bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress and challenges of integrated drug efficacy surveillance for uncomplicated malaria in Thailand
Authors: Sudathip Prayuth , Saejeng Aungkana , Khantikul Nardlada , Thongrad Thannikar , Kitchakarn Suravadee , Sugaram Rungniran , Lertpiriyasuwat Cheewanan , Areechokchai Darin , Gopinath Deyer , Sintasath David , Ringwald Pascal , Naowarat Sathapana , Pinyajeerapat Niparueradee , Bustos Maria Dorina , Shah Jui A.
Published: June 2021

Background

Integrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017–2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure.

Methods

Routine patient data were extracted from the malaria information system for FY2018–FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan–Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin–piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax.

Results

The proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). Plasmodium falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine–artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy (chloroquine efficacy) was 98.5% in FY2018 (n = 2048), 99.1% in FY2019 (n = 2206), and 99.9% in FY2020 (n = 2448), and day 90 efficacy (primaquine efficacy) was 94.8%, 96.3%, and 97.1%, respectively.

Conclusions

In Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.
Application of MALDI-TOF MS to assess clinical characteristics, risk factors, and outcomes associated with anaerobic bloodstream infection: a retrospective observational study
Authors: Watanabe Tsuyoshi , Hara Yuki , Yoshimi Yusuke , Yokoyama-kokuryo Waka , Fujita Yoshiro , Yokoe Masamichi , Noguchi Yoshinori
Published: June 2021

Background

Correctly identifying anaerobic bloodstream infections (BSIs) is difficult. However, a new technique, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), enables more accurate identification and appropriate treatment. Anaerobic BSIs identified by MALDI-TOF MS were retrospectively analyzed to determine the clinical and microbiological features and patient outcomes based on the anaerobic genera or group.

Methods

Medical records of patients with anaerobic BSIs were used to conduct a single-center retrospective cohort study from January 2016 to December 2020 in Nagoya, Japan. Multivariate logistic regression analysis was performed to determine the independent risk factors for in-hospital mortality.

Results

Of the 215 patients with anaerobic BSIs, 31 had multiple anaerobic organisms in the blood culture, including 264 total episodes of anaerobic BSIs. Bacteroides spp. were isolated the most (n = 74), followed by gram-positive non-spore-forming bacilli (n = 57), Clostridium spp. (n = 52), gram-positive anaerobic cocci (GPAC) (n = 27), and gram-negative cocci (n = 7). The median patient age was 76 years; 56.7% were male. The most common focal infection site was intra-abdominal (36.7%). The in-hospital mortality caused by anaerobic BSIs was 21.3%, and was highest with Clostridium spp. (36.5%) and lowest with GPAC (3.7%). Age, solid tumors, and Clostridium spp. were independent risk factors for in-hospital mortality.

Conclusions

We identified current anaerobic BSI trends using MALDI-TOF MS and reported that mortality in patients with anaerobic BSIs patients was highest with Clostridium spp. infections.
Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells
Authors: Palombarini Federica , Masciarelli Silvia , Incocciati Alessio , Liccardo Francesca , Di Fabio Elisa , Iazzetti Antonia , Fabrizi Giancarlo , Fazi Francesco , Macone Alberto , Bonamore Alessandra , Boffi Alberto
Published: June 2021

Background

In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells.

Results

Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation.

Conclusion

The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.

Graphic abstract
Liver injury in COVID-19: clinical features and treatment management
Authors: Yu Dongdong , Du Qingru , Yan Shengguang , Guo Xu-Guang , He Yehao , Zhu Guodong , Zhao Kewei , Ouyang Shi
Published: June 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has spread to many countries around the world. In addition to lung disease, severe cases also displayed varying degrees of liver injury. This article will describe the latest developments regarding coronavirus and the pathogenesis of liver injury, the prone population and clinical characteristics of these patients, as well as providing some suggestions for clinical treatment.
On pickles: biological and sociocultural links between fermented foods and the human gut microbiome
Authors: Flachs Andrew , Orkin Joseph D.
Published: June 2021

Background

The composition of the human microbiome varies considerably in diversity and density across communities as a function of the foods we eat and the places we live. While all foods contain microbes, humans directly shape this microbial ecology through fermentation. Fermented foods are produced from microbial reactions that depend on local environmental conditions, fermentation practices, and the manner in which foods are prepared and consumed. These interactions are of special interest to ethnobiologists because they link investigations of how people shape and know the world around them to local knowledge, food traditions, local flora, and microbial taxa.

Methods

In this manuscript, we report on data collected at a fermentation revivalist workshop in Tennessee. To ask how fermentation traditions are learned and influence macro and micro ecologies, we conducted interviews with eleven people and participated in a four-day craft fermentation workshop. We also collected 46 fermented food products and 46 stool samples from workshop participants eating those fermented foods.

