bluuebunny/crossref_metadata_2025 huggingface dataset:
A Comparative Study of 50-Millesimal Potencies and Centesimal Potencies in the Treatment of Tinea Corporis: An Open, Randomised, Pilot Trial
Authors: Hazra Pallavi , Mukherjee Shyamal Kumar , Ganguly Subhasish , Roy Aniket Singha , Dutta Souvik , Sadhukhan Satarupa , Koley Munmun , Saha Subhranil
Published: December 2021

Introduction Standard management of dermatophytosis involves the use of topical antifungals in limited disease and oral therapy for more extensive cases. Despite the evidences favouring homeopathy in tinea corporis (TC) is inadequate, patients are increasingly opting for it. This trial attempts to assess the feasibility of a trial evaluating individualised homeopathic (IH) medicines in centesimal and 50-millesimal potencies in treating TC.

Methods An open, randomised, pilot feasibility trial was conducted at the dermatology outpatient of D. N. De Homoeopathic Medical College and Hospital, West Bengal, India. Patients were randomised to receive IH medicines in either centesimal potencies (n = 30) or in 50-millesimal potencies (n = 30). Primary outcome measure was intensity of pruritus on a 0 to 10 numeric rating scale; secondary outcomes were Skindex-29 and dermatology life quality index questionnaires—all measured at baseline, and after 6 and 12 weeks of intervention. Group differences were calculated on intention-to-treat (ITT) sample as well as following per protocol (PP) analysis.

Results Recruitment and attrition rates were 69 and 16.7% respectively. Both ITT and PP analysis revealed that intra-group changes in both the primary and secondary outcomes to be statistically significant in both the groups (all p < 0.05, one-way repeated measure analysis of variance). There were no significant group differences over 6 and 12 weeks (all p > 0.05, unpaired t-tests); thus, indicating similar pattern of improvement in both the groups. Most frequently used medicines were Natrum sulphuricum (28.3%), Natrum muriaticum (25%), Sulphur (8.3%) and Bacillinum (6.7%). No harms, unintended effects, homeopathic aggravations or any serious adverse events were reported from either group.

Conclusion An adequately powered trial exploring effectiveness of both scales in TC appeared to be feasible in future. Though the sample size was too small to arrive at any definite conclusion, both centesimal and 50-millesimal potencies of IH medicines appeared to be equally useful in improving pruritus intensity and quality of life in patients suffering from TC.
Clinical Use of Tailored Computed Tomography to Prevent Poststernotomy Dehiscence
Authors: Duman Zihni M. , Timur Barış , Topel Çağdaş , Aksu Timuçin
Published: December 2021

Background Morphological and tissue density analysis of the sternum can be performed in the preoperative computed tomography (CT). The purpose of this study was to analyze morphology and tissue density of sternum in CT and effect for comparison sternal instability.

Methods Patients with sternal instability (n = 61) and sternal stability (n = 66) were enrolled in this study. All of the patients were studied using same thorax CT procedure. All the measurements were performed by one specific cardiovascular radiologist. The Hounsfield units (HUs) were measured in axial sections of the sternum trabecular bone.

Results Sternal instability group mean HU was 75.36 ± 13.19 and sternal stability group HU was 90.24 ± 12.16 (p < 0.000). HU is the statically significant predictor of sternal instability.

Conclusion Our study showed a significant correlation between the mean HU value of sternum and sternal instability. We think that it is important to evaluate the existing thorax CT while performing preoperative risk analysis for sternal dehiscence.
Totally Implantable Venous Access Device (Chemoport) in Oncology: Study of 168 Polyurethane Chemoport Catheter System
Authors: Mittal Gyanendra Swaroop , Sundriyal Deepak , Naik Niranjan B. , Sehrawat Amit
Published: December 2021

Background Chemoport (totally implantable venous access device) and its catheter system are used to administer long-term chemotherapy in cancer patients. The objective of this study was to analyze the complications associated with chemoport insertion in various cancer patients.

Material and Methods A total number of 168 chemoports along with polyurethane catheters were inserted in various cancer patients over a period of 3 years. 9.6 F polyurethane catheters were put by a team of surgical oncologists in operation theater under general or local anesthesia. Analysis of the complications was done until the chemoport was removed due to any reason.

Results Out of 168 patients, 30 (17.85%) developed complications. Complications included arterial puncture, malposition of the catheter tip, pneumothorax, hematoma, seroma, deep vein thrombosis, fracture of the catheter, a reversal of port, infections, and thrombosis of the catheter. Only a few required premature port and catheter removal.

Conclusion There was a low rate of complications associated with chemoport using a polyurethane type of catheter system. However, infection-related complications were comparatively more common in our series. Chemoport requires expert handling, patient education, strict follow-up, and dedicated teamwork to minimize complications.
Proposed Standards and Regulatory Mechanisms for New Homeopathic Drug Development
Authors: Talele Gitanjali , Shah Rajesh
Published: December 2021

Introduction Researchers working with new insights and new targets in new drug discovery in the homeopathy space observe that the path of drug-development and market authorisation has been less travelled and the pathway is not yet well-mapped. The need of the time is to define clear guidelines and regulatory mechanisms to facilitate the process of new drug discovery.

