bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, biological evaluation and molecular docking of new triphenylamine-linked pyridine, thiazole and pyrazole analogues as anticancer agents
Authors: Elmorsy Mohamed R. , Mahmoud Samar E. , Fadda Ahmed A. , Abdel-Latif Ehab , Abdelmoaz Miral A.
Published: November 2022

A new series of pyridine, thiazole, and pyrazole analogues were synthesized. The pyridone analogues 4a-e were synthesized by treating N-aryl-2-cyano-3-(4-(diphenylamino)phenyl)acrylamides 3a-e with malononitrile. Many 4-arylidene-thiazolidin-5-one analogues 6a-d were obtained by Knoevenagel reactions of 4-(diphenylamino)benzaldehyde (1) with their corresponding thiazolidin-5-one derivatives 5a-d. The structural elucidation of the products was proven by the collections of spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Their anti-cancer activity was examined against two cell lines, MDA-MB-231 (mammary carcinomas) and A-549 (lung cancer). Compared with cisplatin as a reference standard drug, 6-amino-4-(4-(diphenylamino)phenyl)-2-oxo-1-(p-tolyl)-1,2-dihydropyridine-3,5-dicarbonitrile (4b) and 6-amino-4-(4-(diphenylamino)phenyl)-1-(4-nitrophenyl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile (4e) exhibited better efficiency against the A-549 cell line, with IC50 = 0.00803 and 0.0095 μM, respectively. Also, these compounds 4b and 4e showed the most potency among the examined compounds against MDA-MB-231 with IC50 = 0.0103 and 0.0147 μM, respectively. The newly synthesized compounds were docked inside the active sites of the selected proteins and were found to demonstrate proper binding. 2-Cyano-2-(4,4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)-N-(p-tolyl)acetamide (6c) offered the highest binding affinity (− 8.1868 kcal/mol) when docked into (PDB ID:2ITO), in addition to 2-cyano-N-(4-(diethylamino)phenyl)-2-(4-(4-(diphenylamino)benzylidene)-5-oxo-3-phenylthiazolidin-2-ylidene)acetamide (6a) gave the highest energy score (− 9.3507 kcal/mol) with (PDB ID:2A4L).
Genetically predicted telomere length and Alzheimer’s disease endophenotypes: a Mendelian randomization study
Authors: Rodríguez-Fernández Blanca , Vilor-Tejedor Natalia , Arenaza-Urquijo Eider M. , Sánchez-Benavides Gonzalo , Suárez-Calvet Marc , Operto Grégory , Minguillón Carolina , Fauria Karine , Kollmorgen Gwendlyn , Suridjan Ivonne , de Moura Manuel Castro , Piñeyro David , Esteller Manel , Blennow Kaj , Zetterberg Henrik , De Vivo Immaculata , Molinuevo José Luis , Navarro Arcadi , Gispert Juan Domingo , Sala-Vila Aleix , Crous-Bou Marta ,   for the ALFA study, Akinci Müge , Beteta Annabella , Brugulat-Serrat Anna , Cacciaglia Raffaele , Cañas Alba , Cumplido Irene , Deulofeu Carme , Dominguez Ruth , Emilio Maria , Falcon Carles , Fuentes Sherezade , Grau-Rivera Oriol , González-de-Echávarri José M. , Hernandez Laura , Genius Patricia , Huesa Gema , Huguet Jordi , Palacios Eva M. , Marne Paula , Menchón Tania , Milà-Alomà Marta , Peña-Gomez Cleofé , Polo Albina , Pradas Sandra , Salvadó Gemma , Shekari Mahnaz , Soteras Anna , Stankeviciute Laura , Vilanova Marc
Published: November 2022

Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer’s disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance,N= 2233; brain age and AD-related signatures,N= 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration,N= 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study, a population of cognitively healthy individuals at risk of AD. A total of 20 single nucleotide polymorphisms associated with TL were used to determine the effect of TL on AD endophenotypes. Analyses were adjusted by age, sex, and years of education. Stratified analyses byAPOE-ɛ4 status and polygenic risk score of AD were conducted. MR analysis revealed significant associations between genetically predicted longer TL and lower levels of CSF Aβ and higher levels of CSF NfL only inAPOE-ɛ4 non-carriers. Moreover, inheriting longer TL was associated with greater cortical thickness in age and AD-related brain signatures and lower levels of CSF p-tau among individuals at a high genetic predisposition to AD. Further observational analyses are warranted to better understand these associations.

Graphical Abstract
Effectiveness of Bacille Calmette-Guerin vaccination policies in reducing infection and mortality of COVID-19: a systematic review
Authors: Obnial Joseph Christian , Suzuki Mystie , Escuadra Catherine Joy , Austria Janine Trixia , Ponce Ma. Jamaica Monique , Cunanan Elaine
Published: November 2022

Background

COVID-19 vaccination has been advocated as the most effective way to curb the pandemic. But with its inequitable distribution and slow rollout, especially in low- to middle- income countries, it will still take a long time before herd immunity is achieved. Alternative measures must therefore be explored to bolster current COVID-19 vaccination efforts. In particular, the Bacille Calmette-Guerin vaccine has been studied extensively as to its proposed conferment of non-specific immunity against different infections, including COVID-19. The aim of this study, therefore, is to evaluate the current evidence on the effectiveness of national BCG vaccination policies in reducing infection and mortality of COVID-19.

