bluuebunny/crossref_metadata_2025 huggingface dataset:
Public participation: healthcare rationing in the newspaper media
Authors: Brendbekken Audun , Robberstad Bjarne , Norheim Ole F.
Published: March 2022

Background

It is impossible to meet all healthcare demands, but an open and fair rationing process may improve the public acceptability of priority setting in healthcare. Decision-making is subject to scrutiny by newspaper media, an important public institution and information source for discussions about rationing. In Norway, healthcare rationing has been subject to public debate both before and after the establishment of “The National System for Managed Introduction of New Health Technologies within the Specialist Health Service” (New Methods) in 2013.

Aim

To describe and assess the development of the public debate on Norwegian healthcare rationing through three cases in print media.

Methods

We purposively sampled Norwegian newspaper articles between 2012 and 2018 concerning three reimbursement decisions in the Norwegian system. The reimbursement decisions were ipilimumab (Yervoy,n = 45) against metastatic melanoma, nivolumab (Opdivo,n = 23) against non-small cell lung cancer, and nusinersen (Spinraza,n = 68) against spinal muscular atrophy. Cases were analysed separately using the qualitative method of systematic text condensation.

Results

Our analysis highlighted four common themes—money, rationales, patient stories, and process—and a unique theme for each case. Ipilimumab was uniquely themed by rationing rejection, nivolumab by healthcare two-tiering, and Spinraza by patients’ rights. We found wide media deliberation among a multitude of stakeholders in all cases. Perceptions of rationing were found to be chiefly aligned with previous empirical research. We found that the media reported more frequently on opposition to rationing compared to findings from previous studies on Norwegian healthcare decision-making attitudes. We think this was influenced by our selection of cases receiving extraordinary media attention, and from media sources being subject to political communication from special interest groups.

Conclusion

We observed that the introduction of New Methods institutionalised Norwegian healthcare rationing and isolated the public debate into conversations between stakeholders and decision makers outside the political sphere. The findings from these three extraordinary debates are not generalisable and should be seen as a stakeholder learning opportunity regarding media coverage and engagement with expensive specialist healthcare decision-making in Norway.
Gene panel diagnostics reveals new pathogenic variants in pulmonary arterial hypertension
Authors: Eichstaedt Christina A. , Saßmannshausen Zoe , Shaukat Memoona , Cao Ding , Xanthouli Panagiota , Gall Henning , Sommer Natascha , Ghofrani Hossein-Ardeschir , Seyfarth Hans-Jürgen , Lerche Marianne , Halank Michael , Kleymann Janina , Benjamin Nicola , Harutyunova Satenik , Egenlauf Benjamin , Milger Katrin , Rosenkranz Stephan , Ewert Ralf , Klose Hans , Hoeper Marius M. , Olsson Karen M. , Lankeit Mareike , Lange Tobias J. , Hinderhofer Katrin , Grünig Ekkehard
Published: March 2022

Background

A genetic predisposition can lead to the rare disease pulmonary arterial hypertension (PAH). Most mutations have been identified in the gene BMPR2 in heritable PAH. However, as of today 15 further PAH genes have been described. The exact prevalence across these genes particularly in other PAH forms remains uncertain. We present the distribution of mutations across PAH genes identified at the largest German referral centre for genetic diagnostics in PAH over a course of > 3 years.

Methods

Our PAH-specific gene diagnostics panel was used to sequence 325 consecutive PAH patients from March 2017 to October 2020. For the first year the panel contained thirteen PAH genes: ACVRL1, BMPR1B, BMPR2, CAV1, EIF2AK4, ENG, GDF2, KCNA5, KCNK3, KLF2, SMAD4, SMAD9 and TBX4.These were extended by the three genes ATP13A3, AQP1 and SOX17 from March 2018 onwards following the genes’ discovery.

Results

A total of 79 mutations were identified in 74 patients (23%). Of the variants 51 (65%) were located in the gene BMPR2 while the other 28 variants were found in ten further PAH genes. We identified disease-causing variants in the genes AQP1, KCNK3 and SOX17 in families with at least two PAH patients. Mutations were not only detected in patients with heritable and idiopathic but also with associated PAH.

Conclusions

Genetic defects were identified in 23% of the patients in a total of 11 PAH genes. This illustrates the benefit of the specific gene panel containing all known PAH genes.
Congenital microtia patients: the genetically engineered exosomes released from porous gelatin methacryloyl hydrogel for downstream small RNA profiling, functional modulation of microtia chondrocytes and tissue-engineered ear cartilage regeneration
Authors: Chen Jianguo , Huang Tianyu , Liu Ruiquan , Wang Chenyu , Jiang Haiyue , Sun Hengyun
Published: March 2022

Background

Mesenchymal stem cells (MSCs) exosomes were previously shown to be effective in articular cartilage repairing. However, whether MSCs exosomes promote mature cartilage formation of microtia chondrocytes and the underlying mechanism of action remains unknown. Additionally, some hurdles, such as the low yield and unsatisfactory therapeutic effects of natural exosomes have emerged when considering the translation of exosomes-therapeutics to clinical practices or industrial production. Herein, we investigated the roles of human adipose-derived stem cells (ADSCs) exosomes in modulating microtia chondrocytes and the underlying mechanism of action. Special attention was also paid to the mass production and functional modification of ADSCs exosomes.

