bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the Chinese Subfamily Anostostomatinae (Orthoptera: Anostostomatidae) IV: One new recorded species Anabropsis (Apteranabropsis) tonkinensis Rehn, 1906
Authors: LU XIANGYI , LIU JING , BIAN XUN
Published: February 2022

This paper is the fourth study of the subfamily Anostostomatinae from China and reports one newly recorded species, Anabropsis (Apteranabropsis) tonkinensis Rehn, 1906. Also, we reported the mitochondrial genome and inferred the phylogenic relationship among the genus Anabropsis based on two specimens. Two complete mitogenomes were 16059 and 16052 bp in size and consisted of 37 genes and a control region. The overall base composition exhibited a clear AT bias. Most protein-coding genes started with the codon ATN and ended with typical stop codons TAA. The phylogenetic analyses based on mitogenomes and several morphological characteristics provided meaningful genetic information for Anabropsis and validated the phylogenetic relationships among the subgenera.
Discovery of a new species of Euphlyctis (Anura: Dicroglossidae) from the western coastal plains of peninsular India
Authors: DINESH K.P. , CHANNAKESHAVAMURTHY B.H. , DEEPAK P. , SHABNAM A. , GHOSH AVRAJJAL , DEUTI KAUSHIK
Published: February 2022

The aquatic frog genus ‘Euphlyctis’ is now considered under two separate genera- Euphlyctis Fitzinger and Phrynoderma Fitzinger, with four valid species in each genus, respectively. The current distribution range of the genus Phrynoderma is restricted to peninsular India and Bangladesh, with a probability of availability in Sri Lanka. The genus Euphlyctis has a wide range of distribution from the Arabian Peninsula and the South Asian countries, with a few historical descriptions treated as junior synonyms of the species Euphlyctis cyanophlyctis in India. A new species of skittering frog, Euphlyctis jaladhara sp. nov. is described here from the surroundings of the Thattekad Bird Sanctuary of Kerala, India, which has a predominant distribution in the western coastal plains of peninsular India and some parts of the Western Ghats. The new species has distinct morphological characters and a high genetic distance that distinguishes it from the sympatric species. Discussions are made concerning the validity of the species E. ghoshi and E. kalasgramensis.
Cotransplantation with RADA16-PRG-Self-Assembled Nanopeptide Scaffolds, Bone Mesenchymal Stem Cells and Brain-Derived Neurotrophic Factor-Adeno-Associated Virus Promote Functional Repair After Acute Spinal Cord Injury in Rats
Authors: Luo Hongbin , Chen Xuemin , Zhuang Peifeng , Wu Songye , Wei Jie , Xu Weihong
Published: February 2022

We transplanted RADA16-PRG self-assembled nanopeptide scaffolds (SAPNSs), bone mesenchymal stem cells (BMSCs), and a brain-derived neurotrophic factor (BDNF)-expressing adeno-associated virus (AAV) into rats subjected to acute spinal cord injury (SCI) to investigate the effects of these
transplantations on acute SCI repair and explore their mechanisms. Forty-eight SCI rats were randomly divided into four groups: BBR, BR, B, and NC groups. Seven and 28 days after SCI, evoked potentials (EPs) and BBB scores were assessed to evaluate the recovery of rats’ motor behavior
and sensory function after injury. HE and toluidine blue staining were performed to investigate the histological structure of the spinal cord tissue of rats from each group, and immunofluorescence staining was used to observe the red fluorescent protein (RFP) intensity of BMSCs and glial fibrillary
acidic protein (GFAP) and neurofilament (NF) in the damaged area in each group. RT–PCR was utilized to detect the expression levels of the BDNF, GFAP, and neuron-specific enolase (NSE) genes in the injured area in each group. The results showed that cotransplantation of RADA16-PRG-SAPNs,
BMSCs, and BDNF-AVV promoted the spinal cord’s motor and sensory function of SCI rats; increased levels of BMSCs, inhabited glial cells proliferation, and promoted neurons proliferations in the injured area; and increased NF, BDNF, and NSE levels and decreased its GFAP in the injured
area. Thus, cotransplantation of RADA16-PRG-SAPNS, BMSCs, and BDNF-AAV can prolong the survival time of BMSCs in rats, reduce the postoperative scarring caused by glial proliferation, and promote the migration and proliferation of neurons in the injured area, resulting in the promotion of
functional repair after acute SCI.
Preparation and Biocompatibility Evaluation of Nanoscale Isoniazide-Loaded Mineralized Collagen Implants for Tuberculous Bone and Joint Repair
Authors: Fang Xu , Dong Jun-Feng , Wang Qian , Feng Aihua , Krishnan Sasirekha , Shoma Suresh K. , Ramalingam Murugan
Published: February 2022

