bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum folate and vitamin B12 levels in cutaneous melanoma
Authors: Tas Faruk , Erturk Kayhan , Soydinc Hilal Oguz
Published: January 2021

Background

Vitamin B12 and folate are the major micronutrients that play significant roles in DNA synthesis. Epidemiological studies and clinical evidences displayed alterations in serum concentrations folate and of vitamin B12 in various human malignancies, yet their roles in patients with melanoma have yet to be understood.

Objective

To assess circulating vitamin B12 and folate concentrations of patients with melanoma and compare them with other malignant tumors and healthy subjects.

Methods

A total of 98 skin melanoma cases from university clinic were enrolled into the study. Serum vitamin B12 and folate concentrations were analyzed by electrochemiluminescence binding assay.

Results

Circulating levels of vitamin B12 in patients with melanoma were similar compared with other malignancies and healthy controls (P > .05). However, melanoma cases had significantly lower serum folate concentrations than healthy control group (P = .04). Melanoma patients with metastatic disease (P = .001) and with short history of disease (P = .05), and those who had active diseases in course of the study (P = .04) had low serum folate concentrations.

Conclusion

Serum levels of folate were found significantly lower in melanoma cases, and this association was stronger for patients with metastatic melanoma; however, no such association was found between melanoma and serum vitamin B12 levels.
A novel classification of glucose profile in pregnancy based on continuous glucose monitoring data
Authors: Inayama Yoshihide , Yamanoi Koji , Shitanaka Shimpei , Ogura Jumpei , Ohara Tsutomu , Sakai Mie , Suzuki Haruka , Kishimoto Ichiro , Tsunenari Toru , Suginami Koh
Published: January 2021

Aim

To investigate the glucose profile of women with and without gestational diabetes mellitus (GDM) by simultaneously analyzing several factors of continuous glucose monitoring (CGM) data.

Methods

CGM was conducted for 2 weeks in the second trimester of pregnant women whose random blood glucose level was ≥100 mg/dl. A 75‐g oral glucose tolerance test was performed around day 7, and the index of hyperglycemia, relative hypoglycemia, and indices of glucose variability were extracted from CGM data. Unsupervised hierarchical clustering was performed to categorize glucose profiles of the participants.

Results

CGM data were obtained from 29 women. Glucose profiles were categorized into three clusters: low glucose levels with less glucose variability group (L group, n = 7); moderate glucose levels with moderate‐to‐high glucose variability group (M group, n = 18); and high glucose levels with high glucose variability group (H group, n = 4). The waveforms of the glucose profiles were very different among the three groups. Women with GDM tended to be more frequent in the H group than in the M and L groups (75.0%, 16.7%, and 14.3%, respectively; p = 0.053). Maternal age was significantly higher and the proportion of multiparous women was significantly larger in the H group compared to L group (p = 0.002 and 0.015, respectively).

Conclusions

A comprehensive analysis of CGM data could help us extract a subgroup of women with characteristics of GDM.
Hypersensitivity reaction to pegylated liposomal doxorubicin administration for Mullerian carcinoma in Japanese women
Authors: Yamaguchi Shinichiro , Yahata Hideaki , Okugawa Kaoru , Kodama Keisuke , Yagi Hiroshi , Yasunaga Masafumi , Ohgami Tatsuhiro , Onoyama Ichiro , Asanoma Kazuo , Kato Kiyoko
Published: January 2021

Aim

PEGylated liposomal doxorubicin (PLD) is a therapeutic agent for gynecological malignancy. Hypersensitivity reaction (HSR) is a major adverse effect that usually disappears after halting administration of PLD. Premedication is usually not necessary before administration of PLD to prevent HSR. Here, we evaluated the frequency of HSR during administration of PLD following premedication in Japanese women.

Methods

We performed PLD administration in 78 patients (386 cycles) between 2013 and 2018. Granisetron hydrochloride and dexamethasone sodium phosphate were administered 30 min before PLD administration. Then, PLD (40 or 30 mg/m2 combined usage with carboplatin) was administered. We retrospectively reviewed the medical records of 78 patients and examined the frequency of HSR.