Results

We firstly used porous gelatin methacryloyl (Porous Gelma) hydrogel with pores size of 100 to 200 μm for 3D culture of passage 2, 4 and 6 ADSCs (P2, P4 and P6 ADSCs, respectively), and obtained their corresponding exosomes (Exo 2, Exo 4 and Exo 6, respectively). In vitro results showed Exo 2 outperformed both Exo 4 and Exo 6 in enhancing cell proliferation and attenuating apoptosis. However, both Exo 4 and Exo 6 promoted chondrogenesis more than Exo 2 did. Small RNA sequencing results indicated Exo 4 was similar to Exo 6 in small RNA profiles and consistently upregulated PI3K/AKT/mTOR signaling pathway. Notably, we found hsa-miR-23a-3p was highly expressed in Exo 4 and Exo 6 compared to Exo 2, and they modulated microtia chondrocytes by transferring hsa-miR-23a-3p to suppress PTEN expression, and consequently to activate PI3K/AKT/mTOR signaling pathway. Then, we designed genetically engineered exosomes by directly transfecting agomir-23a-3p into parent P4 ADSCs and isolated hsa-miR-23a-3p-rich exosomes for optimizing favorable effects on cell viability and new cartilage formation. Subsequently, we applied the engineered exosomes to in vitro and in vivo tissue-engineered cartilage culture and consistently found that the engineered exosomes could enhance cell proliferation, attenuate apoptosis and promote cartilage regeneration.

Conclusions

Taken together, the porous Gelma hydrogel could be applied to exosomes mass production, and functional modification could be achieved by selecting P4 ADSCs as parent cells and genetically modifying ADSCs. Our engineered exosomes are a promising candidate for tissue-engineered ear cartilage regeneration.

Graphical Abstract
Prenatal diagnosis of a novel 7q31.31q31.33 microduplication with a favorable outcome
Authors: Luo Huili , Liu Linlin , Feng Yuexiang
Published: March 2022

Background

Copy number variants (CNVs) are an important source of normal and pathogenic genome variations. Especially CNVs identified in prenatal cases need careful considerations and correct interpretation if those are harmless or harmful variants from the norm.

Case presentation

Herein, we reported a paternally inherited duplication of 7.6 Mb in 7q31.3 with, surprisingly, a favorable outcome. GTG-banding and CMA on the DNA derived from uncultured amniocytes revealed a karyotype: 46,XX.arr[GRCh37] 7q31.31q31.33(118,601,001_126,177,044) × 3. Ultrasound examination showed no dysmorphisms or intrauterine growth restriction in the fetus and the father was clinically normal as well.

Conclusion

Prenatal detection of a 7.6 Mb in 7q31.31 to 7q31.33 duplication in a female fetus turned out to be a yet unreported unbalanced chromosome abnormality. This is another example that parental testing and GTG-banding are necessary additional tests to be done in prenatal cases, before a reliable conclusion on the meaning of an aberration can be drawn.
Improving reusability along the data life cycle: a regulatory circuits case study
Authors: Louarn Marine , Chatonnet Fabrice , Garnier Xavier , Fest Thierry , Siegel Anne , Faron Catherine , Dameron Olivier
Published: March 2022

Background

In life sciences, there has been a long-standing effort of standardization and integration of reference datasets and databases. Despite these efforts, many studies data are provided using specific and non-standard formats. This hampers the capacity to reuse the studies data in other pipelines, the capacity to reuse the pipelines results in other studies, and the capacity to enrich the data with additional information. The Regulatory Circuits project is one of the largest efforts for integrating human cell genomics data to predict tissue-specific transcription factor-genes interaction networks. In spite of its success, it exhibits the usual shortcomings limiting its update, its reuse (as a whole or partially), and its extension with new data samples. To address these limitations, the resource has previously been integrated in an RDF triplestore so that TF-gene interaction networks could be generated with two SPARQL queries. However, this triplestore did not store the computed networks and did not integrate metadata about tissues and samples, therefore limiting the reuse of this dataset. In particular, it does not enable to reuse only a portion of Regulatory Circuits if a study focuses on a subset of the tissues, nor to combine the samples described in the datasets with samples from other studies. Overall, these limitations advocate for the design of a complete, flexible and reusable representation of the Regulatory Circuits dataset based on Semantic Web technologies.

Results

We provide a modular RDF representation of the Regulatory Circuits, called Linked Extended Regulatory Circuits (LERC). It consists in (i) descriptions of biological and experimental context mapped to the references databases, (ii) annotations about TF-gene interactions at the sample level for 808 samples, (iii) annotations about TF-gene interactions at the tissue level for 394 tissues, (iv) metadata connecting the knowledge graphs cited above. LERC is based on a modular organisation into 1,205 RDF named graphs for representing the biological data, the sample-specific and the tissue-specific networks, and the corresponding metadata. In total it contains 3,910,794,050 triples and is available as a SPARQL endpoint.

Conclusion

The flexible and modular architecture of LERC supports biologically-relevant SPARQL queries. It allows an easy and fast querying of the resources related to the initial Regulatory Circuits datasets and facilitates its reuse in other studies.

