bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of double-negative T cells in haematological malignancies: recent progress and future directions
Authors: Chen Xingchi , Wang Dongyao , Zhu Xiaoyu
Published: March 2022

Haematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies. However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common. Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3+CD4−CD8−) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner. In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies. We hope to exploit these cells as a novel therapy for haematologic malignancies.
Movement ecology of vulnerable lowland tapirs between areas of varying human disturbance
Authors: Medici E. P. , Mezzini S. , Fleming C. H. , Calabrese J. M. , Noonan M. J.
Published: March 2022

Background

Animal movement is a key ecological process that is tightly coupled to local environmental conditions. While agriculture, urbanisation, and transportation infrastructure are critical to human socio-economic improvement, these have spurred substantial changes in animal movement across the globe with potential impacts on fitness and survival. Notably, however, human disturbance can have differential effects across species, and responses to human activities are thus largely taxa and context specific. As human disturbance is only expected to worsen over the next decade it is critical to better understand how species respond to human disturbance in order to develop effective, case-specific conservation strategies.

Methods

Here, we use an extensive telemetry dataset collected over 22 years to fill a critical knowledge gap in the movement ecology of lowland tapirs (Tapirus terrestris) across areas of varying human disturbance within three biomes in southern Brazil: the Pantanal, Cerrado, and Atlantic Forest.

Results

From these data we found that the mean home range size across all monitored tapirs was 8.31 km2 (95% CI 6.53–10.42), with no evidence that home range sizes differed between sexes nor age groups. Interestingly, although the Atlantic Forest, Cerrado, and Pantanal vary substantially in habitat composition, levels of human disturbance, and tapir population densities, we found that lowland tapir movement behaviour and space use were consistent across all three biomes. Human disturbance also had no detectable effect on lowland tapir movement. Lowland tapirs living in the most altered habitats we monitored exhibited movement behaviour that was comparable to that of tapirs living in a near pristine environment.

Conclusions

Contrary to our expectations, although we observed individual variability in lowland tapir space use and movement, human impacts on the landscape also had no measurable effect on their movement. Lowland tapir movement behaviour thus appears to exhibit very little phenotypic plasticity in response to human disturbance. Crucially, the lack of any detectable response to anthropogenic disturbance suggests that human modified habitats risk being ecological traps for tapirs and this information should be factored into conservation actions and species management aimed towards protecting lowland tapir populations.
Pediatric sleep outcomes after endoscopy-directed simultaneous lingual tonsillectomy and epiglottopexy
Authors: Maksimoski Matthew , Maurrasse Sarah E. , Hoff Stephen R. , Lavin Jennifer , Valika Taher , Thompson Dana M. , Ida Jonathan B.
Published: March 2022

Background

The purpose of this study was to evaluate the efficacy of sleep endoscopy-directed simultaneous lingual tonsillectomy and epiglottopexy in patients with sleep disordered breathing (SDB), including polysomnography (PSG) and swallowing outcomes.

Methods

A retrospective review was performed of all patients undergoing simultaneous lingual tonsillectomy and epiglottopexy over the study period. PSG objective measures were recorded pre- and postoperatively, along with demographic data, comorbidities, and descriptive data of swallowing dysfunction in the postoperative setting.

Results

A total of 24 patients met inclusion criteria for consideration, with 13 having valid pre- and postoperative PSG data. Successful surgery was achieved in 84.6% of patients, with no difference based on presence of medical comorbidities including Trisomy 21. Median reduction in obstructive apnea–hypopnea index (oAHI) with the procedure was 69.9%. Four patients (16.7%) had postoperative concern for dysphagia, but all objective swallowing evaluations were normal and no dietary modifications were necessary.

Conclusion

Combination lingual tonsillectomy and epiglottopexy in indicated patients has a high rate of success in this single-institutional study without new dysphagia in this population. These procedures are amenable to a combination surgery in appropriately selected patients determined by sleep state endoscopy in the setting of SDB evaluated with drug-induced sleep endoscopy.

Graphical Abstract
Consumers’ adverse drug event reporting via community pharmacists: three stakeholder perception
Authors: Kitisopee Tanattha , Assanee Jirunya , Sorofman Bernard A. , Watcharadmrongkun Suntaree
Published: March 2022

Background

Adverse drug event (ADE) reporting is a significant process to increase consumer care and consumer safety associated with the use of medicines. An in-depth investigation into low ADE reporting by consumers and community pharmacists was undertaken to uncover interventions to improve reporting.

Method

In-depth interviewing of the three parties; consumers, pharmacists and employees of the Pharmacovigilance Center in Thailand, was used to collect the data. They were interviewed about ADE reporting experiences and contributing factors and problems of ADE reporting. Thematic analysis was used to interpret the results.