Results

We identified ten major themes comprised of 29 sub-themes drawn from 326 marked codes in the transcripts. In combination, this analysis allowed us to summarize key experiences with fermentation, particularly those related to a sense of authenticity, place, health, and the discovery of tactile work. From the 605 amplicon sequence variants (ASVs) shared between food and fecal samples, we identified 25 candidate ASVs that are suspected to have been transmitted from fermented food samples to the gut microbiomes of the workshop participants. Our results indicate that many of the foods prepared and consumed during the workshop were rich sources of probiotic microbes.

Conclusions

By combining these qualitative social and quantitative microbiological data, we suggest that variation in culturally informed fermentation practices introduces variation in bacterial flora even among very similar foods, and that these food products can influence gut microbial ecology.
The use of extracorporeal shock wave therapy for the treatment of bone marrow oedema — a systematic review and meta-analysis
Authors: Häußer Jonathan , Wieber Juliane , Catalá-Lehnen Philip
Published: June 2021

Background

Extracorporeal shock wave therapy (ESWT) has been used for various pathologies associated with bone marrow oedema (BME). However, it is still not clear whether ESWT may be favourable in the treatment of BME. Therefore, the aim of this systematic review was to assess the efficacy of ESWT for the treatment of BME.

Methods

MEDLINE was searched for relevant literature with no time constraints. Both randomized and non-randomized trials were included. Case reports and conference abstracts were excluded. Titles and abstracts were screened and full-text articles of included studies were retrieved. Data on the effect of ESWT on pain, function, and the BME area on magnet resonance imaging were extracted.

Results

Pain, function, and magnet resonance imaging results all improved across the studies — regardless of whether it was a randomized or non-randomized study. This effect was consistent across multiple pathologies such as osteonecrosis of the femoral head, BME associated with knee osteoarthritis, Kienböck’s disease, and osteitis pubis. The meta-analysis showed that pain (after 1 month: weighted mean difference (WMD) = − 2.23, 95% CI − 2.58 to − 1.88, P < 0.0001; after 3–6 month: WMD = − 1.72, 95% CI − 2.52 to − 0.92, P < 0.00001) and function (after 1 month: WMD = − 1.59, 95% CI − 2.04 to − 1.14, P < 0.0001; after 3–6 month: WMD = − 2.06, 95% CI − 3.16 to − 0.96, P = 0.0002; after ≥ 12 month: WMD = − 1.20, 95% CI − 1.83 to − 0.56, P = 0.0002) was reduced in terms of ESWT treatment compared to a control group.

Conclusions

Based on the available evidence, ESWT may be an adequate option for conservative therapy in pathologies involving BME.

Trial registration

PROSPERO, CRD42021201719. Registered 23 December 2020
Raloxifene retards the progression of adjacent segmental intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus in ovariectomized rats
Authors: Sun Qi , Nan Xin-Yu , Tian Fa-Ming , Liu Fang , Ping Shao-Hua , Zhou Zhuang , Zhang Liu
Published: June 2021

Background

Adjacent segmental intervertebral disk degeneration (ASDD) is a major complication secondary to lumbar fusion. Although ASSD pathogenesis remains unclear, the primary cause of intervertebral disk degeneration (IVDD) development is apoptosis of nucleus pulposus (NP). Raloxifene (RAL) could delay ASDD by inhibiting NP apoptosis.

Methods

An ASDD rat model was established by ovariectomy (OVX) and posterolateral spinal fusion (PLF) on levels 4–5 of the lumbar vertebrae. Rats in the treatment groups were administered 1 mg/kg/d RAL by gavage for 12 weeks, following which, all animals were euthanized. Lumbar fusion, apoptosis, ASDD, and vertebrae micro-architecture were evaluated.

Results

RAL maintained intervertebral disk height (DHI), delayed vertebral osteoporosis, reduced histological score, and inhibited apoptosis. The OVX+PLF+RAL group revealed upregulated expression of aggrecan and B-cell lymphoma-2 (bcl2), as well as significantly downregulated expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), metalloproteinase-13 (MMP-13), caspase-3, BCL2-associated X (bax), and transferase dUTP nick end labeling (TUNEL) staining. Micro-computed tomography (Micro-CT) analysis revealed higher bone volume fraction (BV/TV), bone mineral density (BMD), and trabecular number (Tb.N), and lower trabecular separation (Tb.Sp) in OVX+PLF+RAL group than in the OVX+PLF group.

