bluuebunny/crossref_metadata_2025 huggingface dataset:
The interactions between interleukin-1 family genes: IL1A, IL1B, IL1RN, and obesity parameters
Authors: Maculewicz Ewelina , Antkowiak Bożena , Antkowiak Oktawiusz , Borecka Anna , Mastalerz Andrzej , Leońska-Duniec Agata , Humińska-Lisowska Kinga , Michałowska-Sawczyn Monika , Garbacz Aleksandra , Lorenz Katarzyna , Szarska Ewa , Dziuda Łukasz , Cywińska Anna , Cięszczyk Paweł
Published: February 2022

Abstract

Background

Obesity has been recognized as a worldwide growing problem, producing many pathologies including the promotion of “proinflammatory state.” The etiology of human obesity is still only partially understood; however, the genetic background has been proved. Its nature is complex, and currently, it appears that the combined effects of the interactions among multiple genes should receive more attention. Due to the fact that obesity promotes proinflammatory conditions, in this study, we investigated the genetic polymorphism of IL-1 family genes in healthy people with normal and elevated body mass index (BMI) and fat %.

Results

The single-nucleotide polymorphisms (SNPs) within the IL1A -889C > T (rs1800587), IL1B + 3954 T > C (rs1143634), and IL1RN -87G > A (rs2234677) genes alone were associated neither with BMI nor fat % values in tested group. The associations between SNP–SNP interaction and BMI for the IL1B × IL1RN interactions were significant for dominant model (p = 0.02) and codominant model (p = 0.03). The same SNP-SNP interaction (IL1B × IL1RN) was associated also with fat % for codominant (p = 0.01) and recessive (p = 0.002) models.

Conclusions

This study further confirmed that IL-1 family genes are involved in genetic background of obesity. It has been shown that interaction IL1B × IL1RN was associated with both BMI and fat % with rare T allele protecting form higher values. Thus, even if certain polymorphisms in single genes of IL-1 family cannot be defined as related to obesity in examined population, the genetic interrelationships should be analyzed.
Exploring protective and risk factors in the home environment in high-risk families – results from the Danish High Risk and Resilience Study—VIA 7
Authors: Thorup Anne Amalie Elgaard , Gantriis Ditte Lou , Greve Aja Neergaard , Henriksen Maria Toft , Zahle Kate Kold , Stadsgaard Henriette , Ellersgaard Ditte , Burton Birgitte Klee , Christiani Camilla Jerlang , Spang Katrine , Hemager Nicoline , Jepsen Jens Richardt Møllegaard , Plessen Kerstin J. , Nordentoft Merete , Mors Ole , Bliksted Vibeke
Published: February 2022

Background

Exposure to inadequate home environment may put the healthy development of familial high-risk children at risk. This study aimed to investigate associations between risk factors and an adequate home environment of children having a parent diagnosed with schizophrenia or bipolar disorder.

Methods

From a cohort of 522 children, data from 463 7-year-old children was included. Of these 172 children had familial risk for schizophrenia, 109 children had familial risk for bipolar disorder, and 190 were population-based controls. As part of a comprehensive battery, all participants were assessed with the Middle Childhood-Home Observation for Measurement of the Environment Inventory (MC-HOME Inventory) measuring the quality of the home environment.

Results

When analyzing all families together, we found that having a parent diagnosed with schizophrenia would have a negative impact on the home environment (ß = -1.08; 95% CI (-2.16;-0.01); p = 0.05), while familial risk for bipolar disorder did not show significant predictive value. Being a single caregiver and child having experienced severe life events from ages 4 to 7 showed significant negative impact, while child having a mental illness diagnosis did not. Being a female caregiver, good social functioning of the caregiver, high child IQ and not being a single caregiver were found to predict positive values for the home environment. We found similar results when analyzing caregivers with and without a diagnosis separately.

Conclusions

Knowledge of what predicts good home environment should be used to inform development of early interventions for families at risk.
Transdiagnostic symptom subtypes across autism spectrum disorders and attention deficit hyperactivity disorder: validated by measures of neurocognition and structural connectivity
Authors: Zhang Manxue , Huang Yan , Jiao Jian , Yuan Danfeng , Hu Xiao , Yang Pingyuan , Zhang Rui , Wen Liangjian , Situ Mingjing , Cai Jia , Sun Xueli , Guo Kuifang , Huang Xia , Huang Yi
Published: February 2022

Backgrounds

Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders that exhibit within-disorder heterogeneity and cross-disorder phenotypic overlap, thus suggesting that the current disease categories may not fully represent the etiologic essence of the disorders, especially for highly comorbid neurodevelopmental disorders. In this study, we explored the subtypes of a combined sample of ASD and ADHD by integrating measurements of behavior, cognition and brain imaging.

Methods

A total of 164 participants, including 65 with ASD, 47 with ADHD, and 52 controls, were recruited. Unsupervised machine learning with an agglomerative hierarchical clustering algorithm was used to identify transdiagnostic symptom clusters. Neurocognition and brain structural connectivity measurements were used to assess symptom clusters. Mediation analysis was used to explore the relationship between transdiagnostic symptoms, neurocognition and brain structural connectivity.

