bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic injury caused by esophageal foreign body-case reports of 3 patients and literature review
Authors: Zeng Liping , Shu Wenbo , Ma Honghai , Hu Jian
Published: June 2020

Objectives:

Ingestion of a foreign body can cause different degrees of damage to esophagus, and several complications are potentially life-threatening if not properly handled. The aortic injury caused by a perforating esophageal foreign body is rare but lethal. The optimal management still remains controversial. The purpose of this report is to describe our experience in the management of the aortic injury caused by esophageal foreign body ingestion.

Methods:

Between January 2015 and December 2015, we retrospectively enrolled cases of esophageal perforation involving the aorta by foreign body. The general parameters, esophageal foreign body, types of aortic injury, treatment, and outcome were analyzed. Additionally, we reviewed the literature of the management of esophageal perforation involving the aorta caused by foreign bodies. The study was approved by the ethics committee of the First Affiliated Hospital, College of Medicine, Zhejiang University, and the need for informed consent was waived (Quick review 2019, No. 609).

Results:

Three cases of esophageal perforation involving the aorta by foreign body was selected in the study. Two male and 1 female patients (range, 51–58 years old) with the aorta involvement caused by a perforating foreign body in the esophagus in 3 forms were identified, including 1 patient with mycotic aortic pseudoaneurysm, 1 patient with aortoesophageal fistula and 1 patient with the aortic intramural hematoma. One patient died of the rupture of the pseudoaneurysm during the preparation of the surgery. The other 2 patients were cured with a multidisciplinary approach, which is an urgent thoracic endovascular aortic repair followed by mediastinal debridement/drainage or endoscopic retrieval. Two of 3 patients were survived until now.

Conclusion:

The management of the aortic injury caused by esophageal foreign body injury is challenging. Early diagnosis and multidisciplinary management is crucial.
Pulmonary sclerosing pneumocytoma in an 18-year-old male patient
Authors: Le Huu Y , Pham Dinh Phuc , Nguyen Khac Tuyen , Hoang Van Ai , Trinh The Son , Do Quyet
Published: June 2020

Rationale:

Pulmonary sclerosing pneumocytoma (PSP) is a rare benign tumor of the lung, mostly presented in Asian middle-aged women. Initially, it was considered as a vascular origin tumor, but then research evidence showed that it was derived from natural epithelial tissue. On imaging, this tumor may be found as a solitary well-circumscribed lung parenchymal lesion, and is often located in juxtapleural or juxtafissural positions. On histopathology, it consists of cuboidal surface cells and stromal round cells, both of which are positive for thyroid transcription factor-1. Here we report a case of a young PSP male patient and review the relevant literature in order to improve our understanding of this disease.

Patient concerns:

An 18-year-old man was referred to our hospital after accidentally finding a lesion on chest X-ray. Contrast-enhanced computed tomography showed a soft tissue mass with homogeneous enhancement in the left lower lobe posterior segment.

Diagnoses:

The diagnosis of PSPs was confirmed by histopathological examination.

Interventions and outcomes:

The patient underwent a thoracoscopic wedge resection and was followed-up after that. One month later, he had good performance status with no recurrent tumors.

Lessons:

PSP in a young man is really uncommon, and is confused with malignant tumors. A histopathological examination is considered as the diagnostic gold standard for this uncommon tumor. Surgery is the main treatment.
Tarsal tunnel syndrome caused by posterior facet talocalcaneal coalition
Authors: Hong Chang Hwa , Lee Hong Seop , Lee Won Seok , Kim Hyun Kwon , Won Sung Hun , Yeo Eui Dong , Jung Ki Jin , Ryu Aeli , Kang Jin Ku , Lee Dhong Won , Kim Woo Jong
Published: June 2020

Rationale:

Tarsal tunnel syndrome (TTS) is a compressive neuropathy of the posterior tibial nerve and its branches. Tarsal coalition is defined as a fibrous, cartilaginous, or osseous bridging of 2 or more tarsal bones. TTS with tarsal coalition is uncommon. Here, we present a rare example of successful surgical management of TTS with posterior facet talocalcaneal coalition.

Patient concerns:

A 74-year-old woman presented with hypoesthesia, numbness, and an intermittent tingling sensation on the plantar area over the right forefoot to the middle foot area. The hypoesthesia and paresthesia of the right foot began 6 years previously and were severe along the lateral plantar aspect. The symptoms were mild at rest and increased during daily activities. Tinel sign was positive along the posteroinferior aspect of the medial malleolus.

Diagnosis:

Lateral ankle radiography showed joint-space narrowing and sclerotic bony changes with a deformed C-sign and humpback sign. Oblique coronal and sagittal computed tomography revealed an irregular medial posterior facet, partial coalition, narrowing, and subcortical cyst formation of the posterior subtalar joint. Magnetic resonance imaging showed an abnormal posterior talocalcaneal coalition compressing the posterior tibia nerve. Electromyography and nerve conduction velocity studies were performed, and the findings indicated that there was an incomplete lesion of the right plantar nerve, especially of the lateral plantar nerve, around the ankle level.

