bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-Action Pt(IV) Prodrugs and Targeted Delivery in Metal-Organic Frameworks: Overcoming Cisplatin Resistance and Improving Anticancer Activity
Authors: Larasati Larasati , Lestari Witri Wahyu , Firdaus Maulidan 
Published: November 2022

AbstractThe conversion of cisplatin Pt(II) into a Pt(IV) complex is a strategy that can be used to overcome cisplatin resistance and side effects, and this involves the functionalization of the axial positions of cisplatin. Using ligands with bioactivity to target specific cancer cell species could lead to targeted treatment and mitigate severe side effects. Furthermore, enhanced cellular uptake could be used to overcome cisplatin resistance. Anchoring the “dual-acting” prodrug in self-assembled hybrid porous metal-organic frameworks (MOFs) has revealed an even more advanced treatment. The exceptional porosity allows high loading of the drug, and the easily tuned functional groups within the frameworks enable various interactions between the drug and the cargo material to optimize controlled release and prevent premature release. Some MOFs have also demonstrated cytotoxicity against several cancer lines. It is expected that the combination of the prodrug and active MOFs could generate a “triple-acting” anticancer agent for more enhanced cancer treatment. This review discusses the development of cisplatin modified with several prodrugs and its anticancer activity in several cancer cell lines. Furthermore, the review summarizes the involvement of cisplatin derivatives in MOFs, highlighting the slow, controlled, and targeted delivery of the drug and its anticancer activity.
Design and development of an eHealth intervention to support self-management in people with musculoskeletal disorders - ‘eHealth: It’s TIME’: a study protocol
Authors: Kelly Marie , Fullen Brona , Martin Denis , Bradley Colin , O'Mahony Billy , McVeigh Joseph G. 
Published: November 2022

Background: Musculoskeletal disorders (MSDs) are a leading cause of global morbidity, with the burden expected to increase in the near future. Self-management, with the support of healthcare professionals, is recommended for many MSDs. However, frequent clinical contact is not feasible. Previous research has highlighted the need for a co-designed eHealth-mediated self-management follow-up support intervention which integrates remote monitoring and behavioural change. Thus, the current study aims to develop and design a user-centred, eHealth-mediated self-management support prototype for people with MSDs. Methods: A three-step, iterative system development cycle will be utilised to develop and design the “eHealth: It’s TIME prototype”. The three-step process will include creating website features and content using two sequential focus groups with people with MSDs (n = 6 – 8); heuristic testing using the 10 heuristic principles of Nielsen (n = 5); and usability testing through in-person 60-minute interviews with people with MSDs (n = 3 – 5) and musculoskeletal physiotherapists (n = 3 – 5). Conclusion: The eHealth: It’s TIME prototype will be a systematically developed, follow-up self-management support intervention guided by behavioural change theory and the preferences of end users.
China-India contemporary relations: Geopolitical challenges to the small states in South Asia
Authors: Pulami Manish Jung 
Published: November 2022

Background: The two Asian giants, India and China, have shown unprecedented growth and development in recent decades. The bilateral relationship between them has experienced turbulences, even wars, but their trade and economic relations date centuries back. These characteristics of cooperation and conflict between India and China with aspirations to become major powers globally have tuned up the competitiveness, along with collaborations in some areas, conflicts and contestations in others. This unique relationship with antagonistic cooperation has implications for South Asian states, particularly the small states. Methods: Realising the research gap on a complete view of contemporary India-China relations and its future repercussions in South Asia, the study hypothesises that the contemporary India-China relations not only have consequences but also brings challenges to the small states in South Asia. The paper primarily focuses on present China-India relations and the geopolitical challenges to the South Asian small states. Hence, it is crucial to comprehend ‘What is the nature and pattern of contemporary China-India relations?’ and ‘What are the geopolitical challenges to the small states because of this unforeseen relation?’ The study revisits the historical relationship between India and China examining the trend of collaborations and contestations between them. It also discusses the increasing forays of China in South Asia and the deepening US-India relationship to counter those looming Chinese influences. Results: Notably, the research identifies severe geopolitical challenges for South Asian small states because of those fluctuations in the relationship. The rise of China and deepening India-USA ties have equally added fuel to the geopolitical competition between India and China. Although there is immense competition, the two countries cooperate in the economic domains. Also, the study points out the challenges for the small states evolving due to the major power politics in and near the region.
Cardiomyopathy and dentistry
Authors: Kaka Shazia , Couzens Sarah , Boyle Carole Ann 
Published: November 2022