Results

We identified three symptom clusters that did not fall within the diagnostic boundaries of DSM. External measurements from neurocognition and neuroimaging domains supported distinct profiles, including fine motor function, verbal fluency, and structural connectivity in the corpus callosum between these symptom clusters, highlighting possible biomarkers for ASD and ADHD. Additionally, fine motor function was shown to mediate the relationship between the corpus callosum and perseveration symptoms.

Conclusions

In this transdiagnostic study on ASD and ADHD, we identified three subtypes showing meaningful associations between symptoms, neurocognition and brain white matter structural connectivity. The fine motor function and structural connectivity of corpus callosum might be used as biomarkers for neurodevelopmental disorders with social skill symptoms. The results of this study highlighted the importance of precise phenotyping and further supported the effects of fine motor intervention on ASD and ADHD.
Integrating early stimulation and play at scale: study protocol for “MAHAY Mikolo”, a multi-arm cluster-randomized controlled trial
Authors: Galasso Emanuela , Ratsifandrihamanana Lisy , Weber Ann M. , Hemlock Caitlin , Col Mathilde , Dieci Maria , Rakotomalala Norotiana , Rambeloson Valerie , Fernald Lia C. H.
Published: February 2022

Background

Hundreds of millions of children living in poverty worldwide are not reaching their full, developmental potential. Programs to promote nurturing and responsive caregiving, such as those in which community health workers (CHWs) conduct home visits to support optimal early childhood development (ECD), have been effective in small trials, but have not achieved similar success at scale. This study will explore two approaches to scale-up: converting a home-visiting model to a group-based model; and integrating the ECD curriculum into an existing government program. The objectives of the study are to: 1) Measure how the integration of ECD activities affects time and task allocation of CHWs and CHW psychosocial wellbeing; 2) Examine how the integration of ECD activities affects caregiver-child dyad participation in standard health and nutrition activities; and 3) Explore how the availability of age-appropriate play materials at home affects caregiver-child dyad participation rates in a group-based ECD program.

Methods

We will randomize 75 communities in rural Madagascar into three arms: 1) [C], which is the status quo (community-based health and nutrition program); 2) [T], which is C + ECD group sessions [T]; and 3) [T +], which is T with the addition of an enhanced play materials package for home use. All children between 6–30 months old at the time of the intervention launch will be eligible to participate in group activities. The intervention will last 12 months and is comprised of fortnightly group sessions in which the CHWs provide caregiver-child dyads with information relating to ECD; CHWs will also include structured time for caregivers to practice the play and child stimulation activities they have learned. We will administer monthly surveys to measure CHW time use and task allocation, and we will leverage administrative data to measure caregiver-child dyad participation in the group sessions.

Discussion

The results from the trial will provide the evidence base required to implement an integrated package of nutrition, health and ECD promotion activities at scale in Madagascar, and findings may be relevant in other low-income countries.

Trial registration

This trial is registered on the AEA Social Science Registry (AEARCTR-0004704) on November 15, 2019 and on ClinicalTrials.gov (NCT05129696) on November 22, 2021.
Biomechanics of extreme lateral interbody fusion with different internal fixation methods: a finite element analysis
Authors: Li Xiao-hua , She Li-jun , Zhang Wei , Cheng Xiao-dong , Fan Jin-peng
Published: February 2022

Background

Establishing a normal L3–5 model and using finite element analysis to explore the biomechanical characteristics of extreme lateral interbody fusion (XLIF) with different internal fixation methods.

Method

The L3–5 CT image data of a healthy adult male volunteer were selected to establish a normal lumbar finite element model (M0). The range of motion (ROM) of L3–4 and L4–5, under flexion, extension, left bending, right bending, left rotation, and right rotation, together with L3–4 disc pressure was analyzed. Then the L4–5 intervertebral disc was excised and implanted with a cage, supplemented by different types of internal fixation, including lateral two-hole plate model (M1), lateral four-hole plate model (M2), VerteBRIDGE plating model (M3), lateral pedicle model (M4), posterior unilateral pedicle screw model (M5) and posterior bilateral pedicle screw model (M6). The ROM,the maximum stress value of the cage, and the maximum stress value of the intervertebral disc of L3–4 were analyzed and studied .

Results

The ROM of L3–4 and L4-L5 segments in the validation model under various motion states was basically consistent with previous reports. The lumbar finite element model was validated effectively. After XLIF-assisted internal fixation, the range of activity in L3–4 segments of each internal fixation model was greater than that of the normal model under various working conditions, among which the M5、M6 model had the larger range of activity in flexion and extension. After the internal fixation of L4–5 segments, the mobility in M1-M6 was significantly reduced under various motion patterns. In terms of flexion and extension, the posterior pedicle fixation model (M5、M6) showed a significant reduction,followed by M2. The maximal von mises cage stress of M1 was obviously greater than that of other models (except the left bending). Compared with M0, the intervertebral disc stress of M1-M6 at L3–4 segments was increased.