Associated website

https://regulatorycircuits-lod.genouest.org
First isolation and identification of Cystobasidium calyptogenae from the oral samples of an elderly patient presenting with angular cheilitis
Authors: Karajacob Alexandria Sonia , Goh Joanne Pei En , Kallarakkal Thomas George , Tay Sun Tee
Published: March 2022

Background

Angular cheilitis, an infection mainly caused by Candida yeasts, is featured by the appearance of inflammatory lesions at the bilateral corners of the mouth, particularly in patients with poor oral hygiene, ill-fitting dentures and old age. The first isolation of an atypical yeast, Cystobasidium calyptogenae, from oral samples of a patient presenting with angular cheilitis is discussed in this study.

Case presentation

Angular cheilitis was diagnosed in a 60-year-old denture-wearing woman who presented with an irritation fibroma on her right lower buccal sulcus over the premolar region. Primary cultures of her oral swab and oral rinse samples grew a pure culture of an uncommon yeast strain resembling Rhodotorula sp. Sequence analysis of the yeast internal transcribed spacer (ITS) gene region and D1D2 domain showed highest similarity (99.6% and 100%, respectively) to C. calyptogenae CBS 9125 type strain. Following 2 weeks of treatment with miconazole/fusidic acid and mouthwash, the oral lesion showed improvement with less erythema. C. calyptogenae was not isolated from the patient’s oral samples upon repeat sampling.

Conclusion

This is the first report on the isolation of C. calyptogenae from human oral samples. The ability of C. calyptogenae to grow at 37 °C and the fact that it was the only yeast species isolated from the patient’s oral samples suggests its pathogenic potential and possible involvement in angular cheilitis. The ubiquitous nature of the Cystobasidium yeast is believed to increase the likelihood of opportunistic infections among immunocompromised individuals. As Cystobasidium is phenotypically indistinguishable from Rhodotorula, an emerging opportunistic pathogen, surveillance using molecular identification in clinical settings is essential in providing accurate diagnosis and treatment of uncommon yeast infections.
Assessing public knowledge, attitudes and determinants of third COVID-19 vaccine booster dose acceptance: current scenario and future perspectives
Authors: Jairoun Ammar Abdulrahman , Al-Hemyari Sabaa Saleh , El-Dahiyat Faris , Jairoun Maimona , Shahwan Moyad , Al Ani Mena , Habeb Mustafa , Babar Zaheer-Ud-Din
Published: March 2022

Background

People with weakened immune systems may not develop adequate protection after taking two doses of the mRNA-combined COVID-19 vaccine. The additional dose may improve the level of protection against Covid-19.

Objectives

Current study aimed to evaluate the knowledge, attitude and determents of third COVID-19 vaccine booster dose acceptance among population in the UAE.

Methods and materials

This is online descriptive cross-sectional community-based study conducted among the students and faculty of Ajman University from 25 August to 20 October 2021. The questionnaire, which was in the English language, encompassed two sections containing 22 items. Section one gathered the demographic details of the respondents, while Section two used 13 questions to evaluate the respondents’ knowledge of and attitude to the third COVID-19 vaccine booster dose.

Results

614 respondents participated in this study. The average knowledge score was 44.6% with a 95% confidence interval (CI) of [41%, 49%]. Better knowledge scores were observed in postgraduates (OR 4.29; 95% CI 2.28–8.11), employees in the healthcare sector (OR 1.62; 95% CI 1.05–2.51), participants who had relatives infected with the Covid-19 (OR 1.46; 95% CI 1.05–2.02), participants who had infected with Covid-19 (OR 2.21; 95% CI 1.43–3.43) and participants who had received first two doses of the COVID-19 vaccine (OR 2.08; 95% CI 1.40–3.11). The average attitude score was 70.2% with a 95% confidence interval (CI) of [69.2%, 71.2%].

Conclusion

Necessary steps should be taken by the government and public health authorities, in line with the local culture, to increase vaccination acceptance and foster positive attitudes towards the vaccine. A suitable approach to this would be to develop an educational framework that could demonstrate the risks of vaccine avoidance or delay to the general population. Moreover, health authorities should pay more attention to the false information being disseminated across the internet, especially social media. Also, healthcare workers should be trained in vaccinology and virology to make sure that they are able to understand important developments in these fields and convey the findings to their patients.
A green strategy to produce potential substitute resource for bear bile using engineered Saccharomyces cerevisiae
Authors: Jin Lina , Yang Li , Zhao Shujuan , Wang Zhengtao
Published: March 2022

Background

Bear bile powder is a precious natural material characterized by high content of tauroursodeoxycholic acid (TUDCA) at a ratio of 1.00–1.50 to taurochenodeoxycholic acid (TCDCA).

Results

In this study, we use the crude enzymes from engineered Saccharomyces cerevisiae to directionally convert TCDCA from chicken bile powder to TUDCA at the committed ratio in vitro. This S. cerevisiae strain was modified with heterologous 7α-hydroxysteroid dehydrogenase (7α-HSDH) and 7β-hydroxysteroid dehydrogenase (7β-HSDH) genes. S. cerevisiae host and HSDH gene combinatorial optimization and response surface methodology was applied to get the best engineered strain and the optimal biotransformation condition, respectively, under which 10.99 ± 0.16 g/L of powder products containing 36.73 ± 6.68% of TUDCA and 28.22 ± 6.05% of TCDCA were obtained using 12.00 g/L of chicken bile powder as substrate.

