bluuebunny/crossref_metadata_2025 huggingface dataset:
Reconstruction and analysis of a large-scale binary Ras-effector signaling network
Authors: Catozzi Simona , Ternet Camille , Gourrege Alize , Wynne Kieran , Oliviero Giorgio , Kiel Christina
Published: March 2022

Background

Ras is a key cellular signaling hub that controls numerous cell fates via multiple downstream effector pathways. While pathways downstream of effectors such as Raf, PI3K and RalGDS are extensively described in the literature, how other effectors signal downstream of Ras is often still enigmatic.

Methods

A comprehensive and unbiased Ras-effector network was reconstructed downstream of 43 effector proteins (converging onto 12 effector classes) using public pathway and protein–protein interaction (PPI) databases. The output is an oriented graph of pairwise interactions defining a 3-layer signaling network downstream of Ras. The 2290 proteins comprising the network were studied for their implication in signaling crosstalk and feedbacks, their subcellular localizations, and their cellular functions.

Results

The final Ras-effector network consists of 2290 proteins that are connected via 19,080 binary PPIs, increasingly distributed across the downstream layers, with 441 PPIs in layer 1, 1660 in layer 2, and 16,979 in layer 3. We identified a high level of crosstalk among proteins of the 12 effector classes. A class-specific Ras sub-network was generated in CellDesigner (.xml file) and a functional enrichment analysis thereof shows that 58% of the processes have previously been associated to a respective effector pathway, with the remaining providing insights into novel and unexplored functions of specific effector pathways.

Conclusions

Our large-scale and cell general Ras-effector network is a crucial steppingstone towards defining the network boundaries. It constitutes a ‘reference interactome’ and can be contextualized for specific conditions, e.g. different cell types or biopsy material obtained from cancer patients. Further, it can serve as a basis for elucidating systems properties, such as input–output relationships, crosstalk, and pathway redundancy.

Graphical abstract
Cementless modular total hip arthroplasty with subtrochanteric transverse shortening osteotomy for high hip dislocations
Authors: Sukur Erhan , Senel Ahmet , Ozdemir Ugur , Akman Yunus Emre , Azboy İbrahim , Ozturkmen Yusuf
Published: March 2022

Background

Performing a total hip arthroplasty for a high hip dislocation is technically demanding and presents several challenges, with appropriate evaluation of the bone morphology of the hip and proper implant selection being critical for successful outcomes.

Objective

The purpose of our study was to evaluate the clinical and radiographic outcomes of cementless modular total hip arthroplasty for the treatment of high hip dislocations with sub-trochanteric transverse shortening osteotomy.

Methods

Sixty-eight hips with a high hip dislocation, were treated using a sub-trochanteric transverse shortening osteotomy and cementless modular total hip arthroplasty, retrospectively reviewed. Hip function was assessed using the Harris hip score, with hip abduction strength evaluated using the Trendelenburg test. Radiographic assessment included the measurement of leg length discrepancy, identification of implant loosening, localization of the hip center, and union at the osteotomy site.

Results

The mean follow-up period was 12.9 (range 5.2–16.8) years. The mean Harris hip score improved from a pre-operative score of 48.6 ± 3.6 to 82.4 ± 4.2 (p < 0.05). The hip was within the true acetabulum in all patients, postoperatively. Osteotomy union was achieved in 67 of the 68 hips (98.5%) in a mean latency of 12.5 ± 0.6 weeks. The mean length of femoral shortening was 66.5 ± 4.5 mm, with a mean pull-down length of the proximal part of 35.5 ± 3.5 mm.

Conclusion

For the treatment of high hip dislocations with satisfactory clinical outcomes, the modular stem offers an adjustable anteversion angle to restore sufficient rotational stability and the transverse osteotomy provides sufficient compression pressure across the osteotomy site to facilitate union.

Trial registrationIt was a retrospective study and approved by Istanbul Research and Training Hospital institutional Ethics Review Board (772-05/02/2016).
Properties of tests for knee joint threshold to detect passive motion following anterior cruciate ligament injury: a systematic review and meta-analysis
Authors: Strong Andrew , Arumugam Ashokan , Tengman Eva , Röijezon Ulrik , Häger Charlotte K.
Published: March 2022

Background

Threshold to detect passive motion (TTDPM) tests of the knee joint are commonly implemented among individuals with anterior cruciate ligament (ACL) injury to assess proprioceptive acuity. Their psychometric properties (PMPs), i.e. reliability, validity and responsiveness, are however unclear. This systematic review aimed to establish the PMPs of existing knee joint TTDPM tests among individuals with ACL injury.

Methods

The databases PubMed, AMED, CINAHL, SPORTDiscus, Web of Science, Scopus, CENTRAL and ProQuest were searched to identify studies that assessed the properties of knee joint TTDPM tests in individuals with ACL injury. The risk of bias for each included study was assessed at the outcome level for each test. Overall quality and levels of evidence for each property were rated according to established criteria. Meta-analyses with mean differences were conducted using random-effects models when adequate data were available.