Conclusions

It is recommended that the posterior bilateral pedicle screw model is the first choice, followed by the lateral four-hole plate model for fixation during XLIF surgery. However, it is still necessary to be aware of the occurrence of adjacent segment degeneration (ASD) in the later stage.
Surgical treatment, complications, reoperations, and healthcare costs among patients with clavicle fracture in England
Authors: Wolf Simone , Chitnis Abhishek S. , Manoranjith Anandan , Vanderkarr Mollie , Plaza Javier Quintana , Gador Laura V. , Holy Chantal E. , Sparks Charisse , Lambert Simon M.
Published: February 2022

Introduction

The clinical and economic burden of clavicle fractures in England is not well documented. This study evaluated rates of surgical treatment, post-surgical complications, reoperations and costs in patients with clavicle fractures using the Clinical Practice Research Datalink (CPRD) database.

Methods

CPRD data were linked to National Health Service Hospital Episode Statistics data. Patients with a diagnosis of clavicle fracture between 2010–2018 were selected in CPRD (date of fracture = index date). Of those, patients with surgical intervention within 180 days from index fracture were identified. Rates of post-surgical complications (i.e., infection, non-union, and mal-union), reoperations (for device removal or for postoperative complications), post-operative costs and median time to reoperations were evaluated up to 2 years after surgery.

Results

21,340 patients with clavicle fractures were identified (mean age 35.0 years(standard deviation (SD): 26.5), 66.7% male). Surgery was performed on 672 patients (3.2% of total cohort) at an average 17.1 (SD: 25.2) days post-fracture. Complications (i.e., infection, non-union, or malunion) affected 8.1% of surgically treated clavicle fracture patients; the rate of infection was 3.5% (95% CI, 1.7%- 5.2%), non-union 4.4% (95% CI, 2.4%-6.5%), and mal-union 0.3% (95% CI, 0%-0.7%). Adjusting for age, gender, comorbidities and time to surgery, the all-cause reoperation rate was 20.2% (13.2%-30.0%) and the adjusted rate of reoperation for implant removal was 17.0% (10.7%-25.9%)—84% of all-cause reoperations were thus performed for implant removal. Median time to implant removal was 254 days. The mean cost of reoperations for all causes was £5,000. The most expensive reoperations were for cases that involved infection (mean £6,156).

Conclusions

Complication rates following surgical clavicle fracture care averaged 8.1%. However, reoperation rates exceed 20%, the vast majority of reoperations being performed for device removal. Technologies to alleviate secondary device removal surgeries would address a significant clinical unmet need.
Liner dissociation in a large-diameter ceramic-bearing acetabular component: a report of five cases
Authors: Kostretzis Lazaros , Martinov Sagi , Lavigne Martin , Massé Vincent , Vendittoli Pascal-André
Published: February 2022

Background

Ceramic-on-ceramic (CoC) bearings for total hip arthroplasty (THA) have been offering very favorable results and survivorship since their introduction. In order to increase range of movement (ROM) and decrease dislocation rates, some manufacturers have introduced larger diameter head (LDH) CoC bearings. This has been achieved with the use of preassembled cup designs, in which the ceramic liner is already fitted into the metal backing and implanted as a monoblock component by the surgeon. In this report we present data from a series of 5 patients with ceramic liner dissociation from a monoblock cup.

Case presentation

All cases were overweight men with acetabular components of 56 or 58 mm. After a mean of 5.5 (range, 3.5-6.7) years, all patients reported sudden pain and audible noise when performing activities of daily living. Liner displacement was suspected on plain radiographs and confirmed by Ct-scan. Pneumarthrosis was present in all cases. Taper modular junction wear and corrosion signs were observed in the four revised patients.

Conclusion

Although one of our case is still treated conservatively, implant revision is probably inevitable. Further LDH CoC implant design should take in consideration this potential complication by avoiding bearing diameters over 40mm and/or improving locking mechanism or by providing a real monoblock acetabular implant.
Projected number of osteoarthritis patients in Austria for the next decades – quantifying the necessity of treatment and prevention strategies in Europe
Authors: Hitzl Wolfgang , Stamm Tanja , Kloppenburg Margreet , Ritter Markus , Gaisberger Martin , van der Zee-Neuen Antje
Published: February 2022

Background

The present study aimed to predict the expected number of patients with osteoarthritis (OA) in Austria up to the year 2080.

Methods

Demographic data and population projections between 2019 and 2080 were obtained from European authorities. Information about recent age- and sex-stratified prevalence of patients with self-reported physician-diagnosed OA was obtained from the Austrian Health Interview Survey (n = 15,771). Projections were stratified by age and sex; sensitivity analyses were performed based on aging, main (most likely), and growth scenarios of the population.

Results

Based on the projection, the overall increase in the total number of patients with OA from 2019 to 2080 will be 38% for men and women. In 2019, the highest number of OA-patients nested in the groups of persons aged 70-79 (n = 238,749) and 60-69 (n = 237,729) years. In 2080, the 80+ age group is predicted to have the highest number of OA with 421,548 individuals (i.e. factor 3.45 and factor 2.48 increase in the male and female group, respectively, compared to 2019), followed by the group aged 70-79 with 314,617 individuals (factor 1.45 and factor 1.28 increase in the male and female group, respectively, compared to 2019). Similar trends were found in the ageing and growing scenarios.

