bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory analyses of biomarkers in blood and stratum corneum in patients with atopic dermatitis
Authors: Maruyama Ayano , Tamagawa-Mineoka Risa , Nishigaki Hiromi , Masuda Koji , Katoh Norito
Published: October 2022

Background:

The pathogenesis of atopic dermatitis (AD) involves various mediators, including cytokines and chemokines, which are produced by immune cells, such as dendritic cells and lymphocytes, and non-immune cells, such as epidermal cells. Several mediators, including thymus and activation-regulated chemokine (TARC), are used as biomarkers for AD severity and activity. However, additional local and systemic biomarkers of AD are required.

Methods:

This study will include 10 male patients with AD and 5 healthy adult males (age range: 20–80 years). The Eczema Area and Severity Index will be used to objectively evaluate the clinical findings. In addition, the severity of eruptions will be assessed on a 5-point scale by scoring symptoms (erythema, edema/papules, oozing/crusting, excoriation, lichenification, and xerosis), and the total intensity will be calculated by adding the symptom scores together. Subjective symptoms will be assessed using a peak pruritus numerical rating scale. Laboratory tests, including measurements of peripheral eosinophil count and serum total immunoglobulin E, TARC, and lactate dehydrogenase levels, will be performed. Using blood samples and extracts of stratum corneum samples obtained by tape stripping, we will conduct an exploratory analysis of protein expression using an antibody array to identify mediators whose levels are significantly altered in patients with AD. After 4 to 8 weeks, blood samples and stratum corneum samples will be collected again from AD patients. Moreover, we will examine whether the candidate proteins can be quantified using enzyme-linked immunosorbent assays.

Discussion:

This is an important study exploring potential local and systemic biomarkers of AD. The results of this study will be clinically meaningful for the discovery of new biomarkers for diagnosing and assessing the severity of AD.
The presence of hypertension during pregnancy determines the future risk of metabolic syndrome: An observational study
Authors: Ju Da-Hye , Lee Hyeyoun , Ha Sang Jin
Published: October 2022

This study aimed to examine the prevalence and time interval of metabolic syndrome (MS) development among women with hypertensive disorders of pregnancy (HDP) compared to women with a normal delivery. Data (4,723,541 deliveries) from 2002 to 2012 from the National Health Insurance System Database in Korea were used to compare women diagnosed with HDP with those with a normal singleton pregnancy. Using the customized database, we conducted a longitudinal analysis of MS development. MS was observed in 20.3% of the patients in the normal delivery group and 37.1% in the HDP group (P < .0001). The time to MS development in the HDP group was significantly shorter than that in the normal delivery group (6.6 ± 3.4 vs 8.2 ± 3.4 years, P < .0001). The HDP group had a significantly increased risk [odd ratio (OR) 1.23; 95% confidence interval (CI), 1.12–1.35] of developing MS, and elevated systolic blood pressure strongly contributed to the increased risk of developing MS (OR 1.644; 95% CI, 1.610–1.678). HDP increased the risk of MS development later in life, and MS development exhibited a shorter time period in women with HDP. Women with HDP should undergo intensive assessment for MS components.
Association between the risk of hepatitis virus-related hepatocellular carcinoma and EGF polymorphism: A PRISMA-compliant updated meta-analysis
Authors: Wang Qinjing , Xu Lingling , Wu Qianbo , Zhang Min , Zhang Jing
Published: October 2022

Background:

The study aims to provide a comprehensive account of the association between the epidermal growth factor (EGF) + 61A/G polymorphism (rs4444903) and susceptibility to virus-related hepatocellular carcinoma (HCC).

Methods:

Electronic searching of the Chinese National Knowledge Infrastructure, Wanfang, Chinese Scientific Journal Database (VIP), PubMed, Web of Science, and Embase was conducted to select eligible studies. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to assess the strength of the association.

Results:

In this study, a total of 18 articles were included with 2692 cases and 5835 controls for assessing the association between rs4444903 and HCC risk. The pooled results showed that the EGF + 61A/G polymorphism was significantly associated with the risk of virus-related HCC in all genetic models. Stratified analyses were conducted based on ethnicity, study quality, source of controls, type of controls, number of cases and genotyping method. The results showed that EGF + 61A/G polymorphisms significantly affect HCC susceptibility in different stratified populations. High heterogeneity was observed across included studies, and meta-regression analysis demonstrated that race, type of controls, and study quality contribute to the observed heterogeneity.

Conclusion:

This pooled analysis found that EGF + 61A/G polymorphism was significantly associated with the risk of HCC.
Sarcopenia among people living with HIV and the effect of antiretroviral therapy on body composition
Authors: Konishi Keiji , Nakagawa Hidenori , Asaoka Tomohiro , Kasamatsu Yu , Goto Tetsushi , Shirano Michinori
Published: October 2022