This article considers the clinical implications of cardiomyopathy and how it impacts on the provision of oral care. Consideration is given to the management of pain and anxiety in this patient group and the provision of safe, effective care. CPD/Clinical Relevance: With an increasingly ageing population, dentists should have the knowledge to safely assess and treat medically compromised patients.
Endodontic surgery. Part 1: an overview
Authors: Jackson Nicholas , Bryce Graeme , George Geoffrey St , Kalsi Poonam 
Published: November 2022

Surgical root canal re-treatment (SRCReT) or root-end surgery is the surgical endodontic technique most commonly studied and undertaken in clinical practice. A range of diagnostic, emergency and corrective surgical procedures may be included under the umbrella of endodontic surgery. The first article in this two-part series uses the best available evidence and clinical examples to provide the clinician with an overview of endodontic surgery. CPD/Clinical Relevance: An updated review of endodontic surgical techniques is of relevance to clinicians.
Scleroderma and its oral implications
Authors: Saeed Khadeeja , Kumar Navdeep 
Published: November 2022

Scleroderma is an autoimmune condition of the connective tissue. It encompasses a range of disorders that can affect the face, skin, limbs and internal organs. Common dental manifestations include xerostomia, dysphagia, microstomia, thickened and tight facial skin and tongue rigidity. This article describes how scleroderma can severely impact and compromise oral health. This can occur due to the restricting nature of sclerodactyly and microstomia seen in severe forms of the disease. Dental professionals must be mindful of this condition and its common oral manifestations. Techniques of how to recognize and manage these patients are discussed. CPD/Clinical Relevance: The dental and oral health implications of scleroderma are relevant to clinical practice.
Xerostomia. Part 1: aetiology and oral manifestations
Authors: Mehrabi Farima , Shanahan Dáire , Davis Gemma 
Published: November 2022

Xerostomia is the subjective sensation of a dry mouth. It can negatively impact oral health and quality of life. The underlying aetiology consists of both local and systemic factors. This two-part series aims to comprehensively review the aetiology and oral manifestations involved with xerostomia. CPD/Clinical Relevance: Early recognition and management of xerostomia is important to limit the adverse effects of this condition
The incidence of musculoskeletal injuries: a systematic review and meta-analysis
Authors: Ponkilainen Ville , Kuitunen Ilari , Liukkonen Rasmus , Vaajala Matias , Reito Aleksi , Uimonen Mikko 
Published: November 2022

Aims The aim of this systematic review and meta-analysis was to gather epidemiological information on selected musculoskeletal injuries and to provide pooled injury-specific incidence rates. Methods PubMed (National Library of Medicine) and Scopus (Elsevier) databases were searched. Articles were eligible for inclusion if they reported incidence rate (or count with population at risk), contained data on adult population, and were written in English language. The number of cases and population at risk were collected, and the pooled incidence rates (per 100,000 person-years) with 95% confidence intervals (CIs) were calculated by using either a fixed or random effects model. Results The screening of titles yielded 206 articles eligible for inclusion in the study. Of these, 173 (84%) articles provided sufficient information to be included in the pooled incidence rates. Incidences of fractures were investigated in 154 studies, and the most common fractures in the whole adult population based on the pooled incidence rates were distal radius fractures (212.0, 95% CI 178.1 to 252.4 per 100,000 person-years), finger fractures (117.1, 95% CI 105.3 to 130.2 per 100,000 person-years), and hip fractures (112.9, 95% CI 82.2 to 154.9 per 100,000 person-years). The most common sprains and dislocations were ankle sprains (429.4, 95% CI 243.0 to 759.0 per 100,000 person-years) and first-time patellar dislocations (32.8, 95% CI 21.6 to 49.7 per 100,000 person-years). The most common injuries were anterior cruciate ligament (17.5, 95% CI 6.0 to 50.2 per 100,000 person-years) and Achilles (13.7, 95% CI 9.6 to 19.5 per 100,000 person-years) ruptures. Conclusion The presented pooled incidence estimates serve as important references in assessing the global economic and social burden of musculoskeletal injuries. Cite this article: Bone Joint Res 2022;11(11):814–825.
Theoretical analysis of quantum key distribution systems when integrated with a DWDM optical transport network
Authors: Vorontsova Irina , Goncharov Roman , Tarabrina Angelina , Kiselev Fedor , Egorov Vladimir 
Published: November 2022