Conclusions

The projected increase in the occurrence of OA will likely lead to a substantial socioeconomic burden for the Austrian healthcare system in the near and far future. The current findings plead for the development of sustainable concepts for the treatment and prevention of OA by European authorities.
Motivations and future plans of the final year students in a Chinese dental school
Authors: Xu Chao , Gao Liang , Zhang Shuai , Zhang Jiamin , Li Chen , Zhang Dongmei , Pan Yaping , Liu Jingbo
Published: February 2022

Background

Understanding dental students’ future career choice and motivation could provide beneficial references for both educators and students, but there were few studies on students in a Chinese dental school. The study aimed to investigate Chinese final year dental students’ the short-term and long-term plans, motivations, and identify the influence of gender on the future plans.

Methods

A total of 265 final year dental school students of the School of Stomatology, China Medical University from 2016 through 2020 were invited to complete an anonymous, 27-item questionnaire. Moreover, almost all of questions were in multiple-choice formats. Data were categorized and analysed using chi-square comparative analyses.

Results

88.3% of respondents decided to pursue a graduate degree after graduating from dental school. Moreover, the single most important reason influencing their plans was “eligible for better jobs” (42.8%). More females than males studied dentistry (222 vs 111), and gender had an influence on the choice of specialty.

Conclusions

This study listed the selection tendency and influencing factors of students in a Chinese dental school for the reference of educators and students. And the results could raise some useful influence and feedback effect on current health and education policy, and on the career development of practicing dentists or dental students.
Impact of COVID-19 pandemic on diagnostic pathology in the Netherlands
Authors: van Velthuysen M. L. F. , van Eeden S. , le Cessie S. , de Boer M. , van Boven H. , Koomen B. M. , Roozekrans F. , Bart J. , Timens W. , Voorham Q. J. M.
Published: February 2022

Background

The COVID-19 pandemic has a huge impact on healthcare provided. The nationwide pathology registry of the Netherlands, PALGA, offers an outstanding opportunity to measure this impact for diseases in which pathology examinations are involved.

Methods

Pathology specimen numbers in 2020 were compared with specimen numbers in 2019 for 5 periods of 4 weeks, representing two lockdowns and the periods in between, taking into account localization, procedure and benign versus malignant diagnosis.

Results

The largest decrease was seen during the first lockdown (spring 2020), when numbers of pathology reports declined up to 88% and almost all specimen types were affected. Afterwards each specimen type showed its own dynamics with a decrease during the second lockdown for some, while for others numbers remained relatively low during the whole year. Generally, for most tissue types resections, cytology and malignant diagnoses showed less decrease than biopsies and benign diagnoses. A significant but small catch-up (up to 17%) was seen for benign cervical cytology, benign resections of the lower gastro-intestinal tract, malignant skin resections and gallbladder resections.

Conclusion

The COVID-19 pandemic has had a significant effect on pathology diagnostics in 2020. This effect was most pronounced during the first lockdown, diverse for different anatomical sites and for cytology compared with histology. The data presented here can help to assess the consequences on (public) health and provide a starting point in the discussion on how to make the best choices in times of scarce healthcare resources, considering the impact of both benign and malignant disease on quality of life.
Enhanced intestinal protein fermentation in schizophrenia
Authors: Liang Ying , Shi Xing , Shen Yang , Huang Zhuoran , Wang Jian , Shao Changjun , Chu Yanan , Chen Jing , Yu Jun , Kang Yu
Published: February 2022

Background

Emerging findings highlighted the associations of mental illness to nutrition and dysbiosis in the intestinal microbiota, but the underlying mechanisms, especially in schizophrenia (SZ), remain unclarified.

Methods

We conducted a case-control study of SZ patients (case to control=100:52) by performing sequencing of the gut metagenome; measurement of fecal and plasma non-targeted metabolome; including short-, medium-, and long-chain fatty acids; and targeted metabolites, along with recorded details of daily intakes of food.

Results

The metagenome analysis uncovered enrichment of asaccharolytic species and reduced abundance of carbohydrate catabolism pathways and enzymes in the gut of SZ patients, but increased abundance of peptidases in contrast to their significantly reduced protein intake. Fecal metabolome analysis identified increased concentrations of many protein catabolism products, including amino acids (AAs), urea, branched short-chain fatty acids, and various nitrogenous derivates of aromatic AAs in SZ patients. Protein synthesis, represented by the abundance of AA-biosynthesis pathways and aminoacyl-tRNA transferases in metagenome, was significantly decreased. The AUCs (area under the curve) of the diagnostic random forest models based on their abundance achieved 85% and 91%, respectively. The fecal levels of AA-fermentative enzymes and products uniformly showed positive correlations with the severity of psychiatric symptoms.

