bluuebunny/crossref_metadata_2025 huggingface dataset:
Directors’ Fiduciary Duties to the Company: A Comparative Study of the UK and Indian Companies Act
Authors: Singh Vijay P
Published: December 2020

The Directors’ duties to the company were governed by the common law of negligence and the equitable principles of fiduciary duties before they were codified in Section 166 Companies Act. 2013 and section 170 of the UK Companies Act 2006. Section 170 of the UK Companies Act provides that the general duties of Directors will be interpreted in the same manner as the common law rules or equitable principles and in interpreting and applying these statutory duties of the director, regard shall be given to the corresponding common law rules and equitable principles. But such provision does not find a place under the Indian Companies Act, 2013. In this article, an endeavor has been made to do a comparative study of the Directors’ duties as conferred by the Indian Companies Act 2013 and the UK Companies Act 2006. Company Directors have the duties to work within the powers, to exercise reasonable skill and care, as well as work for the success of the company. They also have important duties to the shareholders. These duties of the Directors have been examined, analyzed and discussed in this paper, along with the relevant English and Indian case law.
Outcome of community-initiated treatment of drug-resistant tuberculosis patients in Lagos, Nigeria
Authors: Bakare Adebayo M , Udunze Obioha C , Bamidele Janet O , Omoniyi Amos , Osman Eltayeb , Daniel Olusoji J
Published: December 2020

Background

With the improvement in the capacity to diagnose multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients due to the increased number of GeneXpert machines in Nigeria, the number of patients diagnosed surpassed the bed capacity at MDR-TB treatment centres. Community DR-TB treatment is an important option to improve access to care for MDR/RR-TB patients. However, few studies have determined the outcome of community management of MDR-TB patients, which this study aims to address.

Methods

We conducted a retrospective study of MDR/RR-TB patients initiated on treatment in the community in Lagos, Nigeria, between 1 January 2015 and 31 December 2016. Data were retrieved from DR-TB treatment cards/registers. The treatment outcomes of these patients were assessed at the end of treatment and categorized according to national TB guidelines.

Results

A total of 150 DR-TB patients commenced treatment during the study period. Adherence was 64.7%, with the majority of patients experiencing mild (56.5%) adverse drug events. Treatment was successful in 70% of patients. The only predictor of successful treatment was treatment adherence.

Conclusions

The study shows that community initiation of MDR-TB treatment is feasible and results in a high treatment success rate. Adherence counselling before and during treatment is essential for a favourable treatment outcome.
Mycetoma and the Community Dermatology Program, Mexico
Authors: Roberto Estrada , Guadalupe Chávez-López , Guadalupe Estrada-Chávez , Hay Roderick
Published: December 2020

The Community Dermatology Program established in the state of Guerrero, Mexico for almost 30 y provides an adaptable method of detecting and monitoring skin neglected tropical diseases such as mycetoma, which is endemic in the state. The program utilises general and thematic teaching elements combined with distance learning through teledermatology, direct patient consultations and close collaboration with community teams. Using this approach, a picture of mycetoma in Guerrero has emerged, with a focal hot spot located in the southern part of the state in the Costa Chica region. Although in much of Mexico Nocardia infections dominate, in this area there are also substantial numbers of cases of eumycetoma. This combined approach provides a means of early case detection and long-term surveillance through targeted use of a small specialist team.
Novel vaccines for allergen-specific immunotherapy
Authors: Akinfenwa Oluwatoyin , Rodríguez-Domínguez Azahara , Vrtala Susanne , Valenta Rudolf , Campana Raffaela
Published: December 2020

Purpose of review

Allergen-specific immunotherapy (AIT) is a highly economic, effective and disease-modifying form of allergy treatment but requires accurate prescription and monitoring. New molecular approaches are currently under development to improve AIT by reducing treatment-related side effects, cumbersome protocols and patients’ compliance. We review the current advances regarding refined diagnosis for prescription and monitoring of AIT and the development of novel molecular vaccines for AIT. Finally, we discuss prophylactic application of AIT.

Recent findings

There is evidence that molecular allergy diagnosis not only assists in the prescription and monitoring of AIT but also allows a refined selection of patients to increase the likelihood of treatment success. New data regarding the effects of AIT treatment with traditional allergen extracts by alternative routes have become available. Experimental approaches for AIT, such as virus-like particles and cell-based treatments have been described. New results from clinical trials performed with recombinant hypoallergens and passive immunization with allergen-specific antibodies highlight the importance of allergen-specific IgG antibodies for the effect of AIT and indicate opportunities for preventive allergen-specific vaccination.

Molecular allergy diagnosis is useful for the prescription and monitoring of AIT and may improve the success of AIT. Results with molecular allergy vaccines and by passive immunization with allergen-specific IgG antibodies indicate the importance of allergen-specific IgG capable of blocking allergen recognition by IgE and IgE-mediated allergic inflammation as important mechanism for the success of AIT. New molecular vaccines may pave the road towards prophylactic allergen-specific vaccination.
A SEER database cohort of 868 patients with primary tracheal cancers: characteristics and outcomes and the role of bronchoscopic interventions
Authors: Baig Mirza Z. , Weber Joanna F. , Connery Cliff P. , Bhora Faiz Y.
Published: December 2020

Introduction:

Primary tracheal cancers have a yearly prevalence of 2.6 cases per million people. Because of their rarity there is a lack of studies investigating them. In this study, we investigate the clinical characteristics and outcomes of primary tracheal cancers using a large population database.