To investigate the prevalence of sarcopenia among people living with HIV (PLWH) in Japan and analyze the relationship between HIV infection and ART effects on the body composition of Japanese PLWH for more appropriate drug selection and lifestyle guidance. Cross-sectional observational study. We included male patients aged ≥ 60 years whose body composition was measured by InBody 570 body composition analyzer during outpatient visits. Patients were classified by body shape based on body mass index (BMI) and body fat percentage measurements and by tenofovir alafenamide administration. Hidden obesity is a condition wherein the BMI is within the standard range but the body fat percentage is higher than the reference. Patients with low muscle mass and strength were considered to have sarcopenia, whereas those with only low muscle strength were considered to have pre-sarcopenia. In total, 87 patients were included. Based on body shape determined by BMI and body fat percentage, most patients had hidden obesity (40 patients, 46.0%). Sarcopenia was detected in 9 patients (10.3%) and pre-sarcopenia in 14 patients (16.1%). The tenofovir alafenamide (TAF) use group had significantly higher BMI, higher skeletal muscle mass, body fat mass, and skeletal muscle mass index relative to the non-TAF use group. Hidden obesity is a risk for lifestyle diseases. It is important to recognize it based on body composition measurements because it can be missed by BMI measurement alone. Tenofovir alafenamide therapy increases skeletal muscle mass, which may result in the prevention of sarcopenia. To clarify how TAF affects the development of sarcopenia and lifestyle diseases, future studies on a larger cohort are warranted.
Diagnostic dilemma of celiac disease presenting with weight loss and secondary amenorrhea: A case report
Authors: Mumtaz Arif , Khan Qaisar Ali , Asim Nowshad , Baqi Abdul , Iram Sumaira , Majeed Abdul , Tahir Muhammad Junaid , Islam Md. Saiful , Yousaf Zohaib
Published: October 2022

Rationale:

Celiac disease (CD) is autoimmune enteropathy affecting the proximal small intestinal mucosa. It is caused by insensitivity to gluten, a protein predominantly presented in wheat. CD is classically associated with gastrointestinal symptoms. The non-classic clinical presentation of CD can present with other organ involvement. Non-human leukocyte antigens genes are associated with atypical forms.

Patients concern:

We reported a case of 30-year-old female who presented with progressive pallor, amenorrhea, and unexplained weight loss with generalized body weakness. Her body mass index was 20. The patient was having no other systemic manifestations.

Diagnosis:

This paper reports a case of a female patient having CD without its typical features. Her laboratory evaluation revealed microcytic anemia. Anti-TTg IgA and Anti-TTG IgG antibodies were raised, ferritin and folate were low, and there was mild hyperbilirubinemia. However, follicle-stimulating hormone, luteinizing hormone, and serum estradiol levels were normal. She was diagnosed with a case of anemia resulting from malabsorption caused by CD.

Interventions:

A management plan was devised based on a strict gluten-free diet. The patient received supplements containing folates, iron, calcium, zinc, and vitamins A, D, E, B6, and B12.

Outcomes:

After 3 months of treatment with strict gluten-free diet patient showed remarkable improvement. Her hemoglobin level raised with weight gain. Her normal menstrual cycle was restored with complete resolution of symptoms at 1 year follow-up.

Lessons:

The pathogenesis of the atypical CD is multifactorial, but impaired uptake of micronutrients from the duodenum is the most likely cause, even if other common features of classical forms, such as bloating and diarrhea, are absent. Lack of awareness about atypical forms may lead to under-diagnoses of the disease. The physicians should consider the atypical presentations of CD to avoid the under-diagnoses of this multisystem disorder.
Rare magnetic resonance imaging findings of intracranial solitary fibrous tumor: A case report
Authors: Huang Zhicheng , Dai Dongqin , Tang Guangcai
Published: October 2022

Rationale:

Solitary fibrous tumor (SFT) is a rare mesenchymal spindle cell tumor. SFT in the central nervous system (CNS) is rare. This case reports rare magnetic resonance imaging (MRI) findings of intracranial SFT (ISFT).

Patient concerns:

We report a 47-year-old female patient who was found to have weakness in her right limb with walking instability 2 months before the visit.

Diagnoses:

Based on imaging, the provisional diagnosis was meningioma. Postsurgical histopathological diagnosis confirmed World Health Organization (WHO) grade I SFT/hemangiopericytoma (HPC).

Interventions:

The lesion was totally excised. The patient improved remarkably after the operation, without any signs of associated limb movement disorder.

Outcomes:

No local recurrence or metastases were observed in the follow-up 3 months after the surgery.

Lessons:

Intracranial SFT is a rare mesenchymal tumor. Due to different tumor components, imaging manifestations are diverse and lack of characteristics, so preoperative diagnosis is challenging. Our case provides a rare ISFT with significantly decreased signal intensity in T2 weighted images (T2WI), which is an important supplement to the rare imaging findings of intracranial SFT.
Clinical Application of a Modified Local Transposition Flap (Parallelogram Flap) Surgery in Repairing Fingertip Defects
Authors: Zhang Yingkai , Wang Yao , Zhou Jiaqi , He Xianwei , Wu Rongbo
Published: October 2022

Objective

Parallelogram flap was performed for transverse finger amputation with the loss of distal pulp, nails, and bone. This study aimed to compare the clinical effects of parallelogram flap, antegrade homodigital island flaps, and reverse digital artery island flaps in fingertip reconstruction.

Patients and Methods

From January 2017 to January 2021, clinical patient data with parallelogram flaps (78 cases), antegrade homodigital island flaps (78 cases), and reverse digital artery island flaps (78 cases) to repair fingertip defects were collected and analyzed. Two hundred thirty-four cases (234 fingers) were included in our study. All operations were performed by one surgical team. The operation time, 2-point discrimination, total active movement, and the Michigan Hand Questionnaire (MHQ) of the injured fingers were recorded to evaluate the therapeutic effect.

