bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of core muscle strengthening exercise and stretching exercise in middle-aged women with fibromyalgia
Authors: Park Hyeng-Kyu , Song Min-Keun , Kim Dong-Joo , Choi In-Sung , Han Jae-Young
Published: December 2021

Background:

Many studies have reported that exercise is effective for fibromyalgia and various types of exercise are recommended. However, most of exercises lack evidence for fibromyalgia symptoms. We aimed to examine the effect of core muscle strengthening exercise compared to general stretching exercise in fibromyalgia patients.

Methods:

Forty fibromyalgia patients were enrolled. They were provided exercise program twice a week for 4 weeks: core muscle strengthening exercise and general stretching exercise.

Outcome measures were Visual Analogue Scale, Borg Scale, fibromyalgia impact questionnaire (FIQ), widespread pain index, Symptom Severity Scale (SS), and balance scale and measured before and after exercise program. Balance function was assessed by checking the distance of sway on soft pad with eyes open (EO) and with eyes closed (EC).

Results:

After program, FIQ, SS, EO, and eyes closed showed statistically significant differences in the strengthening group while Visual Analogue Scale, Borg scale, FIQ, widespread pain index, SS showed statistically significant differences in stretching group. And EO showed statistically significant differences in the intergroup analysis.

Conclusions:

Both exercise could improve symptoms of fibromyalgia but showed no significantly better efficiency with intergroup analysis. Only some balance function was improved with core muscle strengthening exercise with significant difference. Our study presents preliminary results regarding the comparison between both exercises for fibromyalgia through a randomized controlled trial.
Effectiveness of rehabilitation on pain and function in people affected by hemophilia
Authors: Scaturro Dalila , Benedetti Maria Grazia , Lomonaco Giulia , Tomasello Sofia , Farella Maria Grazia Giuseppina , Passantino Giuseppina , Frizziero Antonio , Letizia Mauro Giulia
Published: December 2021

Introduction:

Literature provides unclear evidence of the effectiveness of many physiotherapy interventions on pain intensity, quality of life, and functional ability in hemophilic patients, and suggests that rehabilitation programs should be focused on functional goals and the disability of patients.

Aim:

The aim of the present study is to present the outcome of a case series of patients with hemophilia in which a rehabilitation program has been carried out on the basis of a specific individual patient's functional impairment.

Methods:

Fifty-one patients were enrolled: 32 patients (Rehab Group) received a rehabilitative treatment, 19 patients for different reasons (living far from the hospital, family problems) did not receive rehabilitation (Control Group). The rehabilitation program was planned with respect to the emergent problems: musculoskeletal pain, joint range of motion limitation, muscle flexibility, walking difficulties, the appearance of hematomas/hemartro, and postural problems. All the patients were assessed at baseline (T0), after 1 month (T1), and after 3 months (T2) through visual analogic scale for musculoskeletal pain, the Hemophilia Joint Health Score for joint range of motion, the Functional Independence Score in Hemophilia for disability, and postural assessment by visual inspection.

Results:

A significant reduction of pain and improvement of Hemophilia Joint Health Score and Functional Independence Score in Hemophilia score was found in the Rehab Group along with the follow-up. Pain in the Control Group was lower with respect to the other group at baseline and significantly decreased after 1 month.

Conclusion:

A rehabilitation program focused on individual impairment of patients with hemophylia determined satisfying results in terms of pain control, functional, and disability improvement in 3 months follow-up.
Factors affecting healing following percutaneous intramedullary fixation of metacarpal fractures
Authors: Kim Chul-Ho , Kim Dong Hwan , Kang Han-Vit , Kim Won Jun , Shin Minkyu , Kim Ji Wan
Published: December 2021

Although percutaneous intramedullary nailing of metacarpal fractures is a straightforward and reliable technique, it is not without complications, and patients experience different outcomes. This study analyzed factors affecting fracture healing time and complication rates in patients who underwent percutaneous intramedullary fixation of metacarpal fractures.

This study was a retrospective review of the 25 patients who underwent retrograde percutaneous Kirschner wire (K-wire) nailing for fracture of the metacarpal shaft or neck at a military hospital between May 2016 and October 2018. Correlation study and multiple regression analysis were performed to evaluate variables (age, smoking history in pack-years, body-mass index, fracture site, number of K-wires used) that affect time to bone union. Clinical features of patients with metacarpal neck fractures and those with metacarpal shaft fractures were also compared.

The metacarpal shaft fractures (as opposed to metacarpal neck fractures) and higher number of K-wire used were associated with longer time to bone union. Mean union time was significantly longer for metacarpal shaft fracture (8.6 weeks) than for metacarpal neck fracture (6.1 weeks) and for patients who received more K-wires than for those who received less (regression coefficient 1.307). One patient suffered fixation failure and required revision operation, and another experienced superficial infection which was treated with intravenous antibiotics.

Percutaneous intramedullary nailing is an effective technique for metacarpal fractures, but fracture site and number of K-wire used affect time to achieve bone union.
Diagnostic utility of CT for abdominal injury in the military setting
Authors: Bai Zhaohui , Wang Bing , Tian Jing , Tong Zhenhua , Lu Hui , Qi Xingshun
Published: December 2021

Background:

It is critical to accurately identify patients with abdominal injury who truly need to undergo laparotomy during the war in timely fashion. The diagnostic utility of computed tomography (CT) for evaluating abdominal injury in the military setting remains uncertain.