Conclusions

RAL can postpone ASDD development in OVX rats through inhibiting extracellular matrix metabolic imbalance, NP cell apoptosis, and vertebral osteoporosis. These findings showed RAL as a potential therapeutic target for ASDD.
Deliberate paradigm shift in research in rare neurodevelopmental disorders
Authors: Bain Jennifer M. , Ardalan Adel , Goldman Sylvie
Published: June 2021

Diagnosis and management of children with rare neurodevelopmental disorders (RNDDs) are complex. The COVID-19 pandemic has forced us to rethink the research activities critical to improve our understanding and treatment of RNDDs, such as creating large international registries and developing natural history studies. In this communication, we reflect on our latest effort in conducting research remotely while providing support, education and feedback to families affected by a specific RNDD. Specifically, we advocate for a deliberate paradigm shift towards virtual family meetings as ecological platforms to enroll and assess individuals with rare disorders. Herein, we demonstrate that such a shift is crucial to substantially increasing geographical and age range coverage, which are essential for capturing the phenotypic variations in RNDDs. Finally, we call on the community to invest in building integrated technological platforms necessary for effective remote research activities, through standardization, collaboration and training.
CD151 drives cancer progression depending on integrin α3β1 through EGFR signaling in non-small cell lung cancer
Authors: Zhu Jianjie , Cai Tingting , Zhou Jieqi , Du Wenwen , Zeng Yuanyuan , Liu Ting , Fu Yulong , Li Yue , Qian Qian , Yang Xiuwei H. , Li Qinglin , Huang Jian-an , Liu Zeyi
Published: June 2021

Background

Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion.

Methods

First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied.

Results

High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs.

Conclusions

Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment.
Site-specific resolution of enthesitis in patients with axial spondyloarthritis treated with tumor necrosis factor inhibitors
Authors: Nissen Michael J. , Möller Burkhard , Ciurea Adrian , Mueller Ruediger B. , Zueger Patrick , Schulz Martin , Ganz Fabiana , Scherer Almut , Papagiannoulis Eleftherios , Hügle Thomas
Published: June 2021

Background

Enthesitis is a hallmark of spondyloarthritis (SpA) with a substantial impact on quality of life. Reports of treatment effectiveness across individual enthesitis sites in real-world patients with axial SpA (axSpA) are limited. We investigated the evolution of enthesitis following tumor necrosis factor inhibitor (TNFi) initiation in axSpA patients, both cumulatively and at specific axial and peripheral sites.

Methods

AxSpA patients in the Swiss Clinical Quality Management Registry were included if they initiated a TNFi, had an available Maastricht Ankylosing Spondylitis Enthesitis Score, modified to include the plantar fascia (mMASES, 0–15), at start of treatment and after 6 and/or 12 months and ≥12 months follow-up. Logistic regression models were utilized to analyze explanatory variables for enthesitis resolution.

Results

Overall, 1668 TNFi treatment courses (TCs) were included, of which 1117 (67%) had active enthesitis at baseline. Reduction in mMASES at the 6- and 12-month timepoints was experienced in 72% and 70% of TCs, respectively. Enthesitis resolution at 6/12 months occurred in 37.9%/43.0% of all TNFi TCs and 40.7%/50.9% of first TNFi TCs. At 6 months, a significant reduction in the frequency of enthesitis was observed at all sites, except for the Achilles tendon and plantar fascia among first TNFi TCs, while at 12 months, reduction was significant at all sites in both TC groups. Enthesitis resolved in 60.3–77% across anatomical sites, while new incident enthesitis occurred in 4.0–13.5% of all TNFi TCs at 12 months. Both baseline and new-incident enthesitis occurred most frequently at the posterior superior iliac spine and the fifth lumbar spinous process. Younger age and lower mMASES at baseline were predictors of complete enthesitis resolution, while female sex and second- or later-line TNFi treatment were associated with persistence of enthesitis at 12 months.

Conclusion

In real-world axSpA patients treated with a TNFi, enthesitis improved in the majority of patients across all anatomical sites. Significant improvement at the Achilles and plantar fascia entheses was observed only at 12 months. Complete and site-specific enthesitis resolution occurred in ≥40% and ≥60% of TCs evaluated at 12 months, with a low incidence of new site-specific enthesitis.

Trial registration

Not applicable.
Evaluation of the WEAP model in simulating subbasin hydrology in the Central Rift Valley basin, Ethiopia
Authors: Abera Abdi Debele , Ayenew Tenalem
Published: June 2021

Background

The subbasin hydrologic behaviors have been altered by many natural and anthropologic factors such as climate change and land development activities. Model-based assessment can be used to simulate both natural hydrological processes, human-induced effects, and management strategies on water resources. For the Ketar subbasin, the WEAP (water evaluation and planning) hydrologic model was developed that aimed at (1) evaluating the application of the WEAP model in the Ketar subbasin, (2) evaluating the demonstration of the WEAP model using model efficiency evaluation criteria, and (3) simulating hydrological processes of the subbasin using the WEAP model.