Overview The article is about the proposed methods for identifying the new homeopathic substances for therapeutic use. An overview of the current regulations for drug development in India is discussed in this article. Method of new drug development in homeopathy, standards and regulatory mechanism for approval of new drugs are proposed with few illustrations and references. An introductory plan, based on the perspective and experience of researcher, practitioner, academician and inventor for drug discovery is proposed.

Discussion An urgent need for setting up the guidelines for new drug discovery has been identified and a basic proposition is made for the same, suggesting practical, pragmatic and achievable measures, and independent regulatory body to encourage drug development and research.
Homoeopathy in the Treatment of Post-Stroke Complications: A Case Report
Authors: Dutta Abhijit
Published: December 2021

Background Long-term muscular and neuropsychiatric complications are common in stroke survivors. The main aim of therapeutic modalities for such cases is to limit the extent of disabilities and subsequent increase in the activity of daily living. Every case is different in pathology and manifestation, so requires an individualistic approach.

Case A 63-year-old man presented with right upper limb weakness, dysarthria and memory weakness after stroke. He had been undergoing conventional physical rehabilitation therapy but due to feasibility issues, he could not continue and opted for homoeopathic treatment. Following a thorough clinical and psychological evaluation, he was treated with homoeopathic medicines tailored to his specific needs. The Medical Research Council scale for muscle power, the Modified Ashworth Scale for muscle spasticity and the Stroke Impact Scale for quality of life after stroke were used to assess outcomes at various time points. Different physical and cognitive domains showed gradual improvement.

Conclusion This case demonstrates the complexities of clinical outcomes following a stroke and how those can be improved through the individualistic approach of homoeopathy. Nevertheless, a firm conclusion regarding causal attribution cannot be drawn from a single case, but a detailed clinical approach may be followed. Large-sample randomised controlled trials are impractical for the individualised approach of therapy or complex clinical conditions; thus, the ‘n-of-1’ trial may be adopted in the long run.
Fagus sylvatica C4 Trituration Proving and Clinical Applications
Authors: Renoux Hélène
Published: December 2021

Fagus sylvatica, the beech, has long been linked to European history, along with the oak. This homeopathic trituration proving reports on the main pathogenetic themes which led to successful prescriptions. Stiffness of the shoulders, alternating symptoms and love for forests appear to be key symptoms. More study of this remedy, and more prescriptions would be necessary to explore widely the many possibilities of this homeopathic medicine.
Evolution of Hair Transplant Surgery in India: A Plastic Surgeon's Perspective
Authors: Ramachandran K.
Published: December 2021

This article is mainly aimed to delve into the history of hair transplant and its evolution in India. As a plastic surgeon in practice for the past 35 years, I have seen hair transplant surgery undergoing various transformations starting with initial use of plugs and flaps. Scalp reduction surgery also played an important role. Plugs slowly gave way to mini- and micrografts. With the incorporation of the microscope and popularizing of strip surgery and improved slivering techniques, mega sessions came to the fore thereby covering large areas. Follicular unit extraction and use of body hair have also been discussed.
Quantum communication with time-bin entanglement over a wavelength-multiplexed fiber network
Authors: Kim Jin-Hun , Chae Jin-Woo , Jeong Youn-Chang , Kim Yoon-Ho
Published: December 2021

In a quantum network involving multiple communicating parties, an important goal is to establish high-quality pairwise entanglement among the users without introducing multiple entangled-photon sources which would necessarily complicate the overall network setup. Moreover, it is preferable that the pairwise entanglement of photons is in the time-bin degree of freedom as the photonic time-bin qubit is ideally suited for fiber-optic distribution. Here, we report an experimental demonstration of a field-deployable quantum communication network involving multiple users, all of whom share pairwise entanglement in the time-bin degree of freedom of photons. In particular, by utilizing a single spontaneous-parametric down-conversion source which produces a broadband pair of photons and the wavelength-division demultiplexing/multiplexing technology, all the communicating parties within the network are always simultaneously ready for quantum communication. To further demonstrate the practical feasibility of a quantum network with time-bin entanglement over a wavelength-multiplexed fiber network, we demonstrate entangled-photon quantum key distribution with three users, each separated by 60 km of optical fibers.
Microwave absorption properties of rare earth alloy Nd2Co17@C/Na2SiO3 composite at elevated temperature (293–723 K) in the X band
Authors: Zou Yang , Qi Zhaohui , Zheng Zuying , He Donglin , Wang Guowu , Wang Tao
Published: December 2021

A variety of new challenges are being faced in the development of high temperature microwave absorbing materials in the X band. Recently, some of the 2:17 phase rare-earth soft magnetic alloys with high permeability and curie temperature have shown potential to be novel X band high temperature microwave absorbing materials. In this paper, a high temperature microwave absorbing material (Nd2Co17@C/Na2SiO3) is prepared with Nd2Co17 as the raw material. After carbon cladding and Na2SiO3 treatment, the composite can work stably at 723 K. The calculated absorption properties display that the reflection loss intensity of the composite with a thickness of 1.5 mm is below −6 dB in the whole X band. Moreover, the thermogravimetric analysis results and static magnetic properties before and after sintering indicate that the material has excellent resistance to oxidation. Rare earth alloy materials provide a new possibility for the research of innovative high temperature absorbing materials.
Inversion method for measuring multi-hole probe surface pressure distribution of supersonic compressible atmospheric flow field
Authors: Zhang Yang-Chun , Zhou Shu-Dao , Ye Song , Wang Min , Yao Tao
Published: December 2021

