bluuebunny/crossref_metadata_2025 huggingface dataset:
Procedural characteristics of pulmonary vein isolation with high-power short-duration setting compared to conventional setting
Authors: Hijioka Naoko , Kaneshiro Takashi , Nehashi Takeshi , Amami Kazuaki , Nodera Minoru , Yamada Shinya , Kamioka Masashi , Ishida Takafumi , Takeishi Yasuchika
Published: January 2022

Purpose

The purpose of this study was to investigate the safety and efficacy of high-power short-duration (HP-SD) ablation compared to conventional ablation in patients with atrial fibrillation (AF).

Methods

We enrolled consecutive 158 drug-refractory symptomatic AF patients (119 males, mean age 63 ± 10 years) who had undergone first radiofrequency pulmonary vein isolation (PVI). PVI was performed using the conventional setting (20–35 W) in 73 patients (Conventional group) and using the HP-SD setting (45–50 W) in 85 patients (HP-SD group). The rate of first pass isolation, remaining gaps after circumferential ablation, dormant conduction, and the radiofrequency application time in each pulmonary vein (PV) were compared between the groups.

Results

The first pass isolation ratio was significantly higher in the HP-SD group than in the Conventional group (81% vs. 65%, P = 0.027) in the right PV, but did not differ in the left PV. The remaining gaps were fewer in the right superior PV (4% vs. 21%, P = 0.001) and left inferior PV (1% vs. 8%, P = 0.032) areas, and the radiofrequency application time in each PV was shorter (right PV, 12.0 ± 8.9 min vs. 34.0 ± 31.7 min, P < 0.001; left PV, 10.6 ± 3.6 min vs. 25.7 ± 22.3 min, P < 0.001) in the HP-SD group than in the Conventional group.

Conclusion

The use of the HP-SD setting might contribute to improve the first pass isolation rate and to shorten the radiofrequency application time in each PV.
Comparison of 3-factor versus 4-factor prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis
Authors: Margraf David J. , Brown Sarah J. , Blue Heather L. , Bezdicek Tamara L. , Wolfson Julian , Chapman Scott A.
Published: January 2022

Background

Patients requiring emergent warfarin reversal (EWR) have been prescribed three-factor prothrombin complex concentrate (PCC3) and four-factor prothrombin complex concentrate (PCC4) to reverse the anticoagulant effects of warfarin. There is no existing systematic review and meta-analysis of studies directly comparing PCC3 and PCC4.

Methods

The primary objective of this systematic review and meta-analysis was to determine the effectiveness of achieving study defined target INR goal after PCC3 or PCC4 administration. Secondary objectives were to determine the difference in safety endpoints, thromboembolic events (TE), and survival during the patients’ hospital stay. Random-effects meta-analysis models were used to estimate the odds ratios (OR), and heterogeneity associated with the outcomes. The Newcastle-Ottawa Scale was used to assess study quality, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.

Results

Ten full-text manuscripts and five abstracts provided data for the primary and secondary outcomes. Patients requiring EWR had more than three times the odds of reversal to goal INR when they were given PCC4 compared to PCC3 (OR = 3.61, 95% CI: 1.97–6.60, p < 0.001). There was no meaningful clinical association or statistically significant result between PCC4 and PCC3 groups in TE (OR = 1.56, 95% CI: 0.83–2.91, p = 0.17), or survival during hospital stay (OR = 1.34, 95% CI: 0.81–2.23, p = 0.25).

Conclusion

PCC4 is more effective than PCC3 in meeting specific predefined INR goals and has similar safety profiles in patients requiring emergent reversal of the anticoagulant effects of warfarin.
RBD-specific antibody responses after two doses of BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine
Authors: Ferenci Tamás , Sarkadi Balázs
Published: January 2022

Background

Limited information is available on the effectiveness of the BBIBP-CorV (Sinopharm, Beijing CNBG) vaccine, especially in the elderly, despite the fact that it is approved in more than 50 countries.

Methods

RBD-specific antibody titres, as a rapidly available and highly predictive surrogate marker, were measured after two doses of the BBIBP-CorV vaccine in 450 subjects. Results were analyzed in a multivariable model accounting for age, sex and time since the administration of the second dose of the vaccine.

Results

Sex and time since the second dose had little association with the antibody titres. Age, however, was highly relevant: measurable antibody levels were present in about 90% of individuals below the age of 50, but antibody production after BBIBP-CorV vaccination was strongly reduced with increasing age. A large number of elderly subjects, reaching 25% at 60 years, and up to 50% at ages over 80, were found not to produce any protective antibody.

