bluuebunny/crossref_metadata_2025 huggingface dataset:
An unusual case of neutrocytic, culture-negative meningitis in an immunocompetent adult
Authors: Suseela Kundoly V , Khan Firosh , Kottoor Santhosh J
Published: May 2021

Patient presenting with fever, acute onset seizure and neck stiffness on examination; deteriorating despite initiation of early treatment for meningitis.
An Adapted Online Family Medicine Training for House Officers Amid Covid-19 Pandemic in Egypt
Authors: Ahmed Marwa M. , Fares Samar , Sayed Asmaa A. , El Sayed Inas T.
Published: May 2021

Introduction

The COVID-19 pandemic is an unprecedented challenge to house officers training programs because of the safety measures.

Objective

This current study aimed to introduce the adaptation of family medicine training for house officers during COVID-19 pandemic and gauge their level of satisfaction with the training.

Methods

Unfortunately, more than one-fourth of the house officers attending the family medicine training turned out to be hospital-admitted or in obligatory home isolation. A time-sensitive plan was proposed to maintain a competent training guaranteeing safety and support of house officers and fulfilling the training objectives in a virtual setting. Three mentors were assigned to each 10 house officers to provide continuous support and monitoring. Tutor and house officer interaction and reflection were maintained through a virtual clinical training session via Zoom application and a daily online discussion of a clinical scenario. Peer interaction was provided through post-webinar and small-group online discussion sessions.

Results

The adapted training was applied on thirteen cohorts of house officers. The response rate was 70% (666 out of 950). Most of them were satisfied with the training (84.6%). Their satisfaction with each modality of the training was encouraging.

Conclusions

During COVID-19 pandemic, successful adaptation of family medicine training has succeeded in fulfilling the training objectives and providing psychological support and engagement for house officers without burdening the hospital-admitted and home-isolated house officers.
Global competences and 21st century higher education – And why they matter
Authors: Robertson Susan L
Published: May 2021

This paper brings issues around forecasting and change to the fore to stimulate a conversation around three related questions: How do we understand the challenges of this global era? What might be the role of higher education in re/shaping this future? What competences might students need and how should be go about developing these?
Acute Liver Failure Due to Toxoplasmosis After Orthotopic Liver Transplantation
Authors: Baldwin Nicholas , Gray Meagan , Patel Chirag R. , Al Diffalha Sameer
Published: May 2021

Solid organ transplant recipients are at risk for a wide range of opportunistic infections, the most common being cytomegalovirus. These infections may occur as reactivation of latent disease, donor-derived, or de novo. In this article, we present a case of acute liver failure secondary to toxoplasmosis following orthotopic liver transplantation. Our patient presented 5 weeks after orthotopic liver transplantation with altered mental status and fatigue. She was found to have disseminated cytomegalovirus infection, which resolved with intravenous ganciclovir; however, she subsequently developed acute liver failure due to toxoplasmosis, which is hypothesized to be donor-derived. Infection with Toxoplasma may be asymptomatic in the immunocompetent host; however, in immunocompromised hosts, such as solid organ transplant recipients, this infection can be life threatening. Though prophylaxis with trimethoprim-sulfamethoxazole may prevent infections with Toxoplasma, it is often held for renal dysfunction, hyperkalemia, or other side effects, placing patients at risk. With 13 cases now reported, routine screening of donor and recipient for toxoplasma exposure may be warranted.
Autologous Matrix-Induced Chondrogenesis With Lateral Ligament Stabilization for Osteochondral Lesions of the Talus in Patients With Ankle Instability
Authors: Ackermann Jakob , Casari Fabio A. , Germann Christoph , Weigelt Lizzy , Wirth Stephan H. , Viehöfer Arnd F.
Published: May 2021

Background:

Autologous matrix-induced chondrogenesis (AMIC) has been shown to result in favorable clinical outcomes in patients with osteochondral lesions of the talus (OLTs). Though, the influence of ankle instability on cartilage repair of the ankle has yet to be determined.

Purpose/Hypothesis:

To compare the clinical and radiographic outcomes in patients with and without concomitant lateral ligament stabilization (LLS) undergoing AMIC for the treatment of OLT. It was hypothesized that the outcomes would be comparable between these patient groups.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Twenty-six patients (13 with and 13 without concomitant ankle instability) who underwent AMIC with a mean follow-up of 4.2 ± 1.5 years were enrolled in this study. Patients were matched 1:1 according to age, body mass index (BMI), lesion size, and follow-up. Postoperative magnetic resonance imaging and Tegner, American Orthopaedic Foot & Ankle Society (AOFAS), and Cumberland Ankle Instability Tool (CAIT) scores were obtained at a minimum follow-up of 2 years. A musculoskeletal radiologist scored all grafts according to the MOCART (magnetic resonance observation of cartilage repair tissue) 1 and MOCART 2.0 scores.

Results:

The patients’ mean age was 33.4 ± 12.7 years, with a mean BMI of 26.2 ± 3.7. Patients with concomitant LLS showed worse clinical outcome measured by the AOFAS (85.1 ± 14.4 vs 96.3 ± 5.8; P = .034) and Tegner (3.8 ± 1.1 vs 4.4 ± 2.3; P = .012) scores. Postoperative CAIT and AOFAS scores were significantly correlated in patients with concomitant LLS ( r = 0.766; P = .002). A CAIT score >24 (no functional ankle instability) resulted in AOFAS scores comparable with scores in patients with isolated AMIC (90.1 ± 11.6 vs 95.3 ± 6.6; P = .442). No difference was seen between groups regarding MOCART 1 and 2.0 scores ( P = .714 and P = .371, respectively).