Results

Seven of 78 (9%) patients showed HSR by PLD administration following premedication. One patient showed cardiopulmonary arrest in 13 min after PLD administration (grade 4). The other six patients showed grade 2 HSR. All patients developed HSR in the first course. The incidence of HSR was significantly higher in patients with allergic history than in patients without allergic history (p = 0.0151).

Conclusions

Clinicians should be aware of the potential for HSR in patients administered PLD, particularly those with allergic history and those receiving the first cycle of PLD, even following premedication.
Eighteenth‐century theater history and performance studies
Authors: Wessel Jane
Published: January 2021

Over the last few decades, theater history has moved beyond a documentary and descriptive approach to become a field that increasingly embraces the “epistemological uncertainty” that comes with studying an unfixed medium. This shift owes much to the flourishing of performance studies in the 1990s and 2000s. This essay examines the effects of performance studies on 18th‐century theater history. Theater historians of earlier periods have long grappled with how to study a medium that is uncapturable by print alone. Performance's ephemerality and its embodiment, in particular, pose challenges to those working in the archives. This essay reviews the recent scholarship that brings together the archival work of theater history with newer performance‐oriented methodologies. The turn to performance studies allows us to better theorize the experiences and identities that archives have sometimes obscured, especially involving women and minorities. Moreover, taking the medium of performance seriously not just as an object of study, but as a mode of constructing and disseminating theater history enables us to experience vicariously sensory elements of performance that traditional print scholarship cannot fully capture.
Differential expression analysis of urinary exosomal circular RNAs in patients with IgA nephropathy
Authors: Luan Rumei , Tian Geng , Ci Xin , Zheng Qian , Wu Linlin , Lu Xuehong
Published: January 2021

Aims

Immunoglobulin A nephropathy (IgAN) is the most common primary glomerular disease to cause end‐stage kidney disease. This study investigated the difference in urinary exosomal circular RNA (circRNA) expression profiles between patients with IgAN and healthy controls (HCs), for better understanding of gene regulation in exosomes of IgAN patients.

Methods

A pairwise comparison of urinary circRNA expression profiles between IgAN patients and HCs was performed using methods, including high‐throughput sequencing and quantitative polymerase chain reaction. Moreover, the potential functions of differentially expressed circRNAs (DECs) in IgAN were investigated by gene ontology (GO) enrichment analysis; Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; and the circRNA‐miRNA‐mRNA network.

Results

We identified 450 upregulated and 26 downregulated circRNAs in the IgAN patients. GO analysis showed that these enriched circRNAs might regulate primary miRNA processing, the ability of angiotensin receptor binding, and stress fibre function. KEGG analysis suggested these DECs may be closely associated with the phosphoinositide‐3‐kinase‐protein kinase B/Akt (PI3K‐Akt) signalling pathways. Network analysis revealed the relationship between circRNAs and their target genes.

Conclusion

The identified DECs may be useful for both researches on molecular aetiology of IgAN and development of potentially novel non‐invasive biomarkers of IgAN.
Shy Girl, a kiwifruit suppressor of feminization, restricts gynoecium development via regulation of cytokinin metabolism and signalling
Authors: Varkonyi‐Gasic Erika , Wang Tianchi , Cooney Janine , Jeon Subin , Voogd Charlotte , Douglas Mikaela J. , Pilkington Sarah M. , Akagi Takashi , Allan Andrew C.
Published: January 2021

Kiwifruit (Actinidia chinensis) is a dioecious, long‐living woody perennial vine. Reduced generation time and induction of hermaphroditism can accelerate crop improvement and facilitate alternative farming for better food security in the face of climate change.

Previous studies identified that CENTRORADIALIS genes CEN and CEN4 act to repress flowering, whilst the male‐specific Shy Girl (SyGl) gene with homology to type‐C cytokinin response regulators could repress gynoecium development in model plants. Here we use CRISPR/Cas9 to mutagenize CEN, CEN4 and SyGl in the male kiwifruit A. chinensis ‘Bruce’.

Biallelic mutations of CEN and CEN4 generated rapid‐flowering male plants, and simultaneous targeting of CEN4 and SyGl gave rise to rapid‐flowering hermaphrodites with restored gynoecial function and viable pollen, providing functional evidence for the role of SyGl in suppression of feminization. Analysis of ovary tissues identified genes that contribute to carpel development and revealed that SyGl affected both cytokinin profiles and the expression of genes involved in cytokinin metabolism and signalling. The plant lines generated by CEN4/SyGl knockout could self‐pollinate and produce fast‐flowering offspring.