Results

Parallelogram flaps (group A), antegrade homodigital island flaps (group B), and reverse digital artery island flaps (group C) had survived postoperatively. The operative duration of group A is the shortest (A < B < C, P < 0.05). At the last 6-month follow-up, there was no difference with the 2-point discrimination of the palmar part of the flaps in group A and group B but better than group C (P < 0.05). There was no difference with the total active movement of injured figures in 3 groups (P > 0.05). The MHQ summary scores in group A were much higher than those in group B and group C (P < 0.05). Evaluation of the MHQ subscale performance showed that the overall hand function, activities of daily living, work performance, and pain score had no differences (P > 0.05), but aesthetics and satisfaction score was the highest in group A (A > B > C, P < 0.05).

Conclusions

The reconstruction of transverse finger amputation using parallelogram flaps can achieve a shorter operation time, a more satisfying appearance. Parallelogram flaps and antegrade homodigital island flaps can both achieve a better sensory recovery. Parallelogram flaps is a better choice for reconstruction of transverse finger amputation with the loss of distal pulp, nails, and bone.
Closed-Incision Negative Pressure Therapy Prevents Major Abdominal Donor-Site Complications in Autologous Breast Reconstruction
Authors: Limpiado MarcArthur , Guest Rachel , Egan Katie G. , Elver Ashlie A. , Johnson Braden M. , Cullom Melissa E. , Nazir Niaman , Holding Julie , Lai Eric C. , Butterworth James A.
Published: October 2022

Background

Outcomes in autologous breast reconstruction continue to improve with refinements in microsurgical techniques; however, donor-site morbidity remains a concern. Closed-incision negative pressure therapy (ciNPT) has been shown to reduce wound complications. Limited evaluation in abdominal donor sites has shown promising results. We hypothesize that ciNPT will reduce abdominal donor-site complications.

Methods

A retrospective chart review was performed of patients who underwent abdominally based autologous free tissue transfer for breast reconstruction by 4 microsurgeons at an academic institution from 2015 to 2020. The application of a commercial ciNPT for donor-site management was at the discretion of the operating surgeon. Demographics, operative details, and management of donor-site complications were analyzed.

Results

Four hundred thirty-three patients underwent autologous breast reconstruction; 212 abdominal donor sites were managed with ciNPT and 219 with standard dressings. Demographics were statistically similar between groups. Abdominal wound healing complications were noted in 30.2% of ciNPT patients (64/212) and 22.8% of control patients (50/219, P = 0.08); however, overall wound complications were attributed to obesity on multivariable analysis. Closed-incision negative pressure therapy significantly decreased complications requiring reoperation (ciNPT 6.2%, 4/64; control 26.5%, 13/51; P = 0.004). There were no significant differences in surgical site infection rates (P = 0.73) and rates of abdominal scar revisions (ciNPT 11.8%, 25/212; control 9.1%, 20/219; P = 0.37).

Conclusions

Use of ciNPT in abdominal donor-site management significantly decreases the incidence of delayed wound healing requiring surgical intervention, with one major wound healing complication prevented for every 6 donor sites managed with ciNPT.
Using a Business Model (the 4 Disciplines of Execution) to Improve Consistency, Efficiency, and Length of Stay in Microvascular Autologous Breast Reconstruction
Authors: Easton Joseph , Roberto Amy , Lax Elizabeth , Reyna Chantal , Dale Elizabeth
Published: October 2022

Background

Autologous free tissue transfer is a common method of breast reconstruction in the United States, but it involves many care teams and can incur a large cost on an institution. The consistency and efficiency of performing these procedures can be improved with a method called the 4 disciplines of execution (4DX).

Methods

Patients that underwent autologous breast reconstruction between 2015 and 2020 were included. Midway through the collection period, several preoperative and intraoperative interventions were implemented using the 4DX. Then, 2 cohorts of patients were analyzed for differences in operative times, length of stay (LOS), and major complications.

Results

Thirty-two total patients were included. The median operative time before interventions were implemented was 828 minutes, and the median operative time after interventions was 619 minutes (P < 0.05). The median LOS in days before interventions was 5 days, and the median LOS after interventions was 3 days (P < 0.05). There were no statistically significant differences in complications before or after the interventions.

Conclusions

The 4DX successfully improved consistency and efficiency in the process of performing autologous breast reconstruction at our institution, as evidenced by a faster median operative time and shorter patient LOS in the hospital.
An Electrical Storm Is Coming!
Authors: Sweeney Michael , Eldrich Samuel
Published: October 2022