Conclusion:

Concurrently performed AMIC and LLS in patients with OLT and ankle instability resulted in clinical outcomes comparable with isolated AMIC if postoperative ankle stability was achieved. However, residual ankle instability was associated with worse postoperative outcomes, highlighting the need for adequate stabilization of ankle instability in patients with OLT.
Policy Life Cycle Analysis of Three Australian State-level Public Policies: Exploring the Political Dimension of Sustainable Development
Authors: Goswami Kuntal , Gerritsen Rolf
Published: May 2021

This article analyses the life cycle of three Australian public policies (Tasmania Together [TT], South Australia’s Strategic Plan [SASP,] and Western Australia’s State Sustainability Strategy [WA’s SSS]). These policies were formulated at the state level and were structured around sustainable development concepts (the environmental, economic, and social dimensions). This study highlights contexts that led to the making of these public policies, as well as factors that led to their discontinuation. The case studies are based on analysis of parliamentary debates, state governments’ budget reports, public agencies’ annual reports, government media releases, and stakeholders’ feedback. The empirical findings highlight the importance of understanding the political dimension of sustainable development. This fact highlights the need to look beyond the traditional three-dimensional view of sustainability when assessing the success (or lack thereof) of sustainable development policies. Equally important, the analysis indicates that despite these policies’ limited success (and even one of these policies not being implemented at all), sustainability policies can have a legacy beyond their life cycle. Hence, the evaluation of these policies is likely to provide insight into the process of policymaking.
Human Development, Per Capita Income Differentials and English as Source of Demographic Dividends Among the Youth in India
Authors: Shariff Abusaleh , Alam Asrar
Published: May 2021

India has a large youthful population; this ‘young nation’ is both a national and international resource that facilitates global value added. Such gains would accrue only when the youth are adequately educated, skilled and occupied in gainful employment. India, however, is staring at a missed opportunity that favours harnessing demographic dividends offered by demographic transition.

Keeping the tradition of high levels of diversity of labour force in India, this article examines the youthful demographic parameters according to socio-religious communities (SRCs). The economic momentum needed to reach a US$5 trillion (GDP) economy can only occur when the youth of India is educated, skilled and employed. A rather rare data set is analysed to explore the importance of English language education in augmenting demographic dividends.

Traditionally, disadvantageous groups, especially Muslims and Scheduled Castes/Scheduled Tribes (SCs/STs), are the youngest in India, yet their share in workforce is lowest when compared to other groups. This article reviews few human development dimensions like the rate of poverty change in the recent past and traces the path of educational transition and human development according to SRCs. A further analysis suggests that irrespective of any SRC identity, knowledge and fluency in English are some of the most dominant discriminatory factors in India in terms of the ability to earn higher incomes.
The 2018 update of the US National Seismic Hazard Model: Ground motion models in the western US
Authors: Powers Peter M , Rezaeian Sanaz , Shumway Allison M , Petersen Mark D , Luco Nicolas , Boyd Oliver S , Moschetti Morgan P , Frankel Arthur D , Thompson Eric M
Published: May 2021

The U.S. Geological Survey (USGS) National Seismic Hazard Model (NSHM) is the scientific foundation of seismic design regulations in the United States and is regularly updated to consider the best available science and data. The 2018 update of the conterminous U.S. NSHM includes significant changes to the underlying ground motion models (GMMs), most of which are necessary to enable the new multi-period response spectra (MPRS) requirements of seismic design regulations that use hazard results for 22 spectral periods and eight site classes. This article focuses on the GMMs used in the western United States (WUS) and is a companion to a recent article on the GMMs used in the central and eastern United States (CEUS). In the WUS, for crustal and subduction earthquakes, two models used in previous versions of the NSHM are excluded to provide consistency over all considered periods and site classes. To more accurately estimate ground motions at long periods in the vicinity of Los Angeles, San Francisco, Salt Lake City, and Seattle, the 2018 NSHM incorporates deep sedimentary basin depth from local seismic velocity models. The subduction GMMs considered lack basin depth terms and are modified to include an additional scale factor to account for this. This article documents the WUS GMMs used in the 2018 NSHM update and provides detail on the changes to GMM medians, aleatory variability, epistemic uncertainty, and site-effect models. It compares each of these components with those considered in prior NSHMs and discusses their total effect on hazard.
Cytokine combinations for human blood stem cell expansion induce cell-type– and cytokine-specific signaling dynamics
Authors: Wang Weijia , Zhang Yang , Dettinger Philip , Reimann Andreas , Kull Tobias , Loeffler Dirk , Manz Markus G. , Lengerke Claudia , Schroeder Timm
Published: May 2021