Conclusions

Our findings revealed apparent dysbiosis in the intestinal microbiome of SZ patients, where microbial metabolism is dominated by protein fermentation and shift from carbohydrate fermentation and protein synthesis in healthy conditions. The aberrant macronutrient metabolism by gut microbes highlights the importance of nutrition care and the potential for developing microbiota-targeted therapeutics in SZ.
Meeting people where they are: implementing hospital-based substance use harm reduction
Authors: Perera Rachel , Stephan Louise , Appa Ayesha , Giuliano Ro , Hoffman Robert , Lum Paula , Martin Marlene
Published: February 2022

Background

Hospital-based addiction care focuses on assessing and diagnosing substance use disorders, managing withdrawal, and initiating medications for addiction treatment. Hospital harm reduction is generally limited to prescribing naloxone. Hospitals can better serve individuals with substance use disorders by incorporating harm reduction education and equipment provision as essential addiction care. We describe the implementation of a hospital intervention that provides harm reduction education and equipment (e.g., syringes, pipes, and fentanyl test strips) to patients via an addiction consult team in an urban, safety-net hospital.

Methods

We performed a needs assessment to determine patient harm reduction needs. We partnered with a community-based organization who provided us harm reduction equipment and training. We engaged executive, regulatory, and nursing leadership to obtain support. After ensuring regulatory compliance, training our team, and developing a workflow, we implemented this harm reduction program that provides education and equipment to individuals whose substance use goals do not include abstinence.

Results

During a 12-month period we provided 195 individuals harm reduction kits.

Conclusions

This intervention allowed us to advance hospital-based addiction care, better educate and engage patients, staff, and clinicians, and reduce stigma. By establishing a community harm reduction partner, obtaining support from hospital leadership, and incorporating feedback from staff, clinicians, and patients, we successfully implemented harm reduction education and equipment provision in a hospital setting as part of evidence-based addiction care.

Trial registration: Commentary, none.
Evaluation of pulmonary function among detergent powder factory workers- a cross sectional study in Semnan, Iran
Authors: Malek Farhad , Ranjbari Elham , Mirmohammadkhani Majid , Pahlevan Daryoush
Published: February 2022

Occupational respiratory diseases are the most prevalent occurring work-related diseases that contribute to global health concerns. The present study aimed to assess pulmonary function among detergent powder factory workers.

In a cross-sectional study, 305 employees working at a detergent powder company in Semnan, Iran were enrolled. Demographic characteristics, health- and job-related information were recorded using a checklist. Subsequently, spirometer was used at baseline, before and after shift-working for recording respiratory ailments and pulmonary function tests (PFT).

According to the results, the mean percentage of all spirometric indices significantly reduced after shift-work including forced vital capacity (FVC) (P < 0.01), forced expiratory volume in one second (FEV1) (P < 0.01), FEV1/FVC ratio (P = 0.038), peak expiratory flow (PEF) (P = 0.13) and forced expiratory flow at 25 and 75% of the pulmonary volume (FEF (25–75)) (P < 0.01). Although the mean percentage of FEV1 significantly improved upon wearing the protective mask (P = 0.014). Moreover, FVC and FEV1 indices were significantly less in smoking workers than in non-smoking participants (P = 0.005 and P = 0.003, respectively).

This study revealed that using effective preventive measures should be tightly performed to promote health conditions. However, despite the occupational health programs for preventing and reducing work-related respiratory diseases, these can be considered as a serious threat for detergent powder factory workers that need to apply more control strategies and health assessment.
Mental health crisis in Somalia: a review and a way forward
Authors: Ibrahim M. , Rizwan H. , Afzal M. , Malik Mamunur Rahman
Published: February 2022

Background

Somalia has been without an effective government since the collapse of the military regime in 1991. Years of conflict, disasters, and insecurity have all contributed to very low scores for most health indicators due to poor governance, protracted conflict, underdevelopment, economic decline, poverty, social and gender inequality, and environmental degradation. The three-decade long protracted conflict has led to widespread psychosocial trauma, social deprivation and substance abuse with devastating consequences on mental health. A WHO study showed Somalia has one of the highest rates of mental illness in the world. The main aim of this study is to assist policy makers in setting priorities for the design and delivery of interventions to promote mental health and psychosocial wellbeing in Somalia.

Methods

The study uses a systematic mapping technique (from January 1991 to May 2020) and data collected from public domain, to collect, collate, and present mental health data mainly from WHO’s Global Health Observatory. Since there is no primary database for Somalia’s public health research, the bibliographic databases used for mental health in this study included Medline, PubMed, CINAHL, PsycINFO, and Google Scholar. Data were extracted using techniques for web data mining for public health.

Results

Systematic mapping of mental health-related issues in Somalia showed that policy-related determinants and mental health services dominated (74.4%), followed by the disaster-related determinants and women’s health consequences (39.3%). The ratio of the number of beds for mental health in general hospitals (per 100,000 population) in Somalia in 2017 is 0.5 compared to the Eastern Mediterranean region (EMR) at 6.4 and globally at 24. One of the biggest casualties of the civil war was loss of essential human resources in healthcare as most either fled the country or were part of the victims of the war.