Interventions:

Surgical decompression was performed. Intraoperatively, the lateral plantar nerve exhibited fibrotic changes and tightening below the posterior facet talocalcaneal coalition. The coalition was excised, and the lateral plantar nerve was released with soft-tissue dissection.

Outcomes:

The patient's symptoms of tingling sensation and hypoesthesia were almost relieved at 4 months postoperatively, but she complained of paresthesia with an itching sensation when the skin of the plantar area was touched. The paresthesia had disappeared almost completely at 8 months after surgery. She had no recurrence of symptoms at the 1-year follow-up.

Lessons:

The TTS with tarsal coalition is rare. Supportive history and physical examination are essential for diagnosis. Plain radiographs and computed tomography or magnetic resonance imaging are helpful to determine the cause of TTS and verify the tarsal coalition. After diagnosis, surgical excision of the coalition may be appropriate for management with a good outcome.
Community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus in a Chinese adult
Authors: Xia Huan , Gao Jinying , Xiu Ming , Li Dan
Published: June 2020

Rationale:

Methicillin-resistant Staphylococcus aureus (MRSA) has been established as an important cause of severe community-acquired pneumonia (CAP) with very high mortality. Panton–Valentine leukocidin (PVL) producing MRSA has been reported to be associated with necrotizing pneumonia and worse outcome. The incidence of community-acquired MRSA (CA-MRSA) pneumonia is very low, as only a few CA-MRSA pneumonia cases were reported in the last few years. We present a case of severe CAP caused by PVL-positive MRSA with ensuing septic shock.

Patient concerns:

A 68-year-old male with no concerning medical history had developed a fever that reached 39.0°C, a productive cough that was sustained for 5 days, and hypodynamia. He was treated with azithromycin and alexipyretic in a nearby clinic for 2 days in which the symptoms were alleviated. However, 1 day later, the symptoms worsened, and he was taken to a local Chinese medicine hospital for traditional medicine treatment. However, his clinical condition deteriorated rapidly, and he then developed dyspnea and hemoptysis.

Diagnosis:

CA-MRSA pneumonia and septic shock. The sputum culture showed MRSA. Polymerase chain reaction of MRSA isolates was positive for PVL genes.

Interventions:

Mechanical ventilation, fluid resuscitation, and antibiotic therapy were performed. Antibiotic therapy included mezlocillin sodium/sulbactam sodium, linezolid, and oseltamivir.

Outcomes:

He died after 12 hours of treatment.

Lessons:

This is a report of severe pneumonia due to PVL-positive CA-MRSA in a healthy adult. CA-MRSA should be considered a pathogen of severe CAP, especially when combined with septic shock in previously healthy individuals.
Primary signet ring cell carcinoma with tubular adenoma of the rectum
Authors: Yang Yong-Ping , Yu Ling-Yun , Shi Jian , Li Jian-Nan , Wang Xin-Yu , Liu Tong-Jun
Published: June 2020

Rationale:

Among the various forms of colorectal carcinomas, primary signet ring cell carcinoma (SRCC) of rectum is infrequent. Primary SRCC with adenoma is even rarer. Due to its low morbidity and lack of obvious manifestations at early stages, it is difficult to make an early diagnosis and perform surgical intervention in time. Herein, we reported a case of primary SRCC with tubular adenoma of rectum and also performed a review of the literature of such cases, in hopes of expanding the general understanding regarding such cases.

Patient concerns:

A 61-year-old male patient presented with rectal bleeding for 1 week.

Diagnoses:

A neoplasm could be palpated through a rectal examination, with a size of 4.0 cm by 3.0 cm, at a distance of 5 cm from the anal edge. Magnetic resonance imaging examination and colonoscopies were performed to confirm the finding, and 4 tissue specimens were obtained for histopathologic biopsy. The result of biopsy was high-grade intraepithelial neoplasia with an adenoma component.

Interventions:

Surgical resection was performed, and histopathologic and immunohistochemical staining examination of the resection confirmed the diagnosis of SRCC with tubular adenoma.

Outcomes:

The patient was discharged from hospital 12 days postsurgery, without any complications. Further chemotherapy and supportive treatments were suggested to him and will be followed at a local hospital.

Lessons:

Primary rectal SRCC has a rather low morbidity. Furthermore, a rectal SRCC with adenoma which was presenting in this case is even more rare. Besides lack of clinical characters, delay of diagnosis and treatment frequently occur. So far, a surgical procedure has still been one of the most effective treatments. Considering of metastasis and the poor prognosis, early diagnosis, in-time radical resection, and a comprehensive followed treatment are recommended for a higher 5-year overall survival.
Association of S100B 3’UTR polymorphism with risk of chronic heart failure in a Chinese Han population
Authors: Chen Yuewu , Chen Xianghong , Yao Maozhong , Chen Lei , Chen Weiwei , Liu Xianxia
Published: June 2020

To study the correlation between single nucleotide polymorphism (SNP) of the 3′ untranslated region (UTR) rs9722 locus inS100Band the risk of chronic heart failure (CHF), plasma levels of S100B protein as well as has-miR-340-3p in a Chinese Han population.