Methods:

PubMed, EMBASE, and Cochrane Library databases were searched. Meta-analyses were performed by using a random-effect model. We pooled the area under the summary receiver operating characteristic curves with standard errors, the Q indexes with standard errors, the sensitivities with 95% confidence intervals (CIs), the specificities with 95% CIs, the positive likelihood ratios with 95% CIs, the negative likelihood ratios with 95% CIs, and the diagnostic odds ratios with 95% CIs. The heterogeneity among studies were evaluated by the I
2 and P value.

Results:

Overall, 5 retrospective studies were included. The area under the summary receiver operating characteristic curve was 0.9761 ± 0.0215 and the Q index was 0.9302 ± 0.0378. The pooled sensitivity was 0.97 (95% CI = 0.92–0.99) without a significant heterogeneity among studies (I
2 = 0%, P = .4538). The pooled specificity was 0.95 (95% CI = 0.93–0.97) with a significant heterogeneity among studies (I
2 = 90.6%, P < .0001). The pooled positive likelihood ratio was 10.71 (95% CI: 2.91–39.43) with a significant heterogeneity among studies (I
2 = 89.2%, P < .0001). The pooled negative likelihood ratio was 0.07 (95% CI = 0.02–0.27) with a significant heterogeneity among studies (I
2 = 57.5%, P = .0516). The pooled diagnostic odds ratio was 177.48 (95% CI = 18.09–1741.31) with a significant heterogeneity among studies (I
2 = 75.9%, P = .0023).

Conclusion:

Diagnostic accuracy of CT for abdominal injury is excellent in the military setting. Further work should explore how to shrink CT equipment for a wider use in wartime.
Effect of etiological factors on treatment success of pediatric facial paralysis
Authors: Çirakli Sevgi
Published: December 2021

Facial paralysis is a clinical condition that causes anxiety in the family and is one of the reasons for urgent admission to the hospital. The purpose of this article is to evaluate to reveal the relationship between etiology and treatment results in childhood facial paralysis.

Thirty-three patients who presented with facial paralysis between May 2018 and May 2020, had adequate follow-up were included in the study. Data were reviewed age, gender, side, etiology, features of family, treatment, results, and recurrences.

The ages of the cases ranged from 21 months to 17 years, with the mean age was 13.1 years. Ten of the cases were male (30.3%), 23 of them were female (69.7%). It was observed that 15 (45.4%) of the paralysis were on the right half of the face, 17 (51.5%) were on the left side of the face, and 1 (3.1%) had bilateral involvement. However, it was learned from the story that 3 cases had recurrence. Thirty-two (96.9%) of the cases were peripheral and 1 (3.1%) had central facial paralysis. No cause could be found in the etiology of other peripheral paralysis cases and it was considered as Bell Paralysis. According to the House Brackmann Stage at the time of admission of 30 patients who were given steroid treatment, 10 patients were evaluated as stage 6, 15 patients as stage 5, and 5 patients as stage 4. After 6 months of follow-up, 27 patients were evaluated as stage 1 and 2 patients as stage 2. Recurrence was not observed in any of the patients who recovered.

It was concluded that etiology determines the success of treatment in facial paralysis.
Surgical management of intraoperatively diagnosed portal annular pancreas
Authors: Abe Nobutaka , Lee Sang-Woong , Shimizu Tetsunosuke , Asakuma Mitsuhiro , Taniguchi Kohei , Tomioka Atsushi , Hirokawa Fumitoshi , Uchiyama Kazuhisa
Published: December 2021

Rationale:

Portal annular pancreas (PAP) is a rare pancreatic anomaly characterized by portal vein encasement in the pancreatic parenchyma. Due to its rarity, PAP may often be missed on preoperative computed tomography (CT) review, and surgeons may face challenges in dealing with an unexpected intraoperative encounter with PAP. We documented 2 such intraoperatively diagnosed cases and illustrated their surgical management.

Patients’ concerns:

In case 1, a 70-year-old man was found to have a 15-mm mass in the pancreatic body and dilatation of the peripheral main pancreatic duct on enhanced CT. Case 2 involved a 46-year-old woman with a history of familial adenomatous polyposis, and rectal cancer with a mass in the duodenal papilla.

Diagnoses:

The patient in case 1 was diagnosed with resectable pancreatic cancer. In case 2, the patient was diagnosed with duodenal papillary carcinoma.

Interventions:

In case 1, the patient underwent distal pancreatectomy with lymph node dissection. In case 2, the patient underwent pancreaticoduodenectomy. Intraoperatively, PAP was observed in both cases. In case 1, after the usual transection at the right border of the portal vein, an additional dissection was performed on the dorsal pancreas using a powered linear stapler. In case 2, an additional section was made in the pancreatic body caudal to the cricoid pancreatic junction so that the pancreatic cross-section was oriented in 1 plane.

Outcomes:

The patient in case 1 was discharged without complications. In case 2, although the patient had a grade-B pancreatic fistula (International Study Group of Pancreatic Fistula Classification), the patient recovered conservatively and was discharged without significant complications. In both cases, a retrospective review identified PAP in patients’ preoperative CT images.