Result

The HPVC received few ADE reports from consumers. Most community pharmacists received ADE reports from consumers; however, the Pharmacovigilance Center received few ADE reports from community pharmacists. ADE reporting of community pharmacists and consumers were influenced by many factors which were categorized into four themes which were (1) “Cognition” (awareness, attitude and responsibility); (2) “Reporting process” (complication, competency, information deficiency, feedback, and resource); (3) “Inducer” (service orientation, acquaintanceship, motivation, severity level, regulatory and reward); and (4) “Obstacle” (doubt, belief and prosecution).

Conclusion

Health professionals should motivate consumers to report ADEs. Building social responsibility and benefits and increasing knowledge of reporting process, channels, and system to both community pharmacists and consumers were recommended. Providing rewards and making community pharmacists feel comfortable to report ADEs by simplifying the ADE form and providing training, guidelines, and an ADR assessment tool can drive them to report ADEs. Feedback to consumers by confirming whether it was ADE and feedback to pharmacists that the Pharmacovigilance Center received their reports and their reports were utilized were also important.
Robot-assisted transhiatal lower esophagectomy and proximal gastrectomy for Siewert type II advanced esophagogastric junction cancer with situs inversus totalis: a case report
Authors: Katano Kaoru , Inaki Noriyuki , Yamaguchi Takahisa , Saito Hiroto , Shimada Mari , Terai Shiro , Okamoto Koichi , Moriyama Hideki , Kinoshita Jun , Nakamura Keishi , Ninomiya Itasu
Published: March 2022

Background

Situs inversus totalis (SIT) is a rare congenital abnormality in which the thoracic and abdominal organs are reversed or mirrored from their usual positions. We herein report the first case of robot-assisted transhiatal lower esophagectomy and proximal gastrectomy with esophagogastrostomy for treatment of Siewert type II advanced esophagogastric junction (EGJ) cancer with SIT.

Case presentation

A 62-year-old man with SIT and intestinal malrotation was diagnosed with T3N0M0 Stage IIA EGJ cancer. Three-dimensional reconstruction of a computed tomography angiogram showed that the common hepatic artery was absent, the proper hepatic artery was derived from the superior mesenteric artery through the gastroduodenal artery, and an accessary left hepatic artery arose from the left gastric artery. The patient underwent robot-assisted transhiatal lower esophagectomy and proximal gastrectomy with D2 lymph node dissection, including lower mediastinal lymphadenectomy. Intraoperative examination revealed minor vascular abnormalities, including three branches of the left gastric artery and two left gastric veins, that had not been recognized preoperatively. The surgery was performed safely, and the patient had an uneventful postoperative course.

Conclusions

Robotic-assisted surgery is efficient even for complex conditions, such as Siewert type II advanced EGJ cancer with SIT.
Relationships between barley consumption and gut microbiome characteristics in a healthy Japanese population: a cross-sectional study
Authors: Matsuoka Tsubasa , Hosomi Koji , Park Jonguk , Goto Yuka , Nishimura Mao , Maruyama Satoko , Murakami Haruka , Konishi Kana , Miyachi Motohiko , Kawashima Hitoshi , Mizuguchi Kenji , Kobayashi Toshiki , Yokomichi Hiroshi , Kunisawa Jun , Yamagata Zentaro
Published: March 2022

Background

Barley contains abundant soluble beta-glucan fibers, which have established health benefits. In addition, the health benefits conferred by the gut bacteria have attracted considerable interest. However, few studies have focused on the barley consumption and gut bacteria of the Japanese population. In this study, we aimed to identify the relationship between the barley consumption and gut bacteria composition of the Japanese population.

Methods

In total, 236 participants were recruited in Japan, and 94 participants with no complications of diabetes, hypertension, or dyslipidemia were selected for the study. We analyzed fecal samples from the participants, their medical check-up results, and responses to questionnaires about dietary habits. The participants were grouped according to their median barley consumption. Then, we assessed the relative abundance of 50 genera. Characteristic bacteria were evaluated for their relationship with barley consumption by multiple regression analysis, adjusted for disease and dietary habits, in all participants. We also analyzed the networks and clustering of the 20 selected genera.

Results

According to the comparison between barley groups, Bifidobacterium, Butyricicoccus, Collinsella, Ruminococcus 2, and Dialister were characteristic candidate bacterias of the group that consumed large amounts of barley (P < 0.05). The relationship between barley consumption and Bifidobacterium remained after adjusting for disease and dietary habits, and that of Butyricicoccus remained after adjusting for disease. Furthermore, network and cluster analyses revealed that barley consumption was directly correlated with Bifidobacterium and Butyricicoccus.