A total of 215 patients with CHF (124 ischemic cardiomyopathy (ICM) and 91 dilated cardiomyopathy (DCM)) and 215 healthy controls were recruited to analyze theS100Brs9722 genotype by Sanger sequencing. The levels of hsa-miR-340-3p in the plasma were detected by RT-PCR, and S100B levels were detected by ELISA.

The risk of CHF inS100Brs9722 locus T allele carriers was 4.24 times higher than that in those with the C allele (95% CI: 2.84–6.33,P < .001). The association ofS100Brs9722 locus SNP with ICM and DCM risk was not affected by factors such as age, gender, and body mass index (BMI). The levels of plasma S100B and hsa-miR-340-3p in patients with ICM and DCM were significantly higher than those in the control group (P < .001). There was no significant difference in plasma S100B levels between patients with ICM and DCM (P > .05). Among ICM, DCM, and control subjects, TT genotype carriers had the highest levels of plasma S100B and hsa-miR-340-3p, followed by the CT genotype and TT genotype, and the difference was statistically significant (P < .05). Plasma hsa-miR-340-3p levels were positively correlated with S100B levels in the control subjects and patients with ICM and DCM.

TheS100Brs9722 locus SNP is associated with CHF risk in a Chinese Han population.
Plasma of Acute Lymphoblastic Leukemia Patients React to the Culture of a Mycovirus Containing Aspergillus flavus
Authors: Tebbi Cameron K. , Badiga Aruna , Sahakian Eva , Arora Anshul I. , Nair Sajitha , Powers John J. , Achille Alex N. , Jaglal Michael V. , Patel Saumil , Migone Felicia
Published: June 2020

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and is also seen in adults. Currently, no plasma-based test for the detection of ALL is available. We have cultured the home of a patient with ALL and isolated a mycovirus containingAspergillus flavus. This culture was subjected to electron microscopy, purification, and mass spectrometry. Using enzyme-linked immunosorbent assay technique, plasma of patients with ALL and long-term survivors of this disease were tested for antibodies, utilizing supernatant of the culture of this organism. The results were compared with 3 groups of controls, including healthy individuals, patients with sickle cell disease, and solid tumors. Using electron microscopy, the isolatedA. flavuscontained mycovirus particles. In chemical analysis, this organism did not produce any aflatoxin. Using an enzyme-linked immunosorbent assay technique, the supernatant of the culture of the mycovirus containingA. flavuscould differentiate ALL patients from each group of controls (P<0.001). These studies provide a new technique for the detection of ALL and may add information for future research regarding leukemogenesis.
Can Pulmonary Function Testing Predict the Functional Outcomes of Poststroke Patients?
Authors: Jeong Yoon Jeong , Kim Gyu Seong , Jeong Yeon Gyu , Moon Hyun Im
Published: June 2020

Objective

Patients with stroke may experience pulmonary dysfunction that reduces movement of the muscles involved in postural control and respiration. This study aimed to evaluate the relationship between postural control and respiratory muscle strength using pulmonary function testing. We sought to identify the respiratory function parameters that predict the functional outcomes patients with stroke at discharge.

Design

We prospectively recruited 52 patients with first-ever stroke within 6 mos of onset. Peak cough flow, maximal inspired pressure, maximal expired pressure, forced vital capacity, and forced expiratory volume in 1 sec were measured at baseline and after 4 wks of rehabilitation. The primary outcomes were trunk balance measured using the Trunk Impairment Scale and functional outcomes measured using the Berg Balance Scale and functional independence measure.

Results

The initial peak cough flow, forced vital capacity, and forced expiratory volume in 1 sec values correlated with the Trunk Impairment Scale scores at admission; only the initial peak cough flow and forced vital capacity were predictive factors for the final Trunk Impairment Scale score. Multivariable linear regression analysis showed that the initial peak cough flow was a significant predictive factor for follow-up test scores at discharge: Berg Balance Scale (P < 0.001) and functional independence measure (P < 0.025).

Conclusion

Initial respiratory function was significantly correlated with trunk balance and the functional outcomes.
Evaluation of the International Classification of Diseases-11 chronic pain classification: study protocol for an ecological implementation field study in low-, middle-, and high-income countries
Authors: Korwisi Beatrice , Treede Rolf-Detlef , Rief Winfried , Barke Antonia
Published: June 2020

Introduction:

The purpose of the present ecological implementation field study is to evaluate the new classification of chronic pain as implemented in the 11th revision of the International Classification of Diseases (ICD-11) with regard to clinical utility and interrater reliability. To evaluate the classification in a variety of settings, the study will be implemented in different low-, middle-, and high-income countries.