A 65-year-old man presented to the emergency department (ED) for evaluation of epigastric and chest pain. On presentation, a 12-lead electrocardiogram revealed a patient in rapid atrial fibrillation (AFib) with anteroseptal myocardial infarction. Treatment of ST-elevation myocardial infarction (STEMI) and rapid AFib were initiated, and the patient was flown to a regional percutaneous coronary intervention center. Two weeks later, the patient presented to the same ED with a LifeVest external defibrillator (Zoll Medical, Chelmsford, MA). The patient received electrical shock in excess of 10 times from the LifeVest prior to ED arrival where he promptly developed ventricular tachycardia (VT). After cardioversion, the VT storm persisted and required multiple cardioversions, resuscitation, intubation, and transfer back to a tertiary cardiac center for electrophysiology studies and internal cardiac defibrillator placement. This case explores the course of a patient's anteroseptal infarction, utilization and description of the LifeVest external defibrillator, and the subsequent visit to the ED in VT storm. It provides insight into the team approach, decision-making process, and managing a complex medical illness. Furthermore, it helps identify methods for emergency providers to improve their approach in both complex and rare cases.
“Endless Vicious Circle ...” Psychosocial Difficulties and Needs of Nurses Working in the Emergency Department During the COVID-19 Pandemic
Authors: Partlak Günüşen Neslihan , Şengün İnan Figen , Serçe Yüksel Özgü , Batıhan Gamze
Published: October 2022

Emergency nurses are one of the groups at risk most during the COVID-19 pandemic. The purpose of the authors of this qualitative study was to reveal the psychosocial difficulties and needs of nurses working in the emergency department of a university hospital during the COVID-19 pandemic. This descriptive phenomenological study was conducted in the emergency department of a university hospital in the West of Turkey. In-depth interviews were conducted with 14 emergency nurses. Colaizzi's descriptive analysis method was used. Findings regarding the psychological difficulties and needs of nurses during the COVID-19 pandemic were collected under the following 4 themes: being a nurse in the emergency department in the pandemic, emotional chaos, living with losses, and the support needs. Not only did the emergency nurses state that working as a nurse in the pandemic was challenging and exhausting but they also emphasized the vital importance of nursing care in the pandemic. During the pandemic, the nurses went through different emotional processes according to the stages of the pandemic. Although they needed psychological support, they were expected to meet organizational requirements.
Emergency Department Use of the HINTS Exam
Authors: Engler Kristiana , Wood John , Cook Calli
Published: October 2022

The Research to Practice column is designed to improve translational research critique skills of advanced practice nurses (APNs). In this issue, the article “Diagnostic Accuracy of the HINTS Exam in an Emergency Department: A Retrospective Chart Review” is discussed in the context of a patient presenting to the emergency department (ED) with acute dizziness. The study was designed to assess the efficacy and appropriate use of the HINTS exam in the ED. Assessing and evaluating dizziness is complex, and with the growing cost associated with the ED assessment of dizziness, appropriate use of the HINTS exam could reduce cost. APNs need to be aware of the appropriateness of use when administering the HINTS exam and how to interpret the findings from the assessment. Improved awareness and education regarding the HINTS exam could streamline the workup of vertigo and dizziness in the ED.
Sitagliptin Versus Placebo to Reduce the Incidence and Severity of Posttransplant Diabetes Mellitus After Kidney Transplantation—A Single-center, Randomized, Double-blind Controlled Trial
Authors: Delos Santos Rowena B. , Hagopian Jennifer C. , Chen Ling , Ramakrishnan Madhuri , Wijeweera Helen , Klein Christina L. , Brennan Daniel C.
Published: October 2022

Background.

Postkidney transplant diabetes mellitus (PTDM) affects cardiovascular, allograft, and recipient health. We tested whether early intervention with sitagliptin for hyperglycemia (blood glucose >200 mg/dL) within the first week of transplant and discontinued at 3 mo could prevent development of PTDM in patients without preexisting diabetes.

Methods.

The primary efficacy objective was to improve 2-h oral glucose tolerance test (OGTT) by >20 mg/dL at 3 mo posttransplant. The secondary efficacy objective was to prevent new onset PTDM, defined as a normal OGTT at 3 mo.

Results.

Sixty-one patients consented, and 50 patients were analyzed. The 3-mo 2-h OGTT (end of treatment) was 141.00 ± 62.44 mg/dL in the sitagliptin arm and 165.22 ± 72.03 mg/dL (P = 0.218) in the placebo arm. The 6-mo 2-h OGTT (end of follow-up) was 174.38 ± 77.93 mg/dL in the sitagliptin arm and 171.86 ± 83.69 ng/dL (P = 0.918) in the placebo arm. Mean intrapatient difference between 3- and 6-mo 2-h OGTT in the 3-mo period off study drug was 27.56 + 52.74 mg/dL in the sitagliptin arm and −0.14 + 45.80 mg/dL in the placebo arm (P = 0.0692). At 3 mo, 61.54% of sitagliptin and 43.48% of placebo patients had a normal 2-h OGTT (P = 0.2062), with the absolute risk reduction 18.06%. There were no differences in HbA1c at 3 or 6 mo between sitagliptin and placebo groups. Participants tolerated sitagliptin well.

Conclusions.