Conclusions

Barley consumption generates changes in the intestinal bacteria of the Japanese population. We found that Bifidobacterium and Butyricicoccus abundance was positively associated with barley consumption.
Stressed portfolio optimization with semiparametric method
Authors: Han Chuan-Hsiang , Wang Kun
Published: March 2022

Tail risk is a classic topic in stressed portfolio optimization to treat unprecedented risks, while the traditional mean–variance approach may fail to perform well. This study proposes an innovative semiparametric method consisting of two modeling components: the nonparametric estimation and copula method for each marginal distribution of the portfolio and their joint distribution, respectively. We then focus on the optimal weights of the stressed portfolio and its optimal scale beyond the Gaussian restriction. Empirical studies include statistical estimation for the semiparametric method, risk measure minimization for optimal weights, and value measure maximization for the optimal scale to enlarge the investment. From the outputs of short-term and long-term data analysis, optimal stressed portfolios demonstrate the advantages of model flexibility to account for tail risk over the traditional mean–variance method.
“This is not how we talk about race anymore”: approaching mixed race in Australia
Authors: Fozdar Farida
Published: March 2022

Discussions about how to talk about race are ubiquitous among academics seeking to balance the recognition that race is a social construct with the very real effects of racial stratification. Naming race is seen as potentially reifying it, but ignoring it invisiblises its effects. Pathologising, celebratory and critical approaches to talking about mixed race can all be found in how mixedness is talked about in Australia (among the public and in scholarly work), and there are differences depending on whether mixedness is Indigenous or migrant. Using my experience of being challenged for speaking too positively about the experience of being mixed in Australia, and a Facebook discussion about Census categories, this paper explores the ways in which mixed race is talked about (and not talked about) in Australia. It argues that we can’t move ‘beyond race’ before actually acknowledging it, something Australia has been very reticent to do, due to its race-based history of colonisation, immigration, and Indigenous child removals. Acknowledging race would enable diversity, and mixedness, to be counted, and therefore to ‘count’, in a context where multiculturalism provides a socio-political environment somewhat supportive of diversity, but where actual measurement is limited. It is argued that acknowledging race may be a necessary intermediate step on the road beyond race, and, for that matter, nation.
Cardiovascular toxicities of androgen deprivation therapy in Asian men with localized prostate cancer after curative radiotherapy: a registry-based observational study
Authors: Li Youquan , Ong Whee Sze , Shwe Ma Than Than , Yit Nelson Ling Fung , Quek Sheriff Zhan Hong , Pang Eric Pei Ping , Looi Wen Shen , Nei Wen Long , Wang Michael Lian Chek , Chua Melvin Lee Kiang , Tan Terence Wee Kiat , Chua Eu Tiong , Ng Choon Ta , Tuan Jeffrey Kit Loong
Published: March 2022

Background

Androgen deprivation therapy (ADT) and radiotherapy (RT) are the mainstay treatment for localized prostate cancer and recurrence after surgery. Cardiovascular (CV) toxicity of ADT is increasingly recognized, and the risk relates to pre-existing risk factors and ADT modalities. Despite ethnic differences in the prevalence of CV risk factors and variations of CV mortality, data on ADT-related cardiotoxicities in the Asian population remain inconclusive. Our registry-based study investigated ADT-related major adverse cardiovascular events (MACE) after primary or salvage RT.

Methods

Our study combined two prospectively established registry databases from National Cancer Center Singapore and National Heart Center Singapore. The primary endpoint is time to first MACE after treatment. MACE is defined as myocardial infarction, stroke, unstable angina, or cardiovascular death. Two types of propensity score adjustments, including ADT propensity score as a covariate in the multivariable regression model and propensity score weighting, were applied to balance baseline features and CV risk factors between RT alone and RT + ADT groups.

Results

From 2000 to 2019, 1940 patients received either RT alone (n = 494) or RT + ADT (n = 1446) were included. After a median follow-up of 10 years (RT) and 7.2 years (RT+ ADT), the cumulative incidence of MACE at 1, 3 and 9 years was 1.2, 5 and 16.2% in RT group, and 1.1, 5.2 and 17.6% in RT + ADT group, respectively. There were no differences in the incidence of MACE between 2 groups (HR 1.01, 95% CI 0.78–1.30,p = 0.969). Pre-treatment CV risk factors were common (80%), and CV disease (15.9%) was the second leading cause of death after prostate cancer (21.1%). On univariate analysis, older age, Indians and Malays, pre-existing CV risk factors, and history of MACE were associated with higher MACE risk. After propensity score adjustments, there remained no significant differences in MACE risk between RT + ADT and RT group on multivariable analysis.

Conclusions

In our registry-based study, ADT is not associated with increased risk of major cardiovascular events among Southeast Asian men with prostate cancer after curative radiotherapy.
Cannabinoids in the management of behavioral, psychological, and motor symptoms of neurocognitive disorders: a mixed studies systematic review
Authors: Bahji Anees , Breward Natasha , Duff Whitney , Absher Nafisa , Patten Scott B. , Alcorn Jane , Mousseau Darrell D.
Published: March 2022

Aim

We undertook this systematic review to determine the efficacy and safety of cannabis-based medicine as a treatment for behavioral, psychological, and motor symptoms associated with neurocognitive disorders.