Methods:

The study will be conducted in 2 phases. Participating pain clinics of the first phase are located in India, Cuba, and New Zealand. Two or more clinicians per study center will use the ICD-11 classification of chronic pain to diagnose 75 to 100 consecutive new chronic pain patients per center. A structured classification algorithm will guide the diagnostic process. Interrater reliability will be analyzed for the first 20 consecutive new patients per center. Before the coding, a training workshop will introduce the clinicians to the new classification. The main outcome parameter of the ecological implementation field study is clinical utility. More specifically, this entails clinical utility ratings, interrater reliability, as well as the exhaustiveness of the classification and the mutual exclusiveness of the new chronic pain categories. Differences between countries with different cultural backgrounds and income levels will be analyzed.

Perspective:

The ecological implementation field study presented here will be implemented in several countries with different income levels. This increases the generalizability of the results and allows initial insight into the global applicability of the new chronic pain classification. A positive evaluation can facilitate the implementation of the classification.
Keeping the Finger on the Pulse: Cardiac Arrhythmias in Hand Surgery Using Local Anesthesia with Adrenaline
Authors: Farkash Uri , Herman Amir , Kalimian Tal , Segal Ohad , Cohen Amir , Laish-Farkash Avishag
Published: June 2020

Background:

The wide-awake local anesthesia no tourniquet (WALANT) technique in hand surgery is gaining popularity. The authors aimed to prospectively analyze the frequency and type of arrhythmias in patients undergoing hand surgery under local anesthesia and to examine whether the addition of adrenaline affects their incidence.

Methods:

Adult patients undergoing hand surgery under local anesthesia were randomized into two groups: group 1, local anesthesia with lidocaine and tourniquet; and group 2, local anesthesia with lidocaine and adrenaline (WALANT). Patients with a history of arrhythmias were excluded. Patients were connected to Holter electrocardiographic monitoring before surgery and up until discharge. The records were blindly compared between the groups regarding types of arrhythmias, and frequency and timing relative to injection and tourniquet inflation.

Results:

One hundred two patients were included between August of 2018 and August of 2019 (age, 59.7 ± 13.6 years; 71 percent women; 51 in each group). No major arrhythmia (ventricular tachycardia, ventricular fibrillation, atrial fibrillation) or arrhythmia-related symptoms were recorded for either group. Minor arrhythmias (including atrial premature beats, ventricular premature beats, and atrial tachycardia) were recorded in 68 patients (66.6 percent), with no statistical difference between the groups. There were three patients with minor arrhythmias during inflation of the tourniquet. Patients in the adrenaline group had 2 percent sinus tachycardia during injection and 4 percent asymptomatic bradyarrhythmias. These findings do not require any further treatment.

Conclusions:

The authors’ results show that hand operations using WALANT technique in patients with no history of arrhythmia are safe and are not arrhythmogenic; therefore, there is no need for routine perioperative continuous electrocardiographic monitoring.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Understanding Factors Influencing Quality Improvement Capacity Among Ambulatory Care Practices Across the MidSouth Region: An Exploratory Qualitative Study
Authors: Varley Allyson L. , Kripalani Sunil , Spain Thomas , Mixon Amanda S. , Acord Erin , Rothman Russell , Limper Heather M.
Published: June 2020

Background and Objective:

Success in choosing and implementing quality metrics, necessary in a value-based care model, depends on quality improvement (QI) capacity—the shared knowledge, understanding, and commitment to continuous improvement. We set out to explore factors influencing QI capacity among ambulatory care practices in the MidSouth Practice Transformation Network.

Methods:

As part of network participation, 82 practices submitted a plan for implementing self-selected quality metrics. This plan asked practices to identify factors that would assist or impede successful implementation of interventions to meet metric targets. We used a qualitative thematic analysis approach to explore barriers and facilitators to developing QI capacity among ambulatory care practices.

Results:

Recurrent facilitators included external change agents, protected time for QI, a framework for improvement, and infrastructure including electronic health record (EHR) capabilities. Frequent barriers included lack of QI knowledge, lack of time, frequent staff turnover, inadequate EHR capabilities, lack of an internal change agent, and a belief that performance was outside of the practice's control.