Conclusion

This study provides a healthy and environmentally friendly way to produce potential alternative resource for bear bile powder from cheap and readily available chicken bile powder, and also gives a reference for the green manufacturing of other rare and endangered animal-derived valuable resource.
Tracheobronchial reconstruction by inverted Barclay’s method for tracheobronchial injury in an 8-year-old girl: a case report
Authors: Suzuki Yamato , Ishizawa Hisato , Kawai Hiroshi , Matsuda Yasushi , Hoshikawa Yasushi
Published: March 2022

Background

Tracheobronchial injury in children is rare but can be highly fatal in severe cases. Therefore, prompt diagnosis and treatment are required. The appropriate treatment method depends on the extent and severity of the injury.

Case presentation

An 8-year-old girl fell from the fifth floor and was transported to a local hospital. She had a tracheobronchial injury, went into cardiopulmonary arrest during transportation to our hospital. She was revived with cardiopulmonary resuscitation, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was commenced. Subsequently, we performed tracheobronchial reconstruction by inverted Barclay’s method for tracheobronchial injury. She was switched from VA-ECMO to venovenous (VV)-ECMO 4 days postoperatively, and VV-ECMO was eventually discontinued 27 days after the surgery. The patient was awake and weaned off the ventilator on postoperative day 58. She was discharged 97 days after the surgery.

Conclusions

Tracheobronchial reconstruction by inverted Barclay’s method is the preferred surgical technique when other reconstruction techniques are expected to cause excessive tension on the anastomosis of the right main bronchus.
Rectal cancer diagnosed after resection of isolated brain metastasis
Authors: Tagayasu Yoshiyuki , Miyamoto Yuji , Sawayama Hiroshi , Ogawa Katsuhiro , Kato Rikako , Yoshida Naoya , Mukasa Akitake , Baba Hideo
Published: March 2022

Background

Brain metastasis of colorectal cancer is infrequent, and isolated brain metastases are more infrequent. Thus, when neurological symptoms, such as paralysis or disturbance of consciousness appear, there is a high probability that the cancer has spread to other organs.

Case presentation

Here, we present a 64-year-old man with a progressive headache, decreased motivation, and aphasia who was diagnosed with a brain tumor in the left frontal region. He underwent a craniotomy, and the brain tumor was diagnosed as adenocarcinoma. We performed a colonoscopy and diagnosed rectal cancer without other distant metastases. After whole-brain radiotherapy (WBRT), low anterior resection for primary rectal tumor was performed using a robotic system. The patient was discharged in good condition and received postoperative adjuvant therapy for rectal cancer. He showed no signs of recurrence after 1 year of follow-up.

Conclusions

We described a rare case of rectal cancer that was diagnosed after resection of isolated brain metastasis. A good prognosis was achieved with surgery and WBRT.
The MultimorbiditY COllaborative Medication Review And DEcision Making (MyComrade) study: a protocol for a cross-border pilot cluster randomised controlled trial
Authors: Hynes Lisa , Murphy Andrew W. , Hart Nigel , Kirwan Collette , Mulligan Sarah , Leathem Claire , McQuillan Laura , Maxwell Marina , Carr Emma , Walkin Scott , McCarthy Caroline , Bradley Colin , Byrne Molly , Smith Susan M. , Hughes Carmel , Corry Maura , Kearney Patricia M. , McCarthy Geraldine , Cupples Margaret , Gillespie Paddy , Newell John , Glynn Liam , Alvarez-Iglesias Alberto , Sinnott Carol
Published: March 2022

Background

While international guidelines recommend medication reviews as part of the management of multimorbidity, evidence on how to implement reviews in practice in primary care is lacking. The MultimorbiditY Collaborative Medication Review And Decision Making (MyComrade) intervention is an evidence-based, theoretically informed novel intervention which aims to support the conduct of medication reviews for patients with multimorbidity in primary care. Our aim in this pilot study is to evaluate the feasibility of a trial of the intervention with unique modifications accounting for contextual variations in two neighbouring health systems (Republic of Ireland (ROI) and Northern Ireland (NI)).

Methods

A pilot cluster randomised controlled trial will be conducted, using a mixed-methods process evaluation to investigate the feasibility of a trial of the MyComrade intervention based on pre-defined progression criteria. A total of 16 practices will be recruited (eight in ROI; eight in NI), and four practices in each jurisdiction will be randomly allocated to intervention or control. Twenty people living with multimorbidity and prescribed ≥ 10 repeat medications will be recruited from each practice prior to practice randomisation. In intervention practices, the MyComrade intervention will be delivered by pairs of general practitioners (GPs) in ROI, and a GP and practice-based pharmacist (PBP) in NI. The GPs/GP and PBP will schedule the time to review the medications together using a checklist. Usual care will proceed in practices in the control arm. Data will be collected via electronic health records and postal questionnaires at recruitment and 4 and 8 months after randomisation. Qualitative interviews to assess the feasibility and acceptability of the intervention and explore experiences related to multimorbidity management will be conducted with a purposive sample of GPs, PBPs, practice administration staff and patients in intervention and control practices. The feasibility of conducting a health economic evaluation as part of a future definitive trial will be assessed.

Discussion

The findings of this pilot study will assess the feasibility of a trial of the MyComrade intervention in two different health systems. Evaluation of the progression criteria will guide the decision to progress to a definitive trial and inform trial design. The findings will also contribute to the growing evidence-base related to intervention development and feasibility studies.

