bluuebunny/crossref_metadata_2025 huggingface dataset:
Why do pregnant women in Iringa region in Tanzania start antenatal care late? A qualitative analysis
Authors: Maluka Stephen Oswald , Joseph Chakupewa , Fitzgerald Sian , Salim Robert , Kamuzora Peter
Published: February 2020

Background

When started early in pregnancy and continued up till childbirth, antenatal care (ANC) can be effective in reducing adverse pregnancy outcomes. While the proportion of women who attend ANC at least once in low income countries is high, most pregnant women attend their first ANC late. In Tanzania, while over 51% of pregnant women complete ≥4 visits, only 24% start within the first trimester. This study aimed to understand the factors that lead to delay in seeking ANC services among pregnant women in Tanzania.

Methods

This qualitative descriptive case study was conducted in two rural districts in Iringa Region in Tanzania. A total of 40 focus group discussions (FGDs) were conducted involving both male and female participants in 20 villages. In addition, 36 semi-structured interviews were carried out with health care workers, members of health facility committees and community health workers. Initial findings were further validated during 10 stakeholders’ meetings held at ward level in which 450 people participated. Data were analysed using thematic approach.

Results

Key individual and social factors for late ANC attendance included lack of knowledge of the importance of early visiting ANC, previous birth with good outcome, traditional gender roles, fear of shame and stigma, and cultural beliefs about pregnancy. Main factors which inhibit early ANC attendance in Kilolo and Mufindi districts include spouse accompany policy, rude language of health personnel and shortage of health care providers.

Conclusions

Traditional gender roles and cultural beliefs about pregnancy as well as health system factors continue to influence the timing of ANC attendance. Improving early ANC attendance, therefore, requires integrated interventions that address both community and health systems barriers. Health education on the timing and importance of early antenatal care should also be strengthened in the communities. Additionally, while spouse accompany policy is important, the implementation of this policy should not infringe women’s rights to access ANC services.
Heterogeneous components of lung adenocarcinomas confer distinct EGFR mutation and PD-L1 expression
Authors: Cai Yiran , Wu Hongbo , Shi Xiaoqin , Dong Yujie , Chang Xiujun , Zhang Li , Zhou Lijuan , Su Dan , Yang Ming
Published: February 2020

Background

Lung adenocarcinoma (LAC) is composed of lepidic, papillary, mucinous, micropapillary and solid components in its parenchyma. Complex responses to therapeutics result from intratumoral heterogeneity. However, it remains confused that what components in a mixed LAC tumor are responsible to the heterogeneous EGFR mutation and PD-L1 expression.

Methods

We investigated EGFR status via laser microdissection to capture spatially separated cancer cell subpopulations and digital droplet PCR to determine the abundance of EGFR sensitizing mutation and naïve T790M. Whilst, PD-L1 expression level via tumor proportion score (TPS) was evaluated by Ventana immunohistochemistry using SP263 antibody. PD-L1 expression levels were tiered in < 1, 1–49% and > =50% groups.

Results

EGFR mutation harbored in 154 (59%) of 261 LAC patients and more frequently occurred in papillary, lepidic and micropapillary constituents. Higher levels of PD-L1 were found in LACs at stage III and IV (68.3%) versus those at stage I and II (31.7%) (P = 0.04). Solid predominant LACs (41.3%) expressed PD-L1 with TPS > =50%, versus mucinous and lepidic LACs (P < 0.01). LACs with solid constituents also had more positive proportion of PD-L1 protein. Cut-offs < 1, 1–49% or > =50% were associated with patients’ progression-free survival and longer in the < 1% group (22.9 month, 95% CI 17.6–28.2) (P < 0.05). LACs consisting of two constituents with PD-L1 TPS < 1% had a better prognosis than the groups with single component and more than two components (P < 0.05). Eighteen LACs (6.9%) had concomitantly deletion in exon 19 or L858R and naïve T790M mutation. The abundance of T790M varied diversely with sensitizing mutation. PD-L1 expression was not concordant in same components and usually negative in the EGFR-mutated constituents. Heterogeneous PD-L1 expression occurred in the vicinity of stromal tissues. 58.8, 29.4 and 11.8% in ALK positive LACs (N = 17) were found PD-L1 expression via cutoffs of < 1, 1–49% and > =50%, respectively (P > 0.05).

Conclusion

Intratumoral genetic heterogeneity of LACs was demonstrated associated with histological patterns. Heterogeneous PD-L1 expression in higher level usually occurred in solid component both in EGFR mutated and EGFR wild-typed LACs. EGFR mutated LACs heterogeneously had sensitizing and resistant mutation and was accompanied with PD-L1 expression, but discordant among histological constituents. Immune checkpoint inhibitor combined with third generation EGFR tyrosine kinase inhibitor should be more effective to these LACs.
Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy
Authors: Chua Ling Ling , Rajasuriar Reena , Lim Yvonne Ai Lian , Woo Yin Ling , Loke P’ng , Ariffin Hany
Published: February 2020

Background

Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy.