Lessons:

Both cases required ingenuity during pancreatectomy. Awareness about PAP and its management will enable surgeons to prepare for unexpected encounters with the condition. Moreover, surgeons (especially pancreatic surgeons) should consider the possibility of PAP while managing pancreatic anomalies to make appropriate treatment decisions.
Exacerbation of branch retinal vein occlusion post SARS-CoV2 vaccination
Authors: Tanaka Hayato , Nagasato Daisuke , Nakakura Shunsuke , Tanabe Hirotaka , Nagasawa Toshihiko , Wakuda Hiroyuki , Imada Yoko , Mitamura Yoshinori , Tabuchi Hitoshi
Published: December 2021

Rationale:

In this paper, we report on 2 patients who developed branch retinal vein occlusion (BRVO) exacerbation 1 day after administration of the BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine.

Patient concerns:

Case 1: A 71 year-old female developed vision loss in her left eye 1 day after receiving a second dose of the SARS-CoV-2 mRNA vaccine. This patient was diagnosed with temporal inferior BRVO and secondary macular edema (ME) in her left eye. ME resolved after 3 doses of intravitreal aflibercept (IVA). After treatment, no recurrence of ME was observed.

Case 2: A 72 year-old man developed vision loss in his right eye 1 day after receiving the first dose of the SARS-CoV-2 mRNA vaccine. This patient was diagnosed with temporal superior BRVO in the right eye without ME. The patient was followed up and did not undergo any additional treatment.

Diagnoses:

Case1: Temporal superior BRVO and secondary ME were observed in the left eye. Her best-corrected visual acuity (BCVA) was 20/30.

Case2: Temporal superior BRVO recurrence and secondary ME were observed in the right eye. BCVA was 20/25.

Interventions:

Case1: Additional dose of IVA was administered. Case2: Two times of Intravitreal ranibizumab was administered twice.

Outcomes:

Case1: Subsequently, ME resolved BCVA was 20/20. Case2: Subsequently, ME resolved BCVA was 20/25.

Lessons:

Both cases showed a possible association between SARS-CoV-2 vaccination and the exacerbation of BRVO.
Association of serum fibroblast growth factor 21 with kidney function in a population-based Chinese cohort
Authors: Zhang Rui , Li Yufeng , Zhou Xianghai , Zhang Fang , Li Meng , Zhang Simin , Zhang Xiuying , Wen Xin , Ji Linong
Published: December 2021

Fibroblast growth factor 21 (FGF21) plays a role in kidney disease. Circulating FGF21 levels are associated with kidney function and progression in patients with type 2 diabetes (T2D). However, the association between FGF21 and kidney function in the general population is still lacking. The aim of this study was to determine the association between FGF21 and kidney function and its progression in a Chinese cohort.

A total of 2425 participants from a population-based survey of diabetes and metabolic syndrome in Pinggu, Beijing, were included in the baseline analysis. After a median follow-up of 12 months, 2402 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 were analyzed in the longitudinal study. The progression of kidney function was defined as an eGFR decline exceeding 3.3% per year. Serum FGF21 levels were measured using an enzyme-linked immunosorbent assay at baseline.

Male sex, body mass index (BMI), homeostasis model assessment of insulin resistance, higher levels of low-density lipoprotein cholesterol (LDL-c), uric acid, and FGF21 were associated with increased odds of a lower eGFR at baseline. The association of FGF21 with lower eGFR was independent of all the potential confounders in multivariable logistic regression (odds ratio, 1.005; 95% confidence interval 1.002–1.008). However, FGF21 was not associated with eGFR decline in the longitudinal analysis (odds ratio, 1.000; 95% confidence interval 0.998–1.001).

Increased serum FGF21 levels were independently associated with lower eGFR in this nonmedicated general population. FGF21 could be a biomarker of kidney function in the general population.
Massive gastrointestinal hemorrhage caused by Henoch-Schoenlein purpura
Authors: Wang Shuo , Tang Hongyan , Du Wei , Ding Yiyi
Published: December 2021

Rationale:

Henoch-Schoenlein purpura (HSP) is a systemic small-vessel vasculitis that commonly occurs in children. Gastrointestinal HSP can rarely progress to gastrointestinal perforation, followed by massive gastrointestinal bleeding.

Patient concerns:

An 8-year-old Chinese boy was transferred to the pediatric intensive care unit of our hospital with an emergency occurrence of purpura, severe hematemesis, large bloody stools, and sharp abdominal pain, and complained of abdominal pain and rash 2 weeks prior.

Diagnosis:

The patient had purpura with lower limb predominance, abdominal pain, and gastrointestinal bleeding. Immunofluorescence microscopy of histological sections showed granular and lumpy IgA focal deposition in the blood vessel walls. He was diagnosed with HSP.

Interventions:

Initially, he was treated with methylprednisolone, posterior pituitary injection, somatostatin, and hemocoagulase, together with the infusion of large blood products. Postoperatively, he was administered nasal continuous positive airway pressure -assisted ventilation, anti-infection treatment, albumin transfusion, platelet transfusion, abdominal drainage, methylprednisolone, fluconazole anti-fungal treatment, and wound dressing.

Outcomes:

There was no evidence of rebleeding, abdominal pain, or purpura at the 2-month follow-up assessment.