Results

Fifty-one studies covering 108 TTDPM tests and 1632 individuals with unilateral ACL injury were included. A moderate-to-strong level of evidence indicated insufficient quality for all of the following: convergent validity, known-groups validity, discriminative validity, responsiveness between subgroups, and responsiveness to intervention. Subgroup meta-analyses for known-groups validity did however find that a starting angle of 15° resulted in significantly worse TTDPM for knees with ACL injury compared to those of asymptomatic persons (mean difference 0.28°; 95% CI 0.03 to 0.53; P = 0.03), albeit based on only three studies. Due to the lack of evidence, it was not possible to estimate the quality of reliability, measurement error, and criterion validity, nor responsiveness from a criterion and construct approach.

Conclusions

Among persons with ACL injury, existing tests of knee joint TTDPM lack either sufficient quality or evidence for their reliability, validity and responsiveness. Significantly worse thresholds for ACL-injured knees compared to those of asymptomatic controls from a 15° starting angle and trends towards significance for some validity measures nevertheless encourage the development of standardised tests. Further research investigating the influence of modifiable test components (e.g. starting angle and motion direction) on the PMPs of knee joint TTDPM tests following ACL injury is warranted.
One year of COVID-19: infection rates and symptoms in patients with inherited metabolic diseases followed by MetabERN
Authors: Paneghetti Laura , Bellettato Cinzia Maria , Sechi Annalisa , Stepien Karolina M. , Scarpa Maurizio
Published: March 2022

Background

Since the beginning of the COVID-19 pandemic, MetabERN has been monitoring the SARS-CoV-2 infection rates within its metabolic community. To gather data on the total number of cases and the severity of symptoms among IMD patients one year into the pandemic, an online survey was distributed among all MetabERN healthcare providers (HCP). Epidemiological analysis was performed by integrating the survey’s data with the MetabERN database.

Results

Survey’s respondents reported a total of 452 cases of COVID-19 among their IMD patients (213 paediatric and 239 adults). Considering the total number of patients followed by the respondents (n = 26,347), the registered prevalence of COVID-19 in the IMD population was of 1716 × 100,000. Italy emerged as the most affected country (25.4% of cases), followed by the United Kingdom (14.2% of cases). Most of the paediatric cases of COVID-19 displayed no or mild symptoms during the disease: 34% of HCP reported having asymptomatic patients in 75–100% of cases, while 37.5% reported mild symptoms in about a quarter of their patients. Similarly to paediatric cases, most adult IMD patients with COVID-19 were asymptomatic or had mild symptoms: about one third of respondents reported 75–100% asymptomatic patients and about 65% of HCP had between 0 and 50% of patients with mild symptoms. The majority of the respondents reported no deaths due to COVID-19 in adult and paediatric patients with IMDs.

Conclusions

Most of MetabERN’s IMD patients who got COVID-19 during the first year of the pandemic had mild symptoms and a positive outcome of the disease. However, fatal events were recorded in paediatric patients; this, together with the lack of information on the long-term effects of COVID-19 in IMDs, call for caution in the metabolic population.
Predicting molecular initiating events using chemical target annotations and gene expression
Authors: Bundy Joseph L. , Judson Richard , Williams Antony J. , Grulke Chris , Shah Imran , Everett Logan J.
Published: March 2022

Background

The advent of high-throughput transcriptomic screening technologies has resulted in a wealth of publicly available gene expression data associated with chemical treatments. From a regulatory perspective, data sets that cover a large chemical space and contain reference chemicals offer utility for the prediction of molecular initiating events associated with chemical exposure. Here, we integrate data from a large compendium of transcriptomic responses to chemical exposure with a comprehensive database of chemical-protein associations to train binary classifiers that predict mechanism(s) of action from transcriptomic responses. First, we linked reference chemicals present in the LINCS L1000 gene expression data collection to chemical identifiers in RefChemDB, a database of chemical-protein interactions. Next, we trained binary classifiers on MCF7 human breast cancer cell line derived gene expression profiles and chemical-protein labels using six classification algorithms to identify optimal analysis parameters. To validate classifier accuracy, we used holdout data sets, training-excluded reference chemicals, and empirical significance testing of null models derived from permuted chemical-protein associations. To identify classifiers that have variable predicting performance across training data derived from different cellular contexts, we trained a separate set of binary classifiers on the PC3 human prostate cancer cell line.

Results

We trained classifiers using expression data associated with chemical treatments linked to 51 molecular initiating events. This analysis identified and validated 9 high-performing classifiers with empirical p-values lower than 0.05 and internal accuracies ranging from 0.73 to 0.94 and holdout accuracies of 0.68 to 0.92. High-ranking predictions for training-excluded reference chemicals demonstrating that predictive accuracy extends beyond the set of chemicals used in classifier training. To explore differences in classifier performance as a function of training data cellular context, MCF7-trained classifier accuracies were compared to classifiers trained on the PC3 gene expression data for the same molecular initiating events.