The conventional method of measuring a multi-hole probe is based on Bernoulli’s equation and suffers from certain model errors. A computational fluid dynamics-based method was used in this study to reduce the theoretical error and establish a parametric model of the surface pressure of a spherical multi-hole pressure probe for measuring compressible flow fields at supersonic velocities. A flow field inversion method based on the parametric model is proposed herein. Numerical simulations were conducted to validate the proposed method. The experiment results show that in the compressible atmospheric flow field within Mach 1.2–1.7, the measurement errors of the inversion method were 1.3% and 2.35% for velocity and angle, respectively, thus verifying the feasibility of the method. Thus, a new method of measuring multi-hole pressure probe atmospheric flow fields was demonstrated.
Correlation between morphology and local mechanical and electrical properties of van der Waals heterostructures
Authors: Vasić Borislav , Ralević Uroš , Aškrabić Sonja , Čapeta Davor , Kralj Marko
Published: December 2021

Properties of van der Waals (vdW) heterostructures strongly depend on the quality of the interface between two dimensional (2D) layers. Instead of having atomically flat, clean, and chemically inert interfaces without dangling bonds, top-down vdW heterostructures are associated with bubbles and intercalated layers (ILs) which trap contaminations appeared during fabrication process. We investigate their influence on local electrical and mechanical properties of MoS2/WS2 heterostructures using atomic force microscopy (AFM) based methods. It is demonstrated that domains containing bubbles and ILs are locally softer, with increased friction and energy dissipation. Since they prevent sharp interfaces and efficient charge transfer between 2D layers, electrical current and contact potential difference are strongly decreased. In order to reestablish a close contact between MoS2 and WS2 layers, vdW heterostructures were locally flattened by scanning with AFM tip in contact mode or just locally pressed with an increased normal load. Subsequent electrical measurements reveal that the contact potential difference between two layers strongly increases due to enabled charge transfer, while local I/V curves exhibit increased conductivity without undesired potential barriers.
Simply equipped ε-Ga2O3 film/ZnO nanoparticle heterojunction for self-powered deep UV sensor
Authors: Mei Tong , Li Shan , Zhang Shaohui , Liu Yuanyuan , Li Peigang
Published: December 2021

In this paper, a ε-Ga2O3 film/ZnO nanoparticle hybrid heterojunction deep ultraviolet (UV) photodetector is described for 254 nm wavelength sensing application. The constructed ε-Ga2O3/ZnO heterojunction photodetector can operate in dual modes which are power supply mode and self-powered mode. Under reverse 5 V bias with 254 nm light intensity of 500 μW cm−2, the photoresponsivity, specific detectivity and external quantum efficiency are 59.7 mA W−1, 7.83 × 1012 Jones and 29.2%. At zero bias, the advanced ε-Ga2O3/ZnO photodetector performs decent self-powered photoelectrical properties with photo-to-dark current ratio of 1.28 × 105, on/off switching ratio of 3.22 × 104, rise/decay times of 523.1/31.7 ms, responsivity of 4.12 mA W−1 and detectivity of 2.24 × 1012 Jones. The prominent photodetection performance lays a solid foundation for ε-Ga2O3/ZnO heterojunction in deep UV sensor application.
Neutrino beam driven instability of magnetosonic waves in the presence of oblique magnetic field and ion-neutral collisional effect in plasmas
Authors: Aftab H , Hussain S , Mahmood S , Haseeb M , Hasnain H
Published: December 2021

The neutrino beam driven instability of fast and slow magnetosonic waves with oblique applied magnetic field in multi-component ion, electron and neutrino beam plasma is studied. The dissipation effects of ion-neutral collisions are also included in the model. The neutrino and electron interactions through electro-weak force are included. It is found that the dissipation of ion collisions has significant effect on the phase velocity of the wave propagation and growth rate of the neutrino beam driven instability. The analytical expression of the growth rate of the fast and slow magnetosonic waves instability is found under the weak neutrino beam approximation and in the absence of ions and neutrals (atoms) collision effect. The numerical illustration of growth rates of the fast and slow magnetosonic waves are also presented with variations of magnetic field angle, neutrino beam energy, neutrino beam density, magnetic field intensity. It is found that the growth rate of the fast magnetosonic wave is maximum in case of the perpendicular directed magnetic field to the direction of wave propagation, while growth rate of slow magnetosonic wave is minimum in that case. It is also noticed that growth rate of fast magnetosonic wave comes out to be larger (of the order tens) than the slow magnetosonic wave case, which is quite different from earlier published results of Type II core-collapse supernova.
A simple and comprehensive electromagnetic theory uncovering complete picture of light transport in birefringent crystals
Authors: Pan Jianbo , Chen Jianfeng , Hong Lihong , Long Li , Li Zhi-Yuan
Published: December 2021