Methods

We conducted a PRISMA-guided systematic review to identify studies using cannabis-based medicine to treat behavioral, psychological, and motor symptoms among individuals with Alzheimer's disease (AD) dementia, Parkinson’s disease (PD), and Huntington’s disease (HD). We considered English-language articles providing original data on three or more participants, regardless of design.

Findings

We identified 25 studies spanning 1991 to 2021 comprised of 14 controlled trials, 5 pilot studies, 5 observational studies, and 1 case series. In most cases, the cannabinoids tested were dronabinol, whole cannabis, and cannabidiol, and the diagnoses included AD (n = 11), PD (n = 11), and HD (n = 3). Primary outcomes were motor symptoms (e.g., dyskinesia), sleep disturbance, cognition, balance, body weight, and the occurrence of treatment-emergent adverse events.

Conclusions

A narrative summary of the findings from the limited number of studies in the area highlights an apparent association between cannabidiol-based products and relief from motor symptoms in HD and PD and an apparent association between synthetic cannabinoids and relief from behavioral and psychological symptoms of dementia across AD, PD, and HD. These preliminary conclusions could guide using plant-based versus synthetic cannabinoids as safe, alternative treatments for managing neuropsychiatric symptoms in neurocognitive vulnerable patient populations.
Azolla pinnata as unconventional feeds for ruminant feeding
Authors: El Naggar Soad , El-Mesery Hany S.
Published: March 2022

Due to the scarcity of concentrate and green fodder and its high prices in animal feeding, the quest for readily available and inexpensive alternative sources has become critical for breeders seeking to minimize the cost of animal production. Azolla is an invasive plant that grows faster in freshwater lakes, rivers, wetlands, and ditches in both temperate and tropical countries by a few precautionary steps with low production costs. It can modify biodiversity and aquatic ecosystems substantially. Azolla has a symbiotic relationship with the nitrogen-fixing blue-green alga Anabaena azollae, which increases the protein content of Azolla, making it one of the greatest alternative feed ingredients as a source of protein, with 25–30% protein, 7–10% amino acids, vitamins (Beta Carotene, vitamin A, vitamin B12), minerals (calcium, potassium, phosphorus, ferrous, magnesium, copper, etc.), and antioxidants. Several studies showed that Azolla can be fed to animals like cow, buffalo, sheep, goat and rabbit because it is easily digestible (because to its high protein and low lignin content), increases feed efficiency, average daily gain of animals, and milk production by 15–20%. Therefore, the present review was aimed to show the possibility of using Azolla as a source of alternative low-cost protein and its impact on animal efficiency.
Chemoinformatic design and profiling of some derivatives of 1, 2, 4-oxadiazole as potential dengue virus NS-5 inhibitors
Authors: Adawara Samuel Ndaghiya , Shallangwa Gideon Adamu , Mamza Paul Andrew , Abdulkadir Ibrahim
Published: March 2022

Background

Dengue virus (DENV) infection is spreading rapidly, especially in the subtropical and tropical regions, placing a huge percentage of the global population at risk and causing repeated outbreaks. DENV protease inhibition has been suggested as a viable therapeutic strategy. Using a computer-aided design approach and the structure-based drug design approach, ten 1, 2, 4-oxadiazole derivatives were designed based on the lead template (34) from our prior study. The design involved the substitution at the phenyl pharmacophore of the lead with methylamine, hydroxyl, and methoxy groups. To compare the anti-DENV efficacy of the optimized designed compounds to the template and other DENV referenced inhibitors targeting the NS-5 protease (PDB ID: 5K5M), they were docked with the DENV NS-5 protease. In silico, ADME characteristics and drug-likeness were also assessed for the compounds.

Results

The molecular docking scores of the designed 1, 2, 4-oxadiazole derivatives varied from − 19.091 to − 29.61 kcal/mol, with excellent hydrogen bond energies in the range of − 3.402 to − 9.0128 kcal/mol, compared to the lead with a score of − 19.10 kcal/mol, and the hydrogen bond energy is − 3.10 kcal/mol, both of which are lower than those of the proposed compounds. Ferentinide, S-adenosyl-l-homocysteine, and Ribavirin were found to have lower binding scores of − 15.8137, − 16.5362, and − 12.446 kcal/mol, respectively, with hydrogen bond energies of − 4.2659, − 10.4372, and − 7.2995 kcal/mol. The developed compounds all followed Lipinski's criteria, meaning they were highly bioavailable, had no potential carcinogenic or mutagenic properties, and posed no concern of cardiovascular toxicity based on the ADMET profile.