Methods:

The Surveillance, Epidemiology and End Results (SEER) database was queried between 1973 and 2016 to identify a retrospective cohort of patients with primary tracheal cancers. Demographic information, tumor characteristics, treatments administered, and survival in months were investigated.

Results:

Eight hundred sixty-eight cases were analyzed. The majority of the patients were male (56.8%) with an average age of 62.13 (±15.67). Squamous cell carcinoma (SCC) was the predominant subtype (42.9%) followed by adenoid cystic carcinoma (ACC) (18.1%). Five-year survival was 21.6% and median survival was 12 months. Patients with ACC had more localized tumors, received surgery more often and had longer survival than patients with SCC (P<0.01). Both groups had best outcomes when treated with surgery. Bronchoscopic intervention was associated with favorable outcomes for ACC. For SCCs, bronchoscopic interventions followed by adjuvant therapy had better outcomes than radiotherapy alone. Cox proportional hazards identified advanced age and stage, radiotherapy and chemotherapy as negative predictors of outcome. Whereas ACC and sarcoma histology and diagnosis between 2010 and 2016 were positive prognosticators.

Conclusions:

Tracheal cancers have poor outcomes with a median survival of 12 months and 5-year survival of only 21.6%. Surgical resection should be the treatment of choice wherever feasible. In patients with ACCs who are not surgical candidates bronchoscopic interventions may provide appropriate treatment and palliation and improved survival. For SCCs, bronchoscopic intervention wherever possible with adjuvant therapy may be favorable to radiotherapy alone.
Histologic transformation from lung squamous cell carcinoma in primary lesion to small cell lung cancer in metastatic lymph node lesion following lobectomy and adjuvant chemotherapy: a case report
Authors: Zhao Xinran , Qin Ye , Zhang Di , Han Yang , Wu Guangping , Zhao Huanyu
Published: December 2020

Introduction:

Lung cancer is the leading cause of cancer death worldwide. Histologic transformation from lung squamous cell carcinoma to small cell lung cancer (SCLC) has become more and more, and its treatment is challenging because of unknown pathogenesis.

Presentation of Case:

A 62-year-old male patient presented with histologic transformation from primary lesion to metastatic recurrence lesion within 3 years following primary lobectomy and adjuvant chemotherapy. The patient had the symptom of cough at the time of initial illness and recurrence. The primary lesion at the root segment of left superior lobe was diagnosed as lung squamous cell carcinoma without gene mutation (including EGFR, ALK, BRAF V600E, etc.), and recurrence lesion at the swollen lymph nodes in mediastinum (4L group) was diagnosed as SCLC. Up to now, the patient was alive for nearly 4 years after first surgery.

Discussion:

Surgical resection is the main treatment for lung cancer patient in early stage. Lymph node metastasis is a big threat for the patients in early stage. Recently, the research reports focused on the mechanism and cases of histologic transformation of lung cancer have become more and more. In this case, histologic transformation from squamous cell carcinoma in primary focus to SCLC in metastatic lymph node lesion following lobectomy and adjuvant chemotherapy. However, there was no gene mutation. This is a very unusual report.

Conclusion:

We analyzed a lung cancer patient with histologic transformation from primary focus to lymphatic metastasis by clinical symptoms, radiologic features, laboratory tests, gene detection, histopathologic characteristics, and immunohistochemical testing. It is helpful to understand the pathogenesis of histologic transformation and metastatic progression for optimizing treatment measures to lung cancer.
The Affordable Care Act and Its Impact on Plastic and Gender-Affirmation Surgery
Authors: Wiegmann Aaron L. , Young Ezra I. , Baker Kellan E. , Khalid Syed I. , Seu Michelle , Shenaq Deana S. , Dorafshar Amir H. , Schechter Loren S.
Published: December 2020

The Affordable Care Act’s provisions have affected and will continue to affect plastic surgeons and their patients, and an understanding of its influence on the current American health care system is essential. The law’s impact on pediatric plastic surgery, craniofacial surgery, and breast reconstruction is well documented. In addition, gender-affirmation surgery has seen exponential growth, largely because of expanded insurance coverage through the protections afforded to transgender individuals by the Affordable Care Act. As gender-affirming surgery continues to grow, plastic surgeons have the opportunity to adapt and diversify their practices.
Significant Dysfunction of Kidney Grafts Exposed to Prolonged Warm Ischemia Is Minimized Through Normothermic Ex Vivo Kidney Perfusion
Authors: Urbanellis Peter , Kollmann Dagmar , Linares Ivan , Ganesh Sujani , Oquendo Fabiola , Mazilescu Laura , Goto Toru , Noguchi Yuki , John Rohan , Konvalinka Ana , Mucsi Istvan , Ghanekar Anand , Bagli Darius , Selzner Markus , Robinson Lisa A.
Published: December 2020

Background.

Normothermic ex vivo kidney perfusion (NEVKP) is an emerging technique for renal graft preservation. We investigated whether NEVKP could improve early function of severely injured grafts and reduce the incidence of significant renal dysfunction (SRD) similar to delayed graft function in a model of donation after circulatory death.