Birefringence production of light by natural birefringent crystal has long been studied and well understood. Here, we develop a simple and comprehensive rigorous electromagnetic theory that allows one to build up the complete picture about the optics of crystals in a friendly way. This theory not only yields the well-known refraction angle and index of ellipse for birefringence crystal, but also discloses many relevant physical and optical quantities that are rarely studied and less understood. We obtain the reflection and transmission coefficient for amplitude and intensity of light at the crystal surface under a given incident angle and show the electromagnetic field distribution within the crystal. We derive the wavefront and energy flux refraction angle of light and the corresponding phase and ray refractive index. We find big difference between them, where the phase refractive index satisfies the classical index of ellipse and Snell’s law, while the ray refractive index does not. Moreover, we disclose the explicit expressions for the zero-reflection Brewster angle and the critical angle for total internal reflection. For better concept demonstration, we take a weak birefringent crystal of lithium niobate and a strong birefringent crystal tellurium as examples and perform simple theoretical calculations. In addition, we perform experimental measurement upon z-cut lithium niobate plate and find excellent agreement between theory and experiment in regard to the Brewster angle. Our theoretical and experimental results can help to construct a clear and complete picture about light transport characteristics in birefringent crystals, and may greatly facilitate people to find rigorous solution to many light–matter interaction processes happening within birefringent crystals, e.g., nonlinear optical interactions, with electromagnetic theory.
Achievements of actively controlled divertor detachment compatible with sustained high confinement core in DIII-D and EAST
Authors: Wang L. , Wang H.Q. , Eldon D. , Yuan Q.P. , Ding S. , Li K.D. , Garofalo A.M. , Gong X.Z. , Xu G.S. , Guo H.Y. , Wu K. , Meng L.Y. , Xu J.C. , Liu J.B. , Chen M.W. , Zhang B. , Duan Y.M. , Ding F. , Yang Z.S. , Qian J.P. , Huang J. , Ren Q.L. , Leonard A.W. , Fenstermacher M. , Lasnier C. , Watkins J.G. , Shafer M.W. , Barr J. , Weisberg D. , McClenaghan J. , Hanson J. , Hyatt A. , Osborne T. , Thomas D. , Humphreys D. , Buttery R.J. , Luo G.-N. , Xiao B.J. , Wan B.N. , Li J.G.
Published: December 2021

The compatibility of efficient divertor detachment with high-performance core plasma is vital to the development of magnetically controlled fusion energy. The joint research on the EAST and DIII-D tokamaks demonstrates successful integration of divertor detachment with excellent core plasma confinement quality, a milestone towards solving the critical plasma–wall-interaction (PWI) issue and core-edge integration for ITER and future reactors. In EAST, actively controlled partial detachment with T
et,div ∼ 5 eV around the strike point and H
98 > 1 in different H-mode scenarios including the high β
P H-mode scenario have been achieved with ITER-like tungsten divertor, by optimizing the detachment access condition and performing detailed experiments for core-edge integration. For active long-pulse detachment feedback control, a 30 s H-mode operation with detachment-control duration being 25 s has been successfully achieved in EAST. DIII-D has achieved actively controlled fully detached divertor with low plasma electron temperature (T
et,div ⩽ 5 eV across the entire divertor target) and low particle flux (degree of detachment, DoD > 3), simultaneously with very high core performance (β
N ∼3, β
P > 2 and H
98 ∼ 1.5) in the high βP scenario being developed for ITER and future reactors. The high-β
P high confinement scenario is characterized by an internal transport barrier (ITB) at large radius and a weak edge transport barrier (ETB, or pedestal), which are synergistically self-organized. Both the high-β
P scenario and impurity seeding facilitate divertor detachment. The detachment access leads to the reduction of ETB, which facilitates the development of an even stronger ITB at large radius in the high β
P scenario. Thus, this strong large radius ITB enables the core confinement improvement during detachment. These significant joint DIII-D and EAST advances on the compatibility of high confinement core and detached divertor show a great potential for achieving a high-performance core plasma suitable for long-pulse operation of fusion reactors with controllable steady-state PWIs.
Accelerating the estimation of collisionless energetic particle confinement statistics in stellarators using multifidelity Monte Carlo
Authors: Law Frederick , Cerfon Antoine , Peherstorfer Benjamin
Published: December 2021

In the design of stellarators, energetic particle confinement is a critical point of concern which remains challenging to study from a numerical point of view. Standard Monte Carlo (MC) analyses are highly expensive because a large number of particle trajectories need to be integrated over long time scales, and small time steps must be taken to accurately capture the features of the wide variety of trajectories. Even when they are based on guiding center trajectories, as opposed to full-orbit trajectories, these standard MC studies are too expensive to be included in most stellarator optimization codes. We present the first multifidelity Monte Carlo (MFMC) scheme for accelerating the estimation of energetic particle confinement in stellarators. Our approach relies on a two-level hierarchy, in which a guiding center model serves as the high-fidelity model, and a data-driven linear interpolant is leveraged as the low-fidelity surrogate model. We apply MFMC to the study of energetic particle confinement in a four-period quasi-helically symmetric stellarator, assessing various metrics of confinement. Stemming from the very high computational efficiency of our surrogate model as well as its sufficient correlation to the high-fidelity model, we obtain speedups of up to 10 with MFMC compared to standard MC.
Critical minerals for electric vehicles: a telecoupling review
Authors: Agusdinata Datu Buyung , Eakin Hallie , Liu Wenjuan
Published: December 2021