Conclusions

This methodology can offer insight in prioritizing candidate perturbagens of interest for targeted screens. This approach can also help guide the selection of relevant cellular contexts for screening classes of candidate perturbagens using cell line specific model performance.
A phase III randomized trial of weight loss to reduce cancer-related fatigue among overweight and obese breast cancer patients: MEDEA Study design
Authors: Di Meglio Antonio , Martin Elise , Crane Tracy E. , Charles Cecile , Barbier Aude , Raynard Bruno , Mangin Anthony , Tredan Olivier , Bouleuc Carole , Cottu Paul H. , Vanlemmens Laurence , Segura-Djezzar Carine , Lesur Anne , Pistilli Barbara , Joly Florence , Ginsbourger Thomas , Coquet Bernadette , Pauporte Iris , Jacob Guillemette , Sirven Aude , Bonastre Julia , Ligibel Jennifer A. , Michiels Stefan , Vaz-Luis Ines
Published: March 2022

Background

Elevated body mass index (BMI) represents a risk factor for cancer-related fatigue (CRF). Weight loss interventions are feasible and safe in cancer survivors, leading to improved cardio-metabolic and quality of life (QOL) outcomes and modulating inflammatory biomarkers. Randomized data are lacking showing that a lifestyle intervention aimed at weight loss, combining improved diet, exercise, and motivational counseling, reduces CRF. Motivating to Exercise and Diet, and Educating to healthy behaviors After breast cancer (MEDEA) is a multi-center, randomized controlled trial evaluating the impact of weight loss on CRF in overweight or obese survivors of breast cancer. Herein, we described the MEDEA methodology.

Methods

Patients (N = 220) with stage I–III breast cancer and BMI ≥ 25 kg/m2, within 12 months of primary treatment, and able to walk ≥ 400 m are eligible to enroll. Participants are randomized 1:1 to health education alone vs. a personalized telephone-based weight loss intervention plus health education. Both arms receive a health education program focusing on healthy living. Patients in the intervention arm are paired with an individual lifestyle coach, who delivers the intervention through 24 semi-structured telephone calls over 1 year. Intervention goals include weight loss ≥ 10% of baseline, caloric restriction of 500–1000 Kcal/day, and increased physical activity (PA) to 150 (initial phase) and 225–300 min/week (maintenance phase). The intervention is based on the social cognitive theory and is adapted from the Breast Cancer Weight Loss trial (BWEL, A011401). The primary endpoint is the difference in self-reported CRF (EORTC QLQ-C30) between arms. Secondary endpoints include the following: QOL (EORTC QLQ-C30, -BR45, -FA12), anxiety, and depression (HADS); weight and BMI, dietary habits and quality, PA, and sleep; health care costs (hospital-admissions, all-drug consumption, sick leaves) and cost-effectiveness (cost per quality-adjusted life-year); and patient motivation and satisfaction. The primary analysis of MEDEA will compare self-reported CRF at 12 months post-randomization between arms, with 80.0% power (two-sided α = 0.05) to detect a standardized effect size of 0.40.

Discussion

MEDEA will test the impact of a weight loss intervention on CRF among overweight or obese BC survivors, potentially providing additional management strategies and contributing to establish weight loss support as a new standard of clinical care.

Trial registration

ClinicalTrials.govNCT04304924
Immediate effects of hybrid assistive limb gait training on lower limb function in a chronic myelopathy patient with postoperative late neurological deterioration
Authors: Kubota Shigeki , Kadone Hideki , Shimizu Yukiyo , Koda Masao , Takahashi Hiroshi , Miura Kousei , Eto Fumihiko , Furuya Takeo , Sankai Yoshiyuki , Yamazaki Masashi
Published: March 2022

Objective

The Hybrid Assistive Limb (HAL) has recently been used to treat movement disorders. Although studies have shown its effectiveness for chronic myelopathy, the immediate effects of HAL gait training on lower limb function have not been clarified. We conducted HAL gait training and examined its immediate effects on a 69-year-old man with re-deterioration of myelopathy in the chronic phase after surgery for compression myelopathy. The HAL intervention was performed every 4 weeks for 10 total sessions. Immediately before and after each session, we analyzed the patient’s walking ability using the 10-m walk test. In the 4th HAL session, the gastrocnemius muscle activity was measured bilaterally using a synchronized motion capture-electromyogram system.

Results

The training effects became steady after the 2nd session. In sessions 2–10, the step length increased from 0.56 to 0.63 m (mean: 0.031 m) immediately after HAL training. The motion capture-electromyogram analyses showed that considerable amounts of gastrocnemius muscle activity were detected during the stance and swing phases before HAL training. During and immediately after HAL training, gastrocnemius activity during the swing phase was diminished. HAL gait training has an immediate effect for inducing a normal gait pattern with less spasticity in those with chronic myelopathy.
Effect of small extracellular vesicles derived from IL-10-overexpressing mesenchymal stem cells on experimental autoimmune uveitis
Authors: Li Yongtao , Ren Xinjun , Zhang Zhihui , Duan Yanan , Li Huan , Chen Shuang , Shao Hui , Li Xiaorong , Zhang Xiaomin
Published: March 2022

Background

Autoimmune uveitis is a sight-threatening intraocular inflammation mainly caused by immune dysregulation. The development of safe and effective therapeutic approaches is urgently needed. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have been demonstrated to inhibit autoimmune responses; however, the immunosuppressive effect of MSC-sEVs is too weak for clinical transfer. In the current study, we investigated the therapeutic effect of IL-10-overexpressing MSC-sEVs (sEV-IL10) on experimental autoimmune uveitis (EAU) and studied the underlying mechanism.