Conclusion:

These findings provide insight into factors influencing the adoption and implementation of QI metrics across a diverse group of ambulatory care practices and suggest that targeting the Inner Setting of practices may be an appropriate approach for developing practice-level QI capacity, which is necessary for success in a value-based care model.
The Importance of Thiopurine S-Methyltransferase Gene Analysis Before Azathioprine Therapy
Authors: Gürbüz Gürkan , Edizer Selvinaz , Yılmaz Ünsal , Ünalp Aycan
Published: June 2020

Neuromyelitis optica is an inflammatory central nervous system syndrome associated with serum aquaporin-4 IgG antibody. Optic nerve and spinal cord involvement is typical. We report a 9-year-old girl with a diagnosis of neuromyelitis optica, who developed azathioprine-induced pancytopenia that was subsequently found to be caused by thiopurine-methyltransferase mutation.
Huperzine A inhibits heroin-seeking behaviors induced by cue or heroin priming in rats
Authors: Ma Baomiao , Cai Yujia , Zhang Xin , Wang Fangmin , Zhuang Dingding , liu Huifeng , Liu Yu , Zhou Wenhua
Published: June 2020

Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50 μg/kg/infusion) under the fixed ratio 1 schedule for 14 days and then drug-seeking was extinguished for 10 days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming. Acute treatment with huperzine A at dose from 0.05 to 0.2 mg/kg potently and dose-dependently suppressed the cue- and heroin-induced reinstatement of heroin-seeking behavior following extinction. Huperzine A at these doses failed to alter either heroin rewarding effect or spontaneous locomotion activity. The study demonstrated that acute treatment with huperzine A inhibited heroin-seeking behavior, suggesting that huperzine A may be used as an adjuvant treatment for heroin relapse and addiction.
Extinction rates of non-avian dinosaur species are uncorrelated with the rate of evolution of phylogenetically informative characters
Authors: Crouch Nicholas M. A.
Published: June 2020

Determining the factors that shape temporal variation in species diversity is an ongoing challenge. One theory is that species exhibiting lower rates of phenotypic evolution should be more likely to go extinct as they are more susceptible to changing environmental conditions. However, little work has been done to assess whether this process shapes comparatively few lineages, or is a common mechanism shaping changes in species diversity. Here, I analyse the correlation between rates of morphological evolution and extinction at the species level using six published morphological matrices of non-avian dinosaurs. I find no correlation between the two rates at different taxonomic scales, suggesting that extinction in these groups is better described by other factors. As there is a strong prior expectation of correlated rates, I suggest that traditional morphological matrices are inappropriate for addressing this question and that the characters governing lineage persistence are independent of those with high phylogenetic signal. This may be comprehensively determined with continued development of phenomic matrices.
Inferring generation-interval distributions from contact-tracing data
Authors: Park Sang Woo , Champredon David , Dushoff Jonathan
Published: June 2020

Generation intervals, defined as the time between when an individual is infected and when that individual infects another person, link two key quantities that describe an epidemic: the initial reproductive number,Rinitial, and the initial rate of exponential growth,r. Generation intervals can be measured through contact tracing by identifying who infected whom. We study how realized intervals differ from ‘intrinsic’ intervals that describe individual-level infectiousness and identify both spatial and temporal effects, including truncating (due to observation time), and the effects of susceptible depletion at various spatial scales. Early in an epidemic, we expect the variation in the realized generation intervals to be mainly driven by truncation and by the population structure near the source of disease spread; we predict that correcting realized intervals for the effect of temporal truncation butnotfor spatial effects will provide the initial forward generation-interval distribution, which is spatially informed and correctly linksrandRinitial. We develop and test statistical methods for temporal corrections of generation intervals, and confirm our prediction using individual-based simulations on an empirical network.
Zeroth-order finite similitude and scaling of complex geometries in biomechanical experimentation
Authors: Ochoa-Cabrero Raul , Alonso-Rasgado Teresa , Davey Keith
Published: June 2020

Scaled experimentation provides an alternative approach to full-scale biomechanical (and biological) testing but is known to suffer from scale effects, where the underlying system behaviour changes with scale. This phenomenon is arguably the overriding principal obstacle to the many advantages that scaled experimentation provides. These include reduced costs, materials and time, along with the eschewal of ethical compliance concerns with the application of substitute artificial materials as opposed to the use of hazardous biological agents. This paper examines the role scale effects play in biomechanical experimentation involving strain measurement and introduces a formulation that overtly captures scale dependencies arising from geometrical change. The basic idea underpinning the new scaling approach is the concept of space scaling, where a biomechanical experiment is scaled by the metaphysical mechanism of space contraction. The scaling approach is verified and validated with finite-element (FE) models and actual physical-trial experimentation using digital image correlation software applied to synthetic composite bone. The experimental design aspect of the approach allows for the selection of three-dimensional printing materials for trial-space analysis in a complex pelvis geometry. This aspect takes advantage of recent advancements in additive manufacturing technologies with the objective of countering behavioural distorting scale effects. Analysis is carried out using a laser confocal microscope to compare the trial and physical space materials and subsequently measured using surface roughness parameters. FE models were constructed for the left hemipelvis and results show similar strain patterns (average percentage error less than 10%) for two of the three trial-space material combinations. A Bland–Altman statistical analysis shows a good agreement between the FE models and physical experimentation and a good agreement between the physical-trial experimentation, providing good supporting evidence of the applicability of the new scaling approach in a wider range of experiments.
miRbiom: Machine-Learning on Bayesian Causal Nets of RBP-miRNA interactions successfully predicts miRNA profiles
Authors: Pradhan Upendra Kumar , Sharma Nitesh Kumar , Kumar Prakash , Kumar Ashwani , Gupta Sagar , Shankar Ravi
Published: June 2020