Methodology

We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients’ microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy.

Results

Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging toBacteroidetesphylum andBacteroidesgenus.The relative abundance ofBacteroidesdecreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health.

Conclusion

Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.
A panel of protein kinase high expression is associated with postoperative recurrence in cholangiocarcinoma
Authors: Padthaisong Sureerat , Thanee Malinee , Namwat Nisana , Phetcharaburanin Jutarop , Klanrit Poramate , Khuntikeo Narong , Titapun Attapol , Loilome Watcharin
Published: February 2020

Background

Cancer recurrence is one of the most concerning clinical problems of cholangiocarcinoma (CCA) patients after treatment. However, an identification of predictive factor on Opisthorchis viverrini (OV)-associated CCA recurrence is not well elucidated. In the present study, we aimed to investigate the correlation of twelve targeted protein kinases with CCA recurrence.

Methods

Twelve protein kinases, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2, 3, 4 (HER2, HER3, HER4), vascular endothelial growth factor receptor 3 (VEGFR3), vascular endothelial growth factor-C (VEGF-C), erythropoietin-producing hepatocellular carcinoma receptor type-A3 (EphA3), EphrinA1, phosphor-serine/threonine kinase 1 (p-Akt1), serine/threonine kinase 1 (Akt1), beta-catenin and protein Wnt5a (Wnt5a) were examined using immunohistochemistry. Pre-operative serum tumor markers, CA19–9 and CEA were also investigated.

Results

Among twelve protein kinases, EGFR, HER4, and EphA3 were associated with tumor recurrence status, recurrence-free survival (RFS) and overall survival (OS). Multivariate cox regression demonstrated that EGFR, HER4, EphA3 or the panel of high expression of these proteins was an independent prognostic factor for tumor recurrence. The combination of high expression of these proteins with a high level of CA19–9 could improve the predictive ability on tumor recurrence. Moreover, the patients were stratified more accurately when analyzed using the combination of high expression of these proteins with primary tumor (T) or lymph node metastasis (N) status.

Conclusion

EGFR, HER4, EphA3 or the panel of high expression of these proteins is an independent prognostic factor for post-operative CCA recurrence.
Effects of the LASIK flap thickness on corneal biomechanical behavior: a finite element analysis
Authors: Fang Lihua , Wang Yan , Yang Ruizhi , Deng Sijing , Deng Jiahao , Wan Linsun
Published: February 2020

Background

It is well known that the biomechanical properties change after LASIK refractive surgery. One reason is the impact of flap creation on the residual stroma. The results have revealed that the change is closely related with the flap thickness in several studies. However, the quantitative relationships between the distributions of displacement and stress on the corneal surface and flap thickness have not been studied. The aim of the study was to quantify evaluate the biomechanical change caused by the LASIK flap.

Methods

By building a finite element model of the cornea, the displacement, the stress and the strain on the corneal surface were analyzed.

Results

The results showed that the corneal flap could obviously cause the deformation of the anterior corneal surface. For example, the displacement of the corneal vertex achieved 15 μm more than that without corneal flap, when the thickness of corneal flap was 120 μm thick. This displacement was enough to cause the change of aberrations in the human eyes. In the central part of the cornea, the stress on the anterior corneal surface increased with flap thickness. But the change in the stress on the posterior corneal surface was significantly less than that on the anterior surface. In addition, the stress in the central part of the anterior corneal surface increased significantly as the intra-ocular pressure (IOP) increase. Furthermore the increase of IOP had a clearly less effect on stress distribution at the edge of the cornea. Distributions of strain on the corneal surface were similar to those of stress.

Conclusions

The changes in the biomechanical properties of cornea after refractive surgery should not be ignored.
High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report
Authors: Mc Glacken-Byrne Aisling B. , Prentice David , Roshandel Danial , Brown Michael R. , Tuch Philip , Yau Kyle S.-Y. , Sivadorai Padma , Davis Mark R. , Laing Nigel G. , Chen Fred K.
Published: February 2020

Background

Congenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses.

Case presentation

The proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation.

Conclusions

In addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.
Blood cell for the differentiation of airway inflammatory phenotypes in COPD exacerbations
Authors: Gao Jie , Chen Bida , Wu Sifang , Wu Feng
Published: February 2020

Background

Measurement of sputum is frequently used to define airway inflammatory subtypes. The venous blood cell is a reliable and simple biomarker, may be used as an alternative procedure to reflect the subtypes. For the aim of verifying the hypothesis that venous blood cell can quantify sputum inflammatory cell to access the airway subtypes in chronic obstructive pulmonary disease of acute exacerbations (AECOPD) and to ascertain the accuracy of the blood cell biomarker.