The rapid growth of electric vehicles adoption, which plays a crucial role to reduce transportation carbon emissions, is leading to a surge in demand for critical minerals such as cobalt, nickel, lithium, and rare earths. Efforts to systematically address the emerging sustainability issues associated with critical minerals have been challenged by complex mineral supply chains, and the distal and geographically dispersed nature of social-ecological impacts from mineral extraction and processing and eventual use. In this review, we apply a bibliometric analysis of the literature in the 2010–2020 period to analyze the state of research on the issues of critical mineral extraction impacts and the global governance responses. We use the concept of telecoupling to structure our literature search and analysis across four themes: (a) critical minerals global trade and supply chain, (b) sustainability and resource policy and governance, (c) mining corporate social responsibility, and (d) information feedback and public discourse. We find a growing attention to the social-ecological implications of critical mineral extraction, but also fragmentation among thematic domains that could impede progress towards more coordinated system governance. Based on the analyses, the paper concludes with a definition of some research and engagement opportunities around the telecoupling themes.
Probing vortex beams based on Talbot effect with two overlapping gratings
Authors: Buathong Sitti , Srisuphaphon Sorakrai , Deachapunya Sarayut
Published: December 2021

In a prior report the optical vortex was characterized using the near-field Talbot effect (Panthong et al 2016 J. Opt.
18 035602; Panthong
et al 2018 Appl. Opt.
57 1657). This near-field technique can resolve both order and charge of the orbital angular momentum state of the vortex beam. We have proposed before that a small open fraction of the grating in the Talbot configuration can improve the image contrast (Srisuphaphon et al 2020 J. Opt. Soc. Am. B 37 2021). In this study, we combine these previously reported techniques, i.e. the Talbot effect for probing an optical vortex and overlapping gratings to manipulate the open fraction. Both theoretical simulation and experimental demonstration are presented here. We believe that our technique can be an alternative method for optical vortex imaging, and could be useful in optical applications.
Doping dependent electronic and magnetic ordering in mixed-valent La1−x
Sr
x
MnO3 thin films
Authors: Payne J A , Bryant C T , Marquez Tavera R , Brown D T , Pekarek T M , Warusawithana M P
Published: December 2021

We have investigated the collective electronic and magnetic orderings of a series of La1−x
Sr
x
MnO3 thin films grown epitaxially strained to (001) oriented strontium titanate substrates as a function of doping, x, for 0 ≤ x ≤ 0.4. We find that the ground states of these crystalline thin films are, in general, consistent with that observed in bulk crystals and thin film samples synthesized under a multitude of techniques. Our systematic study, however, reveal subtle features in the temperature dependent electronic transport and magnetization measurements, which presumably arise due to Jahn-Teller type distortions in the lattice for particular doping levels. For the parent compound LaMnO3 (x = 0), we report evidence of a strain-induced ferromagnetic ordering in contrast to the antiferromagnetic ground state found in bulk crystals.
Three-Dimensional Arterial Distribution Over the Midline of the Nasal Bone
Authors: Cong Li-Yao , Liao Zhi-Feng , Zhang Yun-Song , Li Dong-Ni , Luo Sheng-Kang
Published: December 2021

Background

A comprehensive understanding of arterial variations around the midline of the nose is of great importance for the safety of filler injection.

Objectives

The aim of the study was to clearly define the 3-dimensional location of the arteries along the midline of the nasal bone.

Methods

The arterial structures overlapping the nasal bone along the midline were observed in 79 cadavers.

Results

The present study found that 0 to 3 named arteries per nose segment could be identified. All the arterial structures were located in or above the superficial musculoaponeurotic system layer overlapping the nasal bone. The probability of encountering named arteries at 5 defined points, P1 to P5, was 5/79 (6.3%), 4/79 (5.1%), 1/79 (1.3%), 6/79 (7.6%), and 9/79 (11.4%), respectively. The depth of the main arterial trunk was 1.2 ± 0.4 mm, 1.6 ± 0.6 mm, 1.8 ± 0 mm, 1.0 ± 0.4 mm, and 0.9 ± 0.5 mm below the skin at P1 to P5, respectively.

Conclusions

The authors confirmed that sub-superficial musculoaponeurotic system injection along the midline through a needle is anatomically reliable and that a technique with 1 entry point through the rhinion via a cannula can easily keep the needle sufficiently deep for safe nasal filler injection.
Robust disease module mining via enumeration of diverse prize-collecting Steiner trees
Authors: Bernett Judith , Krupke Dominik , Sadegh Sepideh , Baumbach Jan , Fekete Sándor P , Kacprowski Tim , List Markus , Blumenthal David B
Published: December 2021

Motivation

Disease module mining methods (DMMMs) extract subgraphs that constitute candidate disease mechanisms from molecular interaction networks such as protein–protein interaction (PPI) networks. Irrespective of the employed models, DMMMs typically include non-robust steps in their workflows, i.e. the computed subnetworks vary when running the DMMMs multiple times on equivalent input. This lack of robustness has a negative effect on the trustworthiness of the obtained subnetworks and is hence detrimental for the widespread adoption of DMMMs in the biomedical sciences.