Methods

Mice were randomly grouped and received a single tail vein injection of different sEVs (50 μg) or PBS on day 11 post-immunization. The clinical and histological scores were graded, and the percentage of T helper cell was measured. To investigate the effect of sEVs on the proliferation of T-cells and the differentiation of Th1, Th17 and Treg cells, T-cells were cocultured with sEVs under the corresponding culture conditions. After labeled with PKH-26, sEVs were traced both in vivo and in vitro.

Results

Compared with normal or vector sEV-treated groups, mice in the sEV-IL10-treated group had lower clinical and histological scores with lower percentages of Th1 and Th17 cells in the eyes and higher percentages of Treg cells in the spleen and draining lymph nodes (LN). Furthermore, sEV-IL10 enhanced the suppressive effect of MSC-sEVs on the proliferation of T-cells and differentiation of Th1 and Th17 cells, whereas upregulated the differentiation of Treg cells. Both in vivo and in vitro experiments demonstrated that MSC-sEVs were rapidly enriched in target tissues and internalized by T-cells.

Conclusion

These results suggested that sEV-IL10 effectively ameliorates EAU by regulating the proliferation and differentiation of T-cells, indicating sEVs as a potential novel therapy for autoimmune uveitis or other autoimmune diseases.
Parked on the verge: vocational rehabilitation of long-term unemployed citizens – a mixed methods study
Authors: Andersen Lotte Nygaard , Stochkendahl Mette Jensen , Roessler Kirsten K.
Published: March 2022

Background

Vocational rehabilitation programs (VRP) developing and improving work ability are used in Denmark to assist long-term unemployed citizens with complex problems. The aims of this study were to (1) describe VRP-participants in relation to general health, well-being, work ability and self-efficacy at baseline and one-year follow-up, (2) obtain an understanding of VRP-participants’ personal development towards improving work ability, and (3) explore VRP-participants’ hopes and thoughts about their future.

Methods

In a mixed methods approach, data from a longitudinal survey and semi-structured interviews were collected. In the quantitative longitudinal survey, all participants completed paper questionnaires at baseline and one-year follow-up. For the qualitative semi-structured interviews, VRP participants were recruited with a maximum variation sampling strategy through VRP coordinators and personal contact. Data were analysed by descriptive statistics and systematic text condensation. Following analysis, data were merged and presented in combination according to identified themes.

Results

At baseline and one-year follow-up 146 (response rate 34%) and 74 participants (response rate 52%) respectively, responded to the questionnaire. Seven participants were interviewed. The analysis revealed four themes: 1) Individual explanations of life situation and health; 2) Finding the path; 3) Work as giving meaning to life; 4) Hope for the future. Despite self-reported scores indicating poor general health, lack of well-being, low work ability and low self-efficacy, VRP-activities seemed to have assisted participants in finding meaning in life. VRP-components that may be drivers of successful recovery processes were identified.

Conclusions

VRP-participants experienced life situations that include multifactorial burdens, and low levels of general health, well-being, work ability, and self-efficacy at baseline and 1 year later. From the outset, most did not have a clear goal of employment, but over time, new goals were set as realistic opportunities for re-developing their work ability were explored. Successful core components of VRP were individually tailored programs and support, development of new relationships, and accommodated flexible internships and jobs.

Trial registration

ClinicalTrials.gov Identifier: NCT02641704, date of registration December 29, 2015.
An investigation into the pharmaceutical advertising in Iranian medical journals
Authors: Yousefi Nazila , Sharif Zahra , Chahian Fateme , Mombeini Tayebe , Peiravian Farzad
Published: March 2022

Background

Pharmaceutical advertising is not only considered a key factor in the successful launch of pharmaceutical products, but is also an important source of public health information with a significant impact on consumer choice and behavior. Nowadays, advertising has become the broadest dissemination channel for various products, including medicines, which may ultimately lead to the generalization of self-treatment or mistreatment. Improper drug promotion can exacerbate unhealthy outcomes by making false or misleading claims, using inferior references, and failing to meet international standards. This study aimed to examine the requirements for pharmaceutical advertising from regulatory perspective and the compliance of Iranian pharmaceutical advertisements to related standards and guidelines. It is limited to print advertisements in Iranian national medical journals and magazines.

Method

The present study is a descriptive–analytical study using bibliometric methods. As a first step, a comprehensive review of the national and international regulations on drug advertising was conducted and a comparison of different regulations was provided. In the second step, a checklist was created to evaluate the compliance of drug advertising with the extracted regulations.

Result

The results of the present study show that the claims made in Iranian drug advertisements are 29.10% valid, 27.67% exaggerated, 23.10% controversial, 12.62% misleading, and 6.8% invalid. In general, we found that most medical advertisements in Iranian journals and magazines comply with national laws and regulations. However, many international requirements are not met in these advertisements.