Conclusion

The proposed oxadiazole derivative interacted better with DENV protease (NS-5) than the lead inhibitor as well as the conventional inhibitors. Compounds 34a and 34b had the best ligand-protease interaction and gave the lowest free energy at − 26.54 and − 29.612 kcal/mol, respectively. Hence, they could be suggested as potential therapeutic candidates to inhibit NS-5 RdRp protease. This study has revealed the anti-DENV action of the designed compounds, indicating that synthesis and in vivo studies into their efficacy and mechanism are warranted.
The synergy between food and agri-food suppliers, and the restaurant sector in the World Heritage City of Córdoba (Spain)
Authors: Meneguel Cinthia Rolim de Albuquerque , Hernández-Rojas Ricardo David , Mateos Manuel Rivera
Published: March 2022

The tourist-catering subsector plays an important role in the consolidation and attraction of tourism products and services offered. This research aims to ascertain the importance of synergies, and proactive collaborative and co-operational relations between agri-food suppliers and the restaurants. This is a qualitative, exploratory and descriptive methodology, data source triangulation, information processing using NVIVO12 software. This study identifying that the city of Córdoba offers a variety of gastronomic products and services, and that the supply sector is semi-structured and still in need of improvements of quality, safety and having a wider commercial network. Despite the COVID-19 pandemic, suppliers have reinvented themselves and created new market opportunities to benefit from rapid growth in some sectors; furthermore, they are in a position to offer restaurants a competitive advantage in post-pandemic recovery.
Enhanced photocatalytic activity of novel α-Bi2O3@g-C3N4 composites for the degradation of endocrine-disrupting benzophenone-3 in water under visible light
Authors: Berekute Abiyu Kerebo , Yu Kuo-Pin , Chuang Yi-Hsueh Brad
Published: March 2022

The commonly used benzophenone-3 (BP-3) as ultraviolet filter ingredients is an endocrine-disrupting chemical that has received particular attention owing to its environmental ubiquity, and it poses a threat to aquatic biota and human health. In this study, novel α-Bi2O3@g-C3N4 nanocomposites with different α-Bi2O3 contents and enhanced photocatalytic activity were synthesized by a mixing calcination method. The as-synthesized photocatalysts were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, ultraviolet–visible diffuse reflectance spectroscopy, N2 adsorption/desorption isotherm analysis, electrochemical impedance spectroscopy, photoluminescence spectroscopy and electron paramagnetic resonance (EPR) spectroscopy. The 1 wt% α-Bi2O3@g-C3N4 composite exhibited the highest rate constant of 0.42 h-1 for photocatalytic degradation of BP-3, which was up to 6.3 times higher than that of g-C3N4 (0.07 h-1). The enhanced photocatalytic activity might be due to the enhanced separation of photogenerated electron-hole (e--h+) charge pairs and suppression of e--h+ recombination. Scavenging experiments suggested that •OH, h+ and •O2- worked together in the α-Bi2O3@g-C3N4 photocatalytic process. The EPR spectra demonstrated that the α-Bi2O3@g-C3N4 composites generated considerably more •O2- and •OH than g-C3N4. Finally, cyclic degradation experiments showed the reusability of 1 wt% α-Bi2O3@g-C3N4 for BP-3 removal.
Heterozygous missense variant in the TTN gene causing Tibial muscular dystrophy
Authors: Panwar Deepak , Singh Kumar Gautam , Mathur Shruti , Prasad Bhagwati , Joshi Anita , Lal Vandana , Thatai Atul
Published: March 2022

Background

Tibial muscular dystrophy (TMD), tardive, is a dominantly inherited mild degenerative disorder of anterior tibial muscles. Mutations of Titin (TTN) have been reported in patients with different phenotypes such as skeletal muscular abnormalities or complex overlapping disorders of muscles. Titin (TTN) is a large 363 exon gene that encodes an abundant protein (the longest polypeptide known in nature) expressed in the heart and skeletal muscles.

Methods

DNA from peripheral blood sample was extracted, whole exome sequencing (WES) was performed, and a neuromuscular disorders related gene-filtering strategy was used to analyse the disease-causing mutations. Further, sanger sequencing was applied to confirm the variant.

Results

A novel missense variant (c.41529G > C;p.Arg13843Ser) of TTN gene was identified in a patient with lower limb weakness, occasional tongue fasciculation and mild scoliosis. This variant leads to a substitution of arginine with serine, causing structural changes in titin protein that is responsible for the TMD disease.

Conclusion

The novel variant detected has widened the genetic spectrum of TTN-associated diseases, further functional studies will aid in establishing the clinical diagnosis.
Transcriptome analysis reveals SALL4 as a prognostic key gene in gastric adenocarcinoma
Authors: Sarma Ranjan Jyoti , Subbarayan Sarathbabu , Zohmingthanga John , Chenkual Saia , Zomuana Thomas , Lalruatfela Sailo Tlau , Pautu Jeremy L. , Maitra Arindam , Kumar Nachimuthu Senthil
Published: March 2022

Background

Stomach adenocarcinoma (STAD) dominates 80–90% of gastric cancer (GC). Over the years, it has been realized that the identification of the genes responsible for gastric carcinogenesis is essential to understand the biomarker discovery.