Methods

WEAP-based soil moisture method (rainfall-runoff) hydrology routine is comprised of a lumped, one-dimensional, two-layer soil water accounting that uses empirical functions to designate evapotranspiration, surface runoff, interflow, and deep percolation for a sub-unit at root zone. A catchment is considered as the smallest hydrologic response unit. The catchment’s surface hydrological balance is typically estimated by discretizing the catchment into multiple land uses for which water balance is estimated at root zone.

Results

The monthly measured and simulated streamflow statistics showed a positive strong relationship with R2 of 0.82, NSE of 0.80, and IA of 0.95; and with R2 of 0.91, NSE of 0.91, and IA of 0.98 for calibration and validation periods respectively. Similarly, the mean monthly measured and simulated streamflow showed an agreement with R2 of 0.99, NSE of 0.97, and IA of 0.99, and R2 of 0.94, NSE of 0.93, and IA of 0.93 for the periods of calibration and validation respectively.

Conclusion

The model has demonstrated the capability to represent the hydrologic dynamics of the subbasin both at monthly and mean monthly periods. In general, the overall model performance evaluation statistics show a very good agreement between measured and simulated streamflow at the outlet of the subbasin.
The impact of pest risk management measures on trade: the case of apples from France and Chile
Authors: Federica DeMaria , Sophie Drogue , Pasquale Lubello
Published: June 2021

In this article, we investigate how pest risk management protocols may affect trade flows of fresh apples. We apply our analysis to two major players in the international trade of fresh apples: France and Chile. These two countries have been chosen because they are among the world’s leading apple exporters and although they have similar market shares, they differ in terms of destination markets, seasonality, local conditions and export strategy. In order to assess the impact of pest risk management protocols on international trade of apples from France and Chile, we introduce in a gravity equation beside the traditional variables, a score able to measure their complexity. The results are interesting in the sense that even if the score for France and Chile by main trading partners are rather close, we found that French apples exporters would be more impacted by pest risk management protocols than their Chilean counterparts.
Imaging evaluation of continuous extrapleural intercostal nerve block for minimally invasive cardiac surgery: a case report
Authors: Terauchi Misa , Okutani Hiroai , Ishimoto Daisuke , Shimode Noriko , Takao Yumiko , Hirose Munetaka
Published: June 2021

Background

Spinal nerve block is difficult with minimally invasive cardiac surgery (MICS), because of the risk of serious bleeding complications due to full heparinization. Continuous extrapleural intercostal nerve block (CEINB) is a postoperative pain treatment for intercostal thoracotomy, with fewer complications. Here, we report a case in which imaging evaluation of CEINB with contrast medium was conducted to anatomically confirm the spread of local anesthetics after MICS.

Case presentation

A 65-year-old woman with severe mitral regurgitation underwent mitral valve plasty under general anesthesia via right-sided mini-thoracotomy. A CEINB catheter was placed before the incision was closed, without creating a conventional extrapleural pocket. We conducted an imaging evaluation with a contrast medium via the inserted catheter and confirmed sufficient spread around the intercostal nerve area. In addition, postoperative pain was well controlled by the nerve block.

Conclusions

Imaging evaluation of CEINB with contrast medium could increase analgesic quality and decrease complications post-MICS.
Successful airway management with combined use of a McGRATHTM MAC videolaryngoscope and fiberoptic bronchoscope in a patient with congenital tracheal stenosis diagnosed in adulthood
Authors: Hasegawa Shoko , Koda Kenichiro , Uzawa Masashi , Kimura Haruka , Kimura Rie , Kitamura Takayuki
Published: June 2021

Background

Most patients with congenital tracheal stenosis (CTS) develop respiratory symptoms early in life. CTS remaining undiagnosed until adulthood is rare.

Case presentation

A 51-year-old female was scheduled for cardiovascular surgery. She had undergone laparoscopic surgery 3 years earlier and was found to have a difficult airway. Postoperatively, she was diagnosed with CTS. For the current cardiovascular surgery, combined use of a McGRATHTM MAC videolaryngoscope and fiberoptic bronchoscope allowed sufficient visualization of the glottis and trachea, resulting in successful intubation.

Conclusions

CTS patients have a high probability of difficult intubation. Our experience suggests the efficacy of combined use of a videolaryngoscope and fiberoptic bronchoscope for airway management in CTS patients.
Vasculitis damage index in Behçet’s disease
Authors: Elgengehy Fatema T. , Gamal Sherif M. , Sobhy Nesreen , Siam Ibrahem , Soliman Ahmed M. , Elhady Ghada W. , Gheita Tamer A.
Published: June 2021

Background

Vasculitis damage index (VDI) is a validated damage index for systemic vasculitis, and as Behçet’s disease is considered one of systemic vascular disease we aimed to study the relationship of the vasculitis damage index to clinical manifestations and comorbidity in patients with Behçet’s disease (BD) to determine if VDI could be used to assess damage in patients with BD.