Theoretical research and numerical simulation of the noise influence caused by spontaneous Raman scattering, four-wave mixing, and linear channel cross talk on the performances of quantum key distribution (QKD) systems were conducted. Three types of QKD systems were considered: a coherent one-way QKD protocol, subcarrier-wave QKD system, and continuous-variable QKD integrated with classical dense wavelength division multiplexing (DWDM) channels. We calculate the secure key generation rate for the systems mentioned addressing different channel allocation schemes (i.e., configurations). A uniform DWDM grid is considered with a quantum channel located in the C-band and O-band (at 1310 nm) of a telecommunication window. The systems’ performances are analyzed in terms of the maximal achievable distance values. Configurations for further analysis and investigation are chosen optimally, i.e., their maximal achievable distances are the best.
Extracellular vesicles from focal segmental glomerulosclerosis pediatric patients induce STAT3 activation and mesangial cell proliferation
Authors: Pekkucuksen Naile T. , Liu Lauren P. , Aly Rasha , Shoemaker Lawrence R. , Alli Abdel A. 
Published: November 2022

Introduction
Primary focal segmental glomerulosclerosis (FSGS), a major cause of end-stage kidney disease (ESKD) in adolescents and young adults, is attributable to recognized genetic mutations in a minority of cases. For the majority with idiopathic primary FSGS, the cause of the disease is unknown. We hypothesize that extracellular vesicle (EVs), that carry information between podocytes and mesangial cells, may play a key role in disease progression.

Material & methods
A total of 30 participants (20 primary nephrotic syndrome/ 10 healthy controls) were enrolled in this study. Primary nephrotic syndrome subjects were grouped based on pathologic diagnosis. The FSGS group was compared to healthy control subjects based on demographic and clinical findings. EVs were isolated from the urine of each group before being characterized by Western blotting, transmission electron microscopy, and nanoparticle tracking analysis. The effects of the EVs from each group on normal human mesangial cells and activation of certain pathways were then investigated.

Results
Based on demographic and clinical findings, mean serum creatinine was significantly higher in the FSGS group than the normal healthy control group. The mean size of the EVs in the FSGS group was significantly higher than the healthy control group. The mesangial cells that were challenged with EVs isolated from FSGS patients showed significant upregulation of STAT-3, PCNA, Ki67, and cell proliferation.

Discussion
Our data demonstrate that EVs from FSGS patients stimulate mesangial cell proliferation in association with upregulation of the phospho-STAT-3 pathway. Additional studies are planned to identify the molecular cargo within the EVs from FSGS patients that contribute to the pathogenesis of FSGS.
Vitamin D and rosuvastatin alleviate type-II diabetes-induced cognitive dysfunction by modulating neuroinflammation and canonical/noncanonical Wnt/β-catenin signaling
Authors: Muneeb Muhammad , Mansou Suzan M. , Saleh Samira , Mohammed Reham A. 
Published: November 2022