Although this study did not show a significant difference between groups, it can inform future studies in the use of sitagliptin in the very early posttransplant period.
Genomic and phylogenomic insights into the family Streptomycetaceae lead to the proposal of six novel genera
Authors: Madhaiyan Munusamy , Saravanan Venkatakrishnan Sivaraj , See-Too Wah-Seng , Volpiano Camila Gazolla , Sant’Anna Fernando Hayashi , Faria da Mota Fábio , Sutcliffe Iain , Sangal Vartul , Passaglia Luciane Maria Pereira , Rosado Alexandre Soares
Published: October 2022

The family

Streptomycetaceae

is a large and diverse family within the phylum

Actinomycetota

. The members of the family are known for their ability to produce medically important secondary metabolites, notably antibiotics. In this study, 19 type strains showing low 16S rRNA gene similarity (<97.3 %) to other members of the family

Streptomycetaceae

were identified and their high genetic diversity was reflected in a phylogenomic analysis using conserved universal proteins. This analysis resulted in the identification of six distinct genus-level clades, with two separated from the genus

Streptacidiphilus

and four separated from the genus

Streptomyces

. Compared with members of the genera

Streptacidiphilus

and

Streptomyces

, average amino acid identity (AAI) analysis of the novel genera identified gave values within the range of 63.9–71.3 %, as has been previously observed for comparisons of related but distinct bacterial genera. The whole-genome phylogeny was reconstructed using PhyloPhlAn 3.0 based on an optimized subset of conserved universal proteins, the results of AAI and percentage of conserved proteins (POCP) analyses indicated that these phylogenetically distinct taxa may be assigned to six novel genera, namely Actinacidiphila gen. nov., Mangrovactinospora gen. nov., Peterkaempfera gen. nov., Phaeacidiphilus gen. nov., Streptantibioticus gen. nov. and Wenjunlia gen. nov.
Phylogeny and Genetic Diversity of Philippine Native Pigs (Sus scrofa) as Revealed by Mitochondrial DNA Analysis
Authors: Banayo Joy B. , Manese Kathlyn Louise V. , Salces Agapita J. , Yamagata Takahiro
Published: October 2022

Philippine native pigs (PhNP) are small black pigs domesticated in rural communities in the Philippines. They are valued locally for their various sociocultural roles. Recently, considerable literature has accumulated in the field of native pig production and marketing. However, there is limited research on the genetic diversity of PhNP. No previous study has investigated the evolutionary relatedness among native pigs from various islands and provinces in Luzon and Visayas, Philippines. In addition, a much-debated question is whether the PhNP were interbreeding with or even domesticated from endemic wild pigs. This study aims to clarify some of the uncertainties surrounding the identity and classification of PhNP based on mitochondrial DNA (mtDNA) signatures. Native pig samples (n=157) were collected from 10 provinces in Luzon and the Visayas, Philippines. Approximately 650 base pairs of the mtDNA d-loop control region were sequenced and analyzed together with publicly available sequences. Pairwise-distance analysis showed genetic separation of North and South Luzon (SL) and the clustering of SL with Visayan pigs. Phylogenetic analysis showed that the PhNP clustered within 3 recognized Asian pig domestication centers: D2 (East Asia), D7 (Southeast Asia) and the Cordillera clade (sister to the Lanyu). We identified 19 haplotypes (1-38 samples each), forming 4 haplogroups i.e. North Luzon, South Luzon and Visayas, Asian mix and the Cordillera cluster. No endemic wild pig mtDNA was detected in the native pig population, but the use of wild pig for interspecific hybridization was observed. This study showed that the Philippine native pigs have ancestral origin from at least 3Sus scrofalineage and that they were not domesticated from the endemic wild pigs of the Philippines.
Dashing 2: genomic sketching with multiplicities and locality-sensitive hashing
Authors: Baker Daniel N. , Langmead Ben
Published: October 2022

A genomic sketch is a small, probabilistic representation of the set of k-mers in a sequencing dataset. Sketches are building blocks for large-scale analyses that consider similarities between many pairs of sequences or sequence collections. While existing tools can easily compare 10,000s of genomes, relevant datasets can reach millions of sequences and beyond. Popular tools also fail to considerk-mer multiplicities, making them less applicable in quantitative settings. We describe a method called Dashing 2 that builds on the SetSketch data structure. SetSketch is related to HyperLogLog, but discards use of leading zero count in favor of a truncated logarithm of adjustable base. Unlike HLL, SetSketch can perform multiplicity-aware sketching when combined with the ProbMinHash method. Dashing 2 integrates locality-sensitive hashing to scale all-pairs comparisons to millions of sequences. Dashing 2 is free, open source software available athttps://github.com/dnbaker/dashing2
Comparative Analysis of RNA Secondary Structure Accuracy on Predicted RNA 3D Models
Authors: Kulkarni Mandar , Thangappan Jayaraman , Deb Indrajit , Wu Sangwook
Published: October 2022

RNA structure is conformationally dynamic, and accurate all-atom tertiary (3D) structure modeling of RNA remains challenging with the prevailing tools. Secondary structure (2D) information is the standard prerequisite for most RNA 3D modeling. Despite several 2D and 3D structure prediction tools proposed in recent years, one of the challenges is to choose the best combination for accurate RNA 3D structure prediction. Here, we benchmarked seven small RNA PDB structures (40 to 90 nucleotides) with different topologies to understand the effects of different 2D structure predictions on the accuracy of 3D modeling. The current study explores the blind challenge of 2D to 3D conversions and highlights the performances ofde novoRNA 3D modeling from their predicted 2D structure constraints. Our results show that conformational sampling-based methods such as SimRNA and IsRNA1 depend less on 2D accuracy, whereas motif-based methods account for 2D evidence. Our observations illustrate the disparities in available 3D and 2D prediction methods and may further offer insights into developing topology-specific or family-specific RNA structure prediction pipelines.
A Machine-learning-based Method to Detect Degradation of Motor Control Stability with Applications to Diagnosis of Presymptomatic Parkinson’s Disease
Authors: Shah Vrutangkumar V. , Jadav Shail , Goyal Sachin , Palanthandalam-Madapusi Harish J.
Published: October 2022