Methods.

Kidneys from 30-kg Yorkshire pigs were removed following 120 minutes of warm ischemia (WI). These grafts were then preserved in static cold storage (SCS, n = 6) or subjected to NEVKP (n = 5) for 8 hours before heterotopic autotransplantation. SRD was defined as postoperative day (POD) 4 oliguria <500 mL/24 h with serum K +> 6.0 mmol/L.

Results.

All 4 surviving animals with 120 minutes WI grafts stored with SCS developed SRD, compared with 1/5 in the NEVKP group (P = 0.02). The NEVKP group, when compared with SCS, also demonstrated significantly decreased serum creatinine peak values (1118.51 ± 206.90 µmol/L versus 1675.56 ± 98.15 µmol/L; P = 0.002) and higher creatinine clearance (POD4: 9.05 ± 6.97 mL/min versus 0.89 ± 0.56 mL/min; P = 0.05). By POD7, serum creatinine was not significantly different than baseline in the NEVKP (431.49 ± 492.50 µmol/L versus 90.19 ± 14.15 µmol/L, respectively; P = 0.20) but remained elevated following SCS (1189.25 ± 309.47 µmol/L versus 97.26 ± 29.18 µmol/L, respectively; P < 0.01). Histology demonstrated significantly decreased tubular injury scores compared with SCS grafts (P = 0.03).

Conclusions.

Kidney grafts subjected to 120 minutes WI before retrieval showed significant improvement in function, prevention of SRD, and decreased injury following 8 hours of NEVKP.
Urinary Cell Transcriptome Profiling and Identification of ITM2A, SLAMF6, and IKZF3 as Biomarkers of Acute Rejection in Human Kidney Allografts
Authors: Dooley Bryan J. , Verma Akanksha , Ding Ruchuang , Yang Hua , Muthukumar Thangamani , Lubetzky Michele , Shankaranarayanan Divya , Elemento Olivier , Suthanthiran Manikkam
Published: December 2020

Background.

Identification of a shared gene expression pattern between T cell–mediated rejection (TCMR) and antibody-mediated rejection (AMR) in human kidney allografts may help prioritize targets for the treatment of both types of acute rejection.

Methods.

We performed RNA sequencing and bioinformatics of genome-wide transcriptome profiles of urinary cells to identify novel mRNAs shared between TCMR and AMR and of mechanistic relevance. Customized RT-QPCR assays were then used to validate their abundance in urinary cells. Urinary cell transcriptome profiles and mRNA abundance were assessed in 22 urine samples matched to 22 TCMR biopsies, 7 samples matched to 7 AMR biopsies, and 24 samples matched to 24 No Rejection (NR) biopsies and correlated with biopsy diagnosis.

Results.

RNA sequencing data and bioinformatics identified 127 genes in urine to be shared between TCMR and AMR. We selected 3 novel mRNAs—ITM2A, SLAMF6, and IKZF3—for absolute quantification and validation by customized RT-QPCR assays. The abundance of all 3 mRNAs was significantly higher in urine matched to TCMR or AMR than in urine matched to NR biopsies. Receiver-operating-characteristic curve analysis showed that all 3 mRNAs distinguished TCMR or AMR from NR. Their abundance was similar in patients with TCMR and those with AMR.

Conclusions.

State-of-the-art antirejection therapies are mostly effective to treat TCMR but not AMR. Our identification of mRNAs shared between TCMR and AMR and contributing to T cell–B cell interactions may help prioritize therapeutic targets for the simultaneous treatment of TCMR and AMR.
Radio-frequency chain selection for energy and spectral efficiency maximization in hybrid beamforming under hardware imperfections
Authors: Vlachos Evangelos , Thompson John , Kaushik Aryan , Masouros Christos
Published: December 2020

The next-generation wireless communications require reduced energy consumption, increased data rates and better signal coverage. The millimetre-wave frequency spectrum above 30 GHz can help fulfil the performance requirements of the next-generation mobile broadband systems. Multiple-input multiple-output technology can provide performance gains to help mitigate the increased path loss experienced at millimetre-wave frequencies compared with microwave bands. Emerging hybrid beamforming architectures can reduce the energy consumption and hardware complexity with the use of fewer radio-frequency (RF) chains. Energy efficiency is identified as a key fifth-generation metric and will have a major impact on the hybrid beamforming system design. In terms of transceiver power consumption, deactivating parts of the beamformer structure to reduce power typically leads to significant loss of spectral efficiency. Our aim is to achieve the highest energy efficiency for the millimetre-wave communications system while mitigating the resulting loss in spectral efficiency. To achieve this, we propose an optimal selection framework which activates specific RF chains that amplify the digitally beamformed signals with the analogue beamforming network. Practical precoding is considered by including the effects of user interference, noise and hardware impairments in the system modelling.
Matrix models and deformations of JT gravity
Authors: Witten Edward
Published: December 2020

Recently, it has been found that Jackiw-Teitelboim (JT) gravity, which is a two-dimensional theory with bulk action

−

1

/

2

∫

d

2

x

g

ϕ
(
R
+
2
)