Conclusions

RBD-specific antibody titre, as a correlate of protection for COVID-19 disease susceptibility, should help to evaluate the effectiveness of the BBIBP-CorV vaccine. Results suggest that proper measures should be undertaken to prevent a potential outbreak of COVID-19 in BBIBP-CorV vaccinated but eventually unprotected elderly individuals.
Correction to: Guy’s and St Thomas NHS Foundation active surveillance prostate cancer cohort: a characterisation of a prostate cancer active surveillance database
Authors: Shah Salonee , Beckmann Kerri , Van Hemelrijck Mieke , Challacombe Ben , Popert Rick , Dasgupta Prokar , Rusere Jonah , Zisengwe Grace , Elhage Oussama , Santaolalla Aida
Published: January 2022

An amendment to this paper has been published and can be accessed via the original article.
Kearns–Sayre syndrome with a novel large-scale deletion: a case report
Authors: Zhu Qin , Chen Chunwen , Yao Jingyan
Published: January 2022

Background

Kearns–Sayre syndrome (KSS) is a rare, multisystem mitochondrial encephalomyopathy. We report a case of KSS with a novel 7.6-kb deletion as assessed through a long-range polymerase chain reaction (PCR) study in the blood. In addition, optical coherence tomography angiography (OCTA) confirmed deep retinal capillary atrophy for the first time.

Case presentation

A 13-year-old patient presented with progressive vision loss and difficulty with eye opening and was diagnosed with progressive external ophthalmoplegia and retinitis pigmentosa (RP). The patient also experienced heart block, vestibular dysfunction, growth retardation and multiple demyelinating lesions. A long-range PCR study in the blood revealed a large-scale Chrm: 6341–13,993 deletion, which was first reported and broadened the genetic spectrum of this disease. The patient underwent complete ophthalmic examination, medical history review and gene detection, resulting in a confirmation of the diagnosis of KSS. The patient was given a pair of applicable glasses to wear and was followed up every 3 months. An implantable pacemaker was also installed based on the advice of the physician.

Conclusions

We reported a novel large-scale deletion in the mitochondrial DNA of KSS, and OCTA was used for the first time to confirm deep retinal capillary atrophy. Furthermore, because ophthalmic symptoms are often the primary manifestation of KSS, the relationship between ophthalmology and mitochondrial diseases should be emphasised.
Screening programs for common maternal mental health disorders among perinatal women: report of the systematic review of evidence
Authors: Waqas Ahmed , Koukab Ahmreen , Meraj Hafsa , Dua Tarun , Chowdhary Neerja , Fatima Batool , Rahman Atif
Published: January 2022

Postpartum depression and anxiety are highly prevalent worldwide. Fisher et al., estimated the prevalence of depression and anxiety at 15.6% during the antenatal and 19.8% during the postpartum period. Their impact on maternal and child health is well-recognized among the public health community, accounting for high societal costs. The public health impact of these conditions has highlighted the need to focus on the development and provision of effective prevention and treatment strategies.

In recent decades, some advances have been made in the development of effective universal and targeted screening programmes for perinatal depression and anxiety disorders. Recent research has shown potential benefits of universal and targeted screening for perinatal depression, to identify and treat undiagnosed cases, and help thwart its deleterious consequences. Ethical implications, however, for these screening programmes, without the provision of treatment have often been emphasized.

The present mixed-methods systematic review and meta-analysis was conducted to collate evidence for screening programmes for perinatal depression and anxiety. It aims to answer the following questions, in a global context: For women in the perinatal period, do screening programmes for perinatal depression and anxiety compared with no screening improve maternal mental health and infant outcomes?

A series of meta-analyses reveal a reduction in perinatal depression and anxiety among perinatal women undergoing screening programmes. For the outcome of depressive disorder, meta-analysis indicates a positive impact in favour of the intervention group (OR = 0.55, 95% CI: 0.45 to 0.66,n = 9009), with moderate quality of evidence. A significant improvement (high quality) was also observed in symptoms of anxiety among perinatal women (SMD = − 0.18, 95% CI: − 0.25 to − 0.12,n = 3654).
Outdoor public recreation spaces and social connectedness among adolescents
Authors: Rivera Elise , Veitch Jenny , Loh Venurs H. Y. , Salmon Jo , Cerin Ester , Mavoa Suzanne , Villanueva Karen , Timperio Anna
Published: January 2022

Background

Outdoor public recreation spaces are important settings for leisure and physical activity. Adolescents’ use of these spaces may contribute to social connectedness via social interaction with peers and the community in these settings. However, research on this topic is limited. This exploratory study examined associations of frequency of visitation and physical activity in outdoor public recreation spaces with social connectedness among adolescents in Melbourne, Australia.

Methods

Adolescents self-reported their frequency of visitation to parks, trails, beach/lake, and sports facilities; frequency of physical activity in a park, local street or path, and their street; and social connectedness. Separate analyses were conducted for visitation (n = 349, 15.4 ± 1.6 years, 58% female) and physical activity (n = 441, 15.4 ± 1.6 years, 59% female) using multilevel linear regression models.

Results

No significant associations were observed for frequency of visitation to a park (B = 0.86, 95% CI = − 0.26, 1.99), trails (B = 0.41, 95% CI = − 0.61, 1.44), beach/lake (B = − 0.44, 95% CI = − 1.46, 0.57), or sports facilities (B = 0.64, 95% CI = − 0.43, 1.70), nor for frequency of physical activity in their street (B = − 0.07, 95% CI = − 0.46, 0.31), local street/path (B = − 0.05, 95% CI = − 0.43, 0.33) or in a park (B = 0.23, 95% CI = − 0.14, 0.60) with adolescents’ social connectedness.