Bone and joint tuberculosis is an extremely severe infectious disease that commonly occurs due to the primary infection of a type of mycobacteria, called Mycobacterium tuberculosis. Under the current scenario, there are very limited supplies of bone grafts available for the treatment
of deceased bone, including autogenous bone and synthetic biomaterials. The present study aimed to construct a nanoscale isoniazid-loaded mineralized collagen implant, and then to explore its physicochemical properties and to investigate its biocompatibility suitable for bone and joint repair.
Using type I collagen as raw material and the principle of biomimetic mineralization for self-assembly of bone tissue, a new drug-loaded mineralized collagen implant was constructed by molecular coprecipitation with isoniazid. Its surface morphology, elemental composition, and porosity were
characterized by field emission scanning electron microscope (SEM), X-ray diffraction (XRD), and pycnometer. The performance of the implant was gauged by sustained release and degradation, which were studied using an ultraviolet spectrophotometer and a simulated in vivo environment.
The drug loading and encapsulation rates of the implants were (6.25 ± 0.48)% and (54 ± 2.34)%, respectively. The in vitro release time of the scaffold was more than 12 weeks and the degradation performance was excellent. The scaffold was then implanted into mice, and the
inflammatory reaction of local tissue was observed by Haemotoxylin and Eosin (H&E) and Masson. The in vivo evaluation in mice showed that the scaffold was biocompatible. Overall, compared with traditional drug loading systems, the isoniazid biomimetic mineralized collagen implant
constructed here has better drug release performance, biodegradability, and biocompatibility. This kind of collagen implant may find potential applications in tuberculous bone and joint repair.
Intelligent Nanomedicine Approaches Using Medical Gas-Mediated Multi-Therapeutic Modalities Against Cancer
Authors: Ren Xuechun , Wang Ying , Jia Liangliang , Guo Xiaoqing , He Xinyu , Zhao Zhipeng , Gao Di , Yang Zhe
Published: February 2022

The emerging area of gas-mediated cancer treatment has received widespread attention in the medical community. Featuring unique physical, chemical, and biological properties, nanomaterials can facilitate the delivery and controllable release of medicinal gases at tumor sites, and also serve as ideal platforms for the integration of other therapeutic modalities with gas therapy to augment cancer therapeutic efficacy. This review presents an overview of anti-cancer mechanisms of several therapeutic gases: nitric oxide (NO), hydrogen sulfide (H2S), carbon monoxide (CO), oxygen (O2), and hydrogen (H2). Controlled release behaviors of gases under different endogenous and exogenous stimuli are also briefly discussed, followed by their synergistic effects with different therapeutic modes. Moreover, the potential challenges and future prospects regarding gas therapy based on nanomaterials are also described, aiming to facilitate the advancement of gas therapeutic nanomedicine in new frontiers for highly efficient cancer treatment.
Anti-Vascular Endothelial Growth Factor Drug Conbercept-Loaded Peptide Hydrogel Reduced Angiogenesis in the Neovascular Age-Related Macular Degeneration
Authors: Fan Wen , Li Shasha , Tao Juan , Yu Chenyang , Sun Meng , Xie Zhan , Wu Xinjing , Ge Liang , Wu Yiqun , Liu Yuanfen
Published: February 2022

Age-related macular degeneration (AMD) accounts for 8.7% of the global blindness and neovascular form of AMD (nAMD) occupies a large proportion of severe visual loss and legal blindness caused by AMD with a relatively low incidence rate. Choroidal neovascularization (CNV) is overwhelmingly
responsible for the occurrence of nAMD as bleeding and fluid leakage followed by abnormal formation of blood vessels could directly lead to loss of central vision so that reduce the choroidal angiogenesis is an ideal treatment method of nAMD. VEGF is an important cytokine which promote the
signaling pathway of angiogenesis and the abnormal expression of VEGF is verified in great many CNV cases. Several anti-VEGF drugs have been widely used in clinical treatments such as ranibizumab, bevacizumab and aflibercept. Conbercept, as an originally developed drug in China, has attracted
great attention. For the purpose of better treatment efficacy, our group designed a short chain peptide (Sequence: DDIIIRH-NH2, M.W.880.99) for controlled drug release to remedy the drawback of the short half-time period. The peptide could self-assembled into a stable ‘hydrogel
under pH 7.4 condition and the 3D structure was clearly observed in TEM study. Rheological study exhibited its great injectability so that the hydrogel was a material for intravitreal injection. Statistics exhibited that the hydrogel could release approximately 50% of total conbercept. The
In vitro experiments showed that either dose-dependent or the time-dependent incubation with peptide would not decrease the cell viability of HREC, revealing that the peptide was biocompatible. The most important is that co-incubation with HREC obviously reduced the HREC proliferation
and tube formation induced by VEGF, ensuring its potential for the treatment efficacy of nAMD.
Effect of Polyaniline and Graphene Oxide Modified Carbon Felt on Adsorption and Immobilization of Acidithiobacillus ferrooxidans
Authors: Lu Leizhen , Yang Jun , Wang Gaihong , Yong Xiaoyu , Zhang Yabing , Zhou Jun , Qin Cheng , Chen Jishuang
Published: February 2022