Lessons:

Abdominal HSP should be alert to gastrointestinal perforation when using hormone therapy.
Acupuncture combined with TCM bonesetting in the treatment of distal radius fractures
Authors: Liu Tongxin , Xia Yu , Zhang Yitao , Kuang Gaoyan , Zhou Liangrong
Published: December 2021

Background:

Acupuncture combined with traditional Chinese medicine (TCM) bonesetting is an effective and more acceptable treatment method for distal radius fractures; this study aims to evaluate the clinical efficacy and other relevant factors of it compared with western medicine therapy such as operation.

Methods:

Databases CNKI, Wanfang, VIP, SinoMed, and PubMed were searched for the current study. The retrieval time was from the establishment to November 14, 2021. Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network. RevMan 5.3 and Stata 12.0 were used to perform this research.

Results:

This study will appraise the effectiveness and advantages of acupuncture combined with TCM bonesetting for distal radius fractures in terms of excellent and good rate, length of stay, hospitalization expenses, complication, and other factors.

Conclusion:

This study provides reliable evidence-based support for the clinical efficacy and advantages of acupuncture combined with TCM bonesetting for distal radius fractures.

OSF registration DOI:

10.17605/OSF.IO/BUPE8.
Identifying the hub genes and immune infiltration related to pyroptosis in rheumatoid arthritis
Authors: Xie Wei , Wu Zhengyuan
Published: December 2021

Rheumatoid arthritis (RA) is one of the most common autoimmune joint disorders globally, but its pathophysiological mechanisms have not been thoroughly investigated. Pyroptosis significantly correlates with programmed cell death. However, targeting pyroptosis has not been considered as a therapeutic strategy in RA due to a lack of systematic studies on validated biomarkers. The present study aimed to identify hub pyroptosis biomarkers and immune infiltration in RA. The gene expression profiles of synovial tissues were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed pyroptosis genes (DEPGs). Meanwhile, the CIBERSORT algorithm was used to explore the association between immune infiltration and RA. Consequently, two hub DEPGs (EGFR and JUN) were identified as critical genes in RA. Through gene ontology and pathway enrichment analysis. EGFR and JUN were found to be primarily involved in the ErbB signaling pathway, PD-1 checkpoint pathway, GnRH signaling pathway, etc. Furthermore, for immune infiltration analysis, the pyroptosis genes EGFR and JUN were closely connected with four and one immune cell types, respectively. Overall, this study presents a novel method to identify hub DEPGs and their correlation with immune infiltration, which may provide novel perspectives into the diagnosis and treatment of patients with RA.
Frateuria flava sp. nov., isolated from soil
Authors: Akter Shahina , Lee Sun-Young , Huq Md. Amdadul
Published: December 2021

A Gram-stain-negative, aerobic, rod-shaped and non-motile novel bacterial strain, designated MAH-13T, was isolated from a soil sample. The colonies were observed to be yellow-coloured, smooth, spherical and 1.8–3.0 mm in diameter when grown on nutrient agar medium for 2 days. Strain MAH-13T was found to be able to grow at 20–40 °C, at pH 5.0–10.0 and with 0–1.0% NaCl (w/v). Cell growth occurred on tryptone soya agar, Luria–Bertani agar, nutrient agar and Reasoner's 2A agar. The strain was found to be positive for both oxidase and catalase tests. The strain was positive for hydrolysis of casein, starch, DNA and l-tyrosine. According to 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus

Frateuria

and to be closely related to

Frateuria terrea

DSM 26515T (98.2% similarity),

Dyella thiooxydans

ATSB10T (98.2 %),

Frateuria defendens

HyOGT (97.9 %),

Rhodanobacter glycinis

MO64T (97.8 %) and

Frateuria aurantia

DSM 6220T (97.8 %). The novel strain MAH-13T has a draft genome size of 3 682 848 bp (40 contigs), annotated with 3172 protein-coding genes, 49 tRNA genes and three rRNA genes. The average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between strain MAH-13T and five closely related type strains were in the range of 73.7–85.5 % and 20.7–30.1%, respectively. The genomic DNA G+C content was determined to be 68.0 mol%. The predominant isoprenoid quinone was ubiquinone 8. The major fatty acids were identified as iso-C15:0, iso-C16:0 and summed feature 9 (iso-C17 : 1
ω9c and/or C16:0 10-methyl). On the basis of dDDH and ANI values, genotypic analysis, and chemotaxonomic and physiological data, strain MAH-13T represents a novel species within the genus

Frateuria

, for which the name Frateuria flava sp. nov. is proposed, with MAH-13T (=KACC 19743T=CGMCC 1.13655T) as the type strain.
Safety profile of COVID-19 vaccines in pregnant and postpartum women in brazil
Authors: Qiao Yaping , Lopes de Abreu Ariane de Jesus , Dias Carolina Zampirolli , Meng Xing , Ferreira Rafaela Vansan , Gonçalves Pereira Ramon , Julian Guilherme Silva , Yin Weidong
Published: December 2021

Background

Although COVID-19 vaccines are currently under use in pregnant and postpartum women, there is still lack of evidence regarding safety and effectiveness in these populations. This study aims to describe the safety profile of COVID-19 vaccines in pregnant and postpartum women in the early stage of vaccination campaign in Brazil.