Conclusions

The findings did not support the hypothesis that visiting and being active in outdoor public recreation spaces are associated with adolescents’ social connectedness. Future research should consider the duration and context of outdoor public recreation space use (e.g., sports, socialising, relaxing alone) and whether different types and/or a combination of public spaces are more/less conducive to social connectedness.
Modernising grip dynamometry: Inter-instrument reliability between GripAble and Jamar
Authors: Mutalib Sharah Abdul , Mace Michael , Seager Chloe , Burdet Etienne , Mathiowetz Virgil , Goldsmith Nicola
Published: January 2022

Introduction

Maximum grip strength (MGS) is a reliable biomarker of overall health and physiological well-being. Therefore, an accurate and reliable measurement device is vital for ensuring the validity of the MGS assessment. This paper presents GripAble, a mobile hand grip device for the assessment of MGS. GripAble’s performance was evaluated using an inter-instrument reliability test against the widely used Jamar PLUS+ dynamometer.

Methods

MGS data from sixty-three participants (N = 63, median (IQR) age = 29.0 (29.5) years, 33 M/30 F) from both hands using GripAble and Jamar PLUS+ were collected and compared. Intraclass correlation (ICC), regression, and Bland and Altman analysis were performed to evaluate the inter-instrument reliability and relationship in MGS measurements between GripAble and Jamar PLUS+ .

Results

GripAble demonstrates good-to-excellent inter-instrument reliability to the Jamar PLUS+ with ICC3,1 = 0.906 (95% CI [0.87—0.94]). GripAble’s MGS measurement is equivalent to 69% (95% CI [0.67—0.71]%) of Jamar PLUS+’s measurement. There is a proportional difference in mean MGS between the two devices, with the difference in MGS between GripAble and Jamar PLUS+ increasing with MGS.

Conclusion

The GripAble is a reliable tool for measuring grip strength. However, the MGS readings from GripAble and Jamar PLUS+ should not be interchanged for serial measurements of the same patient, nor be translated directly from one device to the other. A new normative MGS data using GripAble will be collected and accessed through the software for immediate comparison to age and gender-matched subpopulations.
Evaluating the implementation of home delivery of medication by community health workers during the COVID-19 pandemic in Cape Town, South Africa: a convergent mixed methods study
Authors: Mash Robert James , Schouw Darcelle , Daviaud Emmanuelle , Besada Donela , Roman Darrin
Published: January 2022

Background

Primary care services in South Africa have been challenged by increasing numbers of people with communicable and non-communicable chronic diseases. There was a need to develop alternative approaches for stable patients to access medication. With the onset of the coronavirus pandemic there was an urgent need to decongest facilities and protect people from infection. In this crisis the Metro Health Services rapidly implemented home delivery of medication by community health workers. This study aimed to evaluate the implementation of home delivery of medication by community health workers during the coronavirus pandemic in Cape Town, South Africa.

Methods

A convergent mixed methods study evaluated six implementation outcomes: adoption, feasibility, fidelity, coverage, cost, and sustainability of the initiative. Data sources included routinely collected data, a telephonic survey of 138 patients, an analysis of set-up and recurrent costs as well as 17 descriptive exploratory qualitative semi-structured interviews with 68 key informants.

Results

Over a 6-month period 1,054,657 pre-packaged parcels were sent to primary care facilities, 819,649 (77.7%) were delivered and of those 97,297 (11.9%) returned. The additional costs were estimated as 1.3% of a total health budget of R2,2 billion. The initiative was rapidly adopted as it decongested facilities and protected vulnerable patients. Although it was feasible to implement at scale, numerous challenges were encountered, such as incorrect addresses and contact details, transporting parcels, communicating with patients, having a reliable audit trail, and handling out-of-area patients. All role players thought the service should continue and 42.3% of patients reported better adherence to their medication.

Conclusion

Home delivery of medication by community health workers is feasible at scale and affordable. It should continue, but as one of a menu of options for alternative delivery of medication. The following need to be improved: efficiency of the system, the audit trail, adequate support and resources for community health workers, transport of medication, communication with patients, empanelment of patients, governance of the system and training of the community health workers.
Plasma sRAGE levels strongly associate with centrilobular emphysema assessed by HRCT scans
Authors: Klont Frank , Horvatovich Peter , Bowler Russell P. , van Rikxoort Eva , Charbonnier Jean-Paul , Kwiatkowski Marcel , Lynch David A. , Humphries Stephen , Bischoff Rainer , ten Hacken Nick H. T. , Pouwels Simon D.
Published: January 2022

Background

There is a strong need for biomarkers to better characterize individuals with COPD and to take into account the heterogeneity of COPD. The blood protein sRAGE has been put forward as promising biomarker for COPD in general and emphysema in particular. Here, we measured plasma sRAGE levels using quantitative LC–MS and assessed whether the plasma sRAGE levels associate with (changes in) lung function, radiological emphysema parameters, and radiological subtypes of emphysema.