Biological desulfurization plays an increasingly important role in desulfurization industry. A strain of Acidithiobacillus ferrooxidans ZJ-2 with high Fe2+ oxidizing efficiency was in this study isolated and screened to remove hydrogen sulfide from biogas. To further
improve its oxidation efficiency, A. ferrooxidans ZJ-2 was immobilized using carbon felt (CF), modified with graphene oxide (GO) and polyaniline (PANI), as immobilized carrier. The effects of immobilization on strain’s Fe2+ oxidation efficiency and impact of PANI and
GO on CF were also investigated. Raman spectra and atomic force microscopy showed that CF was successfully modified using GO and PANI. Cyclic voltammetry and electrochemical impedance spectroscopy measurements revealed that the electrochemical properties of modified CF were improved, presenting
the following trend in conductivity: CF< GO-modified CF (GO-CF) < PANI-modified CF (PANI-CF) < PANI/GO-modified CF (PANI/GO-CF). The resistance of modified CF was lower than that of unmodified CF, and exhibited the following trend: CF > GO-CF > PANI-CF > GO/PANI-CF. While
PANI-CF inhibited growth of free and immobilized A. ferrooxidans ZJ-2, GO-CF was conducive to microbial growth and increased cell density and oxidation ability of A. ferrooxidans ZJ-2. Thus, the present study developed an immobilized bacterial carrier that had better conductivity
and lower resistance and was efficient in immobilizing A. ferrooxidans and could be used for biogas desulfurization in biological and biochemical combined reactors.
Rosai-Dorfman Disease of the Rectum: Newly Identified Genetic Point Mutations and Robotic Resection
Authors: Lambdin Jacob , Phillips Joshua K. , Kima Elias D. , Paal Edina , Nava Victor E. , Duncan James
Published: February 2022

Rosai-Dorfman disease (RDD) is a rare disease characterized by histiocytic proliferation which typically presents as massive, painless, cervical lymphadenopathy in children or young adults. GI involvement is exceedingly rare with only 20 documented cases to date. Of those 20 cases, only 3 cases have involved the rectum. Here, we present 2 cases of rectal RDD with attention paid to the diagnostic and technical challenges presented by this disease. When presenting as a perirectal mass, RDD can be mistaken for other lesions to include malignancy, leading to surgical removal. We present a video of a robotic low-anterior resection with intracorporeal anastomosis in order to remove a pelvic mass involving the rectum, initially considered to be a stromal tumor. In addition, we describe a copy number variation in AKT and 3 point mutations detected by next generation sequencing, which had not been previously reported in association with this disease.
Curriculum Development in Public Administration in Bangladesh: Lessons from Experience of Others
Authors: Ahmed Nizam
Published: February 2022

This article examines the process of curriculum development for Public Administration in public universities in Bangladesh and explores the extent to which Bangladesh can learn lessons from others’ experiences, especially from countries in the South Asian region. The article compares and contrasts the curriculum and courses offered by different departments of Public Administration and explores reasons for variations. It also analyses measures adopted for the modernisation of curriculum and identifies factors that are likely to retard the progress towards change and improvement. The article argues that the widespread autonomy that different universities enjoy has become counterproductive, leading to a decline in the standard of education and the politicisation of the governing process in the universities. Everything now weighs in party political terms. This, in turn, causes more harm than good. Bangladesh can try to learn, especially from India’s experiences, how to stress on striking a balance between autonomy to be enjoyed by universities and control to be exercised by the government/University Grants Commission (UGC) to ensure that the practice does not differ much from the ideal.
Precision Medicine in Lung Cancer Theranostics: Paving the Way from Traditional Technology to Advance Era
Authors: Guan Xiaoyong , Qin Tian , Qi Tao
Published: February 2022

Precision medicine for lung cancer theranostics is an advanced model combining prevention, diagnosis, and treatment for individual or specific population diseases to match individual patient differences. It involves collection and integration of genome, transcriptome, proteome, and metabolome features of lung cancer patients, combined with clinical characteristics. Subsequently, large data and artificial intelligence (AI) analysis have emerged to identify the most suitable therapeutic targets and personal treatment strategies for treatment of patients with lung cancer. We review the development and challenges associated with diagnosis and therapy of lung cancer from traditional technology, including immunotherapy prediction markers, liquid biopsy, surgery, and tumor immune microenvironment and patient-derived xenograft models, to AI in the era of precision medicine. AI has improved precision medicine and the predictive ability and accuracy of patient outcomes. Finally, we discuss some opportunities and challenges for lung cancer theranostics. Precision medicine in lung cancer can help us find the optimum treatment dose and time for a specific patient, which can advance the development of lung cancer therapeutics.
Overview of recent cases before the Court of Justice of the European Union (September 2021-December 2021)
Authors: Melin Pauline , Sivonen Susanne
Published: February 2022