Methods

A total of 109 patients with BD were recruited from the Rheumatology Department (outpatient and inpatient clinic), Cairo University Hospitals. All patients were subjected to full history taking, clinical examination, and routine laboratory investigations. Disease activity was assessed by the BD current activity form, and the VDI was calculated in all patients. The relationship of the VDI to the disease clinical manifestations was studied. Mann–Whitney and Kruskal Wallis tests were used to estimate differences in quantitative variables. Spearman correlation test was used to test for correlation between quantitative variables.

Results

In the current study, the VDI ranged from 1 to 10, with a mean of 3.5 ± 1.8. It was significantly associated with total thrombosis (P = 0.022); total neurological manifestations (P = 0.000), especially stroke and cranial nerve affection; uveitis (P = 0.005); avascular necrosis (AVN) (P = 0.015); osteoporosis (P = 0.01); impaired vision (P < 0.0001); cataract (P < 0.0001); and diabetes (P = 0.012). Generally, immunosuppressive treatment was significantly associated with VDI (P = 0.039), especially cyclophosphamide (P < 0.0001), biological agent (P = 0.008), chlorambucil (P = 0.003), and anticoagulant (P = 0.02). VDI was also significantly correlated with age (P = 0.033), disease duration (P = 0.029), and duration of eye involvement (P = 0.003).

Conclusion

VDI is significantly associated with most disease parameters of BD, except for parameters such as mucocutaneous manifestations and uncomplicated venous thrombosis; however, further studies may be needed to establish BD-specific damage index.
Study of the role of the transcranial magnetic stimulation on language progress in autism spectrum disorder
Authors: Darwish Mohamed E. , El-Beshlawy Heba W. , Ramadan Ehab S. , Serag Shimaa M.
Published: June 2021

Background

Children with autism spectrum disorder (ASD) are almost universally delayed in the acquisition of spoken language as primary means of communication so they tend to have restricted outcomes in terms of independence and integration. Transcranial magnetic stimulation (TMS) is a promising, emerging tool for the study (study and modulate excitability and plasticity, applied in single pulses to investigate corticospinal excitability, pairs of pulses to study intracortical inhibition and facilitation) and potential treatment of ASD. The purpose of this study is to evaluate the role of repetitive TMS in language progress in children with ASD.

Results

There was a statistically significant clinical improvement in patients receiving active TMS (group I) comparing baseline Childhood Autism Rating Scale (CARS) assessment and after treatment (P ≤ 0.05). There was mild improvement with no significant difference between the patients receiving active TMS (group I) and those of sham TMS (group II), and both groups received language therapy as regard post-treatment CARS. There was significant difference in improvement between the two groups according to eye contact (P ≤ 0.05). There was significant improvement in response to examiner (P ≤ 0.05). There was mild improvement with no statistically significant difference in attention between the two groups. There was significant difference in improvement between the two groups according to active expressive language. There was no statistically significant difference in passive vocabulary between the two groups.

Conclusion

Repetitive transcranial magnetic stimulation (rTMS) over left inferior frontal gyrus may be a safe and effective way of improving language of ASD. The joint application of rTMS and standard language therapy may lead to more rapid improvement in the language progress of children with ASD.
The need for biodiversity champions in psychiatry: the entwined crises of climate change and ecological collapse
Authors: Krzanowski Jacob
Published: June 2021

The past 20 years have seen the disappearance and degradation of biodiversity on earth at unprecedented rates. This phenomenon shares similar drivers to those behind climate change yet requires its own solutions. The twin catastrophes of climate change and biodiversity loss demonstrate how our health is bound up in the vitality of this planet. There has been an increasing effort on the part of healthcare professionals to appreciate this relationship, as evidenced by the growing influence of planetary health as a discipline. However, the health impacts of biodiversity loss have been less focused on than those brought on by climate change. Psychiatry's appreciation of the interface between environments and our health, alongside the evidence for the connection between nature and mental health specifically, prompt psychiatrists to ensure that the institution of healthcare throws its influence equally behind solutions to climate change as well as biodiversity loss.
Management of Women With Breast Cancer and Pathogenic Variants in Genes Other Than BRCA1 or BRCA2
Authors: Robson Mark
Published: June 2021

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in the Journal of Clinical Oncology, to patients seen in their own clinical practice.
Materialities of Abstraction
Authors: Truett Brandon
Published: June 2021