Methods

Three hundred and twenty-four COPD patients (mean FEV1: 63%predicted) and 185 healthy controls from the COPDGene study were selected. Plasma sRAGE was measured by immunoprecipitation in 96-well plate methodology to enrich sRAGE, followed by targeted quantitative liquid chromatography-mass spectrometry. Spirometry and HRCT scans (inspiration and expiration) with a 5-year follow-up were used; both subjected to high quality control standards.

Results

Lower sRAGE values significantly associated with the presence of COPD, the severity of airflow obstruction, the severity of emphysema on HRCT, the heterogeneous distribution of emphysema, centrilobular emphysema, and 5-year progression of emphysema. However, sRAGE values did not associate with airway wall thickness or paraseptal emphysema.

Conclusions

Rather than being a general COPD biomarker, sRAGE is especially a promising biomarker for centrilobular emphysema. Follow-up studies should elucidate whether sRAGE can be used as a biomarker for other COPD phenotypes as well.
Golgi phosphoprotein 3 promotes angiogenesis and sorafenib resistance in hepatocellular carcinoma via upregulating exosomal miR-494-3p
Authors: Gao Ying , Yin Zheng , Qi Yunling , Peng Hong , Ma Wenbin , Wang Ruizhi , Li Wen
Published: January 2022

Background

Golgi phosphoprotein 3 (GOLPH3) has been frequently reported as an oncoprotein in a variety of tumors. However, its role in the cancer-associated intercellular signaling communication has not yet been explored. This study aimed at exploring whether GOLPH3 regulates angiogenesis and sorafenib resistance via exosomal mechanisms in hepatocellular carcinoma (HCC).

Methods

In vivo assays were performed to elucidate the function of GOLPH3 in HCC. Exosomes of HCC cells were isolated by differential centrifugation, and then measured and quantified using nanoparticle tracking analysis (NTA), BCA assay, western blot (WB), and transmission electron microscopy (TEM). Differentially expressed miRNAs in exosome were analyzed and verified through small RNA sequencing (sRNA-seq) and reverse-transcription polymerase chain reaction (RT-PCR). In addition, a series of in vitro assays were performed to determine the function of exosomes and miR-494-3p in HCC. The candidate target gene of miR-494-3p was identified by bioinformatics prediction and dual-luciferase reporter assay.

Results

Downregulation of GOLPH3 expression could suppress angiogenesis and enhance sorafenib sensitivity in HCC. Exosomes derived from GOLPH3 overexpression HCC cells promoted the angiogenesis ability of HUVECs and induced sorafenib resistance in HCC cells. A total of 13 differentially expressed miRNAs between negative control and GOLPH3 knockdown group were found in exosomes. However, GOLPH3 was only associated with miR-494-3p expression level in exosomes derived from HCC cells without affecting total cellular miR-494-3p content. Results confirmed that exosomal miR-494-3p promotes angiogenesis of HUVECs and sorafenib resistance in HCC cells through directly targeting PTEN.

Conclusions

HCC cells with high expression levels of GOLPH3 could promote angiogenesis and sorafenib resistance by enhancing exosomal miR-494-3p secretion to recipient HUVECs and HCC cells, respectively.
Decoquinate liposomes: highly effective clearance of Plasmodium parasites causing severe malaria
Authors: Zeng Sumei , Wang Hongxing , Tao Long , Ning Xiaohui , Fan Yinzhou , Zhao Siting , Qin Li , Chen Xiaoping
Published: January 2022

Background

Severe malaria caused by Plasmodium falciparum leads to most malaria-related deaths globally. Decoquinate (DQ) displays strong activity against multistage infection by Plasmodium parasites. However, the development of DQ as an oral dosage form for the treatment of malaria at the blood stage has not been successful. In this study, liposome formulations of DQ were created for intravenous (IV) injection to suppress Plasmodium berghei, a parasite that causes severe malaria in mice.

Methods

DQ liposomes were prepared by conventional ethanol injection method with slight modifications and encapsulation efficiency evaluated by the well-established centrifugation method. Potency of the DQ liposomes against P. falciparum was assessed in vitro using freshly isolated human red blood cells. The efficacy of the DQ liposomes was examined in the mouse model of severe malaria.

Results

The DQ liposomes were around 150 nm in size and had the encapsulation efficiency rates > 95%. The freshly prepared and lyophilized liposomes were stable after storage at − 20 °C for 6 months. The liposomes were shown to have excellent activity against P. falciparum in vitro with DQ IC50 0.91 ± 0.05 nM for 3D7 (chloroquine sensitive strain) and DQ IC50 1.33 ± 0.14 nM for Dd2 (multidrug resistant strain), which were 18- and 14-fold more potent than artemisinin, respectively. Mice did not have any signs of toxicity after receiving high dose of the liposomes (DQ 500 mg/kg per mouse) by IV injection. In the mouse model of severe malaria, the liposomes had impressive efficacy against P. berghei with DQ ED50 of 0.720 mg/kg.