The concept of ‘working time’ for a period of stand-by time according to a stand-by system applicable to firefighters was interpreted by the Court in MG (C-214/20). In the Y case (C-636/19), the Court interpreted the concept of ‘insured person’ for the purpose of reimbursement of healthcare costs under Directive 2011/24. In the TS case (C-538/19), the Court dealt with another cross-border healthcare case. This time the question was whether a Member State can require an authorisation for cross-border healthcare to be subject to the submission of a medical report drawn up by a doctor from its national public health insurance system in light of Article 20 of Regulation 883/2004 and Article 56 TFEU. In ASGI and APN (C-462/20), the exclusion of third-country nationals from the eligibility to the Italian family card was under scrutiny. In SC (C-866/19), the Court clarified that the principle of aggregation applies to the calculation of the theoretical amount of benefit but not to the calculation of the actual amount of benefit under Article 52(1)(b) of Regulation 883/2004. In K (C-285/20), the Court held that being on sick leave and receiving sickness benefits can be considered as equivalent to the pursuit of an economic activity for the purpose of applying the rules on unemployment benefits for wholly unemployed frontier workers under Article 65(2) and (5) of Regulation 883/2004.
Effect of Perception and Satisfaction on Preference for Mobile Wallet
Authors: Chand Khem , Tiwari Rajesh , Sapna
Published: February 2022

This research article explores the effect of mobile wallet users’ perception and satisfaction on preference for mobile wallets. The paper further examines the mediating effect of satisfaction on preference of m-wallet. Primary data was collected through online survey from 506 mobile wallet users between August and October 2020. The study employed exploratory factor analysis (EFA), confirmatory factor analysis (CFA) and structural equation modelling (SEM). Nine factors were extracted after applying EFA and confirmed by CFA. It was found that preference of using m-wallet was directly and indirectly affected by perception. Satisfaction was found to have partial mediating effect between perception and preference. This is the first article that explored mediating effect of satisfaction for mobile wallet users in India. The study adds satisfaction as a variable in integrated unified theory of acceptance and use of technology model for mobile wallet users. Satisfaction is a partial mediating factor which increases the preference of using the m-wallet.
Navigating moral dimensions and lateral power – The experiences of men with sexual convictions and histories of sexual abuse serving sentences in a therapeutic community
Authors: Kotova Anna , Akerman Geraldine
Published: February 2022

This article examines the moral world of therapeutic penal communities through the lens of the experiences of men with sexual convictions and histories of sexual victimisation. Drawing on the concepts of lateral power and stigma, we discuss how Therapeutic Communities (TCs), which are intensely social communities, operate within three moral dimensions: the institutional set of therapeutic norms, the con code, and the broader sociocultural set of norms that intensely stigmatise sexual offending. Specifically, the focus of this article is how these norms shape the manner in which lateral power is used, navigated and resisted within TCs. We explore the manner in which TC processes are used as tools to enact lateral power over men with sexual offences, and how the three moral dimensions create a messy moral environment within the TC. Importantly, we explore how the residents navigate the morally complex dual identity of offender and victim. We also note that the moral messiness, and the conflicts between the moral dimensions, also raise challenges for how vertical institutional power is exercised. Finally, we point out that the neoliberal individualism inherent in today's sociocultural moral dimension further shapes how men with sexual offences experience the moral community of the TC.
Integrated Production and Transportation Scheduling Method in Hybrid Flow Shop
Authors: Li Wangming , Han Dong , Gao Liang , Li Xinyu , Li Yang
Published: February 2022

The connection between production scheduling and transportation scheduling is getting closer in smart manufacturing system, and both of those problems are summarized as NP-hard problems. However, only a few studies have considered them simultaneously. This paper solves the integrated production and transportation scheduling problem (IPTSP) in hybrid flow shops, which is an extension of the hybrid flow shop scheduling problem (HFSP). In addition to the production scheduling on machines, the transportation scheduling process on automated guided vehicles (AGVs) is considered as another optimization process. In this problem, the transfer tasks of jobs are performed by a certain number of AGVs. To solve it, we make some preparation (including the establishment of task pool, the new solution representation and the new solution evaluation), which can ensure that satisfactory solutions can be found efficiently while appropriately reducing the scale of search space. Then, an effective genetic tabu search algorithm is used to minimize the makespan. Finally, two groups of instances are designed and three types of experiments are conducted to evaluate the performance of the proposed method. The results show that the proposed method is effective to solve the integrated production and transportation scheduling problem.
A one-dimensional elasto-viscoplastic model coupled to damage for the description of creep in wooden materials
Authors: Fothe Thierry , Azeufack Ulrich Gael , Kenmeugne Bienvenu , Fogue Médard
Published: February 2022