Formation of mature miRNAs and their expression is a highly controlled process. It is very much dependent upon the post-transcriptional regulatory events. Recent findings suggest that several RNA binding proteins beyond Drosha/Dicer are involved in the processing of miRNAs. Deciphering of conditional networks for these RBP-miRNA interactions may help to reason the spatio-temporal nature of miRNAs which can also be used to predict miRNA profiles. In this direction, >25TB of data from different platforms were studied (CLIP-seq/RNA-seq/miRNA-seq) to develop Bayesian causal networks capable of reasoning miRNA biogenesis. The networks ably explained the miRNA formation when tested across a large number of conditions and experimentally validated data. The networks were modeled into an XGBoost machine learning system where expression information of the network components was found capable to quantitatively explain the miRNAs formation levels and their profiles. The models were developed for 1,204 human miRNAs whose accurate expression level could be detected directly from the RNA-seq data alone without any need of doing separate miRNA profiling experiments like miRNA-seq or arrays. A first of its kind, miRbiom performed consistently well with high average accuracy (91%) when tested across a large number of experimentally established data from several conditions. It has been implemented as an interactive open access web-server where besides finding the profiles of miRNAs, their downstream functional analysis can also be done. miRbiom will help to get an accurate prediction of human miRNAs profiles in the absence of profiling experiments and will be an asset for regulatory research areas. The study also shows the importance of having RBP interaction information in better understanding the miRNAs and their functional projectiles where it also lays the foundation of such studies and software in future.
Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis
Authors: Mok Chee Keng , Ng Yan Ling , Ahidjo Bintou Ahmadou , Hua Lee Regina Ching , Choy Loe Marcus Wing , Liu Jing , Tan Kai Sen , Kaur Parveen , Chng Wee Joo , Wong John Eu-Li , Wang De Yun , Hao Erwei , Hou Xiaotao , Tan Yong Wah , Mak Tze Minn , Lin Cui , Lin Raymond , Tambyah Paul , Deng JiaGang , Hann Chu Justin Jang
Published: June 2020

COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.
Responsibility for vitamin D supplementation of elderly care home residents in England: falling through the gap between medicine and food
Authors: Williams Joseph , Williams Carol
Published: June 2020

Introduction

Vitamin D supplements are recommended for elderly care home residents with little sunlight exposure. However, their use in care homes is limited and vitamin D deficiency in residents is widespread. This study aimed to understand perceived responsibility for the vitamin D status of residents and the determinants of current practice around supplementation.

Methods

Thirteen semi-structured interviews were conducted with key informants in two areas of Southern England including care home managers, general practitioners (GPs) and public health professionals. Interviews were audio recorded and transcribed verbatim.

Results

Inductive thematic analysis identified four themes – medical framing; professional and sector boundaries; awareness of national guidance; and ethical and practical issues. Vitamin D supplements were not routinely given to residents, and most participants, including the GPs, believed the vitamin D status of residents was the responsibility of the GP. Care home managers felt unable to make decisions about vitamin D and vulnerable to suggestions of wrongdoing in administering over-the-counter vitamin tablets. This results in vitamin D requiring prescription by medical professionals and few care home residents receiving vitamin D supplements.

Conclusion

The medical framing of vitamin D supplements in care homes is a practical barrier to residents receiving them and is out of step with public health recommendations. Vitamin D levels in care home residents could be improved through universal supplementation. This requires a paradigm shift so that vitamin D is understood as a protective nutrient as well as a medicine, and a public health as well as a medical responsibility. The failure to ensure vitamin D adequacy of residents may emerge as a factor in the spread and severity of COVID-19 in care homes and gives increased urgency to addressing this issue.

KEY MESSAGES

What is already known about the subject?

Nutrition guidelines recommend elderly care home residents take vitamin D supplements as a preventative measure. This is rarely implemented in practice and vitamin D inadequacy is widespread.

What are the new findings?

Medical framing of vitamin D in the care sector puts elderly residents at risk of vitamin D deficiency. Vitamin D supplements are perceived as medicines requiring an individual prescription and diagnosis by a medical professional. This is out of step with public health recommendations. The system’s failure to protect the vitamin D status of the elderly in care homes may have implications in the context of COVID-19.

How might these results change the focus of research or practice?