Conclusions

The vast scale of the mental health problems in Somalia and the priority setting guidelines for interventions to address the issues outlined in this paper, prompt a dire need that the Somali government and its national/international partners should prioritize and emphasize the need to invest in the prevention and the treatment of mental illness across the country.
Zebrafish patient-derived xenograft models predict lymph node involvement and treatment outcome in non-small cell lung cancer
Authors: Ali Zaheer , Vildevall Malin , Rodriguez Gabriela Vazquez , Tandiono Decky , Vamvakaris Ioannis , Evangelou Georgios , Lolas Georgios , Syrigos Konstantinos N. , Villanueva Alberto , Wick Michael , Omar Shenga , Erkstam Anna , Schueler Julia , Fahlgren Anna , Jensen Lasse D.
Published: February 2022

Background

Accurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days.

Methods

Using a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients.

Results

The resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days.

Conclusions

We conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.
Small RNAs mediate transgenerational inheritance of genome-wide trans-acting epialleles in maize
Authors: Cao Shuai , Wang Longfei , Han Tongwen , Ye Wenxue , Liu Yang , Sun Yi , Moose Stephen P. , Song Qingxin , Chen Z. Jeffrey
Published: February 2022

Background

Hybridization and backcrossing are commonly used in animal and plant breeding to induce heritable variation including epigenetic changes such as paramutation. However, the molecular basis for hybrid-induced epigenetic memory remains elusive.

Results

Here, we report that hybridization between the inbred parents B73 and Mo17 induces trans-acting hypermethylation and hypomethylation at thousands of loci; several hundreds (~ 3%) are transmitted through six backcrossing and three selfing generations. Notably, many transgenerational methylation patterns resemble epialleles of the nonrecurrent parent, despite > 99% of overall genomic loci are converted to the recurrent parent. These epialleles depend on 24-nt siRNAs, which are eliminated in the isogenic hybrid Mo17xB73:mop1-1 that is defective in siRNA biogenesis. This phenomenon resembles paramutation-like events and occurs in both intraspecific (Mo17xB73) and interspecific (W22xTeosinte) hybrid maize populations. Moreover, siRNA abundance and methylation levels of these epialleles can affect expression of their associated epigenes, many of which are related to stress responses.

Conclusion

Divergent siRNAs between the hybridizing parents can induce trans-acting epialleles in the hybrids, while the induced epigenetic status is maintained for transgenerational inheritance during backcross and hybrid breeding, which alters epigene expression to enhance growth and adaptation. These genetic and epigenetic principles may apply broadly from plants to animals.
Treatment via oral midodrine in a patient with prolonged hypotension following carotid artery stenting: a case report
Authors: Jenab Yaser , Hosseini Kaveh , Abtahi-Eivary Seyed-Mohammad
Published: February 2022

Background

Hypotension and bradycardia are common hemodynamic complications following carotid artery stenting in patients with carotid artery stenosis. Intravenous fluid resuscitation and inotropes such as dopamine are conventional treatments for post-carotid artery stenting hypotension. However, in case of resistant hypotension, there is no clear treatment method. In this report, while intravenous fluid and inotropes did not resolve the patient’s hypotension, oral midodrine treated post-carotid artery stenting hypotension.

Case presentation

In this report, we present an 82-year-old Caucasian man complaining of a single episode of unilateral visual loss. The patient had left internal carotid artery stenosis and underwent carotid artery stenting. After the procedure, he developed prolonged post-carotid artery stenting hypotension, which was resistant to intravenous fluids and inotropes but immediately showed a promising response to oral midodrine.

Conclusion

Oral midodrine can be considered in treatment of post-carotid artery stenting hemodynamic complications.
An improved denoising method for eye blink detection using automotive millimeter wave radar
Authors: Shu Yuhong , Wang Yong , Yang Xiaobo , Tian Zengshan
Published: February 2022

With the development of radar technology, the automotive millimeter wave radar is widely applied in the fields including internet of vehicles, Artificial Intelligence (AI)-based autonomous driving, health monitoring, etc. Eye blink, as one of the most common human activities, can effectively reflect the person’s consciousness and fatigue. The contacted eye blink detection often leads to uncomfortable experience and the camera-based eye blink detection has privacy issues. As an alternative, the non-contacted eye blink detection based on automotive millimeter wave radar resolves the aforementioned issues and has been received much attention. This paper proposes an eye blink detection method using the frequency modulated continuous wave radar. Firstly, the position of the person’s head is estimated by carrying out fast Fourier transform on the intermediate frequency signal, and the signals of the range bins at the head are extracted. Then, the complete ensemble empirical mode decomposition with adaptive noise algorithm is applied to decompose the eye signals into a series of intrinsic mode functions (IMFs), and the singular value decomposition is adopted to constrain the selection and reconstruction of the useful IMFs related to the eye blink signal. Finally, the short-time Fourier transformation and cell average constant false alarm rate are applied to detect the eye blink behavior. Experiments are carried out to validate the effectiveness of the proposed eye blink detection method.
The impact of climate change awareness on behavioral changes in Germany: changing minds or changing behavior?
Authors: Venghaus Sandra , Henseleit Meike , Belka Maria
Published: February 2022