How hematopoietic stem cells (HSCs) integrate signals from their environment to make fate decisions remains incompletely understood. Current knowledge is based on either averages of heterogeneous populations or snapshot analyses, both missing important information about the dynamics of intracellular signaling activity. By combining fluorescent biosensors with time-lapse imaging and microfluidics, we measured the activity of the extracellular-signal–regulated kinase (ERK) pathway over time (ie, dynamics) in live single human umbilical cord blood HSCs and multipotent progenitor cells (MPPs). In single cells, ERK signaling dynamics were highly heterogeneous and depended on the cytokines, their combinations, and cell types. ERK signaling was activated by stem cell factor (SCF) and FMS-like tyrosine kinase 3 ligand in HSCs but SCF, interleukin 3, and granulocyte colony-stimulating factor in MPPs. Different cytokines and their combinations led to distinct ERK signaling dynamics frequencies, and ERK dynamics in HSCs were more transient than those in MPPs. A combination of 5 cytokines recently shown to maintain HSCs in long-term culture, had a more-than-additive effect in eliciting sustained ERK dynamics in HSCs. ERK signaling dynamics also predicted future cell fates. For example, CD45RA expression increased more in HSC daughters with intermediate than with transient or sustained ERK signaling. We demonstrate heterogeneous cytokine- and cell-type–specific ERK signaling dynamics, illustrating their relevance in regulating hematopoietic stem and progenitor (HSPC) cell fates.
Adaptive evolution of Moniliophthora PR-1 proteins towards its pathogenic lifestyle
Authors: Vasconcelos Adrielle A. , José Juliana , Tokimatu Paulo M. , Camargo Antonio P. , Teixeira Paulo J. P. L. , Thomazella Daniela P. T. , do Prado Paula F. V. , Fiorin Gabriel L. , Costa Juliana L. , Figueira Antonio , Carazzolle Marcelo F. , Pereira Gonçalo A. G. , Baroni Renata M.
Published: May 2021

Background

Plant pathogenesis related-1 (PR-1) proteins belong to the CAP superfamily and have been characterized as markers of induced defense against pathogens. Moniliophthora perniciosa and Moniliophthora roreri are hemibiotrophic fungi that respectively cause the witches’ broom disease and frosty pod rot in Theobroma cacao. Interestingly, a large number of plant PR-1-like genes are present in the genomes of both species and many are up-regulated during the biotrophic interaction. In this study, we investigated the evolution of PR-1 proteins from 22 genomes of Moniliophthora isolates and 16 other Agaricales species, performing genomic investigation, phylogenetic reconstruction, positive selection search and gene expression analysis.

Results

Phylogenetic analysis revealed conserved PR-1 genes (PR-1a, b, d, j), shared by many Agaricales saprotrophic species, that have diversified in new PR-1 genes putatively related to pathogenicity in Moniliophthora (PR-1f, g, h, i), as well as in recent specialization cases within M. perniciosa biotypes (PR-1c, k, l) and M. roreri (PR-1n). PR-1 families in Moniliophthora with higher evolutionary rates exhibit induced expression in the biotrophic interaction and positive selection clues, supporting the hypothesis that these proteins accumulated adaptive changes in response to host–pathogen arms race. Furthermore, although previous work showed that MpPR-1 can detoxify plant antifungal compounds in yeast, we found that in the presence of eugenol M. perniciosa differentially expresses only MpPR-1e, k, d, of which two are not linked to pathogenicity, suggesting that detoxification might not be the main function of most MpPR-1.

Conclusions

Based on analyses of genomic and expression data, we provided evidence that the evolution of PR-1 in Moniliophthora was adaptive and potentially related to the emergence of the parasitic lifestyle in this genus. Additionally, we also discuss how fungal PR-1 proteins could have adapted from basal conserved functions to possible roles in fungal pathogenesis.
Inter-species functional compatibility of the Theobroma cacao and Arabidopsis FT orthologs: 90 million years of functional conservation of meristem identity genes
Authors: Prewitt S. F. , Shalit-Kaneh A. , Maximova S. N. , Guiltinan M. J.
Published: May 2021

Background

In angiosperms the transition to flowering is controlled by a complex set of interacting networks integrating a range of developmental, physiological, and environmental factors optimizing transition time for maximal reproductive efficiency. The molecular mechanisms comprising these networks have been partially characterized and include both transcriptional and post-transcriptional regulatory pathways. Florigen, encoded byFLOWERING LOCUS T(FT) orthologs, is a conserved central integrator of several flowering time regulatory pathways. To characterize the molecular mechanisms involved in controlling cacao flowering time, we have characterized a cacao candidate florigen gene,TcFLOWERING LOCUS T(TcFT). Understanding how this conserved flowering time regulator affects cacao plant’s transition to flowering could lead to strategies to accelerate cacao breeding.

Results

BLAST searches of cacao genome reference assemblies identified seven candidate members of theCENTRORADIALIS/TERMINAL FLOWER1/SELF PRUNINGgene family including a single florigen candidate. cDNA encoding the predicted cacao florigen was cloned and functionally tested by transgenic genetic complementation in the Arabidopsisft-10mutant. Transgenic expression of the candidateTcFTcDNA in late flowering Arabidopsisft-10partially rescues the mutant to wild-type flowering time. Gene expression studies reveal thatTcFTis spatially and temporally expressed in a manner similar to that found in Arabidopsis, specifically,TcFTmRNA is shown to be both developmentally and diurnally regulated in leaves and is most abundant in floral tissues. Finally, to test interspecies compatibility of florigens, we transformed cacao tissues withAtFTresulting in the remarkable formation of flowers in tissue culture. The morphology of these in vitro flowers is normal, and they produce pollen that germinates in vitro with high rates.