Methods

A systematic review was conducted between April to August 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA-P) guidelines. Literature was retrieved from PubMed, Cochrane, HERDIN, Web of Science, EBSCO, and Western Pacific Region Index Medicus (WPRIM). Studies conducted from January 2020 to August 2021 that fell within Level 1A to 2C of the Oxford Center for Evidence-Based Medicine were included in the review. Quality assessment was performed using the appropriate Joanna Briggs Institute critical appraisal tool and a quality assessment checklist for ecological studies adapted from Betran et al.

Results

A total of 13 studies were included in this review. Nine studies reported significant association between BCG vaccination policies and COVID-19 outcomes, even when controlling for confounding variables. In addition, among other mandated vaccines, such as pneumococcal, influenza, diphtheria-tetanus-pertussis, and measles, only BCG vaccination showed significant association with decreased COVID-19 adverse outcomes. However, other factors also showed positive association with COVID-19 outcomes, particularly markers of high economic status of countries, higher median age, and greater population densities.

Conclusion

The lower incidence and mortality of COVID-19 in countries with mandated BCG vaccination may not solely be attributable to BCG vaccination policies, but there is still some evidence that demonstrates a possible protective effect. Clinical trials must be continued before recommendations of BCG vaccinations are to be used as an alternative or booster vaccine against COVID-19.
Impact of COVID-19 pandemic on the practice of pediatric dentistry in the United Arab Emirates: a cross-sectional survey
Authors: El Batawi Hisham Yehia , Sawalha Zain , Almomani Mai
Published: November 2022

Background

The aim of this study was to assess the impact of COVID-19 epidemic circumstances on the practice of pediatric dentistry in the United Arab Emirates.

Methods

An online questionnaire was distributed among members of Emirates Club of Pediatric Dentistry. The questionnaire was divided into three sections: (1) dentists’ demographic characteristics, (2) general knowledge and attitude toward COVID-19, (3) practice of pediatric dentistry during COVID-19 pandemic.

Results

Female pediatric dentists were double the males and the age distribution tended towards the younger age group. Most of the participants had a satisfactory level of knowledge about COVID-19 and 100% of them obtained this knowledge from the health authorities. Around one third of the participants were not confident of their ability to work safely during the epidemic. There was a marked diversity between pediatric dentists regarding the priority services to be delivered to children during the COVID-19 peak.

Conclusion

A majority of pediatric dentists in the UAE are well informed regarding COVID-19 and its prevention. The economic impact of the epidemic has disrupted pediatric dentists’ willingness to prioritize certain dental services over others. This is related to safety concerns, financial urge, and patient needs.
Partial agonists of dopamine receptors: theoretical principles of combining antipsychotics including partial agonists to treat schizophrenia
Authors: Cookson John , Pimm Jonathan , Brentnall Andrew
Published: November 2022

Partial agonists such as aripiprazole are often used in addition to a full antagonist such as amisulpride, risperidone or olanzapine in an attempt to mitigate side-effects such as sedation, hyperprolactinaemia and weight gain. However, there can be unintended consequences, including worsening of psychosis. Moreover, previous exposure to a partial agonist may impair the subsequent response to a potent antipsychotic such as haloperidol used to control symptoms of relapse. To understand the mechanisms involved, a method is needed to compare potency in the pharmacological effects of different drugs used in combinations. This article is intended to explore and explain the theoretical principles based on the dopamine hypothesis of schizophrenia. We apply the method to analyse a recently described trial in which two full antagonists (olanzapine and amisulpride) are compared individually and in combination.
Ultrabithorax modifies a regulatory network of genes essential for butterfly eyespot development in a wing sector-specific manner
Authors: Matsuoka Yuji , Monteiro Antónia
Published: November 2022

Nymphalid butterfly species often have a different number of eyespots in forewings and hindwings, but how the hindwing identity gene Ultrabithorax (Ubx) drives this asymmetry is not fully understood. We examined a three-gene regulatory network for eyespot development in the hindwings of Bicyclus anynana butterflies and compared it with the same network previously described for forewings. We also examined how Ubx interacts with each of these three eyespot-essential genes. We found similar genetic interactions between the three genes in fore- and hindwings, but we discovered three regulatory differences: Antennapedia (Antp) merely enhances spalt (sal) expression in the eyespot foci in hindwings, but is not essential for sal activation, as in forewings; Ubx upregulates Antp in all hindwing eyespot foci but represses Antp outside these wing regions; and Ubx regulates sal in a wing sector-specific manner, i.e. it activates sal expression only in the sectors that have hindwing-specific eyespots. We propose a model for how the regulatory connections between these four genes evolved to produce wing- and sector-specific variation in eyespot number.
Walk Smarter, Not Harder: Effects of Cadence Manipulation on Gait Biomechanics in Patients with Patellofemoral Osteoarthritis
Authors: HART HARVI F. , BIRMINGHAM TREVOR B. , SRITHARAN PRASANNA , FISCHER LISA K.
Published: November 2022

Purpose

This study aimed to investigate the effect of walking cadence on knee flexion angular impulse and peak external flexion moment in patients with patellofemoral osteoarthritis (OA).