These results establish that SyGI acts as the suppressor of feminization in kiwifruit and demonstrate the potential for accelerated breeding in an outcrossing horticultural woody perennial.
Ontogenetic development underlies population response to mortality
Authors: Toscano Benjamin J. , Figel Alexandra S. , Rudolf Volker H. W.
Published: January 2021

Understanding demographic responses to mortality is crucial to predictive ecology. While classic ecological theory posits reductions in population biomass in response to extrinsic mortality, models containing realistic developmental change predict the potential for counterintuitive increase in stage‐specific biomass, i.e. biomass overcompensation. Patterns of biomass overcompensation should be predictable based on differences in the relative energetic efficiencies of juvenile maturation and adult reproduction. Specifically, in populations where reproduction is the limiting process, adult‐specific mortality should enhance total reproduction and thus juvenile biomass. We tested this prediction by inducing an array of stage‐specific harvesting treatments across replicate populations of Daphnia pulex. In accordance with reproductive regulation, the greatest biomass response occurred in the juvenile Daphnia stage and this response occurred most strongly in response to adult mortality. Nevertheless, we failed to detect significant biomass overcompensation and instead report largely compensatory effects. In total, our work demonstrates that knowledge of population structure is necessary to accurately predict population dynamics, but cautions that further research is needed to illuminate the factors generating over‐compensatory versus compensatory responses across natural populations.
Qualitative Sensory Testing in Outcome Prediction of Transforaminal Epidural Steroid Injection for Chronic Painful Unilateral Lumbosacral Radiculopathy: Prospective Observational Study
Authors: Vaitkus Alfredas , Šipylaitė Jūratė
Published: January 2021

Background

Transforaminal epidural steroid injection (TFESI) is widely practiced for the treatment of radicular pain. As its effectiveness is still subject to debate, a better patient selection for TFESI is necessary. We aimed to evaluate the potential of bedside‐suitable qualitative sensory testing (QualST) to determine the early effectiveness of TFESI for the treatment of chronic lumbosacral radiculopathy (LSR)‐related pain.

Methods

Thirty‐six patients with chronic painful unilateral LSR were evaluated in a prospective observational study using five standardized sensory tests (10 g monofilament, 200 to 400 mN brush, Lindblom rollers with controlled 25 and 40°C temperature, and 40 g neurological pin). Quality of sensory perceptions on the painful leg was compared to the non‐painful leg and rated as normal sensitivity, hyposensitivity, or hypersensitivity. Pain and related characteristics were evaluated before TFESI, 1 week after and 4 weeks after intervention.

Results

Seven sensory phenotypes were distinguished according to individual sets of sensory disturbances acquired with five sensory tests. Patients were grouped into four groups of allied phenotypes (normal sensitivity, hyposensitivity to 1 to 3 modalities, hyposensitivity to 4 to 5 modalities, and hypersensitivity). The whole study group showed significant improvement in most parameters of outcome measurements. Statistical analysis revealed some significant differences between sensory groups in patient‐reported treatment effect scales after 4 weeks. We also detected significant differences between sensory groups in repeated measures after 1 and 4 weeks in some pain intensity characteristics and patient‐reported treatment effect scales.

Conclusion

QualST might be clinically applicable for detecting patient subgroups that could differ in the early treatment results of radicular pain by TFESI.
Diagnosing the Nation: Scientists, Mothers, and Physicians Confront Nuclear Testing and Civil Defense Through Medical Activism, 1958–1963
Authors: Whitehurst John Robert
Published: January 2021