BackgroundType-II diabetes mellitus (T2DM) is a major risk factor for cognitive impairment. Protecting the brain environment against inflammation, and neurodegeneration, as well as preservation of the BBB veracity through modulating the crosstalk between insulin/AKT/GSK-3β and Wnt/β-catenin signaling, might introduce novel therapeutic targets.PurposeThis study aimed at exploring the possible neuroprotective potential of vitamin D3 (VitD) and/or rosuvastatin (RSV) in T2DM-induced cognitive deficits.MethodsT2DM was induced by a high-fat sucrose diet and a single streptozotocin (STZ) dose. Diabetic rats were allocated into a diabetic control and three groups treated with RSV (15 mg/kg/day, PO), VitD (500 IU/kg/day, PO), or their combination.ResultsAdministration of VitD and/or RSV mitigated T2DM-induced metabolic abnormalities and restored the balance between the anti-inflammatory, IL 27 and the proinflammatory, IL 23 levels in the hippocampus. In addition, they markedly activated both the canonical and noncanonical Wnt/β-catenin cassettes with stimulation of their downstream molecular targets. VitD and/or RSV upregulated insulin and α7 nicotinic acetylcholine (α7nACh) receptors gene expression, as well as blood-brain barrier integrity markers including Annexin A1, claudin 3, and VE-cadherin. Also, they obliterated hippocampal ApoE-4 content, Tau hyperphosphorylation, and Aβ deposition. These biochemical changes were reflected as improved behavioral performance in Morris water maze and novel object recognition tests and restored hippocampal histological profile.ConclusionThe current findings have accentuated the neuroprotective potential of VitD and RSV and provide new incentives to expand their use in T2DM-induced cognitive and memory decline. This study also suggests a superior benefit of combining both treatments over either drug alone.
Communication interventions for medically unexplained symptom conditions in general practice: A systematic review and meta-analysis of randomised controlled trials
Authors: Byrne Ailish Katherine , Scantlebury Arabella , Jones Katherine , Doherty Laura , Torgerson David J. 
Published: November 2022

Background
Medically unexplained symptoms (MUS) account for 3–50% of all General Practitioner (GP) consultations and are difficult to diagnose due to their unknown aetiology, symptom overlap between conditions, and lack of effective treatment options. MUS patients’ and primary care clinicians frequently face challenges during consultations, with GPs reporting difficulty identifying and classifying MUS, whilst patients report stigma and feeling illegitimised by clinicians. Communication interventions have been proposed as a method to facilitate the doctor-patient relationship and aid the management of MUS.

Aim
This systematic review aims to evaluate the effectiveness of primary care based communication interventions at improving MUS patients’ and/or clinician outcomes.

Method
Four electronic databases were searched from inception to November 2021. Two researchers independently undertook screening, data extraction and quality appraisal. Given the heterogeneous nature of the studies identified, narrative syntheses were conducted, along with meta-analyses where possible to pool data.

Results
9 papers from 10 Randomised Controlled Trials were included. The included studies displayed considerable risk of bias and poor reporting. Some limited evidence suggests that communication interventions tailored to MUS and not following a pre-specified model (such as reattribution) could improve pain, mental and physical functioning whilst reattribution training may improve clinician confidence treating MUS. However, methodological limitations mean that these findings should be interpreted with caution.

Conclusion
A range of interventions for improving communication with MUS patients in primary care have been evaluated. However, the heterogeneous nature of existing evidence and poor study quality mean we cannot conclude whether these interventions are effective. Before considering further randomised controlled trials researchers should focus on developing a new or modified communication intervention for MUS patients and their clinicians.

Trail registration
The systematic review was prospectively registered with PROSPERO (registration record CRD42020206437).
Risk factors for mechanical ventilation and ECMO in COVID-19 patients admitted to the ICU: A multicenter retrospective observational study
Authors: Takada Ryo , Takazawa Tomonori , Takahashi Yoshihiko , Fujizuka Kenji , Akieda Kazuki , Saito Shigeru 
Published: November 2022

Background
The primary purpose of this study was to investigate risk factors associated with the need for mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) in COVID-19 patients admitted to the intensive care unit (ICU).

Methods
We retrospectively enrolled 66 consecutive COVID-19 patients admitted to the ICUs of three Japanese institutions from February 2020 to January 2021. We performed logistic regression analyses to identify risk factors associated with subsequent MV and ECMO requirements. Further, multivariate analyses were performed following adjustment for Acute Physiology and Chronic Health Evaluation (APACHE) II scores.