Parkinson’s disease (PD), a neuro-degenerative disorder, is often detected by onset of its motor symptoms such as rest tremor. Unfortunately, motor symptoms appear only when approximately 40%-60% of the dopaminergic neurons in the substantia nigra are lost. In most cases, by the time PD is clinically diagnosed, the disease may already have started 4 to 6 years beforehand. So there is a need for developing a test for detecting PDbeforethe onset of the motor symptoms. This phase of PD is referred to as Presymptomatic PD (PPD). The motor symptoms of Parkinsons Disease are manifestations of instability in the sensorimotor system that develops gradually due to the neuro-degenerative process. In this paper, based on the above insight, we propose a new method that can potentially be used to detect degradation of motor control stability which can be employed for the detection of PPD. The proposed method tracks the tendency of a feedback control system to transition to an unstable state, and uses machine learning algorithm for its robust detection. This method is explored using simulations of a simple pendulum with PID controller as a conceptual representation for both healthy and PPD individuals. We also propose an example task with physiological measurements that can be used with this method and potentially be employed in a clinical setting. We present representative data collected through such a task, thereby demonstrating the feasibility to generate data for the proposed method.

Author summary

Parkinson’s disease (PD) is a neuro-degenerative disorder that develops and progresses over several years. Currently, one is able to diagnose PD only after the appearance of motor symptoms (symptoms in movements of body parts), which unfortunately may be 4 to 6 years after the neuro-degeneration may have started. It has been shown that there are benefits to diagnosing PD at early stages, motivating the need to explore tools for diagnosing PD in the pre-symptomatic stage referred to as Presymptomatic Parkinson’s disease (PPD). In this paper, a novel approach is explored that utilises the insight that the motor symptoms in PD may be seen as an instability in the feedback-control system that controls movements of body parts (sensory-motor loop). The proposed method uses a series of simple movement tasks performed by an individual in a clinic as the input to detect any gradual degradation of movement control that is leading to an instability, but before the instability and consequently the symptoms are manifested. This method is tested through extensive simulations and a potential experimental realisation with preliminary data. While a full-fledged validation will be undertaken as part of future work, initial results show promise and feasibility of further data collection.
MRI: an algorithm to identify metabolic reprogramming during adaptive laboratory evolution using gene expression data
Authors: Yazdanpanah Shaghayegh , Motamedian Ehsan , Shojaosadati Seyed Abbas
Published: October 2022

The development of a method for identifying latent reprogramming in gene expression data resulting from evolution has been a challenge. In this study, a method called Metabolic Reprogramming Identifier (MRI), based on the integration of expression data to a genome-scale metabolic model, has been developed. To identify key genes playing the main role in reprogramming, a MILP problem is presented and maximum utilization of gene expression resources is defined as an objective function. Then, genes with complete expression usage and significant expression difference between wild-type and evolved strains were selected as key genes for reprogramming. This score is also applied to evaluate compatibility of expression pattern with maximal use of key genes. The method was implemented to investigate the reprogramming ofE. coliduring adaptive evolution caused by changing carbon sources. The results indicate the importance of inner membrane in reprogramming ofE. colito adapt to the new environment. The method predicts no reprogramming occurs when switching from glucose to glycerol.
Beyond consensus sequence: a quantitative scheme for inferring transmission using deep sequencing in a bacterial transmission model
Authors: Senghore Madikay , Read Hannah , Oza Priyali , Johnson Sarah , Passarelli-Araujo Hemanoel , Taylor Bradford P , Ashley Stephen , Grey Alex , Callendrello Alanna , Lee Robyn , Goddard Matthew R , Lumley Thomas , Hanage William P , Wiles Siouxsie
Published: October 2022

Genomic surveillance provides a data source complementary to contact tracing to resolve putative transmission chains. However, the role of within-host diversity in transmission is understudied due to a lack of experimental and clinical datasets that capture within-host diversity in both donors and recipients. Here, we assess the utility of deep-sequenced genomic surveillance within a mouse transmission model where the gastrointestinal pathogenCitrobacter rodentiumwas controllably spread during co-housing of infected and naïve animals. We observed that within-host variants were maintained over multiple transmission steps until fixation or elimination. We present a model for inferring the likelihood that a given pair of samples are linked by transmission, by comparing the allelic frequency at variant genomicloci. Our data affirm that within-host single nucleotide variants (iSNVs) can repeatedly pass from donor to recipient along the transmission chain, and the mere sharing of iSNVs between different transmission pairs offers limited confidence in identifying a transmission pair. Beyond the presence and absence of within-host variants, we show that differences arising in the relative abundance of iSNVs can infer transmission pairs with high precision. An important component of our approach is that the inference is based solely on sequence data, without incorporating epidemiological or demographic data for context. Our model, which substantially reduces the number of comparisons a contact tracer needs to consider, may enhance the accuracy of contact tracing and other epidemiological processes, including early detection of emerging transmission clusters.
VACS: VAccination disComfort Scale
Authors: Wallace Manolis , Antonopoulos Stavros , Poulopoulos Vassilis
Published: October 2022