Methods

This is an observational cross-sectional study using data from the Brazilian surveillance information system for adverse events (SI-EAPV) to characterize the safety of COVID-19 vaccines available (Sinovac/Butantan, Pfizer/BioNTech, AstraZeneca and Janssen) in Brazilian pregnant and postpartum women after receiving it from April to August 2021. A descriptive analysis was performed to assess the frequency and incidence rate of the adverse events (AE) for COVID-19 vaccines.

Results

A total of 3,333 adverse events following COVID-19 immunization were reported for the study population in the SIEAPV. The incidence of AE found was 309.4/100,000 doses (95% CI 297.23, 321.51). Regarding the four vaccines available in the country, Sinovac/Butantan had the lowest incidence (74.08/100,000 doses; 95% CI 63.47, 84.69). Systemic events were the most frequent notified for the group (82.07%), followed by local (11.93%) and maternal (4.74%), being most of them classified as non-severe (90.65%).

Conclusion

A similar pattern of AE as stated in other studies was found, with even better results for non-viral vector vaccines, corroborating to the recommendation of vaccination for these groups. Even though, further studies appraising a longer observation time are still needed to provide a broader safety aspect for the vaccines currently under use for this population.
Clemastine induces an impairment in developmental myelination
Authors: Palma Ana , Chara Juan Carlos , Otxoa-Amezaga Amaia , Planas Anna , Matute Carlos , Pérez-Samartín Alberto , Domercq María
Published: December 2021

Abnormalities in myelination are associated to behavioral and cognitive dysfunction in neurodevelopmental psychiatric disorders. Thus, therapies to promote or accelerate myelination could potentially ameliorate symptoms in autism. Clemastine, a histamine H1 antagonist with anticholinergic properties against muscarinic M1 receptor, is the most promising drug with promyelinating properties (Mei et al., 2014). Clemastine penetrates the blood brain barrier efficiently and promotes remyelination in different animal models of neurodegeneration including multiple sclerosis, ischemia and Alzheimer’s disease. However, its role in myelination during development is unknown. We showed that clemastine treatment during development increase oligodendrocyte differentiation in both white and gray matter. However, despite the increase in the number of oligodendrocytes, conduction velocity of myelinated fibers of corpus callosum decreased in clemastine treated mice. Confocal and electron microscopy showed a reduction in the number of myelinated axons and nodes of Ranvier and a reduction of myelin thickness in corpus callosum. To understand the mechanisms leading to myelin formation impairment in the presence of an excess of myelinating oligodendrocytes, we focused on microglial cells which also express muscarinic M1 receptors. Importantly, the population of CD11c+microglia cells, necessary for myelination, as well as the levels of insulin growth factor-1 decrease in clemastine-treated mice. Altogether, these data suggest that clemastine impact on myelin development is more complex than previously thought and could be dependent on microglia-oligodendrocyte crosstalk. Further studies are needed to clarify the role of microglia cells on developmental myelination.
Nfeature: A platform for computing features of nucleotide sequences
Authors: Mathur Megha , Patiyal Sumeet , Dhall Anjali , Jain Shipra , Tomer Ritu , Arora Akanksha , Raghava Gajendra P. S.
Published: December 2021

In the past few decades, public repositories on nucleotides have increased with exponential rates. This pose a major challenge to researchers to predict the structure and function of nucleotide sequences. In order to annotate function of nucleotide sequences it is important to compute features/attributes for predicting function of these sequences using machine learning techniques. In last two decades, several software/platforms have been developed to elicit a wide range of features for nucleotide sequences. In order to complement the existing methods, here we present a platform named Nfeature developed for computing wide range of features of DNA and RNA sequences. It comprises of three major modules namely Composition, Correlation, and Binary profiles. Composition module allow to compute different type of compositions that includes mono-/di-tri-nucleotide composition, reverse complement composition, pseudo composition. Correlation module allow to compute various type of correlations that includes auto-correlation, cross-correlation, pseudo-correlation. Similarly, binary profile is developed for computing binary profile based on nucleotides, mono-nucleotides, di-/tri-nucleotide properties. Nfeature also allow to compute entropy of sequences, repeats in sequences and distribution of nucleotides in sequences. In addition to compute feature in whole sequence, it also allows to compute features from part of sequence like split, start, end, and rest. In a nutshell, Nfeature amalgamates existing features as well as number of novel features like nucleotide repeat index, distance distribution, entropy, binary profile, and properties. This tool computes a total of 29217 and 14385 features for DNA and RNA sequence, respectively. In order to provide, a highly efficient and userfriendly tool, we have developed a standalone package and web-based platform (https://webs.iiitd.edu.in/raghava/nfeature).
Tele-Rapid Response Team (Tele-RRT): Implementation and outcomes of Safety Network System. Before and after cohort study
Authors: Balshi Ahmed N. , Al-Odat Mohammed A. , Alharthy Abdulrahman M. , Alshaya Rayan A. , Alenzi Hanan M. , Dambung Alhadzia S. , Mhawish Huda , Altamimi Saad M. , Aletreby Waleed Th.
Published: December 2021

Background

Rapid Response Teams were developed to provide interventions for deteriorating patients. Their activation depends on timely detection of deterioration. Automated calculation of warning signs may lead to early recognition, and improvement of RRT effectiveness.

Method

This was a “Before” and “After” study, in the “Before” period ward nurses activated RRT after manually recording vital signs and calculating warning scores. In the “After” period, vital signs and warning calculations were automatically relayed to RRT through a wireless monitoring network.