The Limited Test Ban Treaty of 1963, which banned atmospheric nuclear testing, is one of the most powerful treaties regarding nuclear weapons ever passed. This legislation was pushed forward by the Kennedy Administration following the publicization of scientific and medical tests that warned readers about the introduction of man‐made radioisotopes into the bones and bodies of American infants. These scientific and medical tests were performed, publicized, and analyzed by a combination of scientists, concerned mothers, and physicians who respectively organized between 1958 and 1961. Each of these “medical activist” groups worked together during the early Cold War and was able to influence the Kennedy administration, who encouraged their involvement and even partially credited it with the garnishing of public support for the treaty. This multi‐constitutent response to the dangers of radioisotopes offers a window into the nexus of Cold War era concerns over national security, scientific and technological advances, and public health.
Comprehensive pathological assessment of histological subtypes, molecular subtypes based on immunohistochemistry, and tumor‐associated immune cell status in muscle‐invasive bladder cancer
Authors: Ikeda Junichi , Ohe Chisato , Yoshida Takashi , Kuroda Naoto , Saito Ryoichi , Kinoshita Hidefumi , Tsuta Koji , Matsuda Tadashi
Published: January 2021

Molecular assessments of muscle‐invasive bladder cancer (MIBC) have yielded several molecular categorizations associated with basal and luminal subtypes or tumor‐associated immune cell status (TAICs). However, the histological relationships among histological subtypes, molecular subtypes, and TAICs and their clinical implications remain unclear. Thus, we aimed to evaluate the histological associations among these factors and their clinicopathological outcomes. We retrospectively analyzed 106 patients with MIBC who underwent radical cystectomy. The histological subtypes and TAICs were evaluated with hematoxylin and eosin staining, while the basal and luminal molecular subtypes were determined by immunohistochemical expression of cytokeratin (CK) 5/6, CK14, CK20, GATA3 and uroplakin II. Urothelial carcinoma with squamous differentiation and the sarcomatoid variant were highly associated with the basal subtype (P < 0.001 and P = 0.04, respectively). Additionally, high TAICs were significantly correlated with the basal subtype (P < 0.001). Although there was no significant difference in the cancer‐specific survival (CSS) rate between molecular subtypes (P = 0.295), TAICs significantly discriminated CSS rates (P < 0.001). Furthermore, the combination of molecular subtypes and TAICs significantly stratified cancer‐specific mortality rates. In conclusion, a comprehensive pathological evaluation of histological subtypes, molecular subtypes, and TAICs is feasible and can influence the oncological outcome.
Seedling‐derived leaf and root tip as alternative explants for callus induction and plant regeneration in maize
Authors: Wang Chenchen , Ma Haizhen , Zhu Weiwei , Zhang Jiedao , Zhao Xiangyu , Li Xinzheng
Published: January 2021

While being one of the world's most important crops, maize (Zea mays L.) is still relatively difficult to regenerate in tissue culture, which severely limits its improvement by genetic engineering. Currently, immature zygotic embryos provide the predominant material for transformation and regeneration. However, the procedures involved are often laborious and season‐dependent. Therefore, new explants to replace or complement immature embryos are desirable. Here, we exploited root tips and young leaves isolated from 3‐day‐old dark‐grown seedlings as alternative explant sources for establishing plant regeneration. As novel explants, the root tips could generate embryogenic calli similar to that from the young leaves. The rate of primary callus induction from root tips reached 97.2% and almost as high as 98.8% from immature embryos. The difference in callus induction rates among these explants may be closely related to the differences in expression level of stem cell‐related genes in callus tissue. Moreover, the alternative explants are easy to obtain in large quantities. These combined results indicate that explants from seedling‐derived root tips and leaf tissue have the potential to replace immature embryos for plant regeneration and transformation.
Assessing the Trump White House
Authors: Hult Karen M.
Published: January 2021

This essay examines and assesses the dynamics of the White House and broader executive branch under President Donald J. Trump. It probes the performance of key institutional responsibilities, focusing on selected areas of policy and of administration. Evaluated on the effectiveness of achieving the administration's goals and on implications for governance, the Trump presidency receives at best a mixed review. Its accomplishments included boosting conservative presence on the federal courts and moving from multilateral to more dyadic relations in international affairs. Yet, it achieved considerably fewer of its deregulatory goals while neglecting pressing problems and reinforcing concerns with presidential capacity and loss of trust in government.
Ligation of the ligamentum arteriosum and aberrant left subclavian artery in five dogs in which persistent right aortic arch had been diagnosed
Authors: Regier Penny J. , Case J. Brad , Fox‐Alvarez W. Alexander
Published: January 2021

Objective

To determine and report the diagnosis, treatment, and outcome in dogs with persistent right aortic arch (PRAA) with an aberrant left subclavian artery (ALS) that underwent thoracoscopic surgery.