In this article we focus on the discomfort experienced by children during vaccination and ask ourselves how this discomfort could be quantified. We develop VACS, a tool to measure this discomfort as a number in the range 0-25 and apply it to 40 vaccinations of children aged 2 to 12. Our findings show that approximately 40% of the children do not face discomfort during vaccination, but for the rest discomfort of varying degrees is observed. We also find that doctors are content with their patients facing considerably higher discomfort levels that what the children themselves are willing to withstand. Surprisingly, characteristics such as a) gender, b) whether the state’s recommended vaccination program has been implemented in full and even c) prior negative vaccination experiences are found to be poor predictors of vaccination discomfort. Age may be a factor, with younger children experiencing discomfort more often and more intensely, but more research is required in order to validate this. The formulation of VACS opens the door for more systematic work towards the minimization of vaccination discomfort for children.
Alternative splicing in the lung influences COVID-19 severity and respiratory diseases
Authors: Nakanishi Tomoko , Farjoun Yossi , Willett Julian , Allen Richard J. , Guillen-Guio Beatriz , Zhou Sirui , Richards J. Brent
Published: October 2022

Hospital admission for COVID-19 remains common despite the successful development of vaccines and treatments. Thus, there is an ongoing need to identify targets for new COVID-19 therapies. Alternative splicing is an essential mechanism for generating functional diversity in protein isoforms and influences immune response to infection. However, the causal role of alternative splicing in COVID-19 severity and its potential therapeutic relevance is not fully understood. In this study, we evaluated the causal role of alternative splicing in COVID-19 severity and susceptibility using Mendelian randomization (MR). To do so, we performed two-sample MR to assess whethercis-sQTLs spanning 8,172 gene splicing in 5,295 genes were associated with COVID-19 outcomes in the COVID-19 Host Genetics Initiative, including up to 158,840 COVID-19 cases and 2,782,977 population controls. We identified that alternative splicing in lungs, rather than total RNA expression ofOAS1, ATP11A, DPP9andNPNT, was associated with COVID-19 severity.MUC1splicing was associated with COVID-19 susceptibility. Further colocalization analyses supported a shared genetic mechanism between COVID-19 severity with idiopathic pulmonary fibrosis atATP11AandDPP9loci, and with chronic obstructive lung diseases atNPNT. We lastly showed thatATP11A, DPP9, NPNT, andMUC1were highly expressed in lung alveolar epithelial cells, both in COVID-19 uninfected and infected samples. Taken together, these findings clarify the importance of alternative splicing of proteins in the lung for COVID-19 and other respiratory diseases, providing isoform-based targets for drug discovery.
Prefrontal hemodynamics during forward and backward walking, with and without a cognitive task, in people with MS: An fNIRS study
Authors: Kupchenko Yana , Dreyer-Alster Sapir , Broscheid Kim-Charline , Kalron Alon
Published: October 2022

Objective

To investigate the prefrontal cortex (PFC) hemodynamics during forward and as well as backward walking, with and without a cognitive task, in people with MS (pwMS) and healthy controls.

Methods

The observational functional near-infrared spectroscopy (fNIRS) study comprised 18 pwMS and 17 healthy controls. Each subject completed four walking trials: Single task (ST) forward walking, dual task (DT) forward walking, ST backward walking, DT backward walking. PFC activity for all trials was recorded using functional near-infrared spectroscopy (fNIRS). The PFC was subdivided in the frontal eye field (FEF), frontopolar cortex (FPC) and the dorsolateral PFC (DLPFC).

Results

The relative oxygenated hemoglobin (HbO) concentration was higher during the DT forward walking in all PFC subareas compared with the ST forward walking for both groups. The relative HbO concentration was higher during ST backward walking compared with ST forward walking in pwMS (DLPFC, FEF) and the healthy controls (FEF, FPC), specifically during the initial part of the trial. There was no distinct difference in the relative HbO concentration between ST backward walking with DT backward walking in pwMS. In contrast, the relative HbO concentration in the FEF and the FPC increased in healthy controls during DT backward walking compared with ST backward walking, specifically during the second half of the trial.

Conclusions

ST backward walking and DT forward walking impact the hemodynamics at the PFC, although, the difference between pwMS and healthy adults requires further clarification. Future RCT’s are encouraged to examine the impact of an intervention program based on DT forward and backward walking on PFC activity in pwMS.

Impact

The present study demonstrated that backward walking increases activity in the PFC region. Similarly, when performing a cognitive task while walking forward. This information should be considered by PT’s for training, particularly pwMS.
ALCOHOLIC LIVER BIOMARKERS: DETERMINANTS FOR ADMISSION TO REHABILITATION CENTRES DURING THE COVID 19 PERIOD IN KENYA
Authors: Njoroge George , Mwenda Catherine , Mecha Ezekiel , Waithaka Stanley
Published: October 2022