Results

To overcome this problem, we present a new DMMM called ROBUST (robust disease module mining via enumeration of diverse prize-collecting Steiner trees). In a large-scale empirical evaluation, we show that ROBUST outperforms competing methods in terms of robustness, scalability and, in most settings, functional relevance of the produced modules, measured via KEGG (Kyoto Encyclopedia of Genes and Genomes) gene set enrichment scores and overlap with DisGeNET disease genes.

Availability and implementation

A Python 3 implementation and scripts to reproduce the results reported in this article are available on GitHub: https://github.com/bionetslab/robust, https://github.com/bionetslab/robust-eval.

Supplementary information

Supplementary data are available at Bioinformatics online.
MedTator: a serverless annotation tool for corpus development
Authors: He Huan , Fu Sunyang , Wang Liwei , Liu Sijia , Wen Andrew , Liu Hongfang
Published: December 2021

Building a high-quality annotation corpus requires expenditure of considerable time and expertise, particularly for biomedical and clinical research applications. Most existing annotation tools provide many advanced features to cover a variety of needs where the installation, integration and difficulty of use present a significant burden for actual annotation tasks. Here, we present MedTator, a serverless annotation tool, aiming to provide an intuitive and interactive user interface that focuses on the core steps related to corpus annotation, such as document annotation, corpus summarization, annotation export and annotation adjudication.

Availability and implementation

MedTator and its tutorial are freely available from https://ohnlp.github.io/MedTator. MedTator source code is available under the Apache 2.0 license: https://github.com/OHNLP/MedTator.

Supplementary information

Supplementary data are available at Bioinformatics online.
How to promote the child welfare approach? A qualitative content analysis study in Iran
Authors: Takaffoli Marzieh , Arshi Maliheh , Vameghi Meroe , Mousavi Mir Taher , Shati Mohsen
Published: December 2021

Protecting children and developing their well-being have become a great concern in Iran. But policies and services for in-need or at-risk children often follow unintegrated and even incongruous approaches. To address this gap, this study aimed to develop a promoted approach to child welfare to integrate the practices and policies. The conventional qualitative content analysis was applied to in-depth interviews conducted with child welfare experts in Iran. Purposeful and theoretical sampling was used until data saturation was gained by fifty-six qualitative interviews. The interviews were analysed simultaneously using MAXQDA 2018 software. Findings of the study present an approach to reform and promote child welfare in Iran, including four main categories: (i) custodianship of government to child welfare issues; (ii) the holistic, universal and systemic approach to the child welfare system, (iii) child-centred approach; and (iv) family-centred approach. According to the experts’ opinion, in the first place, it is necessary to accept the government’s custodial and responsible role for children that allow authorities to intervene in families regarding children’s best interests. Also, the child-centred approach should be addressed more profoundly and both family-centred and child-centred approaches should be developed concurrently and intently.
A genuine interindividual variability in number and anatomical localization of face-selective regions in the human brain
Authors: Gao Xiaoqing , Wen Minjie , Sun Mengdan , Rossion Bruno
Published: December 2021

Neuroimaging studies have reported regions with more neural activation to face than nonface stimuli in the human occipitotemporal cortex for three decades. Here we used a highly sensitive and reliable frequency-tagging functional magnetic resonance imaging paradigm measuring high-level face-selective neural activity to assess interindividual variability in the localization and number of face-selective clusters. Although the majority of these clusters are located in the same cortical gyri and sulci across 25 adult brains, a volume-based analysis of unsmoothed data reveals a large amount of interindividual variability in their spatial distribution and number, particularly in the ventral occipitotemporal cortex. In contrast to the widely held assumption, these face-selective clusters cannot be objectively related on a one-to-one basis across individual brains, do not correspond to a single cytoarchitectonic region, and are not clearly demarcated by estimated posteroanterior cytoarchitectonic borders. Interindividual variability in localization and number of cortical face-selective clusters does not appear to be due to the measurement noise but seems to be genuine, casting doubt on definite labeling and interindividual correspondence of face-selective “areas” and questioning their a priori definition based on cytoarchitectony or probabilistic atlases of independent datasets. These observations challenge conventional models of human face recognition based on a fixed number of discrete neurofunctional information processing stages.
Compassionate Use of REGEN-COV® in Patients With Coronavirus Disease 2019 (COVID-19) and Immunodeficiency-Associated Antibody Disorders
Authors: Stein David , Oviedo-Orta Ernesto , Kampman Wendy A , McGinniss Jennifer , Betts George , McDermott Margaret , Holly Beth , Lancaster Johnathan M , Braunstein Ned , Yancopoulos George D , Weinreich David M
Published: December 2021

Background

Patients with immunodeficiency-associated antibody disorders are at a higher risk of prolonged/persistent COVID-19 infection, having no viable treatment options.

Methods

A retrospective analysis of patients with primary and/or secondary immunodeficiency-associated antibody disorders who received casirivimab and imdevimab (REGEN-COV®) under emergency compassionate use. Objective were to describe safety and response to REGEN-COV, focusing on the subset of patients who had COVID-19 duration ≥21 days before treatment.