Methods

This study evaluated 287 patients with COPD exacerbations and all four tests were performed on the same day, which are lung function test, bronchodilator reversibility test, sputum cell analysis and blood routine examination.

Results

There was a correlation between sputum eosinophils and blood eosinophils, blood cells derived ratios. There was a weaker relationship to neutrophils between sputum and blood. Sputum neutrophils had not any association with neutrophil/macrophage ratio (NMR) and eosinophil/lymphocyte ratio (ELR) in blood. Blood eosinophils percentage was predictive for eosinophilic COPD exacerbations with an area under the curve (AUC) of 0.672 (p = 0.012). The optimum cutpoint for blood eosinophils percentage was 0.55%. Blood eosinophils absolute count was also predictive sputum eosinophilia at 0.35 × 109/L (AUC = 0.626, p = 0.025). ELR, eosinophil/monocyte ratio (EMR) and eosinophil/neutrophil ratio (ENR) in blood were higher in COPD exacerbations with mixed granulocytic and eosinophilic subtypes.

Conclusion

Eosinophils/neutrophils count parameters were relationship between blood and sputum. Eosinophils in blood and the ratios (ENR, EMR and ELR) may be utilized to assess eosinophilic airway inflammation in COPD exacerbations. Due to weak relationship and poor predictive ability, more researches should be required.
PrEvention of posttraumatic contractuRes with Ketotifen 2 (PERK 2) – protocol for a multicenter randomized clinical trial
Authors: Ademola Ayoola , Hildebrand Kevin A. , Schneider Prism S. , Mohtadi Nicholas G. H. , White Neil J. , Bosse Michael J. , Garven Alexandra , Walker Richard E. A. , Sajobi Tolulope T.
Published: February 2020

Background

Injuries and resulting stiffness around joints, especially the elbow, have huge psychological effects by reducing quality of life through interference with normal daily activities such as feeding, dressing, grooming, and reaching for objects. Over the last several years and through numerous research results, the myofibroblast-mast cell-neuropeptide axis of fibrosis had been implicated in post-traumatic joint contractures. Pre-clinical models and a pilot randomized clinical trial (RCT) demonstrated the feasibility and safety of using Ketotifen Fumarate (KF), a mast cell stabilizer to prevent elbow joint contractures. This study aims to evaluate the efficacy of KF in reducing joint contracture severity in adult participants with operately treated elbow fractures and/or dislocations.

Methods/design

A Phase III randomized, controlled, double-blinded multicentre trial with 3 parallel groups (KF 2 mg or 5 mg or lactose placebo twice daily orally for 6 weeks). The study population consist of adults who are at least 18 years old and within 7 days of injury. The types of injuries are distal humerus (AO/OTA type 13) and/or proximal ulna and/or proximal radius fractures (AO/OTA type 2 U1 and/or 2R1) and/or elbow dislocations (open fractures with or without nerve injury may be included). A stratified randomization scheme by hospital site will be used to assign eligible participants to the groups in a 1:1:1 ratio. The primary outcome is change in elbow flexion-extension range of motion (ROM) arc from baseline to 12 weeks post-randomization. The secondary outcomes are changes in ROM from baseline to 6, 24 & 52 weeks, PROMs at 2, 6, 12, 24 & 52 weeks and impact of KF on safety including serious adverse events and fracture healing. Descriptive analysis for all outcomes will be reported and ANCOVA be used to evaluate the efficacy KF over lactose placebo with respect to the improvement in ROM.

Discussion

The results of this study will provide evidence for the use of KF in reducing post-traumatic joint contractures and improving quality of life after joint injuries.

Trial registration

This study was prospectively registered (July 10, 2018) with ClinicalTrials.gov reference: NCT03582176.
Integration, abundance, and transmission of mutations and transgenes in a series of CRISPR/Cas9 soybean lines
Authors: Michno Jean-Michel , Virdi Kamaldeep , Stec Adrian O. , Liu Junqi , Wang Xiaobo , Xiong Yer , Stupar Robert M.
Published: February 2020

Background

As with many plant species, current genome editing strategies in soybean are initiated by stably transforming a gene that encodes an engineered nuclease into the genome. Expression of the transgene results in a double-stranded break and repair at the targeted locus, oftentimes resulting in mutation(s) at the intended site. As soybean is a self-pollinating species with 20 chromosome pairs, the transgene(s) in the T0 plant are generally expected to be unlinked to the targeted mutation(s), and the transgene(s)/mutation(s) should independently assort into the T1 generation, resulting in Mendellian combinations of transgene presence/absence and allelic states within the segregating family. This prediction, however, is not always consistent with observed results.

Results

In this study, we investigated inheritance patterns among three different CRISPR/Cas9 transgenes and their respective induced mutations in segregating soybean families. Next-generation resequencing of four T0 plants and four T1 progeny plants, followed by broader assessments of the segregating families, revealed both expected and unexpected patterns of inheritance among the different lineages. These unexpected patterns included: (1) A family in which T0 transgenes and mutations were not transmitted to progeny; (2) A family with four unlinked transgene insertions, including two respectively located at paralogous CRISPR target break sites; (3) A family in which mutations were observed and transmitted, but without evidence of transgene integration nor transmission.