Prompt a review of current guidelines and regulations in England to establish responsibility for implementing public health recommendations on vitamin D supplementation in care homes. Further research on feasibility of implementation strategies is needed.
Speeding up eQTL scans in the BXD population using GPUs
Authors: Trotter Chelsea , Kim Hyeonju , Farage Gregory , Prins Pjotr , Williams Robert W. , Broman Karl W. , Sen Śaunak
Published: June 2020

The BXD recombinant inbred strains of mice are an important reference population for systems biology and genetics that have been full sequenced and deeply phenotyped. To facilitate inter-active use of genotype-phenotype relations using many massive omics data sets for this and other segregating populations, we have developed new algorithms and code that enables near-real time whole genome QTL scans for up to 1 million traits. By using easily parallelizable operations including matrix multiplication, vectorized operations, and element-wise operations, we have decreased run-time to a few seconds for large transcriptome data sets. Our code is ideal for interactive web services, such asGeneNetwork.org. We used parallelization of different CPU threads as well as GPUs. We found that the speed advantage of GPUs is dependent on problem size and shape (number of cases, number of genotypes, number of traits). Our results provide a path for speeding up eQTL scans using linear mixed models (LMMs). Our implementation is in the Julia programming language.
Artificial light at night amplifies seasonal relapse of haemosporidian parasites in a widespread songbird
Authors: Becker Daniel J. , Singh Devraj , Pan Qiuyun , Montoure Jesse D. , Talbott Katherine M. , Wanamaker Sarah , Ketterson Ellen D.
Published: June 2020

Urban habitats can shape interactions between hosts and parasites by altering not only exposure rates but also within-host processes. Artificial light at night is common in urban environments, and chronic exposure can impair host immunity in ways that may increase infection. However, studies of causal links between this stressor, immunity, and infection dynamics are rare, particularly in migratory animals. Here, we experimentally tested how artificial light at night affects cellular immunity and haemosporidian parasite intensity across the annual cycle of migrant and resident subspecies of the dark-eyed junco (Junco hyemalis). We monitored an experimental group exposed to light at night and a control group under natural light/dark cycles as they passed through short days simulating early spring to longer days simulating the breeding season, followed by fall migration. Using generalized additive models, we show that artificial light at night increased inflammation, and leukocyte counts were greatest in early spring and fall. At the start of the experiment, few birds had active infections based on microscopy, but PCR revealed many birds had chronic infections. Artificial light at night increased parasitemia across the annual cycle, with strong peaks in spring and fall that were largely absent in control birds. As birds were kept in indoor aviaries to prevent vector exposure, this increased parasitemia indicates relapse of chronic infection during costly life history stages (i.e., reproduction). Although the immunological and parasitological time series were in phase for control birds, cross-correlation analyses also revealed artificial light at night desynchronized leukocyte profiles and parasitemia, which could suggest a general exaggerated inflammatory response. Our study shows how a common anthropogenic influence can shape within-host processes to affect infection dynamics.
Connectome spectral analysis to track EEG task dynamics on a subsecond scale
Authors: Glomb Katharina , Queralt Joan Rue , Pascucci David , Defferrard Michaël , Tourbier Sebastien , Carboni Margherita , Rubega Maria , Vulliemoz Serge , Plomp Gijs , Hagmann Patric
Published: June 2020

We present an approach for tracking fast spatiotemporal cortical dynamics in which we combine white matter connectivity data with source-projected electroencephalographic (EEG) data. We employ the mathematical framework ofgraph signal processingin order to derive the Fourier modes of the brain structural connectivity graph, or “network harmonics”. These network harmonics are naturally ordered by smoothness. Smoothness in this context can be understood as the amount of variation along the cortex, leading to a multi-scale representation of brain connectivity. We demonstrate that network harmonics provide a sparse representation of the EEG signal, where, at certain times, the smoothest 15 network harmonics capture 90% of the signal power. This suggests that network harmonics are functionally meaningful, which we demonstrate by using them as a basis for the functional EEG data recorded from a face detection task. There, only 13 network harmonics are sufficient to track the large-scale cortical activity during the processing of the stimuli with a 50 ms resolution, reproducing well-known activity in the fusiform face area as well as revealing co-activation patterns in somatosensory/motor and frontal cortices that an unconstrained ROI-by-ROI analysis fails to capture. The proposed approach is simple and fast, provides a means of integration of multimodal datasets, and is tied to a theoretical framework in mathematics and physics. Thus, network harmonics point towards promising research directions both theoretically - for example in exploring the relationship between structure and function in the brain - and practically - for example for network tracking in different tasks and groups of individuals, such as patients.
Feeding state functionally reconfigures a sensory circuit to drive thermosensory behavioral plasticity
Authors: Takeishi Asuka , Yeon Jihye , Harris Nathan , Yang Wenxing , Sengupta Piali
Published: June 2020