Conclusion

The DQ liposomes prepared in this study were stable for long term storage and safe for IV injection in mammalian animals. The newly created liposome formulations had excellent activity against Plasmodium infection at the blood-stage, which encourages their application in the treatment of severe malaria.
The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin
Authors: Wang Zehao , Yang Lu , Wu Peng , Li Xing , Tang Yuhui , Ou Xueqi , Zhang Yue , Xiao Xiangsheng , Wang Jin , Tang Hailin
Published: January 2022

Background

Metastasis causes the majority of cancer-related deaths worldwide. Increasing studies have revealed that circRNAs are associated with the carcinogenesis and metastasis of many cancers. Nevertheless, the biological mechanisms of circRNAs in breast cancer (BC) liver metastasis remain extremely ambiguous.

Methods

In this study, we identified circROBO1 from three pairs of primary BC and metastatic liver sites by RNA sequencing. FISH assays and RT-qPCR were conducted to validate the existence and expression of circROBO1. The oncogenic role of circROBO1 was demonstrated both in vitro and in vivo. Western blot, ChIP, RIP, RNA pull-down, and dual-luciferase reporter assays were used to confirm the interaction of the feedback loop among circROBO1, miR-217-5p, KLF5, and FUS. Meanwhile, the regulation of selective autophagy was investigated by immunofluorescence, CoIP, and western blot.

Results

In this study, upregulated expression of circROBO1 was found in BC-derived liver metastases and was correlated with poor prognosis. Knockdown of circROBO1 strikingly inhibited the proliferation, migration, and invasion of BC cells, whereas overexpression of circROBO1 showed the opposite effects. Moreover, overexpression of circROBO1 promoted tumor growth and liver metastasis in vivo. Further research revealed that circROBO1 could upregulate KLF5 by sponging miR-217-5p, allowing KLF5 to activate the transcription of FUS, which would promote the back splicing of circROBO1. Therefore, a positive feedback loop comprising circROBO1/KLF5/FUS was formed. More importantly, we found that circROBO1 inhibited selective autophagy of afadin by upregulating KLF5.

Conclusions

Our results demonstrated that circROBO1 facilitates the carcinogenesis and liver metastasis of BC through the circROBO1/KLF5/FUS feedback loop, which inhibits the selective autophagy of afadin by suppressing the transcription of BECN1. Therefore, circROBO1 could be used not only as a potential prognostic marker but also as a therapeutic target in BC.
Engineering of small-molecule lipidic prodrugs as novel nanomedicines for enhanced drug delivery
Authors: Huang Lingling , Yang Jianmiao , Wang Tiantian , Gao Jianqing , Xu Donghang
Published: January 2022

A widely established prodrug strategy can effectively optimize the unappealing properties of therapeutic agents in cancer treatment. Among them, lipidic prodrugs extremely uplift the physicochemical properties, site-specificity, and antitumor activities of therapeutic agents while reducing systemic toxicity. Although great perspectives have been summarized in the progress of prodrug-based nanoplatforms, no attention has been paid to emphasizing the rational design of small-molecule lipidic prodrugs (SLPs). With the aim of outlining the prospect of the SLPs approach, the review will first provide an overview of conjugation strategies that are amenable to SLPs fabrication. Then, the rational design of SLPs in response to the physiological barriers of chemotherapeutic agents is highlighted. Finally, their biomedical applications are also emphasized with special functions, followed by a brief introduction of the promising opportunities and potential challenges of SLPs-based drug delivery systems (DDSs) in clinical application.

Graphical Abstract
Nos2−/− mice infected with M. tuberculosis develop neurobehavioral changes and immunopathology mimicking human central nervous system tuberculosis
Authors: Poh Xuan Ying , Hong Jia Mei , Bai Chen , Miow Qing Hao , Thong Pei Min , Wang Yu , Rajarethinam Ravisankar , Ding Cristine S. L. , Ong Catherine W. M.
Published: January 2022

Background

Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB.

Methods

We injected twoMycobacterium tuberculosis(M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ andNos2−/−mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains.

Results

Intra-cerebroventricular infection ofNos2−/−mice withM.tbled to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551M.tb, H37RvM.tbinfection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection ofNos2−/−mice withM.tbresembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice.