Background

The increasing frequency of extreme weather events across the globe, the intensifying international debates about the political urgency to mitigate climate change, as well as the respective more action demanding social movements have caused a significant increase in climate change awareness among the population. Little research, however, has systematically analyzed the behavioral impact of this development. Using Germany as a case study, we therefore scrutinize whether the recent increase in climate change awareness triggered mainly changes in public perceptions concerning environmental and sustainability issues or whether it has led to sustainable behavioral shifts. Based on previous research, we considered two routes through which an increase in climate change awareness can instigate changes: (a) directly by leading to behavioral changes towards more sustainable consumption decisions, or (b) indirectly by exerting pressure on the political process.

Results

The analyzed data in the three consumption sectors of mobility, food consumption and housing confirm the continuing prevalence of an attitude–behavior gap: although there is a broad, strongly positive attitude towards climate protection and increasingly high problem awareness of climate change, so far this attitude does not immediately translate into notable behavioral changes. With regard to effects on political agenda setting, however, the effects are much more immediate. The results confirm strong pressure on the political process mainly through shifts in voter behavior.

Conclusions

The results show that the increase in climate change awareness has spurred dynamics in the debate around climate change both among the population and in the political realm. Fueled by the intense media coverage of the Fridays For Future movement and related activities, a snowball effect has been set off, opening a window of opportunity for significant shifts towards more effective and rigorous climate policies. Politicians and decision-makers now have the opportunity to implement sustainability measures with strong support of the population, even if these imply higher costs. Whether there will be further shifts in the current lifestyle towards a more sustainable one, lifestyle changes should be carefully monitored in the coming years, as relevant data are only now becoming available.
Insights into the proteomic profile of newly harvested corn and metagenomic analysis of the broiler intestinal microbiota
Authors: Yin Dafei , Wang Youli , Wang Liqun , Wu Yuqin , Bian Xiaoyi , Aggrey Samuel E. , Yuan Jianmin
Published: February 2022

Background

The use of newly harvested corn in feed causes wet droppings in broilers and increased feed cost which was termed as “new season grain problem”. The present study was conducted to evaluate the proteomic profile of newly harvested corn and the subsequent influence on intestinal microbiol community for broiler chickens.

Methods

Newly harvested corn stored for either half a month (HM) or two months (TM) was used, and the pasting properties, total soluble sugars, and proteomic analysis technology was used to explore the influence of storage on natural aging corn properties. Additionally, seventy-two 7-day-old Ross 308 male broiler chicken were fed with different stored corn. Apparent metabolizable energy (AME), digesta viscosity, intestinal morphology and microbiota were examined to explore the influence of feed corn storage on broiler chickens.

Results

Pasting properties in the TM corn exhibited decreased viscoelastic properties. Proteomic studies found a total of 26 proteins that were differentially expressed between the two treatment groups. Proteins involved in starch and polysaccharides biosynthesis were upregulated in TM compared with HM. Chickens fed on TM diet had higher relative energy utilization compared to the HM birds. With increased corn storage, the relative digesta viscosity decreased significantly (P ≤ 0.05). The total number of goblet cells and lymphocytes was lower in chickens fed the TM diet. The microbiota data showed that the TM chickens had decreased abundance of diarrheal bacteria such as Hungatella hathewayi and Bacteroides fragilis, and increased butyrate-producing bacteria such as Alistipes compared to the HM chickens.

Conclusions

Storage of newly harvested corn induced the synthetic reaction of large molecules and changed the solubility of starch and protein with increasing soluble sugars and decreasing pasting properties that may improve the fermentation of intestinal microbiota, improve the energy utilization and protect gut health without the risk of diarrhea.
Geranylgeranyl diphosphate synthase inhibitor and proteasome inhibitor combination therapy in multiple myeloma
Authors: Haney Staci L. , Varney Michelle L. , Williams Jacob T. , Smith Lynette M. , Talmon Geoffrey , Holstein Sarah A.
Published: February 2022

Background

Multiple myeloma (MM) remains an incurable malignancy, despite the advent of therapies such as proteosome inhibitors (PIs) that disrupt protein homeostasis and induce ER stress. We have pursued inhibition of geranylgeranyl diphosphate synthase (GGDPS) as a novel mechanism by which to target protein homeostasis in MM cells. GGDPS inhibitors (GGSI) disrupt Rab geranylgeranylation, which in turn results in perturbation of Rab-mediated protein trafficking, leading to accumulation of intracellular monoclonal protein, induction of ER stress and apoptosis. Our lead GGSI, RAM2061, has demonstrated favorable pharmacokinetic properties and in vivo efficacy. Here we sought to evaluate if combination therapy with GGSI and PI would result in enhanced disruption of the unfolded protein response (UPR) and increase anti-MM efficacy.