This work focuses on the development of a model for the description of the tertiary creep phenomenon in wooden materials. We stared from an extended standard solid body model capable of best describing primary and secondary creeps. We then modify this model by introducing a damage variable to explain and model the rapid growth of viscoplastic strain during tertiary creep. We obtain a model comprising a reduced number of parameters (05) all physically interpretable; which can be easily determined from the results of creep tests. The proposed model has been tested using the experimental results of creep-rupture tests and it has been shown to be very suitable for describing the three phases of creep, with a relative error of less than 1%. The breaking time proposed by the model is lower, but very close to the experimental breaking time (Err = 0.01). The time to failure is easily accessible, thanks to the simplicity of our model, without necessarily going through heavy algorithms. This represents a significant advantage of our model, which in sum offers both a more realistic way of describing the three phases of creep by fully accounting for the phenomenon of damage during the tertiary phase, and a simple and fast way to analyze the rupture time, compared to other models in the literature. Our model is therefore presented as a good alternative for modeling the behavior of wood material under creep stress.
OsWRKY62 and OsWRKY76 Interact with Importin α1s for Negative Regulation of Defensive Responses in Rice Nucleus
Authors: Xu Xiaohui , Wang Han , Liu Jiqin , Han Shuying , Lin Miaomiao , Guo Zejian , Chen Xujun
Published: February 2022

Background OsWRKY62 and OsWRKY76, two close members of WRKY transcription factors, function together as transcriptional repressors. OsWRKY62 is predominantly localized in the cytosol. What are the regulatory factors for OsWRKY62 nuclear translocation? Results In this study, we characterized the interaction of OsWRKY62 and OsWRKY76 with rice importin, OsIMα1a and OsIMα1b, for nuclear translocation. Chimeric OsWRKY62.1-GFP, which is predominantly localized in the cytoplasm, was translocated to the nucleus of Nicotiana benthamiana leaf cells in the presence of OsIMα1a or OsIMαΔIBB1a lacking the auto-inhibitory importin β-binding domain. OsIMαΔIBB1a interacted with the WRKY domain of OsWRKY62.1, which has specific bipartite positively charged concatenated amino acids functioning as a nuclear localization signal (NLS). Similarly, we found that OsIMαΔIBB1a interacted with the AvrPib effector of rice blast fungus Magnaporthe oryzae, which contains a scattered distribution of positively charged amino acids. Furthermore, we identified a nuclear export signal (NES) in OsWRKY62.1 that inhibited nuclear transportation. Overexpression of OsIMα1a or OsIMα1b enhanced resistance to M. oryzae, whereas knockout mutants decreased resistance to the pathogen. However, overexpressing both OsIMα1a and OsWRKY62.1 were slightly more susceptible to M. oryzae than OsWRKY62.1 alone. Ectopic overexpression of OsWRKY62.1-NES fused gene compromised the enhanced susceptibility of OsWRKY62.1 to M. oryzae. Conclusion These results revealed the existence of NLS and NES in OsWRKY62. OsWRKY62, OsWRKY76, and AvrPib effector translocate to nucleus in association with importin α1s through new types of nuclear localization signals for negatively regulating defense responses.
Efficient link prediction in the protein–protein interaction network using topological information in a generative adversarial network machine learning model
Authors: Balogh Olivér M. , Benczik Bettina , Horváth András , Pétervári Mátyás , Csermely Péter , Ferdinandy Péter , Ágg Bence
Published: February 2022

Background

The investigation of possible interactions between two proteins in intracellular signaling is an expensive and laborious procedure in the wet-lab, therefore, several in silico approaches have been implemented to narrow down the candidates for future experimental validations. Reformulating the problem in the field of network theory, the set of proteins can be represented as the nodes of a network, while the interactions between them as the edges. The resulting protein–protein interaction (PPI) network enables the use of link prediction techniques in order to discover new probable connections. Therefore, here we aimed to offer a novel approach to the link prediction task in PPI networks, utilizing a generative machine learning model.

Results

We created a tool that consists of two modules, the data processing framework and the machine learning model. As data processing, we used a modified breadth-first search algorithm to traverse the network and extract induced subgraphs, which served as image-like input data for our model. As machine learning, an image-to-image translation inspired conditional generative adversarial network (cGAN) model utilizing Wasserstein distance-based loss improved with gradient penalty was used, taking the combined representation from the data processing as input, and training the generator to predict the probable unknown edges in the provided induced subgraphs. Our link prediction tool was evaluated on the protein–protein interaction networks of five different species from the STRING database by calculating the area under the receiver operating characteristic, the precision-recall curves and the normalized discounted cumulative gain (AUROC, AUPRC, NDCG, respectively). Test runs yielded the averaged results of AUROC = 0.915, AUPRC = 0.176 and NDCG = 0.763 on all investigated species.