Conclusions

Intra-cerebroventricular infection ofNos2−/−mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host–pathogen interactions and evaluate therapeutic agents for CNS-TB.
Addressing a silent and neglected scourge in sexual and reproductive health in Sub-Saharan Africa by development of training competencies to improve prevention, diagnosis, and treatment of female genital schistosomiasis (FGS) for health workers
Authors: Jacobson Julie , Pantelias Anastasia , Williamson Megan , Kjetland Eyrun Floerecke , Krentel Alison , Gyapong Margaret , Mbabazi Pamela Sabina , Djirmay Amadou Garba
Published: January 2022

Background

Schistosomiasis is an acute and chronic disease caused by parasitic worms, that can take two main forms: intestinal or urogenital. If left untreated, the urogenital form can lead to female genital schistosomiasis (FGS) in women and girls; frequently resulting in severe reproductive health complications which are often misdiagnosed as sexually-transmitted infections (STIs) or can be confused with cervical cancer. Despite its impact on women’s reproductive health, FGS is typically overlooked in medical training and remains poorly recognized with low awareness both in affected communities and in health professionals. FGS has been described as the one of the most neglected sexual and reproductive health issues in sub-Saharan Africa (Swai in BMC Infect Dis 6:134, 2006; Kukula in PLoS Negl Trop Dis 13:e0007207; Joint United Nations Programme on HIV/AIDS (UNAIDS) 2019). Increased knowledge and awareness of FGS is required to end this neglect, improve women’s reproductive health, and decrease the burden of this preventable and treatable neglected tropical disease.

Methods

We conducted interactive virtual workshops, in collaboration with the World Health Organization (WHO), engaging 64 participants with medical and public health backgrounds from around the world to establish standardized skills (or competencies) for prevention, diagnosis, and treatment of FGS at all levels of the health system. The competencies were drafted in small groups, peer-reviewed, and finalized by participants.

Results

This participatory process led to identification of 27 skills needed for FGS prevention, diagnosis, and management for two categories of health workers; those working in a clinical setting, and those working in a community setting. Among them, ten relate to the diagnosis of FGS including three that involve a pelvic exam and seven that do not. Six constitute the appropriate behaviors required to treat FGS in a clinical setting. Eleven address the community setting, with six relating to the identification of women at risk and five relating to prevention.

Conclusion

Defining the skills necessary for FGS management is a critical step to prepare for proper diagnosis and treatment of women and girls in sub-Saharan Africa by trained health professionals. The suggested competencies can now serve as the foundation to create educative tools and curricula to better train health care workers on the prevention, diagnosis, and management of FGS.
Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles
Authors: Gren Louise , Dierschke Katrin , Mattsson Fredrik , Assarsson Eva , Krais Annette M. , Kåredal Monica , Lovén Karin , Löndahl Jakob , Pagels Joakim , Strandberg Bo , Tunér Martin , Xu Yiyi , Wollmer Per , Albin Maria , Nielsen Jörn , Gudmundsson Anders , Wierzbicka Aneta
Published: January 2022

Background

Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system (‘HVOPM+NOx’ PM1: 93 µg m−3, EC: 54 µg m−3, NO: 3.4 ppm, NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter (‘HVONOx’ PM1: ~ 1 µg m−3, NO: 2.0 ppm, NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study.

Results

The average total respiratory tract deposition of PM1 during HVOPM+NOxwas 27 µg h−1. The estimated deposition fraction of HVO PM1 was 40–50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the HVOPM+NOxexhaust. Compared to FA, exposure to HVOPM+NOxand HVONOxcaused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA,p < 0.03). Especially, exposure to HVOPM+NOxshowed 40–50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the HVONOxexposures (− 18.1, 95% CI: − 27.3 to − 8.8 L min−1,p < 0.001), and for the HVOPM+NOx(− 7.4 (− 15.6 to 0.8) L min−1,p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique).

Conclusion

Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.
Growth pattern trajectories in boys with Duchenne muscular dystrophy
Authors: Stimpson Georgia , Raquq Sarah , Chesshyre Mary , Fewtrell Mary , Ridout Deborah , Sarkozy Anna , Manzur Adnan , Ayyar Gupta Vandana , De Amicis Ramona , Muntoni Francesco , Baranello Giovanni ,   the NorthStar Network, Ambegaonkar Gautam , Alhaswani Zoya , Baxter Alex , Childs Anne-Marie , Chow Gabby , De Goede Christian , Fernandez Miguel , Gibbon Frances , Gowda Vasantha , Guglieri Michela , Hart Tony , Hewawitharana Gemunu , Horrocks Iain , Hughes Imelda , Illingworth Marjorie , Krishnakumar Deepa , Majumdar Anirban , Marini-Bettolo Chiara , Ong Min , Parasuraman Deepak , Ramdas Sithara , Servais Laurent , Skone Kate , Spinty Stefan , Stephens Elma , Straub Volker , Tirupathi Sandya , Thomas Neil , Willis Tracey , White Cathy , Wong Jarod , Wraige Elizabeth , Vijayakumar Kayal , Naismith Karen
Published: January 2022

Objectives

The objective of this study is to analyse retrospective, observational, longitudinal growth (weight, height and BMI) data in ambulatory boys aged 5–12 years with Duchenne muscular dystrophy (DMD).

Background

We considered glucocorticoids (GC) use, dystrophin isoforms and amenability to exon 8, 44, 45, 51 and 53 skipping drug subgroups, and the impact of growth on loss of ambulation. We analysed 598 boys, with 2604 observations. This analysis considered patients from the UK NorthStar database (2003–2020) on one of five regimes: “GC naïve”, “deflazacort daily” (DD), “deflazacort intermittent” (DI), “prednisolone daily” (PD) and “prednisolone intermittent” (PI). A random slope model was used to model the weight, height and BMI SD scores (using the UK90).