Conclusions

Although we found that printed medical advertisements in Iran are roughly compliant with national regulations, there is still a long way to achieve full compliance. Monitoring processes should be improved and clearly defined penalties should be set to avoid misleading claims and their likely health consequences. It is very important in Iran to update the existing rules and regulations for medical advertisements according to international guidelines. More careful monitoring of the content of advertising and the accuracy of claims are also needed.
Ultraprotective versus apneic ventilation in acute respiratory distress syndrome patients with extracorporeal membrane oxygenation: a physiological study
Authors: Graf Peter T. , Boesing Christoph , Brumm Isabel , Biehler Jonas , Müller Kei Wieland , Thiel Manfred , Pelosi Paolo , Rocco Patricia R. M. , Luecke Thomas , Krebs Joerg
Published: March 2022

Background

Even an ultraprotective ventilation strategy in severe acute respiratory distress syndrome (ARDS) patients treated with extracorporeal membrane oxygenation (ECMO) might induce ventilator-induced lung injury and apneic ventilation with the sole application of positive end-expiratory pressure may, therefore, be an alternative ventilation strategy. We, therefore, compared the effects of ultraprotective ventilation with apneic ventilation on oxygenation, oxygen delivery, respiratory system mechanics, hemodynamics, strain, air distribution and recruitment of the lung parenchyma in ARDS patients with ECMO.

Methods

In a prospective, monocentric physiological study, 24 patients with severe ARDS managed with ECMO were ventilated using ultraprotective ventilation (tidal volume 3 ml/kg of predicted body weight) with a fraction of inspired oxygen (FiO2) of 21%, 50% and 90%. Patients were then treated with apneic ventilation with analogous FiO2. The primary endpoint was the effect of the ventilation strategy on oxygenation and oxygen delivery. The secondary endpoints were mechanical power, stress, regional air distribution, lung recruitment and the resulting strain, evaluated by chest computed tomography, associated with the application of PEEP (apneic ventilation) and/or low VT (ultraprotective ventilation).

Results

Protective ventilation, compared to apneic ventilation, improved oxygenation (arterial partial pressure of oxygen, p < 0.001 with FiO2 of 50% and 90%) and reduced cardiac output. Both ventilation strategies preserved oxygen delivery independent of the FiO2. Protective ventilation increased driving pressure, stress, strain, mechanical power, as well as induced additional recruitment in the non-dependent lung compared to apneic ventilation.

Conclusions

In patients with severe ARDS managed with ECMO, ultraprotective ventilation compared to apneic ventilation improved oxygenation, but increased stress, strain, and mechanical power. Apneic ventilation might be considered as one of the options in the initial phase of ECMO treatment in severe ARDS patients to facilitate lung rest and prevent ventilator-induced lung injury.

Trial registration: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013967.
Effect of carbonate apatite as a bone substitute on oral mucosal healing in a rat extraction socket: in vitro and in vivo analyses using carbonate apatite
Authors: Egashira Yuki , Atsuta Ikiru , Narimatsu Ikue , Zhang Xiaoxu , Takahashi Ryosuke , Koyano Kiyoshi , Ayukawa Yasunori
Published: March 2022

Background

Low bone quantity and quality are serious problems that affect the prognosis of implants in the cosmetic field. Therefore, artificial bone substitutes are frequently used. However, whether there is a difference in the effect of either bone substitute on soft tissue healing is unclear given their greatly different absorbability. In this study, we used hydroxyapatite (HAp) and carbonate apatite (CO3Ap) as bone substitutes to analyze the epithelial and connective tissue healing after tooth extraction.

Methods

In vitro, oral mucosa-derived epithelial cells (OECs) collected from 4-day-old Wistar rats were seeded on HAp or CO3Ap and evaluated for adhesion, proliferation, migration, apoptosis, and morphology. Fibroblasts (FBs) were also analyzed for their ability to express collagen. In vivo, the extraction of maxillary right first (M1) and second molars (M2) of 6-week-old male Wistar rats was performed, followed by insertion of HAp or CO3Ap granules into the M1 and M2 sites. The oral mucosal healing process was then evaluated histochemically after 7 and 14 days.

Results

In vitro, high collagen expression by FBs in the CO3Ap group was observed and the surface analysis showed spreading of the FBs on the CO3Ap surface. However, the activity of OECs was suppressed on CO3Ap. Two weeks after CO3Ap implantation, soft tissue healing was observed, and recovery of the connective tissue was observed on the remaining CO3Ap.

Conclusions

Our results suggest that the formation of soft tissues, including connective tissue, was promoted by CO3Ap in the extraction socket within a short period.
The microbiome and resistome of apple fruits alter in the post-harvest period
Authors: Wassermann Birgit , Abdelfattah Ahmed , Müller Henry , Korsten Lise , Berg Gabriele
Published: March 2022

Background

A detailed understanding of antimicrobial resistance trends among all human-related environments is key to combat global health threats. In food science, however, the resistome is still little considered. Here, we studied the apple microbiome and resistome from different cultivars (Royal Gala and Braeburn) and sources (freshly harvested in South Africa and exported apples in Austrian supermarkets) by metagenomic approaches, genome reconstruction and isolate sequencing.