, is dual to a matrix model, that is, a random ensemble of quantum systems rather than a specific quantum mechanical system. In this article, we argue that a deformation of JT gravity with bulk action

−

1

/

2

∫

d

2

x

g

(
ϕ
R
+
W
(
ϕ
)
)

is likewise dual to a matrix model. With a specific procedure for defining the path integral of the theory, we determine the density of eigenvalues of the dual matrix model. There is a simple answer if
W
(0) = 0, and otherwise a rather complicated answer.
Three-phase flow displacement dynamics and Haines jumps in a hydrophobic porous medium
Authors: Alhosani Abdulla , Scanziani Alessio , Lin Qingyang , Selem Ahmed , Pan Ziqing , Blunt Martin J. , Bijeljic Branko
Published: December 2020

We use synchrotron X-ray micro-tomography to investigate the displacement dynamics during three-phase—oil, water and gas—flow in a hydrophobic porous medium. We observe a distinct gas invasion pattern, where gas progresses through the pore space in the form of disconnected clusters mediated by double and multiple displacement events. Gas advances in a process we name three-phase Haines jumps, during which gas re-arranges its configuration in the pore space, retracting from some regions to enable the rapid filling of multiple pores. The gas retraction leads to a permanent disconnection of gas ganglia, which do not reconnect as gas injection proceeds. We observe,
in situ
, the direct displacement of oil and water by gas as well as gas–oil–water double displacement. The use of local
in situ
measurements and an energy balance approach to determine fluid–fluid contact angles alongside the quantification of capillary pressures and pore occupancy indicate that the wettability order is oil–gas–water from most to least wetting. Furthermore, quantifying the evolution of Minkowski functionals implied well-connected oil and water, while the gas connectivity decreased as gas was broken up into discrete clusters during injection. This work can be used to design CO
2
storage, improved oil recovery and microfluidic devices.
Production of mobile invertebrate communities on shallow reefs from temperate to tropical seas
Authors: Fraser K. M. , Lefcheck J. S. , Ling S. D. , Mellin C. , Stuart-Smith R. D. , Edgar G. J.
Published: December 2020

Primary productivity of marine ecosystems is largely driven by broad gradients in environmental and ecological properties. By contrast, secondary productivity tends to be more variable, influenced by bottom-up (resource-driven) and top-down (predatory) processes, other environmental drivers, and mediation by the physical structure of habitats. Here, we use a continental-scale dataset on small mobile invertebrates (epifauna), common on surfaces in all marine ecosystems, to test influences of potential drivers of temperature-standardized secondary production across a large biogeographic range. We found epifaunal production to be remarkably consistent along a temperate to tropical Australian latitudinal gradient of 28.6°, spanning kelp forests to coral reefs (approx. 3500 km). Using a model selection procedure, epifaunal production was primarily related to biogenic habitat group, which explained up to 45% of total variability. Production was otherwise invariant to predictors capturing primary productivity, the local biomass of fishes (proxy for predation pressure), and environmental, geographical, and human impacts. Highly predictable levels of epifaunal productivity associated with distinct habitat groups across continental scales should allow accurate modelling of the contributions of these ubiquitous invertebrates to coastal food webs, thus improving understanding of likely changes to food web structure with ocean warming and other anthropogenic impacts on marine ecosystems.
Mycobacterium helveticum sp. nov., a novel slowly growing mycobacterial species associated with granulomatous lesions in adult swine
Authors: Ghielmetti Giovanni , Rosato Giuliana , Trovato Alberto , Friedel Ute , Kirchgaessner Constanze , Perroulaz Carmen , Pendl Wolfgang , Schulthess Bettina , Bloemberg Guido V. , Keller Peter M. , Stephan Roger , Tortoli Enrico
Published: December 2020

The occurrence of nontuberculous mycobacteria in different hosts and their implication as obligate or opportunistic pathogens remain mainly unclear. Mycobacteriosis in pigs is usually associated with members of the

Mycobacterium avium

complex and, in particular, with ‘

Mycobacterium avium

subsp.

hominissuis

’. Here we describe a novel slow-growing mycobacterial species isolated from lymph nodes obtained from two sows housed in different Swiss farms. The animals presented chronic inappetence and mild diarrhoea. Gross pathology revealed focal caseous lymphadenopathy of the mesenteric lymph nodes. Complete genome sequencing of the two isolates from the two sows was performed. The genomes comprised 5.76 Mb and an average nucleotide identity score of 99.97 %. Whole genome sequence, mycolic acid and matrix-assisted laser desorption ionization-time of flight mass spectrometry analyses revealed that the two isolates were not related to any previously described

Mycobacterium

species. The closest related species was

Mycobacterium parmense

, a slow-growing scotochromogenic mycobacterium first isolated from a cervical lymph node of a 3-year-old child. The name proposed for the new species is

Mycobacterium helveticum

sp. nov. and 16-83T (=DSM 109965T= LMG 2019-02457T) is the type strain.
Kushneria phosphatilytica sp. nov., a phosphate-solubilizing bacterium isolated from a solar saltern
Authors: Du Guang-Xun , Qu Ling-Yun , Hong Xu-Guang , Li Cheng-Hua , Ding De-Wen , Gao Ping , Xu Qin-Zeng
Published: December 2020