Methods

Forty-eight patients with patellofemoral OA underwent repeated quantitative gait analyses on an instrumented treadmill using a randomized crossover design. Walking trials were conducted at a fixed gait speed, under three cadence conditions: (i) preferred cadence, (ii) +10% increased cadence, and (iii) −10% decreased cadence, completed in random order. Using a linear mixed model, we tested the association of cadence conditions with surrogate measures of patellofemoral load (primary outcome measure: knee flexion angular impulse) while controlling for body mass. We then repeated the analyses while sequentially replacing the dependent variable with secondary outcome measures.

Results

Walking with increased cadence decreased (adjusted mean difference [95% confidence interval]) the knee flexion angular impulse (−0.85 N·m·s−1 [−1.52 to −0.18], d = 0.20) and peak knee flexion moment (−4.11 N·m [−7.35 to −0.86], d = 0.24), whereas walking with decreased cadence increased the knee flexion angular impulse (1.83 N·m·s−1 [1.15 to 2.49], d = 0.42) and peak knee flexion moment (3.55 N·m [0.30 to 6.78], d = 0.21). Similar decreases and increases were observed for secondary outcome measures.

Conclusions

Walking with increased cadence, while maintaining a fixed gait speed, reduces knee flexion angular impulse as well as other surrogate measures of knee loading in patients with patellofemoral OA.
Popular Personal Financial Advice versus the Professors
Authors: Choi James J.
Published: November 2022

I survey the advice given by the fifty most popular personal finance books and compare it to the prescriptions of normative academic economic models. Popular advice frequently departs from normative principles derived from economic theory, which should motivate new hypotheses about why households make the financial choices they do, as well as what financial choices households should make. Popular advice is sometimes driven by fallacies, but it tries to take into account the limited willpower individuals have to stick to a financial plan, and its recommended actions are often easily computable by ordinary individuals. I cover advice on savings rates, the advisability of being a wealthy hand-to-mouth consumer, asset allocation, non-mortgage debt management, simultaneous holding of high-interest debt and low-interest savings, and mortgage choices.
Facts and Fantasies about Wage Setting and Collective Bargaining
Authors: Bhuller Manudeep , Moene Karl Ove , Mogstad Magne , Vestad Ola L.
Published: November 2022

In this article, we document and discuss salient features of collective bargaining systems in the OECD countries, with the goal of debunking some misconceptions and myths and revitalizing the general interest in wage setting and collective bargaining. We hope that such an interest may help close the gap between how economists tend to model wage setting and how wages are actually set. Canonical models of competitive labor markets, monopsony, and search and matching all assume a decentralized wage setting where individual firms and workers determine wages. In most advanced economies, however, it is common that firms or employer associations bargain with unions over wages, producing collective bargaining systems. We show that the characteristics of these systems vary in important ways across advanced economies, with regards to both the scope and the structure of collective bargaining.
Σχεδιασμός και ανάπτυξη διαδραστικών συστημάτων εκπαίδευσης-ψυχαγωγίας στη συνεκπαίδευση
Authors: Καϊμάρα Πολυξένη
Published: November 2022