Trial registration

ISRCTN Registry, ISRCTN80017020. Date of confirmation is 4/11/2019.
A review of the potential and constraints for crossbreeding as a basis for goat production by smallholder farmers in Ethiopia
Authors: Kuraz Abebe Belete
Published: March 2022

Background

The purpose of this review was to provide and synthesize validated and up-to-date scientific knowledge on the benefits and drawbacks of crossbreeding as a basis for goat production by Ethiopian smallholder farmers. The majority of Ethiopian smallholder farmers and pastoralists rely on goat production for their livelihoods. Ethiopia's goat population is extensive, with eight genetically recognized indigenous goat breeds. These breeds, on the other hand, do not produce exceptionally well, and their contributions to smallholder farmers and the national economy fall far short of their complete output potential.

Main body of the abstract

In this regard, during the past many years, numerous goat productivity development programs in Ethiopia have collaborated to design and implement crossbreeding as a basis for goat production by smallholder farmers. Crossing indigenous goats (i.e., Afar and Somali goats) with exotic goat breeds, including Saanen, Anglo-Nubian, Toggenburg, and Boer goats, was done primarily to increase the output of indigenous goats. This crossbreeding plan, however, unsuccessful due to a number of factors, including a lack of baseline production data, poorly managed institutional synergies, and little or no consideration of smallholder farmers' needs, opinions, active participation, decisions, and local practices. In addition, insufficient and poor-quality feeds and forages, the termination and weakness of goat genetic improvement projects, disease and parasite incidence, poor veterinary services, and a lack of infrastructure are all major reasons for crossbreeding failure as a basis for goat production by Ethiopian smallholder farmers.

Short conclusion

Crossbreeding as a basis for goat production by Ethiopian smallholder farmers was made possible by the presence of vast indigenous goat breeds with diverse performance parameters throughout the country, as well as the engagement of both governmental and non-governmental groups. In contrast, a lack of baseline production data, a lack of well-organized institutional synergies, and little or no consideration of smallholder farmers' needs, decisions, participation, and local practices were the main roadblocks to planned crossbreeding as a basis for goat production by smallholder farmers in Ethiopia.
Development of the ASSESS tool: a comprehenSive tool to Support rEporting and critical appraiSal of qualitative, quantitative, and mixed methods implementation reSearch outcomes
Authors: Ryan Nessa , Vieira Dorice , Gyamfi Joyce , Ojo Temitope , Shelley Donna , Ogedegbe Olugbenga , Iwelunmor Juliet , Peprah Emmanuel
Published: March 2022

Background

Several tools to improve reporting of implementation studies for evidence-based decision making have been created; however, no tool for critical appraisal of implementation outcomes exists. Researchers, practitioners, and policy makers lack tools to support the concurrent synthesis and critical assessment of outcomes for implementation research. Our objectives were to develop a comprehensive tool to (1) describe studies focused on implementation that use qualitative, quantitative, and/or mixed methodologies and (2) assess risk of bias of implementation outcomes.

Methods

A hybrid consensus-building approach combining Delphi Group and Nominal Group techniques (NGT) was modeled after comparative methodologies for developing health research reporting guidelines and critical appraisal tools. First, an online modified NGT occurred among a small expert panel (n = 5), consisting of literature review, item generation, round robin with clarification, application of the tool to various study types, voting, and discussion. This was followed by a larger e-consensus meeting and modified Delphi process with implementers and implementation scientists (n = 32). New elements and elements of various existing tools, frameworks, and taxonomies were combined to produce the ASSESS tool.

Results

The 24-item tool is applicable to a broad range of study designs employed in implementation science, including qualitative studies, randomized-control trials, non-randomized quantitative studies, and mixed methods studies. Two key features are a section for assessing bias of the implementation outcomes and sections for describing the implementation strategy and intervention implemented. An accompanying explanation and elaboration document that identifies and describes each of the items, explains the rationale, and provides examples of reporting and appraising practice, as well as templates to allow synthesis of extracted data across studies and an instructional video, has been prepared.

Conclusions

The comprehensive, adaptable tool to support both reporting and critical appraisal of implementation science studies including quantitative, qualitative, and mixed methods assessment of intervention and implementation outcomes has been developed. This tool can be applied to a methodologically diverse and growing body of implementation science literature to support reviews or meta-analyses that inform evidence-based decision-making regarding processes and strategies for implementation.
Phyto-factories of anti-cancer compounds: a tissue culture perspective
Authors: Patel Poonam , Patel Vaibhav , Modi Arpan , Kumar Sushil , Shukla Yogesh M.
Published: March 2022

Background

Cancer is one of the most critical but ubiquitous causes of death grappled from past decades. Widely used chemotherapy with cytotoxic activity blocks/ kills the cancer cell. The compounds targeted for anticancerous activity are either derived synthetically or naturally (through plants or microbial origin). Current day, versatile role of plants in medicinal field has been attributed to the secondary metabolites it produces, known for their anticancer activity. Therefore, discovery, identification and commercial production of such novel anticancer drugs is escalated and are centerpiece for pharmaceuticals.

Main body

A biotechnological approach, principally tissue culture, leads the candidacy to be an alternative method for production of anticancer compounds. A wide range of bioactive agents like alkaloids, steroids, phenolics, saponins, flavonoids, and terpenoids are in huge demand commercially. Plant tissue culture applications are constructively more advantageous over conventional methods in terms of their continuous, controlled, aseptic production, large scale and de novo synthesis opportunity. Various bioreactors are used for mass cultivation of bioactive compound at commercial level. For example: stirred tank reactors are used for production of shikonin from Lithospermum erythrorhizon, vincristine from Catharanthus roseus, podophyllotoxin from Podophyllum etc. Strategies like callus culture, suspension culture and hairy root culture are opted for mass cultivation of these bioactives.