A Gram-stain-negative, motile, rod-shaped, non-endospore-forming, aerobic and halophilic bacterium, designated strain YCWA18T, was isolated from the sediment of Jimo-Daqiao saltern in China. This strain was able to grow at NaCl concentrations in the range 0.5–20 % (w/v) with optimum growth at 6 % (w/v) NaCl. Growth occurred at temperatures of 4–40 °C (optimum 28 °C) and pH 4.0–9.0 (optimum 7.0). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YCWA18T belonged to the genus

Kushneria

and shared the highest sequence similarity of 98.7 % with

Kushneria sinocarnis

DSM 23229T. Moreover, the phylogenetic analysis based on the 23S rRNA gene sequence also confirmed the phylogenetic position of this novel strain. The predominant fatty acids were C16 : 0, C17 : 0 cyclo and C12 : 0 3-OH. The major isoprenoid quinone was Q-9 (94.2 %) and the polar lipids were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylethanolamine (PE), an unidentified aminolipid (AL), an unidentified phospholipids (PL) and two unidentified lipids (L). The complete genome of strain YCWA18T consisted of a single, circular chromosome of 3 624 619 bp, with an average G+C content of 59.1 mol%. A genome-based phylogenetic tree constructed using an up-to-date bacterial core gene set (UBCG) showed that strain YCWA18T formed a clade with

K. sinocarnis

DSM 23229T. However, the level of the ANI and dDDH values between strain YCWA18T and

K. sinocarnis

DSM 23229T were 82.3 and 24.6 %, respectively, which were low enough to distinguish strain YCWA18T from

K. sinocarnis

DSM 23229T. Overall, based on the phenotypic, chemotaxonomic, phylogenetic and genomic analyses, strain YCWA18T represents a novel species of genus

Kushneria

. The name Kushneria phosphatilytica sp. nov. is proposed, with the type strain YCWA18T (=CGMCC 1.9149T=NCCB 100306T).
A Light-weight Text Summarizer for Fast Access to Medical Evidence
Authors: Sarker Abeed , Yang Yuan-Chi , Al-Garadi Mohammed Ali
Published: December 2020

The performances of current medical text summarization systems rely on resource-heavy domain-specific knowledge sources, and preprocessing methods (e.g., classification or deep learning) for deriving semantic information. Consequently, these systems are often difficult to customize, extend or deploy in low-resource settings, and are operationally slow. We propose a fast summarization system that can aid practitioners at point-of-care, and, thus, improve evidence-based healthcare. At runtime, our system utilizes similarity measurements derived from pre-trained domain-specific word embeddings in addition to simple features, rather than clunky knowledge bases and resource-heavy preprocessing. Automatic evaluation on a public dataset for evidence-based medicine shows that our system’s performance, despite the simple implementation, is statistically comparable with the state-of-the-art.
A low-cost automized anaerobic chamber for long-term growth experiments and sample handling
Authors: Herrmann Achim J. , Gehringer Michelle M.
Published: December 2020

1

The handling of oxygen sensitive samples and growth of obligate anaerobic organisms requires the stringent exclusion of oxygen, which is omnipresent in our normal atmospheric environment. Anaerobic workstations (aka. Glove boxes) enable the handling of oxygen sensitive samples during complex procedures, or the long-term incubation of anaerobic organisms. Depending on the application requirements, commercial workstations can cost up to 60.000 €. Here we present the complete build instructions for a highly adaptive, Arduino based, anaerobic workstation for microbial cultivation and sample handling, with features normally found only in high cost commercial solutions. This build can automatically regulate humidity, H2levels (as oxygen reductant), log the environmental data and purge the airlock. It is built as compact as possible to allow it to fit into regular growth chambers for full environmental control. In our experiments, oxygen levels during the continuous growth of oxygen producing cyanobacteria, stayed under 0.03 % for 21 days without needing user intervention. The modular Arduino controller allows for the easy incorporation of additional regulation parameters, such as CO2concentration or air pressure. This paper provides researchers with a low cost, entry level workstation for anaerobic sample handling with the flexibility to match their specific experimental needs.

Specifications table

[please fill in right-hand column of the table below]
COVID-19 Risk Stratification and Mortality Prediction in Hospitalized Indian Patients
Authors: Alle Shanmukh , Siddiqui Samreen , Kanakan Akshay , Garg Akshit , Karthikeyan Akshaya , Mishra Neha , Waghdhare Swati , Tyagi Akansha , Tarai Bansidhar , Hazarika Pranjal Pratim , Das Poonam , Budhiraja Sandeep , Nangia Vivek , Dewan Arun , Sethuraman Ramanathan , Subramanian C. , Srivastava Mashrin , Chakravarthi Avinash , Jacob Johnny , Namagiri Madhuri , Konala Varma , Dash Debasish , Jha Sujeet , Pandey Rajesh , Agrawal Anurag , Vinod P. K. , Priyakumar U. Deva
Published: December 2020