Conclusion

We developed a software for the purpose of link prediction in PPI networks utilizing machine learning. The evaluation of our software serves as the first demonstration that a cGAN model, conditioned on raw topological features of the PPI network, is an applicable solution for the PPI prediction problem without requiring often unavailable molecular node attributes. The corresponding scripts are available at https://github.com/semmelweis-pharmacology/ppi_pred.
Rare coding variants in RCN3 are associated with blood pressure
Authors: He Karen Y. , Kelly Tanika N. , Wang Heming , Liang Jingjing , Zhu Luke , Cade Brian E. , Assimes Themistocles L. , Becker Lewis C. , Beitelshees Amber L. , Bielak Lawrence F. , Bress Adam P. , Brody Jennifer A. , Chang Yen-Pei Christy , Chang Yi-Cheng , de Vries Paul S. , Duggirala Ravindranath , Fox Ervin R. , Franceschini Nora , Furniss Anna L. , Gao Yan , Guo Xiuqing , Haessler Jeffrey , Hung Yi-Jen , Hwang Shih-Jen , Irvin Marguerite Ryan , Kalyani Rita R. , Liu Ching-Ti , Liu Chunyu , Martin Lisa Warsinger , Montasser May E. , Muntner Paul M. , Mwasongwe Stanford , Naseri Take , Palmas Walter , Reupena Muagututi’a Sefuiva , Rice Kenneth M. , Sheu Wayne H.-H. , Shimbo Daichi , Smith Jennifer A. , Snively Beverly M. , Yanek Lisa R. , Zhao Wei , Blangero John , Boerwinkle Eric , Chen Yii-Der Ida , Correa Adolfo , Cupples L. Adrienne , Curran Joanne E. , Fornage Myriam , He Jiang , Hou Lifang , Kaplan Robert C. , Kardia Sharon L. R. , Kenny Eimear E. , Kooperberg Charles , Lloyd-Jones Donald , Loos Ruth J. F. , Mathias Rasika A. , McGarvey Stephen T. , Mitchell Braxton D. , North Kari E. , Peyser Patricia A. , Psaty Bruce M. , Raffield Laura M. , Rao D. C. , Redline Susan , Reiner Alex P. , Rich Stephen S. , Rotter Jerome I. , Taylor Kent D. , Tracy Russell , Vasan Ramachandran S. ,   The Samoan Obesity, Lifestyle and Genetic Adaptations Study (OLaGA) Group, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Morrison Alanna C. , Levy Daniel , Chakravarti Aravinda , Arnett Donna K. , Zhu Xiaofeng
Published: February 2022

Background

While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries.

Results

Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10− 7).

Conclusions

Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.
Expiratory central airway collapse during positive pressure ventilation: a case report
Authors: Gaggini Guillaume , Nkamicaniye Link-Mathieu , Meyer Sabrina , Dubois Philippe E.
Published: February 2022

Background

Physiologic narrowing of the central airway occurs during expiration. Conditions in which this narrowing becomes excessive are referred to as expiratory central airway collapse. Expiratory central airway collapse is usually managed by applying positive pressure to the airways, which acts as a pneumatic stent. The particularity of the case reported here included the patient’s left main bronchus being permeable during spontaneous breathing but collapsing during general anaesthesia, despite positive pressure ventilation and positive end-expiratory pressure.

Case presentation

We present the case of a 55-year-old man admitted for the placement of a ureteral JJ stent. Rapid desaturation occurred a few minutes after the onset of anaesthesia. After excluding the most common causes of desaturation, fibreoptic bronchoscopy was performed through the tracheal tube and revealed complete collapse of the left main bronchus. The collapse persisted despite the application of positive end-expiratory pressure and several recruitment manoeuvres. After recovery of spontaneous ventilation, the collapse was lifted, and saturation increased back to normal levels. No evidence of extrinsic compression was found on chest X-rays or computed tomography scans.

Conclusion

Cases of unknown expiratory central airway collapse reported in the literature were usually managed with positive pressure ventilation. This approach has been unsuccessful in the case described herein. Our hypothesis is that mechanical bending of the left main bronchus occurred due to loss of the patient’s natural position and thoracic muscle tone under general anaesthesia with neuromuscular blockade. When possible, spontaneous ventilation should be maintained in patients with known or suspected ECAC.
The injury severity score: an operations perspective
Authors: Dehouche Nassim
Published: February 2022

Background

The statistical evaluation of aggregation functions for trauma grades, such as the Injury Severity Score (ISS), is largely based on measurements of their Pearson product-moment correlation with mortality. However, correlation analysis makes assumptions about the nature of the involved random variables (cardinality) and their relationship (linearity) that may not be applicable to ordinal scores such as the ISS. Moreover, using correlation as a sole evaluation criterion neglects the dynamic properties of these aggregation functions scores.