Conclusions

Genome resequencing provides high-resolution of transgene integration structures and gene editing events. Segregation patterns of these events can be complicated by several potential mechanisms. This includes, but is not limited to, plant chimeras, multiple unlinked transgene integrations, editing of intended and paralogous targets, linkage between the transgene integration and target site, and transient expression of the editing reagents without transgene integration into the host genome.
The influence of cognitive schemas on the mixed anxiety-depressive symptoms of breast cancer patients
Authors: Bredicean Ana Cristina , Crăiniceanu Zorin , Oprean Cristina , Riviș Ioana Alexandra , Papavă Ion , Secoșan Ica , Frandeș Mirela , Giurgi-Oncu Cătălina , Grujic Daciana
Published: February 2020

Background

The surgical treatment of breast cancer involves various psychological consequences, which differ according to individual characteristics. Our study aimed to identify the role that cognitive schemas had in triggering anxiety and depressive symptoms in patients diagnosed with breast cancer that underwent oncological and plastic surgery treatment.

Methods

64 female patients, diagnosed with breast cancer from an Oncology and Plastic Surgery Hospital, were selected to participate in this study between March–June 2018. They were divided into two groups: I. 28 patients who underwent mastectomy surgery; II. 36 patients, who required mastectomy and, subsequently, also chose to undergo breast reconstruction surgery. For the purposes of evaluating a possible change in mental health status, we employed two assessment scales: the Young Cognitive Schema Questionnaire - Short Form 3 (YSQ-S3) and the Romanian version of the Depression Anxiety Stress Scale – 21 (DASS-21R).

Results

Participants who underwent mastectomy and subsequent breast reconstruction surgery employed cognitive schemas that did not generate symptoms of depression or anxiety. In contrast, the cognitive schemas found in women who refused reconstructive breast surgery were significantly correlated with the presence of anxiety-depressive symptoms. The cognitive schema domain of ‘disconnection and rejection’ correlated uncertainly with the presence of anxiety-depressive symptoms for the group with breast reconstruction (Spearman’s ρ = 0.091, p = 0.644), while for the other group the correlation was moderate-strong (Spearman’s ρ = 0.647, p <  0.01). Negative emotional schemas were significantly correlated with the presence of anxiety-depressive symptoms (Spearman’s ρ = 0.598, p <  0.01) in the group of participants without reconstructive surgery.

Conclusion

A correct identification of dysfunctional cognitive schemas and coping mechanisms at the commencement of the combined treatment in breast cancer patients could serve as an indicator for the evolution of their mental health, therefore assisting professionals in establishing the most suitable psychological, psychotherapeutic and psychiatric intervention plan.
Video-based feedback using real consultations for a formative assessment in communication skills
Authors: Dohms M. C. , Collares C. F. , Tibério I. C.
Published: February 2020

Background

Pre-recorded videotapes have become the standard approach when teaching clinical communication skills (CCS). Furthermore, video-based feedback (VF) has proven to be beneficial in formative assessments. However, VF in CCS with the use of pre-recorded videos from real-life settings is less commonly studied than the use of simulated patients.

To explore: 1) perceptions about the potential benefits and challenges in this kind of VF; 2) differences in the CCC scores in first-year medical residents in primary care, before and after a communication program using VF in a curricular formative assessment.

Method

We conducted a pre/post study with a control group. The intervention consisted of VF sessions regarding CCS, performed in a small group with peers and a facilitator. They reviewed clinical consultations pre-recorded in a primary care setting with real patients. Before and after the intervention, 54 medical residents performed two clinical examinations with simulated patients (SP), answered quantitative scales (Perception of Patient-Centeredness and Jefferson Empathy Scale), and semi-structured qualitative questionnaires. The performances were scored by SP (Perception of Patient-Centeredness and CARE scale) and by two blind raters (SPIKES protocol-based and CCOG-based scale). The quantitative data analysis employed repeated-measures ANOVA. The qualitative analysis used the Braun and Clarke framework for thematic analysis.

Results

The quantitative analyses did not reveal any significant differences in the sum scores of the questionnaires, except for the Jefferson Empathy Scale. In the qualitative questionnaires, the main potential benefits that emerged from the thematic analysis of the VF method were self-perception, peer-feedback, patient-centered approach, and incorporation of reflective practices. A challenging aspect that emerged from facilitators was the struggle to relate the VF with theoretical references and the resident’s initial stress to record and watch oneself on video.