The clinical course of coronavirus disease 2019 (COVID-19) infection is highly variable with the vast majority recovering uneventfully but a small fraction progressing to severe disease and death. Appropriate and timely supportive care can reduce mortality and it is critical to evolve better patient risk stratification based on simple clinical data, so as to perform effective triage during strains on the healthcare infrastructure. This study presents risk stratification and mortality prediction models based on usual clinical data from 544 COVID-19 patients from New Delhi, India using machine learning methods. An XGboost classifier yielded the best performance on risk stratification (F1 score of 0.81). A logistic regression model yielded the best performance on mortality prediction (F1 score of 0.71). Significant biomarkers for predicting risk and mortality were identified. Examination of the data in comparison to a similar dataset with a Wuhan cohort of 375 patients was undertaken to understand the much lower mortality rates in India and the possible reasons thereof. The comparison indicated higher survival rate in the Delhi cohort even when patients had similar parameters as the Wuhan patients who died. Steroid administration was very frequent in Delhi patients, especially in surviving patients whose biomarkers indicated severe disease. This study helps in identifying the high-risk patient population and suggests treatment protocols that may be useful in countries with high mortality rates.
Association Between the Swallowing Reflex and the Development of Aspiration Pneumonia in Patients with Dysphagia Admitted to Long-term Care Wards -A Prospective Cohort Study of 60 Days-
Authors: Omura Tomoya , Matsuyama Miwa , Nishioka Shota , Sagawa Shomu , Seto Masaya , Naoe Mitsugu
Published: December 2020

Objective

To investigate the association between the simple swallowing provocation test (SSPT) and development of aspiration pneumonia in patients with dysphagia in long-term care (LTC) wards.

Design

The study design was a prospective cohort study. Subjects were followed for 60 days from admission.

Setting

LTC wards.

Participants

Study subjects were patients with dysphagia aged 65 years or older who were admitted to LTC wards between August 2018 and August 2019. In total, 39 subjects were included in the analysis (20 males, 19 females; mean age 83.8 ± 8.5 years). Subjects were divided into two groups based on SSPT results: normal swallowing reflex (SSPT normal group) and abnormal swallowing reflex (SSPT abnormal group). The covariates were age and sex, primary disease, history of cerebrovascular disease, Glasgow coma scale, body mass index, geriatric nutritional risk index, the mann assessment of swallowing ability, food intake level scale, functional independence measure, and oral health assessment tool.

Interventions

Not applicable.

Main Outcome Measure

The outcome was the incidence of aspiration pneumonia during the first 60 days of hospitalization, and the predictive factor was SSPT: 0.4 ml.

Results

The incidence of aspiration pneumonia was 33.3% in the SSPT normal group and 76.2% in the SSPT abnormal group. The phi coefficient was −0.43, the risk ratio was 2.29, and the 95% confidence interval (95%CI) was 1.14 to 4.58. The predictive factor for aspiration pneumonia was SSPT: 0.4 ml (95% CI: 1.57–26.03).

Conclusions

Our findings suggest that the SSPT provides a valid index for the development of aspiration pneumonia in older patients with dysphagia admitted to LTC wards.
An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility
Authors: Wang Liuyang , Balmat Thomas J. , Antonia Alejandro L. , Constantine Florica J. , Henao Ricardo , Burke Thomas W. , Ingham Andy , McClain Micah T. , Tsalik Ephraim L. , Ko Emily R. , Ginsburg Geoffrey S. , DeLong Mark R. , Shen Xiling , Woods Christopher W. , Hauser Elizabeth R. , Ko Dennis C.
Published: December 2020

While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility. Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb);http://cpag.oit.duke.edu) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by theDPP9locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated thatDPP9was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs with severe COVID-19 demonstrated colocalization of the GWAS signal of theABOlocus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN), pointing to a possible mechanism whereby glycosylation of CD209 byABOmay regulate COVID-19 disease severity. Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches.
Design, Implementation and Feasibility of an Informatics Infrastructure for Standardized Data Acquisition, Transfer, Storage and Export in Psychiatric Clinical Routine
Authors: Blitz R. , Storck M. , Baune B.T. , Dugas M. , Opel N.
Published: December 2020

Background

Empirically driven personalized diagnostic and treatment is widely perceived as a major hallmark in psychiatry. However, databased personalized decision making requires standardized data acquisition and data access, which is currently absent in psychiatric clinical routine.

Objective

Here we describe the informatics infrastructure implemented at the psychiatric university hospital Münster allowing for standardized acquisition, transfer, storage and export of clinical data for future real-time predictive modelling in psychiatric routine.

Methods

We designed and implemented a technical architecture that includes an extension of the EHR via scalable standardized data collection, data transfer between EHR and research databases thus allowing to pool EHR and research data in a unified database and technical solutions for the visual presentation of collected data and analyses results in the EHR. The Single-source Metadata ARchitecture Transformation (SMA:T) was used as the software architecture. SMA:T is an extension of the EHR system and uses Module Driven Software Development to generate standardized applications and interfaces. The Operational Data Model (ODM) was used as the standard. Standardized data was entered on iPads via the Mobile Patient Survey (MoPat) and the web application Mopat@home, the standardized transmission, processing, display and export of data was realized via SMA:T.

Results

The technical feasibility was demonstrated in the course of the study. 19 standardized documentation forms with 241 items were created. In 317 patients, 6,451 instances were automatically transferred to the EHR system without errors. 96,323 instances were automatically transferred from the EHR system to the research database for further analyses.