Methods

This study aims to identify candidate genes for biomarker discovery in STAD. RNA-Seq was performed on three paired tumor-normal and one unpaired tumor samples from four GC patients and investigated for differentially expressed genes (DEGs) using DESeq2. Gene set enrichment analysis were performed. The DEGs were compared with two STAD microarray datasets available on Gene Expression Omnibus (GEO) database. Survival study (OS) were performed using KM-Plotter on the common genes between all the datasets.

Results

Totally, 148 DEGs were identified, wherein 55 genes were upregulated and 93 genes were downregulated with |log2foldchange| > 1 and Benjamini-Hochberg (BH) Adjusted P value < 0.01. Cell adhesion molecule (CAM) Pathway was found to be the most significant among the upregulated genes. Gastric acid secretion and mineral absorption pathways were the most significant pathways among the downregulated genes. Comparison with two GEO datasets followed by OS analysis revealed two upregulating genes, APOC1 and SALL4 with prognostic significance.

Conclusion

Upregulation of APOC1 is associated with marginal overall survival (OS) and SALL4 over-expression was associated with the poor OS using KM-Plotter during 5 years data period. Our study suggests that SALL4 could be a promising biomarker candidate in STAD.
Evaluating research co-production: protocol for the Research Quality Plus for Co-Production (RQ+ 4 Co-Pro) framework
Authors: McLean Robert K. D. , Carden Fred , Graham Ian D. , Aiken Alice B. , Armstrong Rebecca , Bray Judy , Cassidy Christine E. , Daub Olivia , Di Ruggiero Erica , Fierro Leslie A. , Gagnon Michelle , Hutchinson Alison M. , Kislov Roman , Kothari Anita , Kreindler Sara , McCutcheon Chris , Reszel Jessica , Scarrow Gayle
Published: March 2022

Background

Research co-production is an umbrella term used to describe research users and researchers working together to generate knowledge. Research co-production is used to create knowledge that is relevant to current challenges and to increase uptake of that knowledge into practice, programs, products, and/or policy. Yet, rigorous theories and methods to assess the quality of co-production are limited. Here we describe a framework for assessing the quality of research co-production—Research Quality Plus for Co-Production (RQ+ 4 Co-Pro)—and outline our field test of this approach.

Methods

Using a co-production approach, we aim to field test the relevance and utility of the RQ+ 4 Co-Pro framework. To do so, we will recruit participants who have led research co-production projects from the international Integrated Knowledge Translation Research Network. We aim to sample 16 to 20 co-production project leads, assign these participants to dyadic groups (8 to 10 dyads), train each participant in the RQ+ 4 Co-Pro framework using deliberative workshops and oversee a simulation assessment exercise using RQ+ 4 Co-Pro within dyadic groups. To study this experience, we use a qualitative design to collect participant demographic information and project demographic information and will use in-depth semi-structured interviews to collect data related to the experience each participant has using the RQ+ 4 Co-Pro framework.

Discussion

This study will yield knowledge about a new way to assess research co-production. Specifically, it will address the relevance and utility of using RQ+ 4 Co-Pro, a framework that includes context as an inseparable component of research, identifies dimensions of quality matched to the aims of co-production, and applies a systematic and transferable evaluative method for reaching conclusions. This is a needed area of innovation for research co-production to reach its full potential. The findings may benefit co-producers interested in understanding the quality of their work, but also other stewards of research co-production. Accordingly, we undertake this study as a co-production team representing multiple perspectives from across the research enterprise, such as funders, journal editors, university administrators, and government and health organization leaders.
Cellular messenger molecules mediating addictive drug-induced cognitive impairment: cannabinoids, ketamine, methamphetamine, and cocaine
Authors: Sim Hye In , Kim Dae Hyun , Kim Mikyung
Published: March 2022

Background

Cognitive impairment is a commonly reported symptom with increasing life spans. Numerous studies have focused on identifying precise targets to relieve or reduce cognitive impairment; however, its underlying mechanism remains elusive. Most patients or animals exposed to addictive drugs exhibit cognitive impairment. Accordingly, the present review discusses the molecular changes induced by addictive drugs to clarify potential mechanisms that mediate cognitive impairments.

Main body

We investigated changes in cognitive function using four drugs: cannabinoids, ketamine, methamphetamine, and cocaine. Chronic administration of most addictive drugs reduces overall cognitive functions, such as working, spatial, and long-term recognition memories. Levels of several transcription factors involved in neuronal differentiation, as well as functional components of neurotransmitter receptors in neuronal cells, are reportedly altered. In addition, inflammatory factors showed a generally increasing trend. These impairments could be mediated by neuroinflammation, synaptic activity, and neuronal plasticity.