Results

Quantitative (change in oxygenation status and/or viral load) and/or qualitative (physician-reported clinical status) outcomes data are reported from 64 patients. Improvement in ≥1 outcome was observed in 90.6% of the overall patient group. Thirty-seven of these had COVID-19 duration ≥21 days before treatment; median time from diagnosis to REGEN-COV treatment was 60.5 days. Of the 29 patients with COVID-19 duration ≥21 days before treatment and available outcome data, 96.6% showed improvement in ≥1 outcome. In the 14 patients with post-treatment reverse transcription–polymerase chain reaction (RT-PCR) results available, 11 (78.6%) reported a negative RT-PCR following treatment, with 5 (45.5%) and 8 (72.7%) patients reporting a negative RT-PCR within 5 days and 21 days of treatment, respectively. Ten of 85 patients (11.8%) experienced serious adverse events; only one was an infusion-related reaction, possibly related to REGEN-COV. Two deaths were reported; neither were attributed to REGEN-COV.

Conclusions

In this retrospective analysis of immunodeficient patients granted REGEN-COV under emergency compassionate use, REGEN-COV treatment was associated with rapid viral clearance and clinical improvement in patients with longstanding COVID-19. Adverse events were consistent with COVID-19 and its associated complications, and due to patients’ concurrent medical conditions.
Herpes Simplex Virus 2 Meningitis in Adults: A Prospective, Nationwide, Population-Based Cohort Study
Authors: Jakobsen Anna , Skov Marie Thaarup , Larsen Lykke , Trier Petersen Pelle , Brandt Christian , Wiese Lothar , Hansen Birgitte Rønde , Lüttichau Hans Rudolf , Tetens Malte Mose , Helweg-Larsen Jannik , Storgaard Merete , Nielsen Henrik , Bodilsen Jacob
Published: December 2021

Background

Data on the clinical presentation are scarce and prognostic factors of herpes simplex virus type 2 (HSV-2) meningitis remain unknown.

Methods

Prospective, nationwide, population-based database identifying all adults treated for HSV-2 meningitis at departments of infectious diseases in Denmark from 2015 to 2020. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) scores of 1–4 and Extended GOS scores of 1–6. Modified Poisson regression was used to compute relative risks with 95% confidence intervals for unfavorable outcome.

Results

HSV-2 meningitis was diagnosed in 205 patients (76% female; median age [interquartile range (IQR)], 35 [27–49] years) yielding an incidence of 0.7/100 000 population/y. Common symptoms were headache (195 of 204 patients [95%]), photophobia or phonophobia (143 of 188 [76%]), and neck stiffness (106 of 196 [54%]). The median (IQR) time to lumbar puncture was 2.0 (1–4.8) hours, and the median cerebrospinal fluid (CSF) leukocyte count was 360 (166–670) × 10 × 6/L, with a mononuclear predominance of 97% (91%–99%). Lumbar puncture was preceded by brain imaging in 61 of 205 patients (30%). Acyclovir or valacyclovir was administered in 197 of 205 patients (96%) for a median (IQR) of 10 (7–14) days. Unfavorable outcome was observed in 64 of 205 patients (31%) at discharge and 19 of 181 (11%) after 6 months and was not associated with female sex (relative risk [95% confidence interval], 1.08 [.65–1.79]), age ≥35 years (1.28 [.83–1.97]), immunocompromise (1.07 [.57–2.03]), or CSF leukocyte count >1000 × 10 × 6/L (0.78 [.33–1.84]).

Conclusions

HSV-2 meningitis often presented as meningeal symptoms in younger women. Unfavorable outcome at discharge was common and was not associated with sex, age, immunocompromise, or CSF leukocyte count. Sequelae persisted beyond 6 months in one-tenth of patients.
Parent–offspring and inter-offspring responses to conspecific versus heterospecific distress calls in 2 sympatric birds
Authors: Jiang Yuxin , Han Jingru , Zhang Ziqi , Chen Xiangyang , Yang Canchao
Published: December 2021

Distress calls, as a type of alarm call, play important roles in expressing bodily condition and conveying information concerning predation threats. In this study, we examined the communication via distress calls in parent–offspring and inter-offspring interactions. First, we used playback of chick distress calls of 2 sympatric breeders, the vinous-throated parrotbill Sinosuthora webbiana and the oriental reed warbler Acrocephalus orientalis, to the adults/chicks of these 2 species, respectively, and measured the responses of conspecifics or heterospecifics. The playback-to-chicks experiment showed that both species of chicks reduced the number of begging calls and begging duration time as a response to conspecific/heterospecific distress calls compared with natural begging and background noise controls. However, reed warbler chicks also reduced beak opening frequency in the response to conspecific distress calls compared with other playback stimuli. Second, the results of the playback-to-adults experiment showed that reed warbler adults could eavesdrop on distress calls of conspecific neighbors and sympatric heterospecifics. Furthermore, the nest-leaving behavior of reed warblers did not differ significantly when they heard the distress calls of conspecifics or parrotbills. Finally, reed warbler adults responded to heterospecific distress calls more quickly than to conspecific distress calls, and parrotbill adults presented the same response. Our results supported the warn-kin hypothesis and show that chick distress calls play an important role in conveying risk and the condition of chicks to enhance individual fitness. In addition, we also found that eavesdropping on distress calls is a congenital behavior that begins in the chick stage.
Resources for cardiovascular healthcare associated with 30-day mortality in acute myocardial infarction with cardiogenic shock
Authors: Ishii Masanobu , Tsujita Kenichi , Okamoto Hiroshi , Koto Satoshi , Nishi Takeshi , Nakai Michikazu , Sumita Yoko , Iwanaga Yoshitaka , Azuma Nobuyoshi , Matoba Satoaki , Hirata Ken-Ichi , Hikichi Yutaka , Yokoi Hiroyoshi , Ikari Yuji , Uemura Shiro
Published: December 2021