This article recovers the 1918 chapbook that the understudied Vorticist poet and visual artist Jessie Dismorr composed for the American sculptor John Storrs and his wife Marguerite. It examines the ways the chapbook reorients the aesthetic criteria by which we recognize abstraction in the early twentieth century. Studying how Dismorr’s divergent and feminist approach to Vorticist practice exploits “the materialities of abstraction,” or the traces of the material world that evince the outside of the abstract art object, it suggests that these material traces lead us to reimagine the boundary between inside and outside, and thus the way an art object indexes and interacts with the material world. Proposing that the recovery of an object as seemingly inconsequential as an individual chapbook in fact raises questions about how we construct the literary- and art-historical field of modernism, the article situates Dismorr’s work in relation to other feminist understandings in British modernism of the socialized space of artistic practice across media exemplified by Virginia Woolf ’s account of sociability within the Bloomsbury Group, and argues for the importance of such unique objects as chapbooks to the study of material culture within literary history and within art history as well.
Korea's First Museum and the Categorization of “Buddhist Statues”
Authors: Lee Seunghye
Published: June 2021

The establishment of a museum in the precinct of Ch'anggyŏnggung Palace in 1909 marked an important moment in the historiography of Korean art. Although recent studies have examined the founding, organization, and financing of the first Korean museum, the formation of its Buddhist art collection and its historical implications remain unexamined. Given that not a single Buddhist temple was allowed to exist within the capital city, the entry of these objects into the palace demonstrates a radical paradigm shift in the royal court's relation to Buddhist icons. The museum's Buddhist art collection reveals what was available in the art market of the time and what was considered worthy of being collected in a royal museum. Through close examination of Korea's first museum and its collection, this study traces the recontextualization of religious icons into art objects and the historical implications behind the category of “Buddhist statues.”
A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation
Authors: Gücüm Sevinç , Sakson Roman , Hoffmann Marcus , Grote Valerian , Becker Clara , Pakari Kaisa , Beedgen Lars , Thiel Christian , Rapp Erdmann , Ruppert Thomas , Thumberger Thomas , Wittbrodt Joachim
Published: June 2021

Defects in the evolutionarily conserved protein-glycosylation machinery during embryonic development are often fatal. Consequently, congenital disorders of glycosylation (CDG) in human are rare. We modelled a putative hypomorphic mutation described in an alpha-1,3/1,6-mannosyltransferase (ALG2) index patient (ALG2-CDG) to address the developmental consequences in the teleost medaka (Oryzias latipes). We observed specific, multisystemic, late-onset phenotypes, closely resembling the patient's syndrome, prominently in the facial skeleton and in neuronal tissue. Molecularly, we detected reduced levels of N-glycans in medaka and in the patient's fibroblasts. This hypo-N-glycosylation prominently affected protein abundance. Proteins of the basic glycosylation and glycoprotein-processing machinery were over-represented in a compensatory response, highlighting the regulatory topology of the network. Proteins of the retinal phototransduction machinery, conversely, were massively under-represented in the alg2 model. These deficiencies relate to a specific failure to maintain rod photoreceptors, resulting in retinitis pigmentosa characterized by the progressive loss of these photoreceptors. Our work has explored only the tip of the iceberg of N-glycosylation-sensitive proteins, the function of which specifically impacts on cells, tissues and organs. Taking advantage of the well-described human mutation has allowed the complex interplay of N-glycosylated proteins and their contribution to development and disease to be addressed.
Body size affects immune cell proportions in birds and non-volant mammals, but not bats
Authors: Cornelius Ruhs Emily , Becker Daniel J. , Oakey Samantha J. , Ogunsina Ololade , Fenton M. Brock , Simmons Nancy B. , Martin Lynn B. , Downs Cynthia J.
Published: June 2021

Powered flight has evolved several times in vertebrates and constrains morphology and physiology in ways that likely have shaped how organisms cope with infections. Some of these constraints probably have impacts on aspects of immunology, such that larger fliers might prioritize risk reduction and safety. Addressing how the evolution of flight may have driven relationships between body size and immunity could be particularly informative for understanding the propensity of some taxa to harbor many virulent and sometimes zoonotic pathogens without showing clinical disease. Here, we used a comparative framework to quantify scaling relationships between body mass and the proportions of two types of white blood cells – lymphocytes and granulocytes (neutrophils/heterophils) – across 63 bat species, 400 bird species and 251 non-volant mammal species. By using phylogenetically informed statistical models on field-collected data from wild Neotropical bats and from captive bats, non-volant mammals and birds, we show that lymphocyte and neutrophil proportions do not vary systematically with body mass among bats. In contrast, larger birds and non-volant mammals have disproportionately higher granulocyte proportions than expected for their body size. Our inability to distinguish bat lymphocyte scaling from birds and bat granulocyte scaling from all other taxa suggests there may be other ecological explanations (i.e. not flight related) for the cell proportion scaling patterns. Future comparative studies of wild bats, birds and non-volant mammals of similar body mass should aim to further differentiate evolutionary effects and other aspects of life history on immune defense and its role in the tolerance of (zoonotic) infections.
Resemblance in Physical Activity in Families with Children in Time Segments during the Week: The Lolland–Falster Health Study
Authors: PETERSEN THERESE LOCKENWITZ , BRØND JAN CHRISTIAN , KRISTENSEN PETER LUND , AADLAND EIVIND , GRØNTVED ANDERS , JEPSEN RANDI
Published: June 2021

Purpose

Evidence of shared physical activity (PA) habits within families is inconsistent. The present study aimed at examining intrafamily resemblance in PA during different time segments of the week.