Conclusion

VF taken from real-life settings seems to be associated with a significant increase in self-perceived empathy. The study of other quantitative outcomes related to this VF intervention needs larger sample sizes. VF with clinical patients from real healthcare settings appears to be an opportunity for a deeper level of self-assessment, peer-feedback, and reflective practices.
Member species of the Anopheles gambiae complex can be misidentified as Anopheles leesoni
Authors: Dahan-Moss Yael , Hendershot Allison , Dhoogra Minishca , Julius Henry , Zawada Jacek , Kaiser Maria , Lobo Neil F. , Brooke Basil D. , Koekemoer Lizette L.
Published: February 2020

Background

Accurate Anopheles species identification is key for effective malaria vector control. Identification primarily depends on morphological analysis of field samples as well as molecular species-specific identifications. During an intra-laboratory assessment (proficiency testing) of the Anopheles funestus group multiplex PCR assay, it was noted that Anopheles arabiensis can be misidentified as Anopheles leesoni, a zoophilic member of the An. funestus group. The aim of this project was, therefore, to ascertain whether other members of the Anopheles gambiae complex can also be misidentified as An. leesoni when using the standard An. funestus multiplex PCR.

Methods

The An. funestus multiplex PCR was used to amplify DNA from An. gambiae complex specimens. These included specimens from the laboratory colonies and field samples from the Democratic Republic of Congo. Amplified DNA from these specimens, using the universal (UV) and An. leesoni species-specific primers (LEES), were sequence analysed. Additionally, An. leesoni DNA was processed through the diagnostic An. gambiae multiplex PCR to determine if this species can be misidentified as a member of the An. gambiae complex.

Results

Laboratory-colonized as well as field-collected samples of An. arabiensis, An. gambiae, Anopheles merus, Anopheles quadriannulatus, Anopheles coluzzii as well as Anopheles moucheti produced an amplicon of similar size to that of An. leesoni when using an An. funestus multiplex PCR. Sequence analysis confirmed that the UV and LEES primers amplify a segment of the ITS2 region of members of the An. gambiae complex and An. moucheti. The reverse was not true, i.e. the An. gambiae multiplex PCR does not amplify DNA from An. leesoni.

Conclusion

This investigation shows that An. arabiensis, An. gambiae, An. merus, An. quadriannulatus, An. coluzzii and An. moucheti can be misidentified as An. leesoni when using An. funestus multiplex PCR. This shows the importance of identifying specimens using standard morphological dichotomous keys as far as possible prior to the use of appropriate PCR-based identification methods. Should there be doubt concerning field-collected specimens molecularly identified as An. leesoni, the An. gambiae multiplex PCR and sequencing of the internal transcribed spacer 2 (ITS2) can be used to eliminate false identifications.
Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept
Authors: Pistollato Francesca , de Gyves Emilio Mendoza , Carpi Donatella , Bopp Stephanie K. , Nunes Carolina , Worth Andrew , Bal-Price Anna
Published: February 2020

Background

In light of the vulnerability of the developing brain, mixture risk assessment (MRA) for the evaluation of developmental neurotoxicity (DNT) should be implemented, since infants and children are co-exposed to more than one chemical at a time. One possible approach to tackle MRA could be to cluster DNT chemicals in a mixture on the basis of their mode of action (MoA) into ‘similar’ and ‘dissimilar’, but still contributing to the same adverse outcome, and anchor DNT assays to common key events (CKEs) identified in DNT-specific adverse outcome pathways (AOPs). Moreover, the use of human in vitro models, such as induced pluripotent stem cell (hiPSC)-derived neuronal and glial cultures would enable mechanistic understanding of chemically-induced adverse effects, avoiding species extrapolation.

Methods

HiPSC-derived neural progenitors differentiated into mixed cultures of neurons and astrocytes were used to assess the effects of acute (3 days) and repeated dose (14 days) treatments with single chemicals and in mixtures belonging to different classes (i.e., lead(II) chloride and methylmercury chloride (heavy metals), chlorpyrifos (pesticide), bisphenol A (organic compound and endocrine disrupter), valproic acid (drug), and PCB138 (persistent organic pollutant and endocrine disrupter), which are associated with cognitive deficits, including learning and memory impairment in children. Selected chemicals were grouped based on their mode of action (MoA) into ‘similar’ and ‘dissimilar’ MoA compounds and their effects on synaptogenesis, neurite outgrowth, and brain derived neurotrophic factor (BDNF) protein levels, identified as CKEs in currently available AOPs relevant to DNT, were evaluated by immunocytochemistry and high content imaging analysis.

Results

Chemicals working through similar MoA (i.e., alterations of BDNF levels), at non-cytotoxic (IC20/100), very low toxic (IC5), or moderately toxic (IC20) concentrations, induce DNT effects in mixtures, as shown by increased number of neurons, impairment of neurite outgrowth and synaptogenesis (the most sensitive endpoint as confirmed by mathematical modelling) and increase of BDNF levels, to a certain extent reproducing autism-like cellular changes observed in the brain of autistic children.