Conclusions

With the present study, we present the successful implementation of the informatics infrastructure enabling standardized data acquisition, and data access for future real-time predictive modelling in clinical routine in psychiatry. The technical solution presented here might guide similar initiatives at other sites and thus help to pave the way towards future application of predictive models in psychiatric clinical routine.
Identification of SARS-CoV-2-specific immune alterations in acutely ill patients
Authors: Rébillard Rose-Marie , Charabati Marc , Grasmuck Camille , Filali-Mouhim Abdelali , Tastet Olivier , Brassard Nathalie , Daigneault Audrey , Bourbonnière Lyne , Balthazard Renaud , Moratalla Ana Carmena , Solorio Yves Carpentier , Farzam-kia Negar , Fournier Antoine Philippe , Gowing Elizabeth , Jamann Hélène , Lemaître Florent , Mamane Victoria Hannah , Thai Karine , Cailhier Jean-François , Chomont Nicolas , Finzi Andrés , Chassé Michaël , Durand Madeleine , Arbour Nathalie , Kaufmann Daniel E. , Prat Alexandre , Larochelle Catherine
Published: December 2020

Dysregulated immune profiles have been described in symptomatic SARS-CoV-2-infected patients. Whether the reported immune alterations are specific to SARS-CoV-2 infection or also triggered by other acute illnesses remains unclear. We performed flow cytometry analysis on fresh peripheral blood from a consecutive cohort of i) patients hospitalized with acute SARS-CoV-2 infection; ii) patients of comparable age/sex hospitalized for other acute disease (SARS-CoV-2 negative); and iii) healthy controls. Using both data-driven and hypothesis-driven analyses, we found several dysregulations in immune cell subsets (e.g. decreased proportion of T cells) that are similarly associated with acute SARS-CoV-2 infection and non-COVID-19 related acute illnesses. In contrast, we identified specific differences in myeloid and lymphocyte subsets that are associated with SARS-CoV-2 status (e.g. elevated proportion of ICAM-1+mature/activated neutrophils, ALCAM+monocytes, and CD38+CD8+T cells). A subset of SARS-CoV-2-specific immune alterations correlated with disease severity, disease outcome at 30 days and mortality. Our data provides novel understanding of the immune dysregulation that are specifically associated with SARS-CoV-2 infection among acute care hospitalized patients. Our study lays the foundation for the development of specific biomarkers to stratify SARS-CoV-2+patients at risk of unfavorable outcome and uncover novel candidate molecules to investigate from a therapeutic perspective.
Identifying Sequential Complication and Mortality Patterns in Diabetes Mellitus: Comparisons of Machine Learning Methodologies
Authors: Zhou Jiandong , Lee Sharen , Wong Wing Tak , Liu Tong , Roever Leonardo , Jeevaratnam Kamalan , Wu William KK , Wong Ian Chi Kei , Tse Gary , Zhang Qingpeng
Published: December 2020

Background

Diabetes mellitus-related complications adversely affect the quality of life. Better risk-stratified care through mining of sequential complication patterns is needed to enable early detection and prevention.

Methods

Univariable and multivariate logistic regression was used to identify significant variables that can predict mortality. A sequence analysis method termed Prefixspan was applied to identify the most common couple, triple, quadruple, quintuple and sextuple sequential complication patterns in the directed comorbidity pathology network. A knowledge enhanced CPT+ (KCPT+) sequence prediction model is developed to predict the next possible outcome along the progression trajectories of diabetes-related complications.

Findings

A total of 14,144 diabetic patients (51% males) were included. Acute myocardial infarction (AMI) without known ischaemic heart disease (IHD) (odds ratio [OR]: 2.8, 95% CI: [2.3, 3.4]), peripheral vascular disease (OR: 2.3, 95% CI: [1.9, 2.8]), dementia (OR: 2.1, 95% CI: [1.8, 2.4]), and IHD with AMI (OR: 2.4, 95% CI: [2.1, 2.6]) are the most important multivariate predictors of mortality. KCPT+ shows high accuracy in predicting mortality (F1 score 0.90, ACU 0.88), osteoporosis (F1 score 0.86, AUC 0.82), ophthalmological complications (F1 score 0.82, AUC 0.82), IHD with AMI (F1 score 0.81, AUC 0.85) and neurological complications (F1 score 0.81, AUC 0.83) with a particular prior complication sequence.

Interpretation

Sequence analysis identifies the most common pattern characteristics of disease-related complications efficiently. The proposed sequence prediction model is accurate and enables clinicians to diagnose the next complication earlier, provide better risk-stratified care, and devise efficient treatment strategies for diabetes mellitus patients.
Pre-treatment clinical behavioral and blood leukocyte gene expression patterns predict rate of change in response to early intervention in autism
Authors: Lombardo Michael V. , Busuoli Elena Maria , Schreibman Laura , Stahmer Aubyn C. , Pramparo Tiziano , Landi Isotta , Mandelli Veronica , Bertelsen Natasha , Barnes Cynthia Carter , Gazestani Vahid , Lopez Linda , Bacon Elizabeth C. , Courchesne Eric , Pierce Karen
Published: December 2020