Conclusion

We have identified the cacaoCETSgene family, central to developmental regulation in angiosperms. The role of the cacao’s singleFT-like gene (TcFT) as a general regulator of determinate growth in cacao was demonstrated by functional complementation of Arabidopsisft-10late-flowering mutant and through gene expression analysis. In addition, overexpression ofAtFTin cacao resulted in precocious flowering in cacao tissue culture demonstrating the highly conserved function ofFTand the mechanisms controlling flowering in cacao.
Combining targeted metabolite analyses and transcriptomics to reveal the specific chemical composition and associated genes in the incompatible soybean variety PI437654 infected with soybean cyst nematode HG1.2.3.5.7
Authors: Shi Xue , Chen Qiansi , Liu Shiming , Wang Jiajun , Peng Deliang , Kong Lingan
Published: May 2021

Background

Soybean cyst nematode, Heterodera glycines, is one of the most devastating pathogens of soybean and causes severe annual yield losses worldwide. Different soybean varieties exhibit different responses to H. glycines infection at various levels, such as the genomic, transcriptional, proteomic and metabolomic levels. However, there have not yet been any reports of the differential responses of incompatible and compatible soybean varieties infected with H. glycines based on combined metabolomic and transcriptomic analyses.

Results

In this study, the incompatible soybean variety PI437654 and three compatible soybean varieties, Williams 82, Zhonghuang 13 and Hefeng 47, were used to clarify the differences in metabolites and transcriptomics before and after the infection with HG1.2.3.5.7. A local metabolite-calibrated database was used to identify potentially differential metabolites, and the differences in metabolites and metabolic pathways were compared between the incompatible and compatible soybean varieties after inoculation with HG1.2.3.5.7. In total, 37 differential metabolites and 20 KEGG metabolic pathways were identified, which were divided into three categories: metabolites/pathways overlapped in the incompatible and compatible soybeans, and metabolites/pathways specific to either the incompatible or compatible soybean varieties. Twelve differential metabolites were found to be involved in predicted KEGG metabolite pathways. Moreover, 14 specific differential metabolites (such as significantly up-regulated nicotine and down-regulated D-aspartic acid) and their associated KEGG pathways (such as the tropane, piperidine and pyridine alkaloid biosynthesis, alanine, aspartate and glutamate metabolism, sphingolipid metabolism and arginine biosynthesis) were significantly altered and abundantly enriched in the incompatible soybean variety PI437654, and likely played pivotal roles in defending against HG1.2.3.5.7 infection. Three key metabolites (N-acetyltranexamic acid, nicotine and D,L-tryptophan) found to be significantly up-regulated in the incompatible soybean variety PI437654 infected by HG1.2.3.5.7 were classified into two types and used for combined analyses with the transcriptomic expression profiling. Associated genes were predicted, along with the likely corresponding biological processes, cellular components, molecular functions and pathways.

Conclusions

Our results not only identified potential novel metabolites and associated genes involved in the incompatible response of PI437654 to soybean cyst nematode HG1.2.3.5.7, but also provided new insights into the interactions between soybeans and soybean cyst nematodes.
Surgical resection significantly promotes the overall survival of patients with hepatocellular carcinoma: a propensity score matching analysis
Authors: Chen Yaw-Sen , Hsieh Pei-Min , Lin Hung-Yu , Hung Chao-Ming , Lo Gin-Ho , Hsu Yao-Chun , Lu I.-Cheng , Lee Chih-Yuan , Wu Tsung-Chin , Yeh Jen-Hao , Hsiao Pojen , Li Yu-Chan , Wang Ya-Chin , Hsieh Kun-Chou , Lin Chih-Wen
Published: May 2021

Background

The benefits of surgical resection (SR) for various Barcelona Clinic Liver Cancer (BCLC) stages of hepatocellular carcinoma (HCC) remain unclear. We investigated the risk factors of overall survival (OS) and survival benefits of SR over nonsurgical treatments in patients with HCC of various BCLC stages.

Methods

Overall, 2316 HCC patients were included, and their clinicopathological data and OS were recorded. OS was analyzed by the Kaplan-Meier method and Cox regression analysis. Propensity score matching (PSM) analysis was performed.

Results

In total, 66 (2.8%), 865 (37.4%), 575 (24.8%) and 870 (35.0%) patients had BCLC stage 0, A, B, and C disease, respectively. Furthermore, 1302 (56.2%) of all patients, and 37 (56.9%), 472 (54.6%), 313 (54.4%) and 480 (59.3%) of patients with BCLC stage 0, A, B, and C disease, respectively, died. The median follow-up duration time was 20 (range 0–96) months for the total cohort and was subdivided into 52 (8–96), 32 (1–96), 19 (0–84), and 12 (0–79) months for BCLC stages 0, A, B, and C cohorts, respectively. The risk factors for OS were (1) SR and cirrhosis; (2) SR, cirrhosis, and Child–Pugh (C–P) class; (3) SR, hepatitis B virus (HBV) infection, and C–P class; and (4) SR, HBV infection, and C–P class for the BCLC stage 0, A, B, and C cohorts, respectively. Compared to non-SR treatment, SR resulted in significantly higher survival rates in all cohorts. The 5-year OS rates for SR vs. non-SR were 44.0% versus 28.7%, 72.2% versus 42.6%, 42.6% versus 36.2, 44.6% versus 23.5%, and 41.4% versus 15.3% (all P values < 0.05) in the total and BCLC stage 0, A, B, and C cohorts, respectively. After PSM, SR resulted in significantly higher survival rates compared to non-SR treatment in various BCLC stages.