Conclusions

Our findings suggest that the use of human iPSC-derived mixed neuronal/glial cultures applied to a battery of assays anchored to key events of an AOP network represents a valuable approach to identify mixtures of chemicals with potential to cause learning and memory impairment in children.
Expert panel consensus recommendations for diagnosis and treatment of secondary osteoporosis in children
Authors: Galindo-Zavala Rocío , Bou-Torrent Rosa , Magallares-López Berta , Mir-Perelló Concepción , Palmou-Fontana Natalia , Sevilla-Pérez Belén , Medrano-San Ildefonso Marta , González-Fernández Mª. Isabel , Román-Pascual Almudena , Alcañiz-Rodríguez Paula , Nieto-Gonzalez Juan Carlos , López-Corbeto Mireia , Graña-Gil Jenaro
Published: February 2020

Background

Osteoporosis incidence in children is increasing due to the increased survival rate of patients suffering from chronic diseases and the increased use of drugs that can damage bones.

Recent changes made to the definition of childhood osteoporosis, along with the lack of guidelines or national consensuses regarding its diagnosis and treatment, have resulted in a wide variability in the approaches used to treat this disease.

For these reasons, the Osteogenesis Imperfecta and Childhood Osteoporosis Working Group of the Spanish Society of Pediatric Rheumatology has sounded the need for developing guidelines to standardize clinical practice with regard to this pathology.

Methods

An expert panel comprised of 6 pediatricians and 5 rheumatologists carried out a qualitative literature review and provided recommendations based on evidence, when that was available, or on their own experience.

The level of evidence was determined for each section using the Oxford Centre for Evidence-based Medicine (CEBM) system. A Delphi survey was conducted for those recommendations with an evidence level of IV or V. This survey was sent to all members of the SERPE. All recommendations that had a level of agreement higher or equal to 70% were included.

Results

Fifty-one recommendations, categorized into eight sections, were obtained. Twenty-four of them presented an evidence level 4 or 5, and therefore a Delphi survey was conducted. This was submitted electronically and received a response rate of 40%. All recommendations submitted to the Delphi round obtained a level of agreement of 70% or higher and were therefore accepted.

Conclusion

In summary, we present herein guidelines for the prevention, diagnosis and treatment of secondary childhood osteoporosis based on the available evidence and expert clinical experience. We believe it can serve as a useful tool that will contribute to the standardization of clinical practice for this pathology. Prophylactic measures, early diagnosis and a proper therapeutic approach are essential to improving bone health, not only in children and adolescents, but also in the adults they will become in the future.
Morphometric analysis of the coracoid process and glenoid width: a 3D-CT study
Authors: Jia Yaofei , He Na , Liu Jiaxin , Zhang Guangrui , Zhou Jianping , Wu Ding , Wei Baomin , Yun Xiangdong
Published: February 2020

Background

Data regarding the parameters of the coracoid process and glenoid width are insufficient, and information on gender, age, and ethnic differences in the parameters appear lacking in the Chinese population. This study aimed to investigate the morphometric parameters in the coracoid process and glenoid width.

Methods

Using our institution’s electronic database, we selected 84 patients (55 males and 29 females) who underwent a shoulder computed tomography (CT) scan from January 2017 to May 2018 in this study. Mimics19.0 software was used for three-dimensional (3D) reconstruction of CT and to measure the morphometric parameters of the coracoid process and glenoid width. Subgroup analyses stratified by gender and age were conducted and the parameters were compared with previously published reports. All data were statistically analysed by SPSS23.0 Statistical Package.

Results

A positive and significant relationship between the coracoid process and the glenoid width (R > 0.758, P < 0.01) was found. The midpoint width represents 52% (41–62%) of the glenoid width; the midpoint height, 40% (31–53%) of the glenoid width. Significant differences in all parameters between males and females were noted (P < 0.05). No significant differences among the age groups were observed (P > 0.05), whereas significant differences in almost all parameters between the ethnic groups were observed (P < 0.05).

Conclusion

Our results could supplement the information in the shoulder joint database with morphometric parameters and provide a reference for theoretical research on coracoid osteotomy, which may in turn help surgeons in the evaluation of coracoid process transfer.
The position of the aorta relative to the spine in patients with adult degenerative scoliosis
Authors: Liang Yan , Xu Shuai , Zhao Yongfei , Zhu Zhenqi , Mao Keya , Wang Zheng , Liu Haiying
Published: February 2020

Study design

A retrospective analysis was conducted to analyze the position of the aorta by MRI in patients with adult degenerative scoliosis.

Objective

This study aimed to investigate the relative anatomic positions of the aorta and spine in patients with adult degenerative scoliosis (ADS).

Summary of background data

Aorta injury is a rare complication of spinal surgeries. However, there would be a disastrous consequence once it happened. Therefore, knowing about the position of aorta is of great importance.