Conclusions

This review summarizes plant tissue culture as a promising strategy proven to be a colossal breakthrough in reliable and continuous production of existing and novel anticancer compounds and help in combating the increasing future demands.
Taking The Fair Deal to the Fields: Truman’s Commission on Migratory Labor, Public Law 78, and the Bracero Program, 1950–1952
Authors: ROBINSON ROBERT S.
Published: March 2022

From 1950 to 1952 Harry S Truman invested significant personal effort and political capital in an effort to improve the circumstances of migratory farm workers and to revise the Bracero Program with Mexico. To this end, Truman created the high profile President’s Commission on Migratory Labor in American agriculture in 1950. In its report, the commission recommended extending a variety of social legislation and economic protections to domestic farm labor, and it further recommended slowing or ending the importation of foreign, particularly Mexican, workers. The Truman administration energetically worked to convince Congress to act on those recommendations, even enlisting the support of the Mexican government. However, the power of growers’ interests and the conservative bloc in Congress halted any significant reform. Instead, the Bracero Program was further institutionalized in the form of Public Law 78 and remained in effect for more than a decade thereafter.
Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence
Authors: Jiang Cheng , Bhattacharya Abhishek , Linzey Joseph R. , Joshi Rushikesh S. , Cha Sung Jik , Srinivasan Sudharsan , Alber Daniel , Kondepudi Akhil , Urias Esteban , Pandian Balaji , Al-Holou Wajd N. , Sullivan Stephen E. , Thompson B. Gregory , Heth Jason A. , Freudiger Christian W. , Khalsa Siri Sahib S. , Pacione Donato R. , Golfinos John G. , Camelo-Piragua Sandra , Orringer Daniel A. , Lee Honglak , Hollon Todd C.
Published: March 2022

BACKGROUND:

Accurate specimen analysis of skull base tumors is essential for providing personalized surgical treatment strategies. Intraoperative specimen interpretation can be challenging because of the wide range of skull base pathologies and lack of intraoperative pathology resources.

OBJECTIVE:

To develop an independent and parallel intraoperative workflow that can provide rapid and accurate skull base tumor specimen analysis using label-free optical imaging and artificial intelligence.

METHODS:

We used a fiber laser–based, label-free, nonconsumptive, high-resolution microscopy method (<60 seconds per 1 × 1 mm2), called stimulated Raman histology (SRH), to image a consecutive, multicenter cohort of patients with skull base tumor. SRH images were then used to train a convolutional neural network model using 3 representation learning strategies: cross-entropy, self-supervised contrastive learning, and supervised contrastive learning. Our trained convolutional neural network models were tested on a held-out, multicenter SRH data set.

RESULTS:

SRH was able to image the diagnostic features of both benign and malignant skull base tumors. Of the 3 representation learning strategies, supervised contrastive learning most effectively learned the distinctive and diagnostic SRH image features for each of the skull base tumor types. In our multicenter testing set, cross-entropy achieved an overall diagnostic accuracy of 91.5%, self-supervised contrastive learning 83.9%, and supervised contrastive learning 96.6%. Our trained model was able to segment tumor-normal margins and detect regions of microscopic tumor infiltration in meningioma SRH images.

CONCLUSION:

SRH with trained artificial intelligence models can provide rapid and accurate intraoperative analysis of skull base tumor specimens to inform surgical decision-making.
Η απόλυση υπό όρο στην ποινική νομοθεσία των ναρκωτικών
Authors: Τοπαλνάκος Παύλος
Published: March 2022