Method

This cross-sectional study used data from the Danish household-based population study Lolland–Falster Health Study. We assessed time spent in various PA intensities and behaviors using a dual-accelerometer system (Axivity AX3). At least one parent and one child per household provided data for a minimum of three weekdays and one weekend day. We analyzed three time segments: early weekdays, late weekdays, and weekends. A linear mixed model regression analysis was used to estimate intraclass correlation coefficients (ICC) of the total family, parent–child dyads, siblings, and parent–parent dyads for PA outcomes, adjusting for sex, age, parental education, and the interaction between sex and age.

Results

We included 774 parents (57.9% female, 42.8 ± 7 yr) and 802 children (54.2% girls, 11.1 ± 4.3 yr) nested within 523 families. The clustering among the total family was stronger during late weekdays (ICC = 0.11–0.31) and weekends (ICC = 0.14–0.29) than during early weekdays (ICC = 0.02–0.19). We found stronger clustering among siblings (ICC = 0.08–0.47) and between parents (ICC = 0.02–0.52) than between parents and children (ICC < 0.01–0.37). Generally, the clustering was strongest for light PA, and among PA behaviors, walking showed the highest resemblance across all subgroups.

Conclusion

Initiatives to promote children’s PA that involve parent or sibling coparticipation may focus on the time segment and activity types with the highest resemblance. For the family as a whole, promoting walking or limiting sedentary activities may be a potential target for interventions during late weekdays and weekends.

Trial registration: Clinicaltrials.gov (NCT02482896).
Efficacy of Creatine Supplementation and Resistance Training on Area and Density of Bone and Muscle in Older Adults
Authors: CANDOW DARREN G. , CHILIBECK PHILIP D. , GORDON JULIANNE J. , KONTULAINEN SAIJA
Published: June 2021

Purpose

To examine the efficacy of creatine (Cr) supplementation and any sex differences during supervised whole-body resistance training (RT) on properties of bone and muscle in older adults.

Methods

Seventy participants (39 men, 31 women; mean age ± standard deviation: 58 ± 6 yr) were randomized to supplement with Cr (0.1 g·kg−1·d−1) or placebo (Pl) during RT (3 d·wk−1 for 1 yr). Bone geometry (radius and tibia) and muscle area and density (forearm and lower leg) were assessed using peripheral quantitative computed tomography.

Results

Compared with Pl, Cr increased or maintained total bone area in the distal tibia (Cr, Δ +17 ± 27 mm2; Pl, Δ −1 ± 22 mm2; P = 0.031) and tibial shaft (Cr, Δ 0 ± 9 mm2; Pl, Δ −5 ± 7 mm2; P = 0.032). Men on Cr increased trabecular (Δ +28 ± 31 mm2; P < 0.001) and cortical bone areas in the tibia (Δ +4 ± 4 mm2; P < 0.05), whereas men on Pl increased trabecular bone density (Δ +2 ± 2 mg·cm−3; P < 0.01). There were no bone changes in the radius (P > 0.05). Cr increased lower leg muscle density (Δ +0.83 ± 1.15 mg·cm−3; P = 0.016) compared with Pl (Δ –0.16 ± 1.56 mg·cm−3), with no changes in the forearm muscle.

Conclusions

One year of Cr supplementation and RT had some favorable effects on measures of bone area and muscle density in older adults.
Breast tumour volume and blood flow measured by MRI after one cycle of epirubicin and cyclophosphamide-based neoadjuvant chemotherapy as predictors of pathological response
Authors: Stevens William , Farrow Isabelle M , Georgiou Leonidas , Hanby Andrew M , Perren Timothy J , Windel Laura M , Wilson Daniel J , Sharma Nisha , Dodwell David , Hughes Thomas A , Dall Barbara JG , Buckley David L
Published: June 2021

Objectives:

Better markers of early response to neoadjuvant chemotherapy (NACT) in patients with breast cancer are required to enable the timely identification of non-responders and reduce unnecessary treatment side-effects. Early functional imaging may better predict response to treatment than conventional measures of tumour size. The purpose of this study was to test the hypothesis that the change in tumour blood flow after one cycle of NACT would predict pathological response.

Methods:

In this prospective cohort study, dynamic contrast-enhanced MRI was performed in 35 females with breast cancer before and after one cycle of epirubicin and cyclophosphamide-based NACT (EC90). Estimates of tumour blood flow and tumour volume were compared with pathological response obtained at surgery following completion of NACT.