Methods

A retrospective analysis was performed in 90 patients with ADS and 132 participants without spine deformity. ADS patients were divided into several groups such as left scoliosis, left scoliosis with thoracolumbar kyphosis, right scoliosis, and right scoliosis with thoracolumbar kyphosis. The aorta-vertebrae angle (α) and aorta-vertebrae distance (d) in each level of T12–L4 were measured by using a Cartesian coordinate system. t test of independent samples was performed, α and d were compared, and Pearson correlation analysis was employed for α, d, and X-ray radiographic measurements.

Result

The changes of α were not statistically significant (P > 0.05) in LS and LKS groups but d (P < 0.05) was longer in LKS group compared with the control group. In the right malformed group, there was no significant change in the angle (P > 0.05) in the abdominal aorta but longer d (P < 0.05) than the normal group. There was longer d in the RKS group compared with the RS group (P < 0.05). Pearson correlation analysis showed that there was a positive correlation between d and TLK (r = 0.439, P < 0.05).

Conclusion

In patients with ADS, a relative normal position is maintained between the aorta and vertebrae. While the aorta is slightly away from the left pedicle in RS patients and farther away in patients with kyphosis, the angle of kyphosis would become bigger and d becomes longer. Therefore, the surgeons should be aware of the changes of the aorta position to avoid the disastrous vessel injuries.
Correction to: Targeting hypoxia in tumor: a new promising therapeutic strategy
Authors: Bosco Maria Carla , Orazi Gabriella D’. , Del Bufalo Donatella
Published: February 2020

In the original publication of this manuscript [1], Fig. 1 contained a typographical error (‘Metabolic’ incorrectly written as ‘Metabolig’).
ncHMR detector: a computational framework to systematically reveal non-classical functions of histone modification regulators
Authors: Hu Shengen , Huo Dawei , Yu Zhaowei , Chen Yujie , Liu Jing , Liu Lin , Wu Xudong , Zhang Yong
Published: February 2020

Recently, several non-classical functions of histone modification regulators (HMRs), independent of their known histone modification substrates and products, have been reported to be essential for specific cellular processes. However, there is no framework designed for identifying such functions systematically. Here, we develop ncHMR detector, the first computational framework to predict non-classical functions and cofactors of a given HMR, based on ChIP-seq data mining. We apply ncHMR detector in ChIP-seq data-rich cell types and predict non-classical functions of HMRs. Finally, we experimentally reveal that the predicted non-classical function of CBX7 is biologically significant for the maintenance of pluripotency.
Linked optical and gene expression profiling of single cells at high-throughput
Authors: Zhang Jesse Q. , Siltanen Christian A. , Liu Leqian , Chang Kai-Chun , Gartner Zev J. , Abate Adam R.
Published: February 2020

Single-cell RNA sequencing has emerged as a powerful tool for characterizing cells, but not all phenotypes of interest can be observed through changes in gene expression. Linking sequencing with optical analysis has provided insight into the molecular basis of cellular function, but current approaches have limited throughput. Here, we present a high-throughput platform for linked optical and gene expression profiling of single cells. We demonstrate accurate fluorescence and gene expression measurements on thousands of cells in a single experiment. We use the platform to characterize DNA and RNA changes through the cell cycle and correlate antibody fluorescence with gene expression. The platform’s ability to isolate rare cell subsets and perform multiple measurements, including fluorescence and sequencing-based analysis, holds potential for scalable multi-modal single-cell analysis.
Carnelian uncovers hidden functional patterns across diverse study populations from whole metagenome sequencing reads
Authors: Nazeen Sumaiya , Yu Yun William , Berger Bonnie
Published: February 2020

Microbial populations exhibit functional changes in response to different ambient environments. Although whole metagenome sequencing promises enough raw data to study those changes, existing tools are limited in their ability to directly compare microbial metabolic function across samples and studies. We introduce Carnelian, an end-to-end pipeline for metabolic functional profiling uniquely suited to finding functional trends across diverse datasets. Carnelian is able to find shared metabolic pathways, concordant functional dysbioses, and distinguish Enzyme Commission (EC) terms missed by existing methodologies. We demonstrate Carnelian’s effectiveness on type 2 diabetes, Crohn’s disease, Parkinson’s disease, and industrialized and non-industrialized gut microbiome cohorts.
Efficacy of electroacupuncture on acute abdomen emergency care: study protocol for a randomized controlled trial
Authors: Chang Yuan Ya , Chiu Chih Wen , Chen Chia Yun , Chang Chin Fu , Lee Tsung Chieh , Lo Lun Chien , Lee Chia Ying , Chang Kai , Chen Po Wei , Hsieh Chang Ju , Chang Yu Jun , Huang Sung Yen
Published: February 2020

Background

Acute abdomen is a common disease in the emergency department (ED) and usually results in huge medical expenditure. To relieve abdominal pain effectively and reduce bed occupancy rate in emergency rooms, electroacupuncture is a practical method in the treatment of abdominal pain.