Results

All fruits harbor an indigenous, versatile resistome composed of 132 antimicrobial resistance genes (ARGs) encoding for 19 different antibiotic classes. ARGs are partially of clinical relevance and plasmid-encoded; however, their abundance within the metagenomes is very low (≤ 0.03%). Post-harvest, after intercontinental transport, the apple microbiome and resistome was significantly changed independently of the cultivar. In comparison to fresh apples, the post-harvest microbiome is characterized by higher abundance ofEnterobacteriales,and a more diversified pool of ARGs, especially associated with multidrug resistance, as well as quinolone, rifampicin, fosfomycin and aminoglycoside resistance. The association of ARGs with metagenome-assembled genomes (MAGs) suggests resistance interconnectivity within the microbiome. Bacterial isolates of the phylaGammaproteobacteria,AlphaproteobacteriaandActinobacteriaserved as representatives actively possessing multidrug resistance and ARGs were confirmed by genome sequencing.

Conclusion

Our results revealed intrinsic and potentially acquired antimicrobial resistance in apples and strengthen the argument that all plant microbiomes harbor diverse resistance features. Although the apple resistome appears comparatively inconspicuous, we identified storage and transport as potential risk parameters to distribute AMR globally and highlight the need for surveillance of resistance emergence along complex food chains.
Care Outcomes for Chiropractic Outpatient Veterans (COCOV): a single-arm, pragmatic, pilot trial of multimodal chiropractic care for U.S. veterans with chronic low back pain
Authors: Long Cynthia R. , Salsbury Stacie A. , Vining Robert D. , Lisi Anthony J. , Corber Lance , Twist Elissa , Abrams Thad , Wallace Robert B. , Goertz Christine M.
Published: March 2022

Background

Over 25% of veterans seeking care at U.S. Veterans Health Administration facilities have chronic low back pain (LBP), with high rates of mental health comorbidities. The primary objective of this study was to assess the feasibility of participant recruitment, retention, and electronic data collection to prepare for the subsequent randomized trial of multimodal chiropractic care for pain management of veterans with chronic low back pain. The secondary objectives were to estimate effect sizes and variability of the primary outcome and choose secondary outcomes for the full-scale trial.

Methods

This single-arm pilot trial enrolled 40 veterans with chronic LBP at one Veterans Health Administration facility for a 10-week course of pragmatic multimodal chiropractic care. Recruitment was by (1) provider referral, (2) invitational letter from the electronic health record pre-screening, and (3) standard direct recruitment. We administered patient-reported outcome assessments through an email link to REDCap, an electronic data capture platform, at baseline and 5 additional timepoints. Retention was tracked through adherence to the treatment plan and completion rates of outcome assessments. Descriptive statistics were calculated for baseline characteristics and outcome variables.

Results

We screened 91 veterans over 6 months to enroll our goal of 40 participants. Seventy percent were recruited through provider referrals. Mean age (range) was 53 (22–79) years and 23% were female; 95% had mental health comorbidities. The mean number of chiropractic visits was 4.5 (1–7). Participants adhered to their treatment plan, with exception of 3 who attended only their first visit. All participants completed assessments at the in-person baseline visit and 80% at the week 10 final endpoint. We had no issues administering assessments via REDCap. We observed clinically important improvements on the Roland-Morris Disability Questionnaire [mean change (SD): 3.6 (6.1)] and on PROMIS® pain interference [mean change (SD): 3.6 (5.6)], which will be our primary and key secondary outcome, respectively, for the full-scale trial.

Conclusions

We demonstrated the feasibility of participant recruitment, retention, and electronic data collection for conducting a pragmatic clinical trial of chiropractic care in a Veterans Health Administration facility. Using the pilot data and lessons learned, we modified and refined a protocol for a full-scale, multisite, pragmatic, National Institutes of Health-funded randomized trial of multimodal chiropractic care for veterans with chronic LBP that began recruitment in February 2021.

Trial registration

ClinicalTrials.gov NCT03254719
Enhanced thermodynamic, pharmacokinetic and theranostic properties of polymeric micelles via hydrophobic core-clustering of superparamagnetic iron oxide nanoparticles
Authors: Jiang Yixin , Lee Junghan , Seo Jin-Myung , Davaa Enkhzaya , Shin Kyung-Ju , Yang Su-Geun
Published: March 2022

Background

Superparamagnetic iron oxide nanoparticles (SPIO) have been applied for decades to design theranostic polymeric micelles for targeted cancer therapy and diagnostic MR imaging. However, the effects of SPIO on the physicochemical, and biological properties of polymeric micelles have not yet been fully elucidated. Therefore, we investigated potential effect of SPIO on the physical and biological properties of theranostic polymeric micelles using representative cancer drug (doxorubicin; Doxo) and polymer carrier (i.e., poly (ethylene glycol)-co-poly(D,L-lactide), PEG-PLA).

Methods

SPIO were synthesized from Fe(acetyl acetonate)
3
in an aryl ether. SPIO and Doxo were loaded into the polymeric micelles by a solvent-evaporation method. We observed the effect of SPIO-clustering on drug loading, micelle size, thermodynamic stability, and theranostic property of PEG-PLA polymeric micelles. In addition, cellular uptake behaviors, pharmacokinetic and biodistribution study were performed.

Results

SPIO formed hydrophobic geometric cavity in the micelle core and significantly affected the integrity of micelles in terms of micelle size, Doxo loading, critical micelle concentration (CMC) and in vitro dissociation. In vivo pharmacokinetic studies also showed the enhanced Area Under Curve (AUC) and elongated the half-life of Doxo.