Early detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., < 24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predicts 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predicts rate of skill growth, accounting for 13% of the variance treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism post-mortem cortical tissue, and are normatively highly expressed in variety of subcortical and cortical areas important for social-communication and language development. This work indicates for the first time that gene expression can predict the rate of early intervention response and that a key biological factor linked to treatment outcome could be the susceptibility for epigenetic change via mechanisms such as histone acetylation.
Prospective evaluation of accuracy of fine needle aspiration biopsy for breast lesions using the International Academy of Cytology Yokohama System for reporting breast cytopathology
Authors: Agrawal Shruti , Anthony Michael Leonard , Pal Pranoy , Singh Divya , Mehan Anoushika , Singh Ashok , Joshi Prashant , Kumar Arvind , Ravi Bina , Rao Shalinee , Chowdhury Nilotpal
Published: December 2020

Background

Classification of breast leasions into different cytological groups (1-5) can accurately be done using the International Academy of Cytology (IAC) Yokohama System for reporting breast cytopathology. Fine needle aspiration biopsy (FNAB) of breast leasions has been considered to be the primary investigation in detecting breast cancers, especially in low-cost settings. The main objective of this study was to prospectively re-confirm the diagnostic accuracy of breast FNAB using the IAC Yokohama system. Additionally, separate separate secondary subgroup analysis was done to confirm the accuracy of breast FNAB excluding lymph-node positive and lymphadenopathy positive tumors.

Material and methods

A prospective study was done in a tertiary care centre in North India on patients undergoing core-needle /incisional/excisional biopsy of breast lesions between 1st September 2019 to 30th November,2020 (519 biopsies on 487 unique patients). Of these 519 histopathology biopsies, 505 had corresponding FNAB report of the same site. The FNAB was reported using the IAC Yokohama system and the most suitable category was allotted in every case. The rates of malignancy for each category and the accuracy of breast FNAB in diagnosing malignancy were calculated.

Results

Of the total 487 patients, 120 cases were benign on histology, while 367 were malignant. The rates of malignancy in benign, atypical, suspicious and malignant categories were 5%, 25%, 71% and 99.7% respectively. The diagnostic accuracy of atypical, suspicious and malignant categories was calculated as 90.1%, 95.2% and 93.3% respectively.

Conclusion

The high sensitivity and specificity for each scenario for all tumors and for each examined BIRADS category/ies suggest excellent accuracy for Breast FNAB using the IAC Yokohama system.
Identification of SUMO targets required to maintain human stem cells in the pluripotent state
Authors: Mojsa Barbara , Tatham Michael H. , Davidson Lindsay , Liczmanska Magda , Branigan Emma , Hay Ronald T.
Published: December 2020

To determine the role of SUMO modification in the maintenance of pluripotent stem cells we used ML792, a potent and selective inhibitor of SUMO Activating Enzyme. Treatment of human induced pluripotent stem cells with ML792 initiated changes associated with loss of pluripotency such as reduced expression of key pluripotency markers. To identify putative effector proteins and establish sites of SUMO modification, cells were engineered to stably express either SUMO1 or SUMO2 with TGG to KGG mutations that facilitate GlyGly-K peptide immunoprecipitation and identification. A total of 976 SUMO sites were identified in 427 proteins. STRING enrichment created 3 networks of proteins with functions in regulation of gene expression, ribosome biogenesis and RNA splicing, although the latter two categories represented only 5% of the total GGK peptide intensity. The remainder have roles in transcription and chromatin structure regulation. Many of the most heavily SUMOylated proteins form a network of zinc-finger transcription factors centred on TRIM28 and associated with silencing of retroviral elements. At the level of whole proteins there was only limited evidence for SUMO paralogue-specific modification, although at the site level there appears to be a preference for SUMO2 modification over SUMO1 in acidic domains. We show that SUMO is involved in the maintenance of the pluripotent state in hiPSCs and identify many chromatin-associated proteins as bona fide SUMO substrates in human induced pluripotent stem cells.
Female meiosis II and pronuclear fusion require Bicaudal-D
Authors: Vazquez-Pianzola Paula , Beuchle Dirk , Saro Gabriella , Hernández Greco , Maldonado Giovanna , Brunßen Dominique , Meister Peter , Suter Beat
Published: December 2020

DrosophilaClathrin heavy chain (Chc) is transported by the dynein/dynactin microtubule motor through its interaction with the adaptor protein Bicaudal-D (BicD). Here we show thatDrosophilaBicD and Chc localize to centrosomes and spindles during mitosis and to the tandem spindles during female meiosis II. Reducing the activity of BicD::GFP specifically in freshly laid eggs revealed that BicD is essential for the production of normal female meiosis II products and for pronuclear fusion. Chc interacts with BicD and D-TACC, and BicD is needed to correctly localize the microtubule-stabilizing factors D-TACC, clathrin, and Msps to the meiosis II spindles, suggesting that BicD acts by localizing these proteins. In unfertilized eggs, reduced BicD levels cause the female meiotic products to re-enter the cell cycle. As BicD is required to localize the spindle assembly checkpoint (SAC) components Mad2 and BubR1 to the female meiotic products, it appears that BicD functions to localize them to control metaphase arrest of polar bodies. Finally,DrosophilaandC. elegansorthologs ofBicDandtaccare also needed for pronuclear fusion.