Methods

MTT assays were conducted to evaluate the cytotoxic effects of combining RAM2061 with bortezomib in human MM cells. The effects of RAM2061 and/or PI (bortezomib or carfilzomib) on markers of UPR and apoptosis were evaluated by a combination of immunoblot (ATF4, IRE1, p-eIF2a, cleaved caspases and PARP), RT-PCR (ATF4, ATF6, CHOP, PERK, IRE1) and flow cytometry (Annexin-V). Induction of immunogenic cell death (ICD) was assessed by immunoblot (HMGB1 release) and flow cytometry (calreticulin translocation). Cell assays were performed using both concurrent and sequential incubation with PIs. To evaluate the in vivo activity of GGSI/PI, a flank xenograft using MM.1S cells was performed.

Results

Isobologram analysis of cytotoxicity data revealed that sequential treatment of bortezomib with RAM2061 has a synergistic effect in MM cells, while concurrent treatment was primarily additive or mildly antagonistic. The effect of PIs on augmenting RAM2061-induced upregulation of UPR and apoptotic markers was dependent on timing of the PI exposure. Combination treatment with RAM2061 and bortezomib enhanced activation of ICD pathway markers. Lastly, combination treatment slowed MM tumor growth and lengthened survival in a MM xenograft model without evidence of off-target toxicity.

Conclusion

We demonstrate that GGSI/PI treatment can potentiate activation of the UPR and apoptotic pathway, as well as induce upregulation of markers associated with the ICD pathway. Collectively, these findings lay the groundwork for future clinical studies evaluating combination GGSI and PI therapy in patients with MM.
Learning in digital play: a dual case study of video gamers’ independent play
Authors: Toh Weimin , Lim Fei Victor
Published: February 2022

This paper explores the implications of youths’ out-of-school gaming practices for teaching and learning in formal and informal learning contexts. We report on a study where we examined the video game play of two youths using a case study approach. User experience approaches, e.g. the think-aloud protocol and interviews, were grounded in the theoretical framework of social semiotics to analyse the gameplay videos and to discuss the implications for the youths’ learning. The paper contends that youths are demonstrating critical thinking, empathy, and multimodal literacy through their gameplay. We offer suggestions for how adults can use video games for youths’ learning.
Association of CHEK2 I157T and SULT1A1 R213H genetic variants with risk of sporadic colorectal cancer in a sample of Egyptian patients
Authors: Elhady Ghada M. , Elnaggar Mostafa A. , Desouky Lubna M.
Published: February 2022

Background

Recent research proposed an association between functional defects involving CHEK2 I157T and SULT1A1 R213H variants and increased incidence of several types of cancer. A total of 86 unrelated colorectal cancer patients attending the Surgical Oncology Department were recruited in the study. The second group of 152 healthy age- and sex-matched volunteers were included as controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was applied for genotyping. Chi-square test was applied to compare genotype and allele frequencies in the studied groups. The purpose of the present study was to evaluate the association between CHEK2 I157T and SULT1A1 R213H polymorphisms and colorectal cancer.

Results

No significant differences in genotypes were detected between cases and controls in the present study for both CHEK2 I157T and SULT1A1 R213H polymorphisms (χ2 = 1.839; P = 0.399/χ2 = 2.831; P = 0.243), respectively. Likewise, discrepancies in allele frequency for the wild-type or mutant alleles were non-statistically significant in CHEK2 I157T and SULT1A1 R213H (χ2 = 1.231; P = 0.267/χ2 = 0.180; P = 0.671), respectively.

Conclusions

Results of the current study propose that CHEK2 I157T and SULT1A1 R213H polymorphisms are not associated with CRC development in Egyptian population. Further future studies on the functional implications of these polymorphisms are strongly recommended.
Reconceptualising the treatment gap for common mental disorders: a fork in the road for global mental health?
Authors: Roberts Tessa , Miguel Esponda Georgina , Torre Costanza , Pillai Pooja , Cohen Alex , Burgess Rochelle A.
Published: February 2022

In this analysis, we argue that the ‘treatment gap’ for common mental disorders often reflects lack of demand, arising because services fail to address the needs of disadvantaged communities. We propose a route forward for global mental health, with explicit focus on action on the socioeconomic determinants of psychological suffering.
Observation of heavy-ion like phenomena in high-multiplicity p+p collisions at LHC energies
Authors: Dey Kalyan , Mishra A. N. , Tripathy S. K.
Published: February 2022

Suppression of inclusive hadron yields in nuclear systems with respect to the elementary

collisions is believed to be caused by the jet quenching. The quantification of the jet quenching via the nuclear modification factor is difficult to conceive in small systems since it is influenced by several experimental factors such as the estimation of the centrality and the scaling factor. In this article we propose an alternate approach to address this issue and explore the possibility of measuring jet quenching in a high-multiplicity

system using the Pythia8 event generator. We have used a novel approach to estimate the high-multiplicity class in

systems, and the results from the standard method of multiplicity class determination are also presented. Results from this investigation qualitatively show the existence of heavy-ion like behavior in high-multiplicity

collisions which is mainly contributed by the Color Reconnection mechanism.