Consumption of alcohol is a practice world over that dates back to 10,000 Before Christ. Evaluation on the damages caused by the alcohol on the human organs such as the liver is paramount. There is no direct evaluation to liver parenchyma before admission rather blood samples are evaluated to show damage or no damage to the liver cells. The outcome of the blood samples denote the health status of the liver cells before admission. Alcohol biomarkers are usually elevated when there is damage to the liver parenchyma. This was a quantitative descriptive cross sectional study. Purpose sampling was used to select two Counties with the highest number of alcohol consumers. Simple Random sampling method was used to select participants for liver biomarkers. Participants were requested to consent for blood donation and confidentiality was maintained. Blood samples collected were separated for serum and cells using centrifuge within one hour after donation. The samples were transported for storage using cool boxes and temperature was maintained between −8 and +8 degrees during transportation. The blood samples were stored at −8 and +8 degrees in the deep freezer. Majority (97%) of the participants had alanine aminotransferase levels of 41 to 80 IU/L. Eighty eight percent of the participants had aspartate aminotransferase elevated to between 35 and 68 IU/L. Gamma Glutamyl aminotransferase was elevated in all of the participants while alanine phosphatase was elevated in 99% of the participants. Most participants had elevated liver biomarkers before admission to rehabilitation centre.
The effect of environmental information on evolution of cooperation in stochastic games
Authors: Kleshnina Maria , Hilbe Christian , Šimsa Štěpán , Chatterjee Krishnendu , Nowak Martin A.
Published: October 2022

Many human interactions feature the characteristics of social dilemmas where individual actions can have consequences for the group and the environment. The feedback between behavior and environment can be studied with the framework of stochastic games. In stochastic games, the state of the environment can change, depending on the choices made by group members. Past work suggests that such feedback can reinforce cooperative behaviors. In particular, cooperation can evolve in stochastic games even if it is infeasible in each separate repeated game. In stochastic games, participants have an interest in conditioning their strategies on the state of the environment. Yet in many applications, precise information about the state could be scarce. Here, we study how the availability of information (or lack thereof) shapes evolution of cooperation. Already for simple examples of two state games we find surprising effects. In some cases, cooperation is only possible if there is precise information about the state of the environment. In other cases, cooperation is only possible if there is no information about the state of the environment. We systematically analyze all stochastic games of a given complexity class, to determine when receiving information about the environment is better, neutral, or worse for evolution of cooperation.
Extreme mito-nuclear discordance within Anthozoa, with notes on unique properties of their mitochondrial genomes
Authors: Quattrini Andrea M. , Snyder Karen , Purow-Ruderman Risa , Seiblitz Isabela G.L. , Hoang Johnson , Floerke Natasha , Ramos Nina I. , Wirshing Herman H. , Rodriguez Estefanía , McFadden Catherine S.
Published: October 2022

Whole mitochondrial genomes are often used in phylogenetic reconstruction. However, discordant patterns in species relationships between mitochondrial and nuclear phylogenies are commonly observed. Within Anthozoa (Phylum Cnidaria), mitochondrial-nuclear discordance has not yet been examined using a large and comparable dataset. Here, we used data obtained from target-capture enrichment sequencing to assemble and annotate mitochondrial genomes and reconstruct phylogenies for comparisons to phylogenies inferred from 100s of nuclear loci obtained from the same samples. The datasets comprised 108 hexacorals and 94 octocorals representing all orders and >50% of extant families. Results indicated rampant discordance between datasets at every taxonomic level. This discordance is not attributable to substitution saturation, but rather likely caused by recent and ancient introgressive hybridization and selection. We also found strong purifying selection across the mitochondrial genomes, cautioning their use in analyses that rely on assumptions of neutrality. Furthermore, unique properties of the mitochondrial genomes were noted, including genome rearrangements and the presence ofnad5introns. Specifically, we note the presence of the homing endonuclease in ceriantharians. This large dataset of mitochondrial genomes further demonstrates the utility of off-target reads generated from target-capture data for mitochondrial genome assembly and adds to the growing knowledge of anthozoan evolution.
Intra-host viral populations of SARS-CoV-2 in immunosuppressed patients with hematologic cancers
Authors: Fournelle Dominique , Mostefai Fatima , Brunet-Ratnasingham Elsa , Poujol Raphael , Grenier Jean-Christophe , Gálvez José Héctor , Pagliuzza Amélie , Levade Inès , Moreira Sandrine , Lapierre Simon Grandjean , Chomont Nicolas , Kaufmann Daniel E. , Craig Morgan , Hussin Julie G.
Published: October 2022

Throughout the SARS-CoV-2 pandemic, several variants of concern (VOC) have been identified, many of which share recurrent mutations in the spike protein’s receptor binding domain (RBD). This region coincides with known epitopes and can therefore have an impact on immune escape. Protracted infections in immunosuppressed patients have been hypothesized to lead to an enrichment of such mutations and therefore drive evolution towards VOCs. Here, we show that immunosuppressed patients with hematologic cancers develop distinct populations with immune escape mutations throughout the course of their infection. Notably, by investigating the co-occurrence of substitutions on individual sequencing reads in the RBD, we found quasispecies harboring mutations that confer resistance to known monoclonal antibodies (mAbs) such as S:E484K and S:E484A. Furthermore, we provide the first evidence for a viral reservoir based on intra-host phylogenetics. Our results on viral reservoirs can shed light on protracted infections interspersed with periods where the virus is undetectable as well as an alternative explanation for some long-COVID cases. Our findings also highlight that protracted infections should be treated with combination therapies rather than by a single mAbs to clear pre-existing resistant mutations.