Results

The daily regime subgroups had significant yearly height stunting compared to the GC naïve subgroup. Notably, the average height change for the DD subgroup was 0.25 SD (95% CI − 0.30, − 0.21) less than reference values. Those with affected expression of Dp427, Dp140 and Dp71 isoforms were 0.77 (95% CI 0.3, 1.24) and 0.82 (95% CI 1.28, 0.36) SD shorter than those with Dp427 and/or Dp140 expression affected respectively. Increased weight was not associated with earlier loss of ambulation, but taller boys still ambulant between the age of 10 and 11 years were more at risk of losing ambulation.

Conclusion

These findings may provide further guidance to clinicians when counselling and discussing GCs commencement with patients and their carers and may represent a benchmark set of data to evaluate the effects of new generations of GC.
Development of a novel combined nomogram model integrating deep learning-pathomics, radiomics and immunoscore to predict postoperative outcome of colorectal cancer lung metastasis patients
Authors: Wang Renjie , Dai Weixing , Gong Jing , Huang Mingzhu , Hu Tingdan , Li Hang , Lin Kailin , Tan Cong , Hu Hong , Tong Tong , Cai Guoxiang
Published: January 2022

Limited previous studies focused on the death and progression risk stratification of colorectal cancer (CRC) lung metastasis patients. The aim of this study is to construct a nomogram model combing machine learning-pathomics, radiomics features, Immunoscore and clinical factors to predict the postoperative outcome of CRC patients with lung metastasis. In this study, a total of 103 CRC patients having metastases limited to lung and undergoing radical lung resection were identified. Patch-level convolutional neural network training in weakly supervised manner was used to perform whole slides histopathological images survival analysis. Synthetic minority oversampling technique and support vector machine classifier were used to identify radiomics features and build predictive signature. The Immunoscore for each patient was calculated from the density of CD3+ and CD8+ cells at the invasive margin and the center of metastatic tumor which were assessed on consecutive sections of automated digital pathology. Finally, pathomics and radiomics signatures were successfully developed to predict the overall survival (OS) and disease free survival (DFS) of patients. The predicted pathomics and radiomics scores are negatively correlated with Immunoscore and they are three independent prognostic factors for OS and DFS prediction. The combined nomogram showed outstanding performance in predicting OS (AUC = 0.860) and DFS (AUC = 0.875). The calibration curve and decision curve analysis demonstrated the considerable clinical usefulness of the combined nomogram. Taken together, the developed nomogram model consisting of machine learning-pathomics signature, radiomics signature, Immunoscore and clinical features could be reliable in predicting postoperative OS and DFS of colorectal lung metastasis patients.
sPLINK: a hybrid federated tool as a robust alternative to meta-analysis in genome-wide association studies
Authors: Nasirigerdeh Reza , Torkzadehmahani Reihaneh , Matschinske Julian , Frisch Tobias , List Markus , Späth Julian , Weiss Stefan , Völker Uwe , Pitkänen Esa , Heider Dominik , Wenke Nina Kerstin , Kaissis Georgios , Rueckert Daniel , Kacprowski Tim , Baumbach Jan
Published: January 2022

Meta-analysis has been established as an effective approach to combining summary statistics of several genome-wide association studies (GWAS). However, the accuracy of meta-analysis can be attenuated in the presence of cross-study heterogeneity. We present sPLINK, a hybrid federated and user-friendly tool, which performs privacy-aware GWAS on distributed datasets while preserving the accuracy of the results. sPLINK is robust against heterogeneous distributions of data across cohorts while meta-analysis considerably loses accuracy in such scenarios. sPLINK achieves practical runtime and acceptable network usage for chi-square and linear/logistic regression tests. sPLINK is available at https://exbio.wzw.tum.de/splink.
Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence
Authors: Bestry Mitchell , Symons Martyn , Larcombe Alexander , Muggli Evelyne , Craig Jeffrey M. , Hutchinson Delyse , Halliday Jane , Martino David
Published: January 2022

Background

Prenatal alcohol exposure (PAE) is associated with a range of adverse offspring neurodevelopmental outcomes. Several studies suggest that PAE modifies DNA methylation in offspring cells and tissues, providing evidence for a potential mechanistic link to Fetal Alcohol Spectrum Disorder (FASD). We systematically reviewed existing evidence on the extent to which maternal alcohol use during pregnancy is associated with offspring DNA methylation.

Methods

A systematic literature search was conducted across five online databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, EMBASE, Google Scholar and CINAHL Databases were searched for articles relating to PAE in placental mammals. Data were extracted from each study and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) was used to assess the potential for bias in human studies.

