups for better understanding of safety and effectiveness of new treatments. [ABSTRACT FROM AUTHOR]

The historic place of Meycauayan was derived from the term 'makawayan' where it is believed that the church made from nipa and bamboo was established here. Because of its historical geographic development, as it is being nailed as the first province before it became Bulacan, it could spring enriched experiences and cultural narratives shared through its language. The jewelry industry serves as the heart of livelihood, aside from leather, handicrafts, forge welding, etc. Even though Meycauayan was named as the jewelry capital, there is a decline over the years. Only a few were still pursuing it, since it is their livelihood, particularly at Brgy. Calvario. The aim of this study is to examine the initial existing language register from the glossary of words embedded in the jewelry-making process, as well as explore the situation of it in this modern age. Value Chain Process and Systemic Functional Linguistic by M.A.K. Halliday will be served as a framework, the words that come from the jewelry-making process were analyzed and its meaning aligned to the industry. This paper also discussed some concepts related to sociolinguistics that strengthened the domain of the jewelry industry in the city of Meycauayan and would contribute to the local and provincial industries. [ABSTRACT FROM AUTHOR]

Gastroenterology has been an early leader in bridging the gap between artificial intelligence (AI) model development and clinical trial validation, and in recent years we have seen the publication of several randomized clinical trials examining the role of AI in gastroenterology. As AI applications for clinical medicine advance rapidly, there is a clear need for guidance surrounding AI‐specific study design, evaluation, comparison, analysis and reporting of results. Several initiatives are in the publication or pre‐publication phase including AI‐specific amendments to minimum reporting guidelines for clinical trials, society task force initiatives aimed at priority use cases and research priorities, and minimum reporting guidelines that guide the reporting of clinical prediction models. In this paper, we examine applications of AI in clinical trials and discuss elements of newly published AI‐specific extensions to the Consolidated Standards of Reporting Trials and Standard Protocol Items: Recommendations for Interventional Trials statements that guide clinical trial reporting and development. We then review AI applications at the pre‐trial level in both endoscopy and other subfields of gastroenterology and explore areas where further guidance is needed to supplement the current guidance available at the pre‐trial level. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium that inhabits the gastric environment of 60.3% of the world's population. It is well established that this microorganism is related to the development of gastroduodenal disorders, of which chronic gastritis, peptic ulcer, mucosa-associated lymphoma and gastric adenocarcinoma stand out. However, since the 1980s, increasing evidence has associated this infection with various extragastric manifestations. Aim: Through a review of clinical trials, to synthesize the evidence on the treatment of H. pylori infections. Method: This is an exploratory study, based on the literature review method. The database chosen for the selection of papers was PUBMED, using the following search strategy: "helicobacter pylori"[title] AND treatment[title]. Studies published in the year 2022 were evaluated and any work that discussed the proposed theme and was a clinical trial was initially included in the sample. Results: Initially, nine studies were identified that met the aforementioned search strategy. After reading the titles and abstracts, no text was excluded. Conclusion: In general, the effectiveness of high-dose dual regimens is comparable to triple and quadruple regimens, with the advantage of inducing fewer adverse effects in patients. Furthermore, the use of probiotics was effective in replacing bismuth in quadruple regimens, leading to greater eradication of H. pylori. However, its administration to prevent changes in the intestinal microbiota remains controversial. Finally, the administration of nitazoxanide replacing metronidazole in triple therapies proved to be more effective, mainly due to the resistance acquired by H. pylori to metronidazole. [ABSTRACT FROM AUTHOR]