Conclusions

SR conferred significant survival benefits to patients with HCC of various BCLC stages and should be considered a recommended treatment for select HCC patients, especially patients with BCLC stage B and C disease.
Barriers to initiating SGLT2 inhibitors in diabetic kidney disease: a real-world study
Authors: Jeong Su Jin , Lee Seung Eun , Shin Dong Hyun , Park Ie Byung , Lee Hui Seung , Kim Kyoung-Ah
Published: May 2021

Background

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) and chronic kidney disease (CKD) having estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) > 30 mg/g. However, SGLT2i is currently underprescribed among eligible, at-risk patients for CKD progression. We analyzed prescription patterns and barriers to initiating SGLT2i in patients with T2D and CKD in real practice.

Methods

A total of 3,703 consecutive outpatients with T2D from four teaching hospitals during six months (2019 ~ 2020) were reviewed. Five eGFR categories (G1, ≥ 90; G2, 60–89; G3ab, 30–59; G4-5, < 30 mL/min/1.73 m2) and three UACR categories (A1, < 30; A2, 30–300; A3, > 300 mg/g) were used to define CKD status.

Results

Overall, 25.8 % patients received SGLT2i in the following eGFR and albuminuria categories: G1 (A1, 31 %; A2, 48 %; A3, 45 %); G2 (A1, 18 %; A2, 24 %; A3, 30%); and G3 (A1, 9 %; A2, 7 %; A3, 13 %).

Total prevalence estimate of CKD was 33.8 % (n = 1,253), of whom 25.6 % patients received SGLT2i. We defined eGFR ≥ 45 mL/min/1.73 m2 and UACR ≥ 30 mg/g as high-risk CKD group eligible for SGLT2i (n = 905), of whom 32.9 % patients were treated with an SGLT2i. In this high-risk group, SGLT2i initiation showed negative correlations with age ≥ 65 years and recent hospitalization. Conversely, HbA1c level, body mass index (BMI), presence of diabetic retinopathy, and previous heart failure events were positively correlated with SGLT2i initiation.

Conclusions

Only 32.9 % of T2D with CKD eligible for SGLT2i is currently treated with SGLT2i in real-world clinical practice. The older patient group and clinical inertia are the main barriers to initiate SGLT2i for eligible patients. Clinicians should change the glucocentric approach and focus on reducing renal events in T2D.
The association between ambient air pollution and birth defects in five major ethnic groups in Liuzhou, China
Authors: Huang Xiaoli , Chen Jichang , Zeng Dingyuan , Lin Zhong , Herbert Carly , Cottrell Lesley , Liu Liu , Ash Arlene , Wang Bo
Published: May 2021

Background

Studies suggest that exposure to ambient air pollution during pregnancy may be associated with increased risks of birth defects (BDs), but conclusions have been inconsistent. This study describes the ethnic distribution of major BDs and examines the relationship between air pollution and BDs among different ethnic groups in Liuzhou city, China.

Methods

Surveillance data of infants born in 114 registered hospitals in Liuzhou in 2019 were analyzed to determine the epidemiology of BDs across five major ethnic groups.

Concentrations of six air pollutants (PM2.5, PM10, SO2, CO, NO2, O3) were obtained from the Liuzhou Environmental Protection Bureau. Logistic regression was used to examine the associations between ambient air pollution exposure and risk of BDs.

Results

Among 32,549 infants, 635 infants had BDs, yielding a prevalence of 19.5 per 1000 perinatal infants. Dong ethnic group had the highest prevalence of BDs (2.59%), followed by Yao (2.57%), Miao (2.35%), Zhuang (2.07%), and Han (1.75%). Relative to the Han ethnic group, infants from Zhuang, Miao, Yao and Dong groups had lower risks of congenital heart disease, polydactyly, and hypospadias. The Zhuang ethnic group had higher risks of severe thalassemia, cleft lip and/or palate, and syndactyls. Overall BDs were positively correlated with air pollutants PM10 (aOR =1.14, 95% CI:1.12 ~ 2.43; aOR =1.51, 95% CI:1.13 ~ 2.03 for per 10μg/mg3 increment) and CO (aOR =1.36, 95% CI:1.14 ~ 2.48; aOR =1.75, 95% CI:1.02 ~ 3.61 for every 1 mg /m3 increment) in second and third month of pregnancy. SO2 was also significantly associated with BDs in the second month before the pregnancy (aOR = 1.31; 95% CI: 1.20 ~ 3.22) and third month of pregnancy (aOR =1.75; 95% CI:1.02 ~ 3.61). Congenital heart disease, polydactyl, cleft lip and/or palate were also significantly associated with PM10, SO2 and CO exposures. However, no significant association was found between birth defects and O3, PM2.5 and NO2 exposures (P > 0.05).

Conclusion

This study provides a comprehensive description of ethnic differences in BDs in Southwest China and broadens the evidence of the association between air pollution exposure during gestation and BDs.
Osteitis Fibrosa Cystica and pathological fractures—the classic but neglected skeletal manifestation of primary hyperparathyroidism: a case report
Authors: Vanitcharoenkul Ekasame , Singsampun Nontouch , Unnanuntana Aasis , Sirinvaravong Sirinart
Published: May 2021

Background

Osteitis fibrosa cystica is the classic manifestation of primary hyperparathyroidism (PHPT), occurs after prolonged exposure of bone to high serum parathyroid hormone (PTH) level. It has become increasingly rare due to early detection of PHPT.