Internal state alters sensory behaviors to optimize survival strategies. The neuronal mechanisms underlying hunger-dependent behavioral plasticity are not fully characterized. Here we show that feeding state regulatesC. elegansnegative thermotaxis behavior by engaging a modulatory circuit whose activity gates the output of the core thermotaxis network. Feeding state does not alter the activity of the core thermotaxis circuit comprised of AFD thermosensory and AIY interneurons. Instead, prolonged food deprivation potentiates temperature responses in the AWC sensory neurons, which inhibit the postsynaptic AIA interneurons to override and disrupt AFD-driven thermotaxis behavior. Acute inhibition and activation of AWC and AIA, respectively, restores negative thermotaxis in starved animals. We find that state-dependent modulation of AWC-AIA temperature responses requires INS-1 insulin-like peptide signaling from the gut and DAF-16 FOXO function in AWC. Our results describe a mechanism by which functional reconfiguration of a sensory network via gut-brain signaling drives state-dependent behavioral flexibility.
Quantifying the wave resistance of a swimmer
Authors: Dickson Thomas A. J. , Taunton Dominic , Banks Joe , Hudson Dominic , Turnock Stephen
Published: June 2020

Abstract

Quantifying the wave resistance of a swimmer as a function of depth assists in identifying the optimum depth for the glide phases of competition. Previous experiments have inferred how immersed depth influences the drag acting on a swimmer [1], but have not directly quantified the magnitude of wave resistance. This research experimentally validates the use of thin-ship theory for quantifying the wave resistance of a realistic swimmer geometry. The drag and wave pattern of a female swimmer mannequin were experimentally measured over a range of depths from 0.05m to 1.00m at a speed of 2.50 m/s. Numerical simulations agree with experiment to confirm that there were negligible reductions in wave resistance below a depth of 0.40m. Larger swimming pool dimensions are shown to be significant at reducing wave resistance at speeds above 2.0 m/s and depths below 0.40m. Truncating the swimmer’s body at the upper thigh increases the wave resistance at speeds below 2.0m/s but is not significant at higher speeds, indicating that the upper body is the main contributor to the wave system. Numerical experiments indicate that rotating the shoulders towards the surface is more influential than the feet, demonstrating the impact of the upper body on wave resistance.
Genome-wide association study of flowering time reveals complex genetic heterogeneity and epistatic interactions in rice
Authors: Liu Chang , Tu Yuan , Liao Shiyu , Fu Xiangkui , Lian Xingming , He Yuqing , Xie Weibo , Wang Gongwei
Published: June 2020

Since domestication, rice has cultivated in a wide range of latitudes with different day lengths. Selection of diverse natural variations in heading date and photoperiod sensitivity is critical for adaptation of rice to different geographical environments. To unravel the genetic architecture underlying natural variation of rice flowering time, we conducted a genome wide association study (GWAS) using several association analysis strategies with a diverse worldwide collection of 529O. sativaaccessions. Heading date was investigated in three environments under long-day or short-day conditions, and photosensitivity was evaluated. By dividing the whole association panel into subpopulations and performing GWAS with both linear mixed models and multi-locus mixed-models, we revealed hundreds of significant loci harboring novel candidate genes as well as most of the known flowering time genes. In total, 127 hotspots were detected in at least two GWAS. Universal genetic heterogeneity was found across subpopulations. We further detected abundant interactions between GWAS loci, especially inindica. Functional gene families were revealed from enrichment analysis of the 127 hotspots. The results demonstrated a rich of genetic interactions in rice flowering time genes and such epistatic interactions contributed to the large portions of missing heritability in GWAS. It suggests the increased complexity of genetic heterogeneity might discount the power of increasing the sample sizes in GWAS.
EMC2: A versatile algorithm for robust tracking of calcium dynamics from individual neurons in behaving animals
Authors: Lagache Thibault , Hanson Alison , Pérez-Ortega Jesús E. , Fairhall Adrienne , Yuste Rafael
Published: June 2020

Measuring the activity of neuronal populations with calcium imaging can capture emergent functional properties of neuronal circuits with single cell resolution. However, the motion of freely behaving animals, together with the intermittent detectability of calcium sensors, can hinder automatic long-term monitoring of neuronal activity and the subsequent functional characterization of neural circuits. We report the development and open-source implementation of a multi-step cellular tracking algorithm (Elastic Motion Correction and Concatenation or EMC2) that compensates for the intermittent disappearance of moving neurons by integrating local deformation information from detectable neurons. We demonstrate the accuracy and versatility of our algorithm using calcium imaging data from two-photon volumetric microscopy in visual cortex of awake mice, and from confocal microscopy in behavingHydra, which experiences major body deformation during its contractions. We quantify the performance of our algorithm using ground truth manual tracking of neurons, along with synthetic time-lapse sequences, covering a wide range of particle motions and detectability parameters. By monitoring the calcium activity of the same neuronal populations along several days in layer 2/3 of visual cortex of mice, we report important turn-over within the active neurons across days, with only few neurons that remained active across days. Then, by combining automatic tracking of single neuron activity over long time-lapse sequences with statistical clustering, we characterize and map neuronal ensembles in behavingHydra. We document the existence three major non-overlapping ensembles of neurons (CB, RP1 and RP2) whose activity correlates with contractions and elongations. Our results prove that the EMC2algorithm can be used as a robust platform for neuronal tracking in behaving animals.