Results

The “After” group had significantly lower incidence and rates of cardiopulmonary resuscitation compared to the “Before” group (2.3 / 1000 inpatient days versus 3.8 / 1000 inpatient days respectively, p = 0.01), the “Before” group had a significantly higher hospital length of stay, and significantly fewer visits by the RRT. In multivariable logistic regression model, being in the “After” group decreases odds of CPR by 30% (OR = 0.7 [95% CI: 0.44 – 0.97]; p = 0.02). There was no difference between groups in unplanned ICU admission or readmission.

Conclusion

Automated activation of the RRT resulted in significant reduction of CPR events and rate, reduction of hospital length of stay, and increase in the number of visits by the RRT. There was no difference in unplanned ICU admission or readmission.
Attention enhances category representations across the brain with strengthened residual correlations to ventral temporal cortex
Authors: Keller Arielle S. , Jagadeesh Akshay , Bugatus Lior , Williams Leanne M. , Grill-Spector Kalanit
Published: December 2021

How does attention enhance neural representations of goal-relevant stimuli while suppressing representations of ignored stimuli across regions of the brain? While prior studies have shown that attention enhances visual responses, we lack a cohesive understanding of how selective attention modulates visual representations across the brain. Here, we used functional magnetic resonance imaging (fMRI) while participants performed a selective attention task on superimposed stimuli from multiple categories and used a data-driven approach to test how attention affects both decodability of category information and residual correlations (after regressing out stimulus-driven variance) with category-selective regions of ventral temporal cortex (VTC). Our data reveal three main findings. First, when two objects are simultaneously viewed, the category of the attended object can be decoded more readily than the category of the ignored object, with the greatest attentional enhancements observed in occipital and temporal lobes. Second, after accounting for the response to the stimulus, the correlation in the residual brain activity between a cortical region and a category-selective region of VTC was elevated when that region’s preferred category was attended vs. ignored, and more so in the right occipital, parietal, and frontal cortices. Third, we found that the stronger the residual correlations between a given region of cortex and VTC, the better visual category information could be decoded from that region. These findings suggest that heightened residual correlations by selective attention may reflect the sharing of information between sensory regions and higher-order cortical regions to provide attentional enhancement of goal-relevant information.
Astrocytes in the dorsal vagal complex are not activated by systemic glucoprivation and their chemogenetic activation does not elicit homeostatic glucoregulatory responses in mice
Authors: MacDonald Alastair J , Pye Katherine R , Beall Craig , Ellacott Kate L J
Published: December 2021

The dorsal vagal complex (DVC) is a brainstem site regulating diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes are purported to play an active role in regulating DVC function and, by extension, physiological parameters. Previous work has demonstrated that DVC astrocytes directly sense hormones that regulate food intake and blood glucose and are critical for their effect. In addition, DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons, including catecholaminergic neurons, to low glucose is conditional on intact astrocyte signalling in slice preparations suggesting astrocytes are possibly the primary sensors of glucose deprivation (glucoprivation). Based on these findings we hypothesised that if DVC astrocytes act as glucoprivation sensors in vivo they would both show a response to systemic glucoprivation and drive physiological responses to restore blood glucose. We found that 2 hours of systemic glucoprivation induced neither FOS nor glial fibrillary acidic protein (GFAP)-immunoreactivity in DVC astrocytes, specifically those in the nucleus of the solitary tract (NTS). Furthermore, we found that while chemogenetic activation of DVC astrocytes suppressed food intake by reducing both meal size and meal number, this manipulation also suppressed food intake under conditions of glucoprivation. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin-induced hypoglycaemia. In male mice chemogenetic DVC astrocyte activation did not alter glucose tolerance, in female mice the initial glucose excursion was reduced, suggesting enhanced glucose absorption. Taken together this suggests that as a whole-population DVC astrocytes do not function as glucoprivation sensors in vivo in mice. Instead, we propose that DVC astrocytes play an indispensable, homeostatic role to maintain the function of glucoregulatory neuronal circuitry.
Disrupting inferior frontal cortex activity alters affect decoding efficiency from clear but not from ambiguous affective speech
Authors: Ceravolo Leonardo , Moisa Marius , Grandjean Didier , Ruff Christian , Frühholz Sascha
Published: December 2021

The evaluation of socio-affective sound information is accomplished by the primate auditory cortex in collaboration with limbic and inferior frontal cortex (IFC)—often observed during affective voice classification. Partly opposing views have been proposed, with IFC either coding cognitive processing challenges in case of sensory ambiguity or representing categorical object and affect information for clear voices. Here, we presented clear and ambiguous affective speech to two groups of human participants during neuroimaging, while in one group we inhibited right IFC activity with transcranial magnetic stimulation. IFC activity inhibition led to faster affective decisions, more accurate choice probabilities, reduced auditory cortical activity and increased fronto-limbic connectivity for clear affective speech. This indicates a more intermediate functional property of the IFC than assumed—namely with normal activity representing a more deliberate form of affective sound processing (i.e., enforcing cognitive analysis) that flags categorical sound decisions with precaution (i.e., representation of categorical uncertainty).