Σημαντική προϋπόθεση για μια κοινωνία χωρίς διακρίσεις είναι η ισότιμη εκπαίδευση. Το αποτέλεσμα της πολιτικής για ισότιμη εκπαίδευση ήταν η διαμόρφωση των συνθηκών για συνεκπαίδευση όλων των μαθητών στα σχολεία της γειτονιάς τους. Σκοπός της παρούσας διδακτορικής διατριβής είναι η διερεύνηση της επίδρασης των διαδραστικών συστημάτων εκπαίδευσης-ψυχαγωγίας στην επιτυχημένη εφαρμογή της συνεκπαίδευσης παιδιών με και χωρίς ειδικές εκπαιδευτικές ανάγκες ή/και αναπηρία και η δημιουργία μιας νέας μεθοδολογίας σχεδιασμού συμπεριληπτικών εκπαιδευτικών υλικών. Για τον σκοπό αυτό σχεδιάστηκε, αναπτύχθηκε και αξιολογήθηκε ένα διαδραστικό εκπαιδευτικό σύστημα λαμβάνοντας υπόψη βασικές παραμέτρους των μοντέλων εκπαιδευτικού σχεδιασμού. Το εκπαιδευτικό περιεχόμενο του συστήματος επικεντρώνεται στις δραστηριότητες καθημερινής ζωής και ονομάζεται Waking Up In the Morning (WUIM). Δημιουργήθηκε με βάση μια νέα διαμεσική μεθοδολογία που αναπτύχθηκε ώστε να ενισχύει το κίνητρο για μάθηση συνδυάζοντας τα παραδοσιακά παιχνίδια με σύγχρονες διαδικασίες παραγωγής ταινιών αλλά και νέα μέσα όπως την παραγωγή βίντεο 360 μοιρών, κανόνες και περιβάλλοντα παιχνιδιών εικονικής και επαυξημένης πραγματικότητας. Η παιδαγωγική τεκμηρίωση του WUIM βασίζεται στην εκλεκτικιστική προσέγγιση, η οποία ενσωματώνει τις επικρατούσες εκπαιδευτικές παρεμβάσεις στον χώρο της ειδικής αγωγής και εκπαίδευσης, τις αρχές των ονομαζόμενων παραδοσιακών θεωριών μάθησης, όπως είναι ο συμπεριφορισμός, οι θεωρίες επεξεργασίας πληροφοριών και ο εποικοδομισμός με τα παρακλάδια του, τη διαφοροποιημένη διδασκαλία, τον καθολικό σχεδιασμό για τη μάθηση, την πολυμεσική μάθηση, τη διαμεσική μάθηση, τις αρχές σχεδιασμού των παιχνιδιών, την τεχνολογία αιχμής και το ερευνητικό πεδίο της εμπειρίας του χρήστη. Οι παραδοσιακές και σύγχρονες θεωρίες για τη μάθηση αντλούν το περιεχόμενό τους από την εκπαιδευτική ψυχολογία, τον ιδιαίτερο αυτό κλάδο της ψυχολογίας που ειδικεύεται στην κατανόηση της διδασκαλίας και της μάθησης σε εκπαιδευτικά περιβάλλοντα. Το WUIM αξιολογήθηκε στο πεδίο από δυνητικούς χρήστες (παιδιά με αναπηρία και ειδικούς θεραπευτές). Ως εργαλείο συλλογής δεδομένων χρησιμοποιήθηκε μια νέα κλίμακα που κατασκευάστηκε στο πλαίσιο της έρευνας, η οποία καταγράφει όλους τους παράγοντες που διαμορφώνουν συνολικά τις απόψεις των χρηστών σχετικά με τη μαθησιακή εμπειρία, όταν παίζουν παιχνίδια. Τα αποτελέσματα της αξιολόγησης οδήγησαν στο συμπέρασμα ότι το WUIM πληροί τις προϋποθέσεις για να αποτελέσει μια καλή πρακτική και οδηγό δημιουργίας περιεχομένου για τη συνεκπαίδευση. Καθώς η μάθηση δεν πραγματοποιείται στο κενό, με τους εκπαιδευτικούς να θεωρούνται το κλειδί της επιτυχίας για την εφαρμογή οποιασδήποτε καινοτομίας, η διατριβή εγείρει, επίσης, ερευνητικά ερωτήματα σχετικά με τη στάση των εκπαιδευτικών ως προς τη συνεκπαίδευση και τα ψηφιακά εκπαιδευτικά παιχνίδια, όπως και για τα ηθικά ζητήματα και τις ανησυχίες που σχετίζονται με τη χρήση της τεχνολογίας αιχμής από τα παιδιά.
Effectiveness, survival and safety of guselkumab attending to basal characteristics in moderate-to-severe psoriatic patients: a cohort study
Authors: Ruiz-Villaverde Ricardo , Rodriguez-Fernandez-Freire Lourdes , Armario-Hita Jose C. , Pérez-Gil Amalia , Vasquez Chinchay Fiorella , Galán-Gutiérrez Manuel
Published: November 2022

Background: Psoriasis is a chronic inflammatory disease which can impact quality of life. In the past decade multiple biologic treatments have been released with encouraging results. Guselkumab is a monoclonal antibody targeting IL-23p19. Multiple randomized clinical trials have demonstrated its efficacy in psoriasis, but response differences among patient subpopulations have not been extensively reported. Furthermore, patients in real life are often non-eligible for clinical trials and their responses may differ from pivotal studies.

Methods: This is a retrospective, observational study of real clinical practice of patients receiving guselkumab treatment in Spain. Patients treated with guselkumab were included between February 2019 to December 2021. This study evaluates the potential differential effect of baseline demographic and disease characteristics on therapeutic responses to guselkumab. We measured effectiveness and survival by the psoriasis area and severity index, the dermatology life quality index as well as Kaplan meier curves, respectively. Categorical and quantitative variables are reported with frequencies, and with mean and standard deviation, respectively. Differences between groups in psoriasis area and severity index and dermatology life quality index, were calculated using a mixed-effects analysis. Survival was calculated using Kaplan meier curves and log-rank tests.

Results: A total of 87 patients were included. In this study, our objective was to evaluate the effectiveness, safety and survival of guselkumab attending to demographic characteristics. No differences in psoriasis area and severity index or dermatology life quality index baseline values or therapeutic responses were noted at 52 weeks of follow-up among all the subgroups analysed (age, sex, psoriasis duration, body mass index, and comorbidities). A difference in drug survival was only seen between gender groups.

Conclusions: Our research has demonstrated the consistency of guselkumab effectiveness across patient subgroups. No baseline features affected the effectiveness or drug survival of guselkumab, except for lower drug survival in female patients.
Psychological support of the management staff of educational organizations of the Ministry of Internal Affairs of Russia in the aspect of psychological resources of stress resistance
Authors: Tikhonova Elena
Published: November 2022

The article discusses the features of psychological support for the leadership of educational organizations of the Ministry of Internal Affairs of Russia in the aspect of psychological resources of stress resistance. Psychological support is considered as an integral and complex system of psychological assistance, carried out within the framework of the activities of psychological services and is a basic component of the process of socio-psychological support. The contradiction between the increased need for psychological support of the subject of management and the lack of a clear regulation of this activity has been revealed, which has led to the need to obtain additional information about the organization of psychological support for the management of educational organizations, in particular, in the aspect of psychological resources of stress resistance. A study is described in which 46 practical psychologists, employees of the departments (departments) of the psychological work of educational organizations of the Ministry of Internal Affairs of Russia took part. The results of the study made it possible to draw a conclusion about the relevance of the problem of psychological resources of stress resistance for the management team, the directions preferred by psychologists in the technologies for implementing the request to increase psychological resources. The conclusion is made about the need for a continuous expansion of psychologists' ideas about modern psychotechnologies.
A Case of Anti-Caspr2 Autoimmune Encephalitis Associated with Adenocarcinoma of the Lung
Authors: Pé D’Arca Barbosa Fábio , Vara-Luiz Francisco , Albuquerque Ana , Valada Marques Ana , Spencer Vanda
Published: November 2022