Methods

We analyze the domain and ordinal properties of the ISS comparatively to arbitrary linear and cubic aggregation functions. Moreover, we investigate the axiomatic properties of the ISS as a multicriteria aggregation procedure. Finally, we use a queuing simulation with various empirical distributions of Abbreviated Injury Scale (AIS) grades reported in the literature, to evaluate the queuing performance of the three aggregation functions.

Results

We show that the assumptions required for the computation of Pearson’s product-moment correlation coefficients are not applicable to the analysis of the association between the ISS and mortality. We suggest the use of Mutual Information, a information-theoretic statistic that is able to assess general dependence rather than a specialized, linear view based on curve-fitting. Using this metric on the same data set as the seminal study that introduced the ISS, we show that the sum of cubes conveys more information on mortality than the ISS. Moreover, we highlight some unintended, undesirable axiomatic properties of the ISS that can lead to bias in its use as a patient triage criterion. Lastly, our queuing simulation highlights the sensitivity of the queuing performance of different aggregation procedures to the underlying distribution of AIS grades among patients.

Conclusions

Viewing the ISS, and other possible aggregation functions for multiple AIS scores, as mere operational indicators of the priority of care, rather than cardinal measures of the response of the human body to multiple injuries (as was conjectured in the seminal study introducing the ISS) offers a perspective for their construction and evaluation on more robust grounds than the correlation coefficient. In this regard, Mutual Information appears as a more appropriate measure for the study of the association between injury severity and mortality, and queuing simulations as an actionable way to adapt the choice of an aggregation function to the underlying distribution of AIS scores.
Assessing transferability in systematic reviews of health economic evaluations – a review of methodological guidance
Authors: Weise Alina , Büchter Roland Brian , Pieper Dawid , Mathes Tim
Published: February 2022

Objective

For assessing cost-effectiveness, Health Technology Assessment (HTA) organisations may use primary economic evaluations (P-HEs) or Systematic Reviews of Health Economic evaluations (SR-HEs). A prerequisite for meaningful results of SR-HEs is that the results from existing P-HEs are transferable to the decision context (e.g, HTA jurisdiction). A particularly pertinent issue is the high variability of costs and resource needs across jurisdictions. Our objective was to review the methods documents of HTA organisations and compare their recommendations on considering transferability in SR-HE.

Methods

We systematically hand searched the webpages of 158 HTA organisations for relevant methods documents from 8th January to 31st March 2019. Two independent reviewers performed searches and selected documents according to pre-defined criteria. One reviewer extracted data in standardised and piloted tables and a second reviewer checked them for accuracy. We synthesised data using tabulations and in a narrative way.

Results

We identified 155 potentially relevant documents from 63 HTA organisations. Of these, 7 were included in the synthesis. The included organisations have different aims when preparing a SR-HE (e.g. to determine the need for conducting their own P-HE). The recommendations vary regarding the underlying terminology (e.g. transferability/generalisability), the assessment approaches (e.g. structure), the assessment criteria and the integration in the review process.

Conclusion

Only few HTA organisations address the assessment of transferability in their methodological recommendations for SR-HEs. Transferability considerations are related to different purposes. The assessment concepts and criteria are heterogeneous. Developing standards to consider transferability in SR-HEs is desirable.
Borrowing information across patient subgroups in clinical trials, with application to a paediatric trial
Authors: Turner Rebecca M. , Turkova Anna , Moore Cecilia L. , Bamford Alasdair , Archary Moherndran , Barlow-Mosha Linda N. , Cotton Mark F. , Cressey Tim R. , Kaudha Elizabeth , Lugemwa Abbas , Lyall Hermione , Mujuru Hilda A. , Mulenga Veronica , Musiime Victor , Rojo Pablo , Tudor-Williams Gareth , Welch Steven B. , Gibb Diana M. , Ford Deborah , White Ian R. ,   and the ODYSSEY Trial Team
Published: February 2022

Background

Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group within the same trial, while allowing for differences between populations. Our aim was to develop methods for eliciting expert opinions about differences in treatment effect between patient populations, and to incorporate these opinions into a Bayesian analysis.

Methods

We used an interaction parameter to model the relationship between underlying treatment effects in two subgroups. Elicitation was used to obtain clinical opinions on the likely values of the interaction parameter, since this parameter is poorly informed by the data. Feedback was provided to experts to communicate how uncertainty about the interaction parameter corresponds with relative weights allocated to subgroups in the Bayesian analysis. The impact on the planned analysis was then determined.