Conclusions

Clustered SPIO in micelles largely affects not only MR imaging properties but also biological and physical properties of polymeric micelles.
Serum 25-hydroxy vitamin D levels in age-related macular degeneration
Authors: Pérez Serena Antonio , Martínez Betancourt Daisy Paola , González del Valle Fernando , Ruiz-Moreno José M.
Published: March 2022

Background

The aim of this study was to determine the 25-hydroxy vitamin D (25(OH)D) levels in age-related macular degeneration (AMD) patients.

Methods

Age-related macular degeneration (AMD) patients were classified into four groups: early AMD (N = 10), intermediate AMD (N = 12), advanced atrophic AMD (N = 19) and advanced neovascular AMD (N = 52) after undergoing fundus photography. Serum 25(OH)D levels of all subjects were evaluated. From a random control group of 326 patients whose 25(OH)D levels had been measured, a group of 93 were selected to match the age range of the AMD group. We measured 25(OH)D levels during the same period to rule out seasonal variation.

Results

A total of 93 AMD patients (36 males and 57 females) and 93 healthy individuals (39 males and 54 females) were enrolled in this study with the mean age of 78.96 ± 8.46 vs. 78.80 ± 8.35, respectively. The patients affected by AMD had statistically significant lower 25(OH)D levels (15 ± 10 ng/mL) than the healthy subjects control group (21 ± 14 ng/mL) (p = 0.004). However, the median 25(OH)D levels in early AMD, intermediate AMD, advanced atrophic AMD and advanced neovascular AMD (12.5 ± 7.3; 15 ± 11; 15 ± 8 and 17 ± 11.5, respectively) were not statistically significant (p = 0.442).

Conclusion

This study shows that patients affected by AMD had lower vitamin D levels compared to healthy subjects. Further research is necessary to investigate the possible association between 25(OH)D levels and AMD.
Decisive role of histopathology of lens capsule in the diagnosis of chronic fungal postoperative endophthalmitis
Authors: Loredo e Silva Mathias Paulo , da Silva Oliveira Rodrigo Magno , Lage Bruno Freitas , Freitas Clóvis Arcoverde , Pedrosa Moisés Salgado , Nehemy Márcio Bittar , Vasconcelos-Santos Daniel Vítor
Published: March 2022

We report three cases of refractory chronic endophthalmitis after cataract surgery presenting to a referral center, and with repeated negative cultures. Initial treatment consisted of intravitreal and systemic antibiotics, with partial improvement. After subsequent worsening, pars plana vitrectomy, intraocular lens explantation and en bloc capsulectomy were performed. Histopathological examination revealed multiple filamentous fungal structures, sequestered between anterior/posterior lens capsule in all cases. Chronic postoperative fungal endophthalmitis may manifest with negative cultures possibly associated with sequestration of the microorganism into the capsular bag. Careful histopathological examination of lens capsule in these cases may be essential for a definite diagnosis.
Prospects of quantum computing for molecular sciences
Authors: Liu Hongbin , Low Guang Hao , Steiger Damian S. , Häner Thomas , Reiher Markus , Troyer Matthias
Published: March 2022

Molecular science is governed by the dynamics of electrons and atomic nuclei, and by their interactions with electromagnetic fields. A faithful physicochemical understanding of these processes is crucial for the design and synthesis of chemicals and materials of value for our society and economy. Although some problems in this field can be adequately addressed by classical mechanics, many demand an explicit quantum mechanical description. Such quantum problems require a representation of wave functions that grows exponentially with system size and therefore should naturally benefit from quantum computation on a number of logical qubits that scales only linearly with system size. In this perspective, we elaborate on the potential benefits of quantum computing in the molecular sciences, i.e., in molecular physics, chemistry, biochemistry, and materials science.
Acute vision loss in Guillain–Barré syndrome: A case series and review of literature
Authors: Ranjan Abhay , Solanke Ramdas Pandurangrao , Sinha Neetu , Bhushan Vidya
Published: March 2022

Background

Acute vision loss in Guillain–Barré syndrome  is rarely reported in literature. No case of vision loss in Guillain–Barré syndrome due to Angle closure glaucoma  has been reported in AIDP variant GBS.

Case presentation

We report three patients with an acute inflammatory demyelinating polyradiculoneuropathy subtype of GBS who developed acute vision loss during the course of disease. Two patients had autonomic dysfunction with hypertension, in which  one patient presented with painful acute vision loss and was diagnosed with Angle closure glaucoma and another patient had painless vision loss which was due to posterior reversible encephalopathy syndrome. Third patient presented with bilateral papilledema with raised cerebrospinal fluid protein and intracranial pressure. Vision in all the three patients improved after treatment.