Autoimmune encephalitis (AIE) is an inflammatory brain condition with multiple aetiologies but is mainly associated with paraneoplastic syndromes. Several antibodies described in AIE are being investigated in relation to different cancers, including antibodies against Contactin-associated protein-like 2 (Caspr2), which have been associated with thymoma but very rarely with lung cancer. The authors present the case of a 72-year-old man with cardiovascular risk factors, who presented with a 3-week history of left hemichorea following a first unprovoked seizure the week before, with no other signs or symptoms. The patient was submitted to extensive aetiological investigation, testing positive for anti-Caspr2 antibodies in the cerebrospinal fluid. AIE was diagnosed after other possible causes had been excluded. A PET scan showed signs of abnormal metabolism, with a lung biopsy confirming lung adenocarcinoma. This case highlights a very rare association and the importance of a thorough aetiological investigation for neurological complaints.
Consent and the law
Authors: Ellis Hannah , Ellis Peter
Published: November 2022

Hannah Ellis and Peter Ellis discuss consent and the law in relation to kidney care and how it is applied to clinical practice
UK Renal Registry publishes its 24th annual report
Authors:   UK Renal Registry, Annual Report Team
Published: November 2022

This article details how the UK Renal Registry is changing to meet the needs of the kidney community
Non-medical midwifery prescribing of an antiemetic for a glucose tolerance test: a case study
Authors: Anderson Natalie
Published: November 2022

This is a case study of a 26-week pregnant woman requiring an antiemetic before a glucose tolerance test and the prescribing decision that a non-medical midwifery prescriber needed to make in the outpatient setting. The case study demonstrates how the prescriber demonstrated the Royal Pharmaceutical Society competencies. The Calgary-Cambridge model was used to assess the patient. There are no local or national guidelines for this situation with very limited evidence available to assess the effectiveness of the different antiemetics. The consultant's advice in the local setting is to prescribe a cyclizine 50mg tablet. This case study evaluates the available evidence and guidelines and concludes that prescribing cyclizine in this scenario is reasonable in the absence of any good evidence.
Comparison of ligamentization potential between anterior cruciate ligament-derived cells and adipose-derived mesenchymal stem cells reseeded to acellularized tendon allograft
Authors: Park Jinsung , Jo Sungsin , Lee Myung-Kyu , Kim Tae-Hwan , Sung Il-Hoon , Lee Jin K.
Published: November 2022

Aims

To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs).

Methods

Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.

Results

In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs.

Conclusion

ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786.
Service delivery atTitle Xsites inTexasduring theCOVID‐19 pandemic
Authors: Burke Kristen Lagasse , Sierra Gracia , Lerma Klaira , White Kari
Published: November 2022

Context

The important role of Title X sites in supporting publicly funded reproductive healthcare was elevated during the COVID‐19 pandemic, as many people experienced economic uncertainty and changed their fertility preferences. In this study, we assessed changes in service delivery during the first year of the COVID‐19 pandemic at Title X‐supported sites in Texas, a large state with a high uninsured rate and a diverse Title X network.

Methods

Using surveys of Title X‐funded organizations in Texas from April and November 2020, we examined the percentage of organizations reporting service modifications. With administrative data on 507,947 client encounters between March 2019 and March 2021, we assessed change in client volume at the onset of the pandemic and evaluated the association between regional COVID‐19 case rates and the provision of key Title X services.

Results

In April 2020, most organizations (78%) limited in‐person operations while implementing telehealth (74%) and contactless contraception (67%). Network‐wide encounter volume declined by 26% at pandemic onset (incidence rate ratio [IRR] = 0.74, 95% confidence interval [CI] = 0.65, 0.84). Health departments experienced the steepest declines in encounter volume (IRR = 0.43, 95% CI = 0.36–0.50). Weekly encounters, particularly for long‐acting reversible method placement/removal and sexually transmitted infection testing, decreased as COVID‐19 rates increased.

Conclusions

Investment in public health infrastructure, including providing robust support to health departments as well as rebuilding and expanding the Title X network, is essential to safeguarding access to publicly funded reproductive healthcare during and after the pandemic.
Quantitative evaluation of transdermal drug delivery patches on human skin with in vivo THz-TDS
Authors: Ding Xuefei , Costa Gonçalo , Hernandez-Serrano A. I. , Stantchev Rayko I. , Nurumbetov Gabit , Haddleton David M. , Pickwell-MacPherson Emma
Published: November 2022

Transdermal drug delivery (TDD) has been widely used in medical treatments due to various advantages, including delivering drugs at a consistent rate. However, variations in skin hydration can have a significant effect on the permeability of chemicals. Therefore, it is essential to study the changes in skin hydration induced by TDD patches for better control of the delivery rate. In this work, in vivo terahertz (THz) spectroscopy is conducted to quantitatively monitor human skin after the application of patches with different backing materials and propylene glycol concentrations. Changes in skin hydration and skin response to occlusion induced by other patches are investigated and compared. Our work demonstrates the potential application of in vivo THz measurements in label-free, non-invasive evaluation of transdermal patches on human skin and further reveals the mechanism behind the effect.
Laser-induced assembly of Au nano-polyhedron clusters as stable 3D superstructures with ultrabroadband plasmonic resonance for promoting multi-band SERS
Authors: Li Shuang , Cui Qingqiang , Wang Chang , Zhang Mengya , Zheng Linqi , Chen Ming
Published: November 2022