Results:

Tumour blood flow at baseline (mean ± SD; 0.32 ± 0.17 ml/min/ml) reduced slightly after one cycle of NACT (0.28 ± 0.18 ml/min/ml). Following treatment 15 patients were identified as pathological responders and 20 as non-responders. There were no relationships found between tumour blood flow and pathological response. Conversely, tumour volume was found to be a good predictor of pathological response (smaller tumours did better) at both baseline (area under the receiver operating characteristic curve 0.80) and after one cycle of NACT (area under the receiver operating characteristic curve 0.81).

Conclusion & advances in knowledge:

The change in breast tumour blood flow following one cycle of EC90 did not predict pathological response. Tumour volume may be a better early marker of response with such agents.
Lung MRI with hyperpolarised gases: current & future clinical perspectives
Authors: Stewart Neil J , Smith Laurie J , Chan Ho-Fung , Eaden James A , Rajaram Smitha , Swift Andrew J , Weatherley Nicholas D , Biancardi Alberto , Collier Guilhem J , Hughes David , Klafkowski Gill , Johns Christopher S , West Noreen , Ugonna Kelechi , Bianchi Stephen M , Lawson Rod , Sabroe Ian , Marshall Helen , Wild Jim M
Published: June 2021

The use of pulmonary MRI in a clinical setting has historically been limited. Whilst CT remains the gold-standard for structural lung imaging in many clinical indications, technical developments in ultrashort and zero echo time MRI techniques are beginning to help realise non-ionising structural imaging in certain lung disorders. In this invited review, we discuss a complementary technique – hyperpolarised (HP) gas MRI with inhaled 3He and 129Xe – a method for functional and microstructural imaging of the lung that has great potential as a clinical tool for early detection and improved understanding of pathophysiology in many lung diseases. HP gas MRI now has the potential to make an impact on clinical management by enabling safe, sensitive monitoring of disease progression and response to therapy. With reference to the significant evidence base gathered over the last two decades, we review HP gas MRI studies in patients with a range of pulmonary disorders, including COPD/emphysema, asthma, cystic fibrosis, and interstitial lung disease. We provide several examples of our experience in Sheffield of using these techniques in a diagnostic clinical setting in challenging adult and paediatric lung diseases.
Explaining withdrawal’s persistence: correlates of withdrawal use in Albania, Armenia, Jordan, and Turkey observed in a cross-sectional study
Authors: Fruhauf Timothee , Al-Attar Ghada , Tsui Amy O.
Published: June 2021

Background: Withdrawal dominates the contraceptive method mix in a geographical cluster of countries in South-Eastern Europe and Western Asia that have, in part, reached low fertility. This study examines the socio-demographic determinants associated with withdrawal use in Armenia, Albania, Jordan and Turkey that could explain withdrawal’s persistence and inform contraceptive programs in these unique settings.

Methods: Cross-sectional data on 31,569 married women 15 to 49 years were drawn from the Demographic and Health Surveys in Albania (2017-2018), Armenia (2015-2016), Jordan (2017-2018), and Turkey (2013). For each country, multinomial regression models estimating withdrawal use among all women and logistic regression models estimating withdrawal use among contraceptive users were used to evaluate the association with age, marital duration, parity, education, residence, and household wealth.

Results: The socio-demographic determinants associated with withdrawal use varied by country among all women and among all contraceptive users. While these associations were not all significant for all four countries general trends included that women were more likely to use withdrawal than not use contraception, but less likely to use withdrawal than other methods with increasing parity, higher education, and greater household wealth. Measures of association are reported by country for each correlate.

Conclusions: Despite the similar contraceptive mix in these four countries, no single set of factors was found to explain withdrawal’s persistence. Withdrawal’s prevalence in this geographical cluster may instead result from different balances of intertwined circumstances that include couples’ fertility decisions, access to modern contraception and availability of abortion services.
Enteritis cystica profunda with lipoma in the second portion of the duodenum: a case report
Authors: Shim Beom Jin , Park Seung Keun , Park Hee Ug , Park Tae Young
Published: June 2021

Enteritis cystica profunda (ECP), a rare and benign condition, is defined as the displacement of the glandular epithelium into the submucosa and more profound layers of the small intestinal wall leading to the formation of mucin-filled cystic spaces. ECP frequently occurs in the ileum or jejunum and is associated with diseases such as Crohn disease and Peutz-Jeghers syndrome. ECP also develops in the absence of known pathology. ECP in the duodenum is very rare and mostly occurs without associated conditions. In this report, we present a rare case of ECP without an associated disease, in the second portion of the duodenum distal to the ampulla of Vater and coexisting with lipoma within the polypoid lesion.