Animals

Dogs with PRAA and an ALS (n = 5).

Study design

Short case series.

Methods

Medical records were reviewed from 2014 to 2019. Dogs that underwent thoracoscopy for PRAA with an ALS at an academic referral hospital were included. Signalment, clinical signs, diagnostic imaging, surgical approach, complications, and short‐ and long‐term outcomes were recorded.

Results

Persistent right aortic arch with an ALS was identified in five dogs. Dogs initially underwent a three‐port intercostal thoracoscopic approach, and an intercostal thoracotomy was performed in converted cases. In all five dogs, the ligamentum arteriosum (LA) and ALS were divided; three were performed by a thoracoscopy alone. Two cases were converted because of poor exposure (1) and requirement to temporary occlude an ALS (1). The ALS was ligated and divided in all dogs without apparent negative effects. No intraoperative or postoperative complications occurred. Four dogs had resolution of regurgitation, three of which required diet modification. One dog had reported regurgitation when it was excited. Median follow‐up was 188 days (range, 150‐1133).

Conclusion

Ligation and division of both the LA and the ALS in all dogs in this case series was safe and allowed for improvement in clinical signs and good to excellent long‐term outcomes. In addition, both thoracoscopy and thoracotomy were used safely and successfully for ligation and transection of the LA and ALS in all dogs.
Impact of ENaC downregulation in transgenic mice on the outcomes of acute lung injury induced by bleomycin
Authors: Aubin Vega Mélissa , Chupin Cécile , Massé Chantal , Dagenais André , Berthiaume Yves , Brochiero Emmanuelle
Published: January 2021

New Findings

What is the central question of this study?

How does the downregulation of ENaC, the major driving force for alveolar fluid clearance, impact acute lung injury outcomes induced by bleomycin, featuring alveolar damage, as observed during ARDS exudative phase?

What is the main finding and its importance?

ENaC downregulation in αENaC(−/−)Tg+ mice did not elicit a substantial worsening impact on the main bleomycin outcomes. In ARDS patients, both ENaC alteration and alveolar damage are observed. Thus, novel therapeutic avenues, favouring alveolar integrity restauration, in addition to lung oedema resolution capacity, mainly driven by ENaC, would be essential.

The exudative phase of acute respiratory distress syndrome (ARDS) is characterized by extended alveolar damage, resulting in accumulation of protein‐rich inflammatory oedematous fluid in the alveolar space. Na+ reabsorption through ENaC channels is a major driving force for alveolar fluid clearance (AFC) in physiological and pathological conditions. It has previously been shown that partial αENaC impairment in transgenic (αENaC(−/−)Tg+) mice results in reduced AFC in basal conditions and increased wet/dry ratio after thiourea‐induced lung oedema, a model in which the integrity of the alveolar epithelium is preserved. The goal of this study was to further investigate the impact of αENaC downregulation in αENaC(−/−)Tg+ mice using an experimental model of acute lung injury induced by bleomycin. A non‐significant trend in enhanced weight loss and mortality rates was observed after the bleomycin challenge in αENaC(−/−)Tg+ compared to wild‐type (WT) mice. Bronchoalveolar lavage analyses revealed increased TNFα levels and protein concentrations, as indexes of lung inflammation and alveolar damage, in αENaC(−/−)Tg+ mice, compared to WT, at day 3 post‐bleomycin, although a statistical difference was no longer measured at day 7. Differential immune cell counts were similar in WT and αENaC(−/−)Tg+ mice challenged with bleomycin. Moreover, lung weight measurements indicated similar oedema levels in WT mice and in transgenic mice with impaired ENaC channels. Altogether, our data indicated that change in ENaC expression does not elicit a significant impact on lung oedema level/resolution in the bleomycin model, featuring alveolar damage.
Influence of Blade Tip Surface Roughness on the Performance of a Single-Stage Axial Flow Compressor
Authors: Kodancha Pradyumna , Salunkhe Pramod B.
Published: January 2021

Numerical investigations are carried out in a single-stage subsonic axial flow compressor to unravel the