Case presentation

A 37-year-old woman was referred to our institution for fixation of multiple fractures of upper and lower extremities that had been reoccurring in the past 5 years. Her medical history showed right-shoulder, left-elbow, and right-femur fractures after a fall 5 years previously. One month ago, she sustained fractures of the right distal humerus, left tibia, and left femur without history of trauma. Upon arrival to our hospital, a thorough review of her plain radiographs demonstrated brown tumors at multiple sites, along with a salt-and-pepper appearance of the skull and a rugger-jersey spine, compatible with osteitis fibrosa cystica. Patient was diagnosed with PHPT, confirmed by high-corrected serum calcium (13.6 [8.6–10.0] mg/dl), low serum phosphate (2.2 [2.5–4.5] mg/dL), high serum alkaline phosphatase (1482 [35–105] U/L), and significantly elevated parathyroid hormone (PTH 3850 [15–65] pg/mL). A histologically confirmed, 2.5-cm parathyroid adenoma was removed by parathyroidectomy. Ten days later, closed reduction and internal fixation of the left proximal femoral shaft was performed. Pain and ambulation were significantly improved 6 months postoperatively. At the 1.5-year follow-up, fracture unions and complete mineralization of brown tumors were noted; the patient could ambulate with neither pain nor an assistive device.

Conclusions

PHPT has become more asymptomatic in countries where routine calcium screening is performed. Nevertheless, the classic skeletal involvement, osteitis fibrosa cystica, should not be overlooked, particularly in young patients who present with a low-energy fracture.
Newly designed solid coupling medium for reducing trapped air pockets during extracorporeal shock wave lithotripsy_ a phantom study
Authors: Wang Chien-Sheng , Li Ching-Chia , Wu Wen-Jeng , Liou Wen-Chin , Lin Yusen Eason , Chen Wei-Chuan
Published: May 2021

Introduction

Air pockets between the lithotripter head and body surface are almost inevitably generated when applying a handful of gel onto the contact portion of the treatment head and that on the patient’s skin during coupling procedure. These air pockets can compromise the transmission of acoustic energy of shock wave and may significantly affect efficacy of stone disintegration. Comparing to conventional gel, this study aims to investigate efficacy of stone disintegration by using a proprietary isolation-coupling pad (“icPad”) as the coupling medium to reduce trapped air pockets during ESWL procedure.

Method

In this phantom study, Dornier lithotripter (Delta-2 RC, Dornier MedTech Europe GmbH Co., Germany) was used with a proprietary gel pads (icPad, Diameter = 150 mm, Thickness = 4 mm and 8 mm). The lithotripter was equipped with inline camera to observe the trapped air pockets between the contact surface of the lithotripter head. A testing and measuring device were used to observe experimental stone disintegration using icPad and semi-liquid gel. The conventional semi-liquid gel was used as control for result comparison.

Results

The stone disintegration rate of icPad 4 mm and 8 mm after 200 shocks of energy at level 2 were significantly higher than that of the semi-liquid gel (disintegration rate 92.3%, 85.0% vs. 45.5%, respectively, p < 0.001). The number of shocks for complete stone disintegration by icPad of 4 mm and 8 mm at the same energy level 2 were significantly lower than that of the semi-liquid gel (the number of shocks 242.0 ± 13.8, 248.7 ± 6.3 vs. 351.0 ± 54.6, respectively, p = 0.011). Furthermore, quantitative comparison of observed air pockets under Optical Coupling Control (OCC) system showed that the area of air pockets in semi-liquid group was significantly larger than that of the group using icPad (8 mm) and that of the group using icPad (8 mm) after sliding (332.7 ± 91.2 vs. 50.3 ± 31.9, 120.3 ± 21.5, respectively, p < 0.05).

Conclusion

The advantages of icPad includes: (1) reduced the numbers of shock wave and increased stone disintegration rate due to icPad’s superior efficacy; (2) significantly reduce trapped air pockets in ESWL coupling. Due to the study limitation, more data are needed to confirm our observations before human trials.
A qualitative study on continuous deep sedation until death as an alternative to assisted suicide in Switzerland
Authors: Tomczyk Martyna , Dieudonné-Rahm Nathalie , Jox Ralf J.
Published: May 2021

Background

According to the European Association for Palliative Care, decisions regarding palliative sedation should not be made in response to requests for assisted dying, such as euthanasia or assisted suicide. However, several studies show that continuous deep sedation until death (CDSUD) – a particular form of sedation – has been considered as an alternative to these practices in some countries. In Switzerland, where assisted suicide is decriminalized and CDSUD is not legally regulated, no studies have comprehensively investigated their relation. Our study aimed to identify and describe the experience among palliative care physicians of CDSUD as a potential alternative to assisted suicide in the French-speaking part of Switzerland.

Methods

We performed an exploratory multicentre qualitative study based on interviews with palliative care physicians in the French-speaking part of Switzerland and conducted linguistic and thematic analysis of all interview transcripts. The study is described in accordance with COREQ guidelines.