Σκοπός της παρούσας διατριβής ήταν η καταγραφή των ειδικών ρυθμίσεων που εισάγονται για την απόλυση υπό όρο στις σχετικές με τα ναρκωτικά διατάξεις. Μετά από μία ανάλυση του θεσμού σε επίπεδο γενικών ρυθμίσεων του Π.Κ. προκειμένου να αναδειχθεί η νομική φύση και ο χαρακτήρας αυτού, καθώς και οι σκοποί τους οποίους επιδιώκει να υπηρετήσει ως ένα κοινοτικό μέτρο εναλλακτικό του εγκλεισμού, εξετάστηκαν, σ’ ένα πρώτο επίπεδο, οι προϋποθέσεις ενεργοποίησης των ειδικών αυτών διατάξεων και τα καίρια νομικά ζητήματα που ανακύπτουν κατά την εφαρμογή τους. Το κύριο βάρος έπεσε στις ειδικές απολύσεις που προβλέπονται στο άρθρο 35§§1 και 2 ν. 4139/2013 στις οποίες κυριαρχεί ο θεραπευτικός χαρακτήρας, ενώ, παράλληλα, εξετάστηκαν και τα ζητήματα που άπτονται της απόλυσης υπό όρο των ανηλίκων και των νεαρών ενηλίκων κρατουμένων που παρακολούθησαν θεραπευτικό πρόγραμμα απεξάρτησης εντός των καταστημάτων κράτησης, καθώς και οι διατάξεις του άρθρου 27§5 ν. 4139/2013 και του νέου άρθρου 105Β§1 περ. γ΄ Π.Κ., οι οποίες, παρότι δεν έχουν θεραπευτικό προσανατολισμό, ωστόσο, εισάγουν ειδικές ρυθμίσεις για την απόλυση υπό όρο κρατουμένων που έχουν καταδικαστεί για πράξεις σχετικές με τα ναρκωτικά. Σε δεύτερο επίπεδο, εκκινώντας από τα ιδιαίτερα χαρακτηριστικά των ειδικών αυτών απολύσεων, προσδιορίστηκε ο χαρακτήρας και η φύση τους, καθώς και το δικαιοπολιτικό υπόβαθρο στο οποίο ερείδεται η εισαγωγή τους. Σε τρίτο και τελευταίο επίπεδο, εξετάστηκε η σχέση των ειδικών αυτών απολύσεων με την απόλυση υπό όρο των γενικών διατάξεων του Π.Κ. υπό το πρίσμα τόσο της αναγκαιότητας και της σκοπιμότητας εισαγωγής ειδικών ρυθμίσεων για την απόλυση υπό όρο των συγκεκριμένων κατηγοριών κρατουμένων, όσο και της συμβατότητας των εκάστοτε λειτουργιών που καλείται να επιτελέσει ο θεσμός σε όλες αυτές τις διατάξεις με τις λειτουργίες που υπηρετεί κατά προορισμό ο θεσμός, όπως αυτός τίθεται στο γενικό κανονιστικό πλαίσιο του Π.Κ. Στις τελικές σκέψεις που ακολουθούν αναδείχθηκε η πολυλειτουργικότητα του θεσμού, η οποία φαίνεται να αφήνει το πλέον εναργές αποτύπωμά της στο πρόσφορο έδαφος των σχετικών με τα ναρκωτικά ρυθμίσεων και διατυπώθηκαν ορισμένες προτάσεις, οι οποίες, de lege ferenda, θα μπορούσαν να επαναφέρουν τον θεσμό εγγύτερα στη φύση του.
A digital territory to be appropriated: the state and the nationalization of cyberspace
Authors: Koulos Thanos
Published: March 2022

Next to land, water, air and space, cyberspace is the complex socio-technical setting often called the ‘fifth domain’. Nationalism has taken over the organization of the first four domains, in the form of constructing national states, national territorial waters and national airspace. The basic proposition of this article is that the ideology of nationalism has also infiltrated the fifth domain – cyberspace – in two ways. First, through state-led cyber-nationalism via official government websites that present ‘national’ achievements and propagate the official state positions on disputes about territory, symbols or history. Second, through individual communities who use the internet to sustain a sense of national belonging and/or to promote and disseminate their nationalist ideals. Both ways are important in an online national identity (re)production framework that, in a fluid, global, modern world, functions supportively towards the traditional national identity (re)production mechanisms.

This article aims to examine the patterns of the nationalization of cyberspace through an analysis of state-led institutions and government websites that aim to enhance national identity and the sense of national belonging in a globalized world, as well as to propagate official state positions. It will focus on Greek, Dutch, US and Israeli websites. The term ‘nationalization’ in this context denotes the ideological charging of the cyber-footprint of the nation: how the internet produces and re-produces the nation, how the users partake in the national community by way of ‘consuming’ the digitalized national ideology, and the way cyber-nationalism defines people’s sense of belonging.
Antimicrobial resistance: One Health approach
Authors: Velazquez-Meza Maria Elena , Galarde-López Miguel , Carrillo-Quiróz Berta , Alpuche-Aranda Celia Mercedes
Published: March 2022

In this research, a review of antimicrobial resistance (AMR) is conducted as part of the One Health approach. A review of publications, which included "antimicrobial resistance" and "One Health," was conducted. Among the global health problems, AMR is the one that most clearly illustrates the One Health approach. AMR is a critical global problem affecting humans, the environment, and animals. This is related to each of these three components due to the irresponsible and excessive use of antimicrobials in various sectors (agriculture, livestock, and human medicine). Improper management of antimicrobials, inadequate control of infections, agricultural debris, pollutants in the environment, and migration of people and animals infected with resistant bacteria facilitate the spread of resistance. The study aimed to analyze the problem of AMR from a health perspective to analyze the different actors involved in One Health.
Teaching strategies in motivating global English learners
Authors: Komlosi-Ferdinand Flora
Published: March 2022

English has undoubtedly become a global language. Within the last decades, however, societies and individuals have changed, became more complex, and identities, emotions and social spaces have been dramatically affected and re-negotiated by globalisation (Heyward, 2004; Tanu, 2016). This opinion article focuses on the author’s researches and experiences in Central Asia and Eastern Europe as a teacher and lecturer. Based on her previous researches and observations the author offers a new framework that addresses students’ needs and preferences for learning Global English. According to the Adaptive Relatability Motivation Framework, learners should be provided with culturally less invasive, identitysafe and emotionally more accommodating learning environment, where they can become more engaged, autonomous and adaptive in their own learning processes. Thus, learners will be able to continually relate their needs, social spaces and motivations to the successful use of the target language. The framework’s concepts are summarized in four points that give a more pragmatic view on its use. These four points are further detailed, offering how these ideas can be implemented in an empirical fashion by educators and students.
Can the ultrasound echogenicity of normal parotid and submandibular glands be used as a reference standard for normal thyroid echogenicity?
Authors: Choi Insik , Na Dong Gyu
Published: March 2022