Conclusion

Patient with GBS, with autonomic dysfunction and hypertension or elevated cerebrospinal fluid protein may present with acute vision loss during the course of the disease. Early diagnosis and management  help to improve vision and prevent permanent vision loss in these patients.
Supporting undergraduate students’ developing water literacy during a global pandemic: a longitudinal study
Authors: Mostacedo-Marasovic Silvia-Jessica , Lally Diane , Petitt Destini N. , White Holly , Forbes Cory
Published: March 2022

To prepare students to address water-related challenges, undergraduate STEM education must provide them with opportunities to learn and reason about water issues. Water in Society is an introductory-level, innovative, and interdisciplinary undergraduate course offered annually at a large midwestern university. The course focuses on both disciplinary concepts and civic engagement, and is designed around a variety of interactive, research-based practices to support students’ learning, engagement with authentic data, scientific models and modeling, and collaboration and learning among peers. This study aims to evaluate, “how have student outcomes and perceptions changed over five years of the course?”.The results are based on data from students (n =326) in five consecutive years of the course, during which time the course transitioned from a face-to-face model to fully asynchronous online model due, in part, to impacts of the COVID-19 pandemic. The particularly rapid and abrupt transition between 2020 and 2021 in response to COVID-19 led to many course changes, including modes of communication between instructors and students and opportunities for collaboration. Here, multiple measures are used to evaluate students’ learning about water concepts, model-based reasoning about socio-hydrologic systems, and perceptions of the course across all five years. By the end of each iteration of the course, students improved their knowledge of hydrologic concepts, independent of the course format or other student-level variables. However, results also show that students’ performance on complex socio-hydrologic systems modeling tasks, as well as their overall satisfaction with the course, decreased in Year 5 when the course was fully online. Results provide insight into efforts to move undergraduate STEM courses online and specific evidence of the COVID-19 pandemic’s impacts on undergraduate STEM teaching and learning about water.
Interleukin-4 gene intron 3 VNTR polymorphism in adult acute myeloid leukemia
Authors: Safwat Nesma A. , Najjar Marwa R. El , Saeed Alia M. , Mohamed Haydi S.
Published: March 2022

Background

The proliferation of acute myeloid leukemia (AML) blast into the bone marrow microenvironment is controlled by cytokines. Interleukin-4 (IL-4) has recently been discovered to suppress the development and persistence of AML cells selectively. Intron three of the Interleukin-4 (IL-4) gene contains a 70-bp minisatellite region polymorphism that may influence gene transcriptional activity and subsequently affect the production level of IL4. We investigated the IL-4 gene intron three variable number tandem repeat (VNTR) polymorphism as a molecular marker in AML associated with clinical and laboratory variables and a prognostic factor for therapeutic response and disease outcome.

Results

IL-4 gene intron three minisatellite regions polymorphism was assessed in 60 adult AML patients and 60 healthy controls, comparable concerning age and gender, using polymerase chain reaction. Three study marker genotypes were detected in AML patients; P1/P1 (3%), P1/P2 (40%), and P2/P2 (56.7%). The frequency of P2 alleles was significantly more in AML patients than in healthy controls (76.7% versus 25%; P < 0.001). Compared to the heterozygous group and P1/P1 carriers, AML patients with the homozygous P2/P2 genotype had a higher total leucocytic count and increased blast percentages in bone marrow or peripheral blood, besides a lower platelet count. P2P2 genotype was also significantly associated with poor therapeutic response, higher susceptibility to disease recurrence and shorter overall survival and disease-free survival.

Conclusion

The IL-4 intron 3 VNTR polymorphism could be included in the molecular risk stratification of AML to predict poor disease. This information can be utilized in incorporating biological therapy into the present therapeutic protocols to enhance chemotherapy regimens’ current low response rates.
Expression and diagnostic values of MIAT, H19, and NRON long non-coding RNAs in multiple sclerosis patients
Authors: Amiri Mehrnoosh , Mokhtari Mohammad Javad , Bayat Mahnaz , Safari Anahid , Dianatpuor Mehdi , Tabrizi Reza , Borhani-Haghighi Afshin
Published: March 2022

Background

Multiple sclerosis (MS) is a chronic inflammatory disease. Various long non-coding RNAs (lncRNAs) appear to have an important role in the pathophysiology of MS. This study aimed at evaluating the expression levels of lncRNAs, MIAT, H19, and NRON in peripheral blood of MS cases to a healthy control group. We collected blood samples of 95 MS cases (76 relapsing–remitting (RR) and 19 secondary progressive (SP) MS) and 95 controls. We used quantitative real-time PCR for the evaluation of gene expression. The correlation between expression with clinical parameters was analyzed by a multiple linear regression model. Receiver operating characteristic (ROC) curve analysis was carried out to detect the diagnostic potential of lncRNAs levels according to the area under the curve (AUC).

Results

MIAT, H19, and NRON were significantly increased in the RRMS and SPMS subgroups compared to the controls. We found that the H19 and MIAT expression significantly were higher in SPMS compared with RRMS. Patients with RRMS had a greater level of the average NRON expression is compared with SPMS patients. The expression level of H19 significantly was higher in females relative to male patients. Based on the area under curve (AUC) values, NRON had the best performance in the differentiation of MS patients from controls (AUC = 0.95, P < 0.0001). A combination of MIAT, H19, and NRON expression levels could be useful in differentiating MS patients with 93.6% sensitivity, 98.9% specificity, and diagnostic power of 0.96 (P < 0.0001).

Conclusions

The levels of MIAT, H19, and NRON in peripheral blood could be important biomarkers for MS diagnosis.