Multi-band surface-enhanced Raman spectroscopy (SERS) via multiple excitation wavelengths operated on broadband resonant substrate can empower a high-dimensional comprehensive molecular diagnosis of complex analytes. Herein, we demonstrate an extraordinary multi-resonant SERS active substrate that is composed of three-dimensional (3D) hierarchical plasmonic Au superstructures (SS) with both horizontal and vertical close-packed nano-polyhedron clusters on fluorine-doped tin oxide-coated (FTO) support. The stable solid-state Au SS can be simplistically developed by ultraviolet laser irradiation of FTO plate in HAuCl4 solution that facilitates photoexcited reduction of Au ions and then anisotropic nucleation of Au atoms. The 3D Au SS with ultrabroadband plasmonic resonance ranging from visible light to near-infrared region (400∼2000nm) provide remarkable enhanced multi-band SERS performances under 532, 633 and 785 nm excitation wavelengths, in comparison with the reference normal Au nanoparticles (NPs). Especially, the 785 nm NIR excitation of the generated SERS substrate enables the ultra-low detection limit of crystal violet (CV) molecules to be achieved as low as 10−16 M, which is obviously better than many previous works. The ultrahigh multi-band SERS activity is highly related the strong synergetic coupling effects of these interconnected Au nano-polyhedrons with hybridized multiple plasmonic modes. Besides, the ingenious Au configuration also possesses excellent SERS spatial uniformity, long-term stability and reproducibility, having more promising potentials for practical operation. Therefore, the versatile 3D plasmonic SS may grant attractive alternative pathway toward robust multi-band SERS analyses in the near future.
Leveraging pleiotropy for joint analysis of genome-wide association studies with per trait interpretations
Authors: Taraszka Kodi , Zaitlen Noah , Eskin Eleazar
Published: November 2022

We introduce pleiotropic association test (PAT) for joint analysis of multiple traits using genome-wide association study (GWAS) summary statistics. The method utilizes the decomposition of phenotypic covariation into genetic and environmental components to create a likelihood ratio test statistic for each genetic variant. Though PAT does not directly interpret which trait(s) drive the association, a per trait interpretation of the omnibus p-value is provided through an extension to the meta-analysis framework, m-values. In simulations, we show PAT controls the false positive rate, increases statistical power, and is robust to model misspecifications of genetic effect.

Additionally, simulations comparing PAT to three multi-trait methods, HIPO, MTAG, and ASSET, show PAT identified 15.3% more omnibus associations over the next best method. When these associations were interpreted on a per trait level using m-values, PAT had 37.5% more true per trait interpretations with a 0.92% false positive assignment rate. When analyzing four traits from the UK Biobank, PAT discovered 22,095 novel variants. Through the m-values interpretation framework, the number of per trait associations for two traits were almost tripled and were nearly doubled for another trait relative to the original single trait GWAS.
Transcriptomic analysis supports a role for the nervous system in regulating growth and development of Fasciola hepatica juveniles
Authors: Robb Emily , McCammick Erin M. , Wells Duncan , McVeigh Paul , Gardiner Erica , Armstrong Rebecca , McCusker Paul , Mousley Angela , Clarke Nathan , Marks Nikki J. , Maule Aaron G.
Published: November 2022

Fasciola spp. liver flukes have significant impacts in veterinary and human medicine. The absence of a vaccine and increasing anthelmintic resistance threaten sustainable control and underscore the need for novel flukicides. Functional genomic approaches underpinned by in vitro culture of juvenile Fasciola hepatica facilitate control target validation in the most pathogenic life stage. Comparative transcriptomics of in vitro and in vivo maintained 21 day old F. hepatica finds that 86% of genes are expressed at similar levels across maintenance treatments suggesting commonality in core biological functioning within these juveniles. Phenotypic comparisons revealed higher cell proliferation and growth rates in the in vivo juveniles compared to their in vitro counterparts. These phenotypic differences were consistent with the upregulation of neoblast-like stem cell and cell-cycle associated genes in in vivo maintained worms. The more rapid growth/development of in vivo juveniles was further evidenced by a switch in cathepsin protease expression profiles, dominated by cathepsin B in in vitro juveniles and by cathepsin L in in vivo juveniles. Coincident with more rapid growth/development was the marked downregulation of both classical and peptidergic neuronal signalling components in in vivo maintained juveniles, supporting a role for the nervous system in regulating liver fluke growth and development. Differences in the miRNA complements of in vivo and in vitro juveniles identified 31 differentially expressed miRNAs, including fhe-let-7a-5p, fhe-mir-124-3p and miRNAs predicted to target Wnt-signalling, which supports a key role for miRNAs in driving the growth/developmental differences in the in vitro and in vivo maintained juvenile liver fluke. Widespread differences in the expression of neuronal genes in juvenile fluke grown in vitro and in vivo expose significant interplay between neuronal signalling and the rate of growth/development, encouraging consideration of neuronal targets in efforts to dysregulate growth/development for parasite control.
Field evaluation of rapid diagnostic tests to determine dengue serostatus in Timor-Leste
Authors: Arkell Paul , Tanesi Maria , Gomes Nelia , Joao Josefina C. , Oakley Tessa , Bosco Frederico , Yan Jennifer , Fancourt Nicholas S. S. , Francis Joshua R.
Published: November 2022