Results
At ICU admission, the risk factors for subsequent MV identified were: higher age (Odds Ratio (OR) 1.04, 95% Confidence Interval (CI) 1.00–1.08, P = 0.03), higher values of APACHE II score (OR 1.20, 95% CI 1.08–1.33, P < 0.001), Sequential Organ Failure Assessment score (OR 1.53, 95% CI 1.18–1.97, P < 0.001), lactate dehydrogenase (LDH) (OR 1.01, 95% CI 1.00–1.02, p<0.001) and C-reactive protein (OR 1.09, 95% CI 1.00–1.19, P = 0.04), and lower values of lymphocytes (OR 1.00, 95% CI 1.00–1.00, P = 0.02) and antithrombin (OR 0.95, 95% CI 0.91–0.95, P < 0.01). Patients who subsequently required ECMO showed lower values of estimated glomerular filtration rate (OR 0.98, 95% CI 0.96–1.00, P = 0.04) and antithrombin (OR 0.94, 95% CI 0.88–1.00, P = 0.03) at ICU admission. Multivariate analysis showed that higher body mass index (OR 1.19, 95% CI 1.00–1.40, P = 0.04) and higher levels of LDH (OR 1.01, 95% CI 1.01–1.02, P < 0.01) were independent risk factors for the need for MV. Lower level of antithrombin (OR 0.94, 95% CI 0.88–1.00, P = 0.03) was a risk factor for the need for ECMO.

Conclusion
We showed that low antithrombin level at ICU admission might be a risk factor for subsequent ECMO requirements, in addition to other previously reported factors.
EXPANDING PROTON FLASH CAPABILITIES TO kGy /s WITHIN ms FOR CLINICAL APPLICATIONS AT HZB
Authors: Kourkafas Georgios , Bundesmann Juergen , Denker Andrea , Dittwald Alina , Fanselow Timo , Heufelder Jens , Otman Mert , Weber Andreas 
Published: November 2022

Background and aimsThe HZB Cyclotron facility is able to deliver proton FLASH irradiation, providing beamtime to Charité – Universitätsmedizin Berlin for in vivo and in vitro experiments. For these studies, a spread-out Bragg peak with a maximum dose rate of 100 Gy/s has been applied within 200 ms at a maximum energy of 68 MeV. Since then, various system upgrades have been implemented with the aim to increase the achieved dose rate and shorten the irradiation time. The involved components and their performance are presented below.
MethodsBetween the cyclotron and its injector, an electrostatic deflector has been installed, which is controlled by an FPGA board and acts as an adjustable beam shutter, providing irradiation times down to 1 ms. Within such short durations, the delivered beam intensity can be safely increased without damaging the vacuum window at the beam exit and without reaching the radiation safety limits. The increased dose rates from a mm-focused beam are then measured by an Advanced Markus Chamber (PTW-Freiburg, Germany) and monitored by an in-house developed transparent ionization chamber, connected to a UNIDOS webline electrometer (PTW-Freiburg, Germany).
ResultsBoth ionization chambers have shown a linear response with respect to the beam current for dose rates up to 4 kGy/s. An irradiation time of 1 ms has been achieved with a statistical fluctuation of 4%, while the clinical requirement of <2% dose uncertainty can be achieved with irradiation times longer than 2.5 ms.
ConclusionsThe updated FLASH capabilities of the HZB Cyclotron enable a reliable delivery, measurement and monitoring of proton dose rates in the order of several kGy/s within few ms. In combination with the available 3D range modulator, the parameter space for systematic clinical experiments is broadened remarkably.
Obszary depopulacyjne w makroregionie centralnym i ich analiza pod kątem zaawansowania starości demograficznej w drugiej dekadzie XXI w.
Authors: Majdzińska Anna 
Published: November 2022

W opracowaniu postawione zostały dwa cele badawcze: analiza natężenia procesów depopulacyjnych w makroregionie centralnym w drugiej dekadzie XXI w. (w szczególności: identyfikacja gmin charakteryzujących się corocznym ubytkiem populacji oraz wskazanie czynników (typów) depopulacji na tych obszarach), a także analiza zaawansowania tych jednostek administracyjnych pod względem procesu demograficzne- go starzenia się.
W badaniu wykorzystano wskaźniki natężenia i struktury. Dokonano też klasyfikacji gmin według typów przyrostu i ubytku populacji, której podstawę stanowiła koncepcja własna nawiązująca do metody Webba (1963). W opracowaniu użyto danych GUS dla województw i gmin makroregionu centralnego w latach 2011–2020.