Results

We included 10 interviews conducted in four palliative care units. Our linguistic analysis shows four main types of sedation, which we called ‘rapid CDSUD’, ‘gradual CDSUD’, ‘temporary sedation’ and ‘intermittent sedation’. CDSUD (rapid or gradual) was not considered an alternative to assisted suicide, even if a single situation has been reported. In contrast, ‘temporary’ or ‘intermittent sedation’, although not medically indicated, was sometimes introduced in response to a request for assisted suicide. This was the fact when there were barriers to an assisted suicide at home (e.g., when transfer home was impossible or the patient wished not to burden the family).

Conclusion

These preliminary results can guide clinical, ethical, linguistic and legal reflection in this field and be used to explore this question more deeply at the national and international levels in a comparative, interdisciplinary and multiprofessional approach. They can also be useful to update Swiss clinical guidelines on palliative sedation in order to include specific frameworks on various sedation protocols and sedation as an alternative to assisted suicide. Potential negative impacts of considering palliative sedation as an alternative to assisted suicide should be nuanced by open and honest societal debate.
Effectiveness of self-managed continuous monitoring for maintaining high-quality early essential newborn care compared to supervision visit in Lao PDR: a cluster randomised controlled trial
Authors: Horiuchi Sayaka , Rattana Sommana , Saysanasongkham Bounnack , Kounnavongsa Outhevanh , Kubota Shogo , Inoue Mariko , Yamaoka Kazue
Published: May 2021

Background

Thousands of neonatal deaths are expected to be averted by introducing the Early Essential Newborn Care (EENC) in the Western Pacific Region. In Lao People’s Democratic Republic (Lao PDR), the government adopted the EENC programme and expanded it to district hospitals. With the expansion, maintaining the quality of EENC has become difficult for the government.

Methods

A cluster randomised controlled trial with four strata based on province and history of EENC coaching was implemented to evaluate the effectiveness of self-managed continuous monitoring compared with supervisory visit in Lao PDR between 20 July 2017 and 2 April 2019. Health workers who were routinely involved in maternity care were recruited from 15 district hospitals in Huaphanh (HP) and Xiangkhouang (XK) provinces. The primary endpoint was the score on the determinants of EENC performance measured by the Theory of Planned Behaviour (TPB). Secondary endpoints were set as the knowledge and skill scores. A linear mixed-effects model was applied to test the effects of intervention over time on the endpoints.

Results

Among 198 recruited health workers, 46 (23.2%) did not complete the final evaluation. TPB scores were 180.9 [Standard Deviation: SD 38.6] and 182.5 [SD 37.7] at baseline and 192.3 [SD 30.1] and 192.3 [SD 28.4] at the final evaluation in the intervention and control groups, respectively. There was no significant difference in changes between the groups in the adjusted model (2.4, p = 0.650). Interviews with participants revealed that district hospitals in HP regularly conducted peer reviews and feedback meetings, while few hospitals did in XK. Accordingly, in stratified analyses, the TPB score in the intervention group significantly increased in HP (15.5, p = 0.017) but largely declined in XK (− 17.7, p = 0.047) compared to the control group after adjusting for covariates. Skill scores declined sharper in the intervention group in XK (− 8.78, p = 0.026), particularly in the practice of managing nonbreathing babies.

Conclusions

The study indicates that self-managed continuous monitoring is effective in improving behaviour among district health workers; however, additional measures are necessary to support its proper implementation. To maintain resuscitation skills, repeated practice is necessary.

Trial registration

This trial was registered at UMIN Clinical Trials Registry on 15/6/2017. Registration number is UMIN000027794.
Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis
Authors: Wang Yi-yi , Duan Hua , Wang Sha , Quan Yong-jun , Huang Jun-hua , Guo Zheng-chen
Published: May 2021

Adenomyosis (ADS) is an estrogen-dependent gynecological disease with unspecified etiopathogenesis. Local hyperestrogenism may serve a key role in contributing to the origin of ADS. Talin1 is mostly identified to be overexpressed and involved in the progression of numerous human carcinomas through mediating cell proliferation, adhesion and motility. Whether Talin1 exerts an oncogenic role in the pathogenesis of ADS and puts an extra impact on the efficacy of estrogen, no relevant data are available yet. Here we demonstrated that the adenomyotic eutopic and ectopic endometrial stromal cells (ADS_Eu_ESC and ADS_Ec_ESC) treated with β-estradiol (β-E2) presented stronger proliferative and pro-angiogenetic capacities, accompanied by increased expression of PCNA, Ki67, VEGFB and ANGPTL4 proteins. Meanwhile, these promoting effects were partially abrogated by Fulvestrant (ICI 182780, an estrogen-receptor antagonist). Aberrantly upregulation of Talin1 mRNA and protein level was observed in ADS endometrial specimens and stromal cells. Through performing functional experiments in vitro, we further determined that merely overexpression of Talin1 (OV-Talin1) also enhanced ADS stromal cell proliferation and pro-angiogenesis, while the most pronounced facilitating effects were found in the co-intervention group of OV-Talin1 plus β-E2 treatment. Results from the xenograft nude mice model showed that the hypodermic endometrial lesions from co-intervention group had the highest mean weight and volume, compared with that of individual OV-Talin1 or β-E2 treatment. The expression levels of PCNA, Ki67, VEGFB and ANGPTL4 in the lesions were correspondingly elevated the most in the co-intervention group. Our findings unveiled that overexpressed Talin1 might cooperate withβ-E2 in stimulating ADS endometrial stromal cell proliferation and neovascularization, synergistically promoting the growth and survival of ectopic lesions. These results may be beneficial to provide a new insight for clarifying the pathogenesis of ADS.
Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities
Authors: Mullick Ranajoy , Sutar Jyoti , Hingankar Nitin , Deshpande Suprit , Thakar Madhuri , Sahay Seema , Ringe Rajesh P. , Mukhopadhyay Sampurna , Patil Ajit , Bichare Shubhangi , Murugavel Kailapuri G. , Srikrishnan Aylur K. , Goyal Rajat , Sok Devin , Bhattacharya Jayanta
Published: May 2021

Background

The potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and a few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype Cenvsobtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.25, PGDM1400 and PGT121.