Conclusion

This review outlines the effects of acute or chronic drug use and potential molecular alterations in the central nervous system. In the central nervous system, addictive drug-induced changes in molecular pathways associated with cognitive function might play a pivotal role in elucidating the pathogenesis of cognitive impairment.
Good for the planet and good for our health: the evidence for whole-food plant-based diets
Authors: Pye Alison , Bash Kristin , Joiner Adam , Beenstock Jane
Published: March 2022

There is growing interest in the health and environmental benefits of whole-food plant-based (WFPB) diets. The current global food system is harmful to our planet and is a key driver of climate change, pollution and biodiversity loss. A transition to WFPB diets will mitigate against these impacts and potentially reduce agriculture greenhouse gas emissions by up to 80%. Emerging evidence suggests that such diets also have significant physical and mental health benefits and can be useful in preventing and treating a range of conditions. Psychiatrists therefore have an important role to play in promoting WFPB diets among patients.
Breast Cancer Care Timeliness Framework: A Quality Framework for Cancer Control
Authors: Mohd Mujar Noor Mastura , Dahlui Maznah , Emran Nor Aina , Hadi Imisairi Abdul , Yan Yang Wai , Arulanantham Sarojah , Chea Chan Hooi , Mohd Taib Nur Aishah
Published: March 2022

PURPOSE

The aim of this study is to determine the pathway that women follow for Breast Cancer Care (BCC) and the time intervals from symptom discovery to treatment initiation and to develop a quality matrix framework.

METHODS

A retrospective cohort study was conducted at six tertiary centers in Malaysia. All women with newly diagnosed breast cancer were interviewed, and a medical records review was conducted using a structured questionnaire. The BCC timeliness framework showed that the total time between a woman discovering their first breast changes and the date of initial treatment was divided into three distinct intervals: presentation interval, diagnostic interval, and treatment interval. Four diagnosis subintervals, referral, biopsy, report, and diagnosis resolution intervals, were also looked into.

RESULTS

The BCC timeliness framework was used to capture important time points. The median total time, presentation interval, diagnostic interval, and treatment interval were 4.9 months (range, 1 month to 10 years), 2.4 months (range, 7 days to 10 years), 26 days (range, 4 days to 9.3 months), and 21 days (range, 1 day to 7.2 months), respectively. Meanwhile, the median time for the diagnosis subinterval of referral, biopsy, report, and diagnosis resolution was 8 days (range, 0 day to 8 months), 0 day (range, 0 day to 20 days), 7 days (range, 3 days to 3.5 months), and 4 days (range, 1 day to 1.8 months), respectively.

CONCLUSION

The BCC timeliness framework is based on the current sequenced trajectory of the BCC journey. Clarity in the measurement of timeliness provides a standardized language for monitoring and outcome research. It can serve as a quality indicator for community and hospital-based breast cancer programs.
Cost Effectiveness of Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India—A Model-Based Economic Analysis
Authors: Gupta Nidhi , Nehra Prerika , Chauhan Akashdeep Singh , Mehra Nikita , Singh Ashish , Krishnamurthy Manjunath Nookala , Rajsekhar Kavitha , Kalaiyarasi Jayachandran Perumal , Roy Partha Sarathi , Malik Prabhat Singh , Mathew Anisha , Malhotra Pankaj , Kataki Amal Chandra , Dixit Jyoti , Gupta Sudeep , Kumar Lalit , Prinja Shankar
Published: March 2022

PURPOSE

Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India.

METHODS

Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty.

RESULTS

Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy.

CONCLUSION

Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.
Aneurysmal Oscillation of the Capnogram: A Case Report
Authors: Saini Kulbhushan , Singh Avneet , Mishra Anand Kumar , Gupta Rekha , Walia Sheenam , Negi Sunder
Published: March 2022

Variations in the alveolar plateau phase of the capnogram are often confused with spontaneous breathing efforts in an intubated patient. The oscillations in the capnogram due to a large ascending thoracic aneurysm are a separate entity from cardiogenic oscillations, and can be an indicator of underlying bronchial or lung compression.
Single-cell genomics revolutionizes plant development studies across scales
Authors: Zhu Mingyuan , Taylor Isaiah W. , Benfey Philip N.
Published: March 2022

Understanding the development of tissues, organs and entire organisms through the lens of single-cell genomics has revolutionized developmental biology. Although single-cell transcriptomics has been pioneered in animal systems, from an experimental perspective, plant development holds some distinct advantages: cells do not migrate in relation to one another, and new organ formation (of leaves, roots, flowers, etc.) continues post-embryonically from persistent stem cell populations known as meristems. For a time, plant studies lagged behind animal or cell culture-based, single-cell approaches, largely owing to the difficulty in dissociating plant cells from their rigid cell walls. Recent intensive development of single-cell and single-nucleus isolation techniques across plant species has opened up a wide range of experimental approaches. This has produced a rapidly expanding diversity of information across tissue types and species, concomitant with the creative development of methods. In this brief Spotlight, we highlight some of the technical developments and how they have led to profiling single-cell genomics in various plant organs. We also emphasize the contribution of single-cell genomics in revealing developmental trajectories among different cell types within plant organs. Furthermore, we present efforts toward comparative analysis of tissues and organs at a single-cell level. Single-cell genomics is beginning to generate comprehensive information relating to how plant organs emerge from stem cell populations.
Ena/VASP proteins in cell edge protrusion, migration and adhesion
Authors: Faix Jan , Rottner Klemens
Published: March 2022