Results

The methods were applied to an ongoing non-inferiority trial designed to compare antiretroviral therapy regimens in 707 children living with HIV and weighing ≥ 14 kg, with an additional group of 85 younger children weighing < 14 kg in whom the treatment effect will be estimated separately. Expert clinical opinion was elicited and demonstrated that substantial borrowing is supported. Clinical experts chose on average to allocate a relative weight of 78% (reduced from 90% based on sample size) to data from children weighing ≥ 14 kg in a Bayesian analysis of the children weighing < 14 kg. The total effective sample size in the Bayesian analysis was 386 children, providing 84% predictive power to exclude a difference of more than 10% between arms, whereas the 85 younger children weighing < 14 kg provided only 20% power in a standalone frequentist analysis.

Conclusions

Borrowing information from a larger subgroup or subgroups can facilitate estimation of treatment effects in small subgroups within a clinical trial, leading to improved power and precision. Informative prior distributions for interaction parameters are required to inform the degree of borrowing and can be informed by expert opinion. We demonstrated accessible methods for obtaining opinions.
Objective disease activity assessment and therapeutic drug monitoring prior to biologic therapy changes in routine inflammatory bowel disease clinical practice: TARGET-IBD
Authors: Click Benjamin , Barnes Edward L. , Cohen Benjamin L. , Sands Bruce E. , Hanson John S. , Rubin David T. , Dubinsky Marla C. , Regueiro Miguel , Gazis Derek , Crawford Julie M. , Long Millie D.
Published: February 2022

Background

Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients.

Methods

TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained.

Results

525 patients (71.4% Crohn’s disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18–39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01–2.50).

Conclusion

Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.
Excess fatty acids induce pancreatic acinar cell pyroptosis through macrophage M1 polarization
Authors: Xia Wenwen , Lu Zhaomin , Chen Wei , Zhou Jianjun , Zhao Yan
Published: February 2022

Free fatty acid derived from hyperlipidemia contributes to the development of inflammation in the pancreas. Here we explore the molecular mechanisms of fatty acid-induced pancreatitis through cellular experiments and the construction of a mouse model of hyperlipidemic pancreatitis. We found that palmitic acid stimulation leads to M1 polarization of macrophage, which secretes cathepsin S via exosomes to pancreatic acinar cells and leads to activation of the caspase1-mediated classical pyrolysis pathway, resulting in inflammation and pancreatic tissue damage. In vivo experiments have also demonstrated that the high levels of fatty acids induced by hyperlipidaemia exacerbate the development of pancreatitis, and that cathepsin S inhibitors significantly alleviate hyperlipidemic pancreatitis. Therefore, cathepsin S may be a new target for the clinical treatment of hyperlipidemic pancreatitis.
Distal radius fractures in the superelderly: an observational study of 8486 cases from the Swedish fracture register
Authors: Sagerfors Marcus , Jakobsson Hugo , Thórdardóttir Ásgerdur , Wretenberg Per , Möller Michael
Published: February 2022

Background

The distal radius fracture (DRF) is the most common fracture in adults. With an ageing population, the number of wrist fractures in the superelderly (≥ 80 years) is expected to rise. Optimal treatment for displaced DRFs remains controversial, especially in the superelderly group. In addition, basic knowledge of the outcome after a DRF in this heterogenic group is lacking. The aim of this study was to study injury characteristics, treatment and outcome of DRFs in superelderly patients using data from a large national register.

Methods

We used prospectively collected data from the Swedish Fracture Register. All distal radius fractures registered between April 2012 and December 2018 in patients ≥ 80 years of age were included. Data on epidemiology, fracture type, trauma mechanism and treatment are registered by the physician treating the patient. Patients are also sent a subjective outcome questionnaire including EQ-5D, EQ-VAS and Short Musculoskeletal Function Assessment questionnaire (SMFA-score) at the time of injury and after 12 months. The 12-month questionnaire was sent to those who had completed the questionnaire at the time of injury. A Mann–Whitney U-test was used to assess differences between treatment methods.

Results

Mean age for this population was 86 years (80–105 years), a majority of the patients were female (86.7%). The dominating injury mechanism was a simple fall (74.6%) in the patient’s residence. The majority of fractures were AO type A (70%) followed by AO type C (20.9%) and type B (8.6%). The incidence of open fractures was significantly higher in females (2.6%) compared to males (1.5%). A majority of the fractures were treated with a cast (87.5%) with volar locking plate as the second most common treatment method (6.6%). Patient-reported outcome measures (PROMs) EQ-5D, EQ-VAS and the Arm Hand Function Index of the SMFA-score deteriorated somewhat one year after injury compared to pre-injury. PROMs did not correlate to treatment with cast or a volar plate.

Conclusions

This nationwide register study provides detailed data on DRFs in the superelderly regarding epidemiology, treatment and self-reported outcome. A good self-reported outcome is possible, but many patients do not recover completely. PROMs did not correlate to type of treatment. The frequency of open fractures was significantly higher in females. The reason for this is unclear but different skin thickness in older males versus females may be one explanation.