Purpose: This study aimed to determine whether the normal parotid gland (PG) and submandibular gland (SMG) can be used as reference standards for normal thyroid echogenicity.Methods: In total, 1,302 consecutive patients with normal salivary glands were included in this study. The echogenicity of the SMG and PG was assessed during real-time ultrasound examinations, and the glands were categorized as hyperechogenic, isoechogenic, and hypoechogenic relative to the thyroid parenchyma in patients without diffuse thyroid disease (group 1, n=1,106) and with diffuse thyroid disease (group 2, n=196). The frequency of the echogenicity categories of the normal PG and SMG was assessed according to patients’ age.Results: In group 1, the normal PG showed isoechogenicity in 94.0% and hypoechogenicity or hyperechogenicity in 6.0%, and the normal SMG showed isoechogenicity in 73.6% and hypoechogenicity in 26.4% of patients (P<0.001). There was no significant association of the frequency of isoechoic PG with age (P=0.834); however, there was a trend for an increasing frequency of isoechoic SMG with aging (22.9%-81.4%) (P<0.001). Similar findings were found in group 2 patients without decreased thyroid echogenicity.Conclusion: The normal PG was mostly isoechoic to the normal thyroid parenchyma, whereas the normal SMG showed hypoechogenicity at various frequencies according to age. The echogenicity of the normal PG can be used as an alternative reference standard for normal thyroid echogenicity; however, the normal SMG is not suitable for a reference standard when assessing thyroid nodule echogenicity in patients who have diffuse thyroid disease with decreased parenchymal echogenicity.
Bases conceptuales y herramientas gráficas para investigar cómo funcionan los rasgos funcionales
Authors: Rolhauser Andrés G.
Published: March 2022

Functional traits constitute a promising research avenue to explain and predict ecological patterns at different levels of organization (genotypes, populations, communities) because they link individual responses to environmental conditions. However, Argentine ecologists and botanists seem not to have explored this line of research as much as colleagues in other parts of the world. With this work I intend to promote the use of functional traits among local and regional readers. Amalgamating often conflicting definitions proposed by other authors, I define functional traits as morphological characteristics that affect a chain of physiological and ecological processes that I refer to as function, vital rate, and population fitness. The purpose of this definition is to emphasize the mechanistic relationship between plant structure and function. The practical benefits are straightforward: predicting the future of a plant or a group of plants from their physical properties, which are generally easier to obtain than physiological or phenological measures. Next, I use two types of graphical tools to discuss the functionality of four key traits: potential plant height, seed mass, leaf mass per area, and leaf size. These graphical tools are (i) path diagrams that show direct or indirect, positive or negative connections between traits and fitness and (ii) cartesian graphs that describe the functional relationships between traits and vital rates that, when combined, result in optimum trait–fitness relationships. Theory indicates that such optimum relationships would be the norm rather than the exception, even though functional traits are generally interpreted as “indicators” of plant functions, which exclusively implies linear relationships. These graphical tools may help us produce predictions that guide data generation and contribute to fill important information gaps regarding the mechanistic link between plant form and population fitness. Although functional traits alone are unlikely to offer complete explanations or infallible predictions, ignoring them would deny us an irreplaceable source of information to understand and predict plant population and community responses to environmental conditions in a changing world.
Progressing nemaline myopathy in a patient repeatedly operated on the spine: clinical case and literature review
Authors: Prudnikova O. G. , Kotelnikov A. O. , Migalkin N. S. , Filimonova G. N.
Published: March 2022

Objective. To present a clinical case of a patient with spinal deformity associated with myopathy, which was initially undiagnosed and assessed as secondary myopathy after performed spinal surgeries.

Material and Methods. Study design: clinical observation and review of the literature. A 51-year-old female patient has been repeatedly operated on for scoliotic deformity of the spine with progressing neurological disorders. Clinical and complex radiological assessment (spinal telemetry in sitting position, CT, MRI) of the pathology was performed. In connection with the atypical course of the disease, a pathohistological study of muscle tissue fragments was performed with their fixation in a solution of 10 % neutral formalin. After histological processing, the fragments were embedded in paraffin and stained with hematoxylin-eosin by the Masson trichromic method and by the PTAH method. The preparations were examined using the Pannoramic MIDI II BF hardware and software complex to obtain digital images using the Whole slide imaging technology in the Single layer and Extended focus modes and an AxioScope.A1 stereomicroscope with a digital camera.

Results. Two patterns of distribution of nemaline rods of various density and configuration stained dark blue (by PTAH) were identified in sarcoplasm of parts of muscular tissues: diffusely throughout the myocyte and forming clusters of various sizes in transverse sections, and as filamentous structures – in longitudinal ones. Extensive fields of fatty degeneration, transformation of fibers into lipocytes, contracturely changed fibers, pictures of myophaga and areas of fibrosis of the interstitial space associated with residual myocytes were noted. Intramuscular nervous conductors were subjected to complete involution, singular nervous fibers were deformed, internal space was fibrotic. Neuromuscular spindles had unusually increased connective tissue capsule filled with lipocytes. Arterial vessels had fibrosis of t. adventicia and t. media, narrowed or obliterated lumen, and venous vessels were thin-walled and tortuous, which causes their permeability and can cause hemorrhage. The revealed changes in myocytes with the presence of nemaline rods are characteristic of primary nemaline myopathy.

Conclusion. The atypicality of clinical manifestations, primarily of the neurological status in scoliosis, requires excluding neuromuscular disease by conducting a histopathological examination of the surgical material.