Aims

Although primary percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS), such as extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pumping (IABP), have been widely used for acute myocardial infarction (AMI) patients with cardiogenic shock (AMICS), their in-hospital mortality remains high. This study aimed to investigate the association of cardiovascular healthcare resources with 30-day mortality in AMICS.

Methods and results

This was an observational study using a Japanese nationwide administrative data (JROAD-DPC) of 260 543 AMI patients between April 2012 and March 2018. Of these, 45 836 AMICS patients were divided into three categories based on MCS use: with MCS (ECMO with/without IABP), IABP only, or without MCS. Certified hospital density and number of board-certified cardiologists were used as a metric of cardiovascular healthcare resources. We estimated the association of MCS use, cardiovascular healthcare resources, and 30-day mortality. The 30-day mortality was 71.2% for the MCS, 23.9% for IABP only, and 37.8% for the group without MCS. The propensity score-matched and inverse probability-weighted Cox frailty models showed that primary PCI was associated with a low risk for mortality. Higher hospital density and larger number of cardiologists in the responsible hospitals were associated with a lower risk for mortality.

Conclusion

Although the 30-day mortality remained extremely high in AMICS, indication of primary PCI and improvement in providing cardiovascular healthcare resources associated with the short-term prognosis of AMICS.
Patience, Risk-Taking, and Human Capital Investment Across Countries
Authors: Hanushek Eric A , Kinne Lavinia , Lergetporer Philipp , Woessmann Ludger
Published: December 2021

Patience and risk-taking—two preference components that steer intertemporal decision-making—are fundamental to human capital investment decisions. To understand how they contribute to international skill differences, we combine Programme for International Student Assessment tests with the Global Preference Survey. We find that opposing effects of patience (positive) and risk-taking (negative) together account for two-thirds of the cross-country variation in student skills. In an identification strategy addressing unobserved residence country features, we find similar results when assigning migrant students their country-of-origin preferences in models with residence country fixed effects. Associations of national preferences with family and school inputs suggest that both may act as channels.
Overlapping effects of miR-21 inhibition and drugs for idiopathic pulmonary fibrosis in the post-myocardial infarction setting
Authors: Aimo A , Iborra Egea O , Passino C , Emdin M
Published: December 2021

Background

Intracoronary infusion of a specific miR-21 inhibitor after reperfused MI has been reported to reduce cardiac fibrosis and hypertrophy and improve cardiac function in pigs. Possible drawbacks of anti-miR-21 therapy are the high costs of this therapy, and the need for intracoronary administration, preferably some days after reperfusion. Oral drugs with anti-fibrotic actions could have similar effects than anti-miR-21, while overcoming the limitations of anti-miR-21. We tested this hypothesis by examining the two oral drugs approved for idiopathic pulmonary fibrosis (nintedanib and pirfenidone).

Methods

We identified the regulatory profile of miR-21, which included 588 target genes. Only 99 of these interactions were supported by information from reporter gene assays. The biological significance of these 99 targets was evaluated through over-representation analysis, and 13 genes were identified as potentially related to cardiovascular diseases. We retrieved all known targets and main downstream interactions of nintedanib and pirfenidone from Drugbank. Finally, we cross-validated these datasets by using neural network analyses to search for protein-protein interactions, focusing on those shared by miR-21 inhibition, nintedanib and pirfenidone.

Results

Nintedanib and anti-miR21 had many targets in common, which could indicate an overlap in their corresponding mechanisms of action. The proto-oncogene SRC, which participates in gene transcription, immune response, apoptosis and migration, emerged as the leading signaling effector. By blocking SRC expression and many downstream effectors of SRC, as well as platelet-derived growth factor, nintedanib could decreased miR-21 expression. The molecular effects of nintedanib include inhibition of inflammation, fibrosis and angiogenesis, and then ultimately a relief from I/R injury, in a similar fashion than anti-miR-21. Contrary to nintedanib, no overlap between the effects of pirfenidone and anti-miR-21 was found.

Conclusion

Because of the remarkably strong overlapping with the targets of miR-21, there is a stronger rationale to assess nintedanib than pirfenidone as a cardioprotective therapy. If confirmed by experimental evidence, nintedanib could enter the stage of clinical trials to assess its efficacy in human patients with STEMI.

Funding Acknowledgement

Type of funding sources: None.