Methods/design

Five hundred patients will be randomly and evenly divided into experimental and control groups. Both groups should have their basic information taken and their bilateral acupuncture points ( Hegu (LI 4), Neiguan (PC6), Zusanli (ST 36), Shangjuxu (ST37), Xiajuxu (ST39), Taichong (LR3), and Taibai (SP3)) will be intervened by electroacupuncture or vaccaria Seeds, in this clinical study. Electroacupuncture has been introduced to this experiment as an auxiliary technique. The experimental group will receive real electroacupuncture, but the control group will receive a placebo electroacupuncture in which transcutaneous electrical nerve stimulation will not be turned on. After the intervention, we will evaluate the difference in abdominal pain, the length of stay at the emergent observation ward, and the proportion of revisits with abdominal pain.

Discussion

In Taiwan, medical expenditure is increasing annually because of the higher bed occupancy caused by acute abdominal pain in the hospital. We expect that the combined treatment of electroacupuncture and modern medical treatment will not only reduce bed occupancy and the length of ED stay but also effectively decrease the rate of readmission and revisits by 72 h. By means of electroacupuncture, the spiraling cost of health care can eventually be reduced.

Trial registration

ClinicalTrials.gov identifier: NCT03199495. Registered on 27 June 2017.
In silico evolution of Aspergillus niger organic acid production suggests strategies for switching acid output
Authors: Upton Daniel J. , McQueen-Mason Simon J. , Wood A. Jamie
Published: February 2020

Background

The fungus Aspergillus niger is an important industrial organism for citric acid fermentation; one of the most efficient biotechnological processes. Previously we introduced a dynamic model that captures this process in the industrially relevant batch fermentation setting, providing a more accurate predictive platform to guide targeted engineering. In this article we exploit this dynamic modelling framework, coupled with a robust genetic algorithm for the in silico evolution of A. niger organic acid production, to provide solutions to complex evolutionary goals involving a multiplicity of targets and beyond the reach of simple Boolean gene deletions. We base this work on the latest metabolic models of the parent citric acid producing strain ATCC1015 dedicated to organic acid production with the required exhaustive genomic coverage needed to perform exploratory in silico evolution.

Results

With the use of our informed evolutionary framework, we demonstrate targeted changes that induce a complete switch of acid output from citric to numerous different commercially valuable target organic acids including succinic acid. We highlight the key changes in flux patterns that occur in each case, suggesting potentially valuable targets for engineering. We also show that optimum acid productivity is achieved through a balance of organic acid and biomass production, requiring finely tuned flux constraints that give a growth rate optimal for productivity.

Conclusions

This study shows how a genome-scale metabolic model can be integrated with dynamic modelling and metaheuristic algorithms to provide solutions to complex metabolic engineering goals of industrial importance. This framework for in silico guided engineering, based on the dynamic batch growth relevant to industrial processes, offers considerable potential for future endeavours focused on the engineering of organisms to produce valuable products.
Unstimulated whole saliva flow for diagnosis of primary Sjögren’s syndrome: time to revisit the threshold?
Authors: Lacombe Valentin , Lacout Carole , Lozac’h Pierre , Ghali Alaa , Gury Aline , Lavigne Christian , Urbanski Geoffrey
Published: February 2020

Background

Unstimulated whole saliva (UWS) flow rate is one of the ACR/EULAR 2016 criteria for primary Sjögren’s syndrome (pSS). With a single threshold of ≤ 0.1 mL/min, UWS flow does not take into account the age- and sex-related physiological variations. Furthermore, it has a low sensitivity for the diagnosis of pSS (about 50%), contrary to the screening test for xerophthalmia, Schirmer’s test (sensitivity of about 70%). We aimed to identify UWS thresholds allowing better performances for a screening test for pSS comparable to Schirmer’s test, and considering age- and sex-related variations.

Methods

A prospective cohort of 185 patients with oral and/or ocular dryness was classified into 3 groups: men, women < 50 (< 50 years old), and women ≥ 50 (≥ 50 years old). The diagnostic performances of UWS flow rate in these groups were compared in terms of sensitivity, specificity, positive and negative predictive values, and ROC curves. The identification of thresholds that optimize diagnostic performances was carried out using Youden’s index.

Results

The diagnostic performances of UWS flow rate varied according to age and sex. UWS had poor diagnostic performances whatever the threshold in the women ≥ 50 group. The threshold of 0.2 mL/min had a sensitivity of ≥ 70% and a specificity of ≥ 50% in both men and women < 50 groups. In the whole population and compared to the current cutoff, a threshold of 0.2 mL/min increased sensitivity (+ 19.8%) and positive (+ 2.3%) and negative (+ 7.0%) predictive values, with a better specificity (65.2%) than Schirmer’s test.

Conclusion

For objective assessment of xerostomia, raising the threshold of the UWS flow rate to 0.2 mL/min would optimize its screening performances for pSS.