Teaser

Inferior frontal cortex enforces cognitive analyses during affect decisions with different levels of sensory ambiguity.
The neural cell adhesion molecule NrCAM regulates development of hypothalamic tanycytes
Authors: Moore Alex , Chinnaiya Kavitha , Kim Dong Won , Brown Sarah , Stewart Ian , Robins Sarah , Dowsett Georgina , Muir Charlotte , Travaglio Marco , Lewis Jo E. , Ebling Fran , Blackshaw Seth , Furley Andrew , Placzek Marysia
Published: December 2021

Hypothalamic tanycytes are neural stem and progenitor cells, but little is known of how they are regulated. Here we provide evidence that the cell adhesion molecule, NrCAM, regulates tanycytes in the adult niche. NrCAM is strongly expressed in adult mouse tanycytes. Immunohistochemical and in situ hybridization analysis revealed that NrCAM loss of function leads to both a reduced number of tanycytes and reduced expression of tanycyte-specific cell markers, along with a small reduction in tyrosine hydroxylase-positive arcuate neurons. Similar analyses of NrCAM mutants at E16 identify few changes in gene expression or cell composition, indicating that NrCAM regulates tanycytes, rather than early embryonic hypothalamic development. Neurosphere and organotypic assays support the idea that NrCAM governs cellular homeostasis. Single-cell RNA sequencing (scRNA-Seq) shows that tanycyte-specific genes, including a number that are implicated in thyroid hormone metabolism, show reduced expression in the mutant mouse. However, the mild tanycyte depletion and loss of markers observed in NrCAM-deficient mice were associated with only a subtle metabolic phenotype.
Protein Posttranslational Signatures Identified in COVID-19 Patient Plasma
Authors: Vedula Pavan , Tang Hsin-Yao ,   The UPenn COVID Processing Unit, Speicher David W. , Kashina Anna
Published: December 2021

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious virus of the coronavirus family that causes coronavirus disease-19 (COVID-19) in humans and a number of animal species. COVID-19 has rapidly propagated in the world in the past 2 years, causing a global pandemic. Here, we performed proteomic analysis of plasma samples from COVID-19 patients compared to healthy control donors in an exploratory study to gain insights into protein-level changes in the patients caused by SARS-CoV-2 infection and to identify potential proteomic and posttranslational signatures of this disease. Our results suggest a global change in protein processing and regulation that occurs in response to SARS-CoV-2, and the existence of a posttranslational COVID-19 signature that includes an elevation in threonine phosphorylation, a change in glycosylation, and a decrease in arginylation, an emerging posttranslational modification not previously implicated in infectious disease. This study provides a resource for COVID-19 researchers and, longer term, will inform our understanding of this disease and its treatment.

Key Points

Plasma from COVID-19 patients exhibits prominent protein- and peptide-level changes

Proteins from COVID-19 patient plasma exhibit prominent changes in several key posttranslational modifications
Crystal structures and functional analysis of the ZnF5-WWE1-WWE2 region of PARP13/ZAP define a new mode of engaging poly(ADP-ribose)
Authors: Kuttiyatveetil Jijin R. A. , Soufari Heddy , Dasovich Morgan , Uribe Isabel R. , Cheng Shang-Jung , Leung Anthony K. L. , Pascal John M.
Published: December 2021

PARP13/ZAP acts against multiple viruses through recognizing and promoting degradation of cytoplasmic viral mRNA. PARP13 has four N-terminal Zn-finger motifs that bind CG-rich nucleotide sequences, and a C-terminal ADP ribosyltransferase fold similar to other PARPs. A central region predicted to contain a fifth Zn-finger and two tandem WWE domains is implicated in binding poly(ADP-ribose); however, there are limited insights into the structure and function of this PARP13 region (ZnF5-WWE1-WWE2). Here, we present crystal structures of ZnF5-WWE1-WWE2 from mouse PARP13 in complex with ADP-ribose and with ATP. ZnF5-WWE1-WWE2 crystallized as a dimer with major contacts formed between WWE1 and WWE2 originating from different monomers, indicative of a more compact monomeric arrangement of the tandem WWE domains. Solution scattering experiments and biophysical analysis indicated a monomer in solution, suggesting that the crystal dimer represents domain swapping that could potentially represent a PARP13 conformation assumed when signaling viral RNA detection. The crystal structure and binding studies demonstrate that WWE2 interacts with ADP-ribose and ATP, whereas WWE1 does not have a functional binding site. The shape of the WWE2 binding pocket disfavors interaction with the ribose-ribose linkage of poly(ADP-ribose). Binding studies with poly(ADP-ribose) ligands indicate that WWE2 serves as an anchor for preferential binding to the terminal end of poly(ADP-ribose), and the composite structure of ZnF5-WWE1-WWE2 forms an extended surface to engage polymer chains of ADP-ribose. This model represents a novel mode of poly(ADP-ribose) recognition and provides a structural framework for investigating poly(ADP-ribose) impact on PARP13 function.
MDITRE: scalable and interpretable machine learning for predicting host status from temporal microbiome dynamics
Authors: Maringanti Venkata Suhas , Bucci Vanni , Gerber Georg K.
Published: December 2021