Results

Forty-three articles were identified for inclusion. Twenty-six animal studies and 16 human studies measured offspring DNA methylation in various tissues using candidate gene analysis, methylome-wide association studies (MWAS), or total nuclear DNA methylation content. PAE dose and timing varied between studies. Risk of bias was deemed high in nearly all human studies. There was insufficient evidence in human and animal studies to support global disruption of DNA methylation from PAE. Inconclusive evidence was found for hypomethylation at IGF2/H19 regions within somatic tissues. MWAS assessing PAE effects on offspring DNA methylation showed inconsistent evidence. There was some consistency in the relatively small number of MWAS conducted in populations with FASD. Meta-analyses could not be conducted due to significant heterogeneity between studies.

Conclusion

Considering heterogeneity in study design and potential for bias, evidence for an association between PAE and offspring DNA methylation was inconclusive. Some reproducible associations were observed in populations with FASD although the limited number of these studies warrants further research.

Trail Registration: This review is registered with PROSPERO (registration number: CRD42020167686).
Drift-diffusion models for the simulation of a graphene field effect transistor
Authors: Nastasi Giovanni , Romano Vittorio
Published: January 2022

A field effect transistor having the active area made of monolayer graphene is simulated by a drift-diffusion model coupled with the Poisson equation. The adopted geometry, already proposed in (Nastasi and Romano in IEEE Trans. Electron. Devices 68:4729–4734, 2021, 10.1109/TED.2021.3096492), gives a good current-ON/current-OFF ratio as it is evident in the simulations. In this paper, we compare the numerical simulations of the standard (non-degenerate) drift-diffusion model, that includes the Einstein diffusion coefficient, with the degenerate case.
Validation and test–retest repeatability performance of parametric methods for [11C]UCB-J PET
Authors: Tuncel Hayel , Boellaard Ronald , Coomans Emma M. , Hollander-Meeuwsen Marijke den , de Vries Erik F. J. , Glaudemans Andor W. J. M. , Feltes Paula Kopschina , García David Vállez , Verfaillie Sander C. J. , Wolters Emma E. , Sweeney Steven P. , Ryan J. Michael , Ivarsson Magnus , Lynch Berkley A. , Schober Patrick , Scheltens Philip , Schuit Robert C. , Windhorst Albert D. , De Deyn Peter P. , van Berckel Bart N. M. , Golla Sandeep S. V.
Published: January 2022

[11C]UCB-J is a PET radioligand that binds to the presynaptic vesicle glycoprotein 2A. Therefore, [11C]UCB-J PET may serve as an in vivo marker of synaptic integrity. The main objective of this study was to evaluate the quantitative accuracy and the 28-day test–retest repeatability (TRT) of various parametric quantitative methods for dynamic [11C]UCB-J studies in Alzheimer’s disease (AD) patients and healthy controls (HC). Eight HCs and seven AD patients underwent two 60-min dynamic [11C]UCB-J PET scans with arterial sampling over a 28-day interval. Several plasma-input based and reference-region based parametric methods were used to generate parametric images using metabolite corrected plasma activity as input function or white matter semi-ovale as reference region. Different parametric outcomes were compared regionally with corresponding non-linear regression (NLR) estimates. Furthermore, the 28-day TRT was assessed for all parametric methods. Spectral analysis (SA) and Logan graphical analysis showed high correlations with NLR estimates. Receptor parametric mapping (RPM) and simplified reference tissue model 2 (SRTM2) BPND, and reference Logan (RLogan) distribution volume ratio (DVR) regional estimates correlated well with plasma-input derived DVR and SRTM BPND. Among the multilinear reference tissue model (MRTM) methods, MRTM1 had the best correspondence with DVR and SRTM BPND. Among the parametric methods evaluated, spectral analysis (SA) and SRTM2 were the best plasma-input and reference tissue methods, respectively, to obtain quantitatively accurate and repeatable parametric images for dynamic [11C]UCB-J PET.
Optimal control of an HIV infection model with logistic growth, celluar and homural immune response, cure rate and cell-to-cell spread
Authors: Akbari Najmeh , Asheghi Rasoul
Published: January 2022

In this paper, we propose an optimal control problem for an HIV infection model with cellular and humoral immune responses, logistic growth of uninfected cells, cell-to-cell spread, saturated infection, and cure rate. The model describes the interaction between uninfected cells, infected cells, free viruses, and cellular and humoral immune responses. We use two control functions in our model to show the effectiveness of drug therapy on inhibiting virus production and preventing new infections. We apply Pontryagin maximum principle to study these two control functions. Next, we simulate the role of optimal therapy in the control of the infection by numerical simulations and AMPL software.
On three-dimensional Hall-magnetohydrodynamic equations with partial dissipation
Authors: Du Baoying
Published: January 2022

In this paper, we address the Hall-MHD equations with partial dissipation. Applying some important inequalities (such as the logarithmic Sobolev inequality using BMO space, bilinear estimates in BMO space, Young’s inequality, cancellation property, interpolation inequality) and delicate energy estimates, we establish an improved blow-up criterion for the strong solution. Moreover, we also obtain the existence of the strong solution for small initial data, the smallness conditions of which are given by the suitable Sobolev norms.