The live attenuated tetravalent CYD-TDV vaccine (Dengvaxia) is effective but has scarcely been used due to safety concerns among seronegative recipients. Rapid diagnostic tests (RDTs) which can accurately determine individual dengue serostatus are needed for use in pre-vaccination screening. This study aimed to determine the performance of existing RDTs (which have been designed to detect levels of immunoglobulin G, IgG, associated with acute post-primary dengue) when repurposed for detection of previous dengue infection (where concentrations of IgG are typically lower). A convenience sample of four-hundred-and-six participants including 217 children were recruited during a community serosurvey. Whole blood was collected by phlebotomy and tested using Bioline Dengue IgG/IgM (Abbott) and Standard Q Dengue IgM/IgG (SD Biosensor) RDTs in the field. Serum samples from the same individuals were also tested at National Health Laboratory. The Panbio indirect IgG ELISA was used as a reference test. Reference testing determined that 370 (91.1%) participants were dengue IgG seropositive. Both assays were highly specific (100.0%) but had low sensitivity (Bioline = 21.1% and Standard Q = 4.6%) when used in the field. Sensitivity was improved when RDTs were used under laboratory conditions, and when assays were allowed to run beyond manufacturer recommendations and read at a delayed time-point, but specificity was reduced. Efforts to develop RDTs with high sensitivity and specificity for prior dengue infection which can be operationalised for pre-vaccination screening are ongoing. Performance of forthcoming candidate assays should be tested under field conditions with blood samples, as well as in the laboratory.
Knowledge, experiences, and practices of women affected by female genital schistosomiasis in rural Madagascar: A qualitative study on disease perception, health impairment and social impact
Authors: Schuster Angela , Randrianasolo Bodo Sahondra , Rabozakandraina Oliva Onintsoa , Ramarokoto Charles Emile , Brønnum Dorthe , Feldmeier Hermann
Published: November 2022

Background

Female genital schistosomiasis (FGS) is a neglected manifestation of urogenital schistosomiasis caused by S. haematobium. The disease presents with symptoms such as pelvic pain, vaginal discharge and bleeding and menstruation disorders, and might lead to infertility and pregnancy complications. The perspectives of women with FGS have not been studied systematically. The aim of the study was to understand knowledge, experiences, and practices of women with FGS.

Methods

We performed a qualitative study with seventy-six women diagnosed of having FGS, in the Ambanja district in Northwest Madagascar. Data collection was either through focus group discussion (N = 60) or in an individual semi-structured interview (N = 16). FGS was diagnosed by colposcopy. The data was analysed using Mayring´s qualitative content analysis.

Results

Knowledge on how the disease is acquired varied and ideas on prevention remained vague. Patients suffered from vaginal discharge and pelvic complaints. Some women expressed unbearable pain during sexual intercourse and compared their pain to an open wound being touched. FGS considerably impaired women´s daily activities and their quality of life. Infertility led to resignation and despair, conflicts with the partner and to social exclusion from the community. Women fearing to sexually transmit FGS refrained from partnership and sexual relations. Many women with FGS reported stigmatisation. A coping strategy was to share strain with other women having similar complaints. However, concealing FGS was a common behaviour which led to social isolation and delayed health care seeking.

Conclusions

Our study underlines that FGS has an important impact on the sexual health of women and on their social life in the community. Our results highlight the importance of providing adequate health education and structural interventions, such as the supply of water and the provision of sanitation measures. Further, correct diagnosis and treatment of FGS in adolescent girls and women should be available in all S. haematobium-endemic areas.

Trial registration

The qualitative study was embedded in a randomised controlled trial (RCT) in which two doses of praziquantel were compared (https://clinicaltrials.gov/ct2/show/NCT04115072).
Evaluation of plasma viral-load monitoring and the prevention of mother-to-child transmission of HIV-1 in three health facilities of the Littoral region of Cameroon
Authors: Kafack Etienne Verlain Fouedjio , Fokam Joseph , Nana Theophile Njamen , Saniotis Arthur , Halle-Ekane Gregory Edie
Published: November 2022

Background

Prevention of mother-to-child transmission (PMTCT) has reduced HIV incidence among new-borns. However, PMTCT remains concerning in sub-Saharan Africa due to bottlenecks including viral load (VL) monitoring during pregnancy. We assessed VL coverage and materno-foetal outcomes of pregnancy among HIV-infected women within the Cameroonian context.

Methods

A hospital-based study was conducted among HIV-infected mothers and their babies in three facilities of the Littoral region of Cameroon from January 2019 to May 2021. Maternal VL-coverage was monitored during pregnancy (VL>1000 copies/ml or unknown were classified as MTCT high-risk group); HIV early infant diagnosis (EID) was evaluated by PCR at six-weeks after birth, and EID results were analysed according to maternal VL; p<0.05 was considered statistically significant.