Longitudinal microbiome datasets are being generated with increasing regularity, and there is broad recognition that these studies are critical for unlocking the mechanisms through which the microbiome impacts human health and disease. Yet, there is a dearth of computational tools for analyzing microbiome time-series data. To address this gap, we developed an open-source software package, MDITRE, which implements a new highly efficient method leveraging deep-learning technologies to derive human-interpretable rules that predict host status from longitudinal microbiome data. Using semi-synthetic and a large compendium of publicly available 16S rRNA amplicon and metagenomics sequencing datasets, we demonstrate that in almost all cases, MDITRE performs on par or better than popular uninterpretable machine learning methods, and orders-of-magnitude faster than the prior interpretable technique. MDITRE also provides a graphical user interface, which we show through use cases can readily derive biologically meaningful interpretations linking patterns of microbiome changes over time with host phenotypes.
DNA methylation in transposable elements disrupts the connection between three-dimensional chromatin organization and gene expression upon rice genome duplication
Authors: Sun Zhenfei , Wang Yunlong , Song Zhaojian , Zhang Hui , Ma Min , Wang Pan , Fang Yaping , Cai Detian , Li Guoliang , Fang Yuda
Published: December 2021

Polyploidy serves as a major force in plant evolution and domestication of cultivated crops. However, the relationship and underlying mechanism between three-dimensional (3D) chromatin organization and gene expression upon rice genome duplication is largely unknown. Here we compared the 3D chromatin structures between diploid (2C) and autotetraploid (4C) rice by high-throughput chromosome conformation capture analysis, and found that 4C rice presents weakened intra-chromosomal interactions compared to its 2C progenitor. Moreover, we found that changes of 3D chromatin organizations including chromatin compartments, topologically associating domain (TAD) and loops uncouple from gene expression. Moreover, DNA methylations in the regulatory sequences of genes in compartment A/B switched regions and TAD boundaries are not related to their expressions. Importantly, in contrast to that there was no significant difference of methylation levels in TEs in promoters of differentially expressed genes (DEGs) and non-DEGs between 2C and 4C rice, we found that the hypermethylated transposable elements across genes in compartment A/B switched regions and TAD boundaries suppress the expression of these genes. We propose that the rice genome doubling might modulate TE methylation which results in the disconnection between the alteration of 3D chromatin structure and gene expression.
Understanding the source of METTL3-independent m6A in mRNA
Authors: Poh Hui Xian , Mirza Aashiq H. , Pickering Brian F. , Jaffrey Samie R.
Published: December 2021

N6-methyladenosine (m6A) is a highly prevalent mRNA modification which promotes degradation of transcripts encoding proteins that have roles in cell development, differentiation, and other pathways. METTL3 is the major methyltransferase that catalyzes the formation of m6A in mRNA. As 30–80% of m6A can remain in mRNA after METTL3 depletion by CRISPR/Cas9-based methods, other enzymes are thought to catalyze a sizable fraction of m6A. Here, we re-examined the source of m6A in the mRNA transcriptome. We characterized mouse embryonic stem cell lines which continue to have m6A in their mRNA after Mettl3 knockout. We show that these cells express alternatively spliced Mettl3 transcript isoforms that bypass the CRISPR/Cas9 mutations and produce functionally active methyltransferases. We similarly show that other reported METTL3 knockout cell lines express altered METTL3 proteins. We find that gene dependency datasets show that most cell lines fail to proliferate after METTL3 deletion, suggesting that reported METTL3 knockout cell lines express altered METTL3 proteins rather than have full knockout. Finally, we reassessed METTL3’s role in synthesizing m6A using a genomic deletion of Mettl3, and found that METTL3 is responsible for >95% of m6A in mRNA. Overall, these studies suggest that METTL3 is responsible for the vast majority of m6A in the transcriptome, and that remaining m6A in putative METTL3 knockout cell lines is due to the expression of altered but functional METTL3 isoforms.
The Omicron variant mutation at position 28,311 in the SARS-CoV-2 N gene does not perturb CDC N1 target detection
Authors: Bei Yanxia , Vrtis Kyle B. , Borgaro Janine G. , Langhorst Bradley W. , Nichols Nicole M.
Published: December 2021

The emergence of new SARS-CoV-2 variants necessitates the reevaluation of current COVID-19 tests to ensure continued accuracy and reliability. The new SARS-CoV-2 variant, Omicron, is heavily mutated, with over 50 mutations within its RNA genome. Any of these mutations could adversely affect the ability of diagnostic assays to detect the virus in patient samples, potentially leading to inconclusive or false negative results. In fact, the U.S. Food and Drug Administration (FDA) has identified over two dozen diagnostic tests that contain a gene target that is expected to have “significantly reduced sensitivity due to a mutation in the SAS-CoV-2 Omicron variant”1. Additionally, one of the U.S. Centers for Disease Control and Prevention (CDC) Emergency Use Authorization (EUA) targets for COVID-19 tests, 2019-nCoV_N1, overlaps an Omicron mutation within the sequence targeted by the fluorescent probe. This target from the CDC has been used in many other EUA assays. Using in vitro transcribed (IVT) N gene RNA representing the wild-type (GenBank/GISAID ID MN908947.3) and Omicron variant (BA.1, GISAID ID EPI_ISL_6752027), we evaluated the performance of two different amplification protocols, both of which include the CDC 2019-nCoV_N1 primer-probe set. Both assays were able to detect the mutant N1 sequence as efficiently as the wild-type sequence. Consequently, these data suggest that diagnostic assays that use the 2019-nCoV-N1 primer-probe set are unlikely to be impacted by currently circulating Omicron lineage viruses.