Results

We found significant variations in the susceptibility of Indian clade C to these four bnAbs. These variations were found to be distinct to that observed in African subtype C based on the existing datasets and concordant with their sequence diversity. Trend analysis indicated an increasing neutralization resistance observed over time with CAP25-VRC26.25, PGDM1400 and PGT121 when tested on pseudoviruses expressingenvsobtained from 1999 to 2016. However, inconsistent trend in neutralization susceptibility was observed, when pseudoviruses expressingenvsobtained from three followed up individuals were examined. Finally, through predictive analysis of the 98 Indian subtype C including those assessed in the present study by employing additive model implemented in CombiNAber (http://www.hiv.lanl.gov), we observed two possibilities where combinations of three bnAbs (VRC01/CAP56-VRC26.25/PGT121 and PGDM1400/CAP256-VRC26.25/PGT121) could achieve near 100% neutralization coverage.

Conclusions

Our findings not only indicate disparate intra-clade C genetic vis-à-vis neutralization diversities but also warrant the need for more comprehensive study using additional isolates towards comparing inter and intra-clade neutralization diversities which will be necessary for selecting the bnAb combinations suitable for optimal coverage of the region-specific HIV-1 circulating subtypes. Expanding these efforts is imperative for designing efficacious bnAb based intervention strategies for India as well as subtype C in general.
Functional conservation in genes and pathways linking ageing and immunity
Authors: Fabian Daniel K. , Fuentealba Matías , Dönertaş Handan Melike , Partridge Linda , Thornton Janet M.
Published: May 2021

At first glance, longevity and immunity appear to be different traits that have not much in common except the fact that the immune system promotes survival upon pathogenic infection. Substantial evidence however points to a molecularly intertwined relationship between the immune system and ageing. Although this link is well-known throughout the animal kingdom, its genetic basis is complex and still poorly understood. To address this question, we here provide a compilation of all genes concomitantly known to be involved in immunity and ageing in humans and three well-studied model organisms, the nematode wormCaenorhabditis elegans, the fruit flyDrosophila melanogaster, and the house mouseMus musculus. By analysing human orthologs among these species, we identified 7 evolutionarily conserved signalling cascades, the insulin/TOR network, three MAPK (ERK, p38, JNK), JAK/STAT, TGF-β, and Nf-κB pathways that act pleiotropically on ageing and immunity. We review current evidence for these pathways linking immunity and lifespan, and their role in the detrimental dysregulation of the immune system with age, known as immunosenescence. We argue that the phenotypic effects of these pathways are often context-dependent and vary, for example, between tissues, sexes, and types of pathogenic infection. Future research therefore needs to explore a higher temporal, spatial and environmental resolution to fully comprehend the connection between ageing and immunity.
Introduction to collection: confronting the challenges of health research in humanitarian crises
Authors: Mistry Amit S. , Kohrt Brandon A. , Beecroft Blythe , Anand Nalini , Nuwayhid Iman
Published: May 2021

Background

Humanitarian crises, such as armed conflict, forced displacement, natural disasters, and major disease outbreaks, take a staggering toll on human health, especially in low-resource settings. Yet there is a dearth of robust evidence to inform the governments, non-governmental organizations (NGOs), and other humanitarian organizations on how to best respond to them. The Fogarty International Center of the U.S. National Institutes of Health commissioned a collection of Research in Practice articles that highlights the experiences of scientists conducting research in the context of humanitarian crises. Unlike traditional research papers, the case analyses in this collection go beyond what research was completed and focus on why the research was important and how it was conducted in these extremely challenging settings.

Discussion

The papers selected for this collection span 27 countries, cover a broad range of humanitarian crises, and discuss a wide variety of disease and health risk factors. Of the 23 papers in the collection, 17 include an author from the affected country and five papers were authored by humanitarian NGOs. Throughout the collection, 43% of the authors were from low- and middle-income countries.

Across the collection, some general themes emerged that are broadly applicable. Importantly, there is a clear need for more, high-quality research to address evidence gaps. Community engagement, already a key element to global health research, was highlighted as especially important for research involving populations dealing with severe trauma and disruption. Partnership with humanitarian actors, including local governments, local and international NGOs, and UN agencies, was found to be a critical strategy as well.

Conclusion

A variety of audiences will find this collection useful. Global health educators can utilize papers to facilitate discussion around public health practice and equitable partnerships, among other topics. Humanitarian response organizations may use the collection to consider how research may inform and improve their work. Global health researchers, funders, and other stakeholders may use the collection to stimulate dialogue around key scientific research questions and better appreciate the importance of conducting research in humanitarian crises in the context of achieving broader global health goals.