Results

Of 135 HIV-infected pregnant women enrolled (median [IQR] age 39 [27–37] years), VL-coverage during antenatal care (ANC) was 50.4% (68/135), with a lower VL-coverage in 2019 (37.5% vs. 61.9%, p = 0.0069). Married women vs. single (61.8% vs. 42.5%, p = 0.0275) and those on treatment before vs. during pregnancy (56.7% vs. 5.8%, p = 0.0043) had a higher VL-coverage, respectively. Among those with known VL, 10.3% (7/68) had high (VL>1000 copies/mL), 22.1% (15/68) had low (50–1000 copies/mL), and 67.6% (46/68) had undetectable (<50 copies/mL) VL, suggesting an overall viral suppression (<1000copies/mL) of 89.7% (61/68). Vaginal delivery was 80.75% (109/135) regardless of VL, including 81.1% (59/74) women in the high-risk group. EID coverage was 88.1% (119/135) and the rate of HIV-1 MTCT was 1.68% (2/119). Both HIV-positive infants were from the high-risk group, had prolonged labour, had vaginal delivery and were breastfed.

Conclusion

In these Cameroonian settings, VL-coverage remains suboptimal (below 90%) among ANC attendees, and women at high-risk of MTCT mainly have vaginal delivery. Viral suppression rate remains below the target (below 90%) for accelerating the elimination of MTCT. HIV-MTCT persists, and might be driven essentially by poor VL monitoring. Thus, achieving an optimal PMTCT performance requires a thorough compliance to virologic assessment during ANC.
Effect of a one-time financial incentive on linkage to chronic hypertension care in Kenya and Uganda: A randomized controlled trial
Authors: Hickey Matthew D. , Owaraganise Asiphas , Sang Norton , Opel Fredrick J. , Mugoma Erick Wafula , Ayieko James , Kabami Jane , Chamie Gabriel , Kakande Elijah , Petersen Maya L. , Balzer Laura B. , Kamya Moses R. , Havlir Diane V.
Published: November 2022

Background

Fewer than 10% of people with hypertension in sub-Saharan Africa are diagnosed, linked to care, and achieve hypertension control. We hypothesized that a one-time financial incentive and phone call reminder for missed appointments would increase linkage to hypertension care following community-based screening in rural Uganda and Kenya.

Methods

In a randomized controlled trial, we conducted community-based hypertension screening and enrolled adults ≥25 years with blood pressure ≥140/90 mmHg on three measures; we excluded participants with known hypertension or hypertensive emergency. The intervention was transportation reimbursement upon linkage (~$5 USD) and up to three reminder phone calls for those not linking within seven days. Control participants received a clinic referral only. Outcomes were linkage to hypertension care within 30 days (primary) and hypertension control <140/90 mmHg measured in all participants at 90 days (secondary). We used targeted minimum loss-based estimation to compute adjusted risk ratios (aRR).

Results

We screened 1,998 participants, identifying 370 (18.5%) with uncontrolled hypertension and enrolling 199 (100 control, 99 intervention). Reasons for non-enrollment included prior hypertension diagnosis (n = 108) and hypertensive emergency (n = 32). Participants were 60% female, median age 56 (range 27–99); 10% were HIV-positive and 42% had baseline blood pressure ≥160/100 mmHg. Linkage to care within 30 days was 96% in intervention and 66% in control (aRR 1.45, 95%CI 1.25–1.68). Hypertension control at 90 days was 51% intervention and 41% control (aRR 1.22, 95%CI 0.92–1.66).

Conclusion

A one-time financial incentive and reminder call for missed visits resulted in a 30% absolute increase in linkage to hypertension care following community-based screening. Financial incentives can improve the critical step of linkage to care for people newly diagnosed with hypertension in the community.
Spatial proliferation of African swine fever virus in South Korea
Authors: Tiwari Shraddha , Dhakal Thakur , Tiwari Ishwari , Jang Gab-Sue , Oh Yeonsu
Published: November 2022

The African swine fever virus (ASFV) was first detected in South Korea on a pig farm in September 2019. Despite active preventive measures to control the spread of ASFV, outbreaks on pig farms and in wild boar have been increasing. In this study, we investigated the spatial contamination area using the minimum convex polygon (MCP) approach, and growth rate using a logistic diffusion model. On the basis of the ASFV outbreak locations recorded from September 17th, 2019, to May 20th, 2022, the MCP area for the second week was 618.41 km2 and expanded to 37959.67 km2 in the final week. The maximum asymptote of the logistic function was considered as the land area of South Korea, and we estimated logistic growth rates of 0.022 km2 per week and 0.094 km2 per month. Administrative bodies should implement preventive and quarantine measures for infectious diseases. The results of this study will be a reference for epidemiologists, ecologists, and policy makers and contribute to the establishment of appropriate quarantine measures for disease control and management.
The pandemic as a political weapon: Analysis of Spanish press editorials during the COVID-19 health crisis
Authors: Mateu Anna , Sapiña Lucía , Domínguez Martí
Published: November 2022

The COVID-19 pandemic caused by the new SARS-CoV-2 coronavirus represents the greatest crisis the world has faced in recent decades. Especially during the first waves, Spain was one of the European countries most affected by the pandemic. Although several studies have been carried out on the media coverage of the crisis, they have largely focused on the news genre. This study examines newspaper editorials’ approach to the issue, helping to analyse the perspective offered in opinion genres. To this end, the editorials of four Spanish newspapers were analysed from January 2020 to August 2021 (N = 243). The results reflect a strong politicization of the pandemic, both echoing and reinforcing political tension, and leaving more technical or scientific issues on a secondary plane.