The tightly coordinated, spatiotemporal control of actin filament remodeling provides the basis of fundamental cellular processes, such as cell migration and adhesion. Specific protein assemblies, composed of various actin-binding proteins, are thought to operate in these processes to nucleate and elongate new filaments, arrange them into complex three-dimensional (3D) arrays and recycle them to replenish the actin monomer pool. Actin filament assembly is not only necessary to generate pushing forces against the leading edge membrane or to propel pathogens through the cytoplasm, but also coincides with the generation of stress fibers (SFs) and focal adhesions (FAs) that generate, transmit and sense mechanical tension. The only protein families known to date that directly enhance the elongation of actin filaments are formins and the family of Ena/VASP proteins. Their mechanisms of action, however, in enhancing processive filament elongation are distinct. The aim of this Review is to summarize our current knowledge on the molecular mechanisms of Ena/VASP-mediated actin filament assembly, and to discuss recent insights into the cell biological functions of Ena/VASP proteins in cell edge protrusion, migration and adhesion.
Biological constraints on configural odour mixture perception
Authors: Coureaud Gérard , Thomas-Danguin Thierry , Sandoz Jean-Christophe , Wilson Donald A.
Published: March 2022

Animals, including humans, detect odours and use this information to behave efficiently in the environment. Frequently, odours consist of complex mixtures of odorants rather than single odorants, and mixtures are often perceived as configural wholes, i.e. as odour objects (e.g. food, partners). The biological rules governing this ‘configural perception’ (as opposed to the elemental perception of mixtures through their components) remain weakly understood. Here, we first review examples of configural mixture processing in diverse species involving species-specific biological signals. Then, we present the original hypothesis that at least certain mixtures can be processed configurally across species. Indeed, experiments conducted in human adults, newborn rabbits and, more recently, in rodents and honeybees show that these species process some mixtures in a remarkably similar fashion. Strikingly, a mixture AB (A, ethyl isobutyrate; B, ethyl maltol) induces configural processing in humans, who perceive a mixture odour quality (pineapple) distinct from the component qualities (A, strawberry; B, caramel). The same mixture is weakly configurally processed in rabbit neonates, which perceive a particular odour for the mixture in addition to the component odours. Mice and honeybees also perceive the AB mixture configurally, as they respond differently to the mixture compared with its components. Based on these results and others, including neurophysiological approaches, we propose that certain mixtures are convergently perceived across various species of vertebrates/invertebrates, possibly as a result of a similar anatomical organization of their olfactory systems and the common necessity to simplify the environment's chemical complexity in order to display adaptive behaviours.
Fuzzy MCDM models for selection of the tourism development site: the case of Azerbaijan
Authors: Nuriyev Aziz M.
Published: March 2022

Background: One of the vital issues in promoting the sustainable tourism industry in developing countries, including Azerbaijan, is the well-grounded selection of tourism sites. Applying traditional approaches as a solution to this task, does not provide a relevant result in all cases in these countries due to local specifics of the tourism, the incompleteness of statistical data, the high-level uncertainty of the internal and external environment, and the questionable reliability of the available information.

Methods: Since the statistical data are limited, and conventional formalization tools used for uncertainty description do not consider the reliability degree of the data, it is suggested to make decisions based on the Z-extension of fuzzy logic. A Delphi panel with the expert group is conducted to obtain the information required for the model development. Fuzzy Z-information-based TOPSIS and PROMETHEE methods are applied for the problem solution. Within these approaches Z-number-based procedures of the decision matrix normalization, defining the distance between solutions and the preference function, and swing weights determination are realized. Direct computations with Z-numbers are implemented. 

Results: By applying Z-number-based multi-criteria decision-making methods, five potential regions of Azerbaijan have been evaluated for six criteria. The criteria reflect government policy to the development of the regions, economical, geographical, environmental factors, and infrastructure of the locations. Derived solutions are comparable in sense of sites ranking, and similar results were obtained using both methods. Direct calculations allow obtaining results based on the linguistic Z-evaluations of experts without distorting transformations.

Conclusion: The managerial decision-making problems in the tourism sector, raised due to the aforementioned barriers, can be successfully resolved by applying Z-number-based multi-criteria approaches. The obtained results allow increasing a range of the decision-making tasks under a high degree of uncertainty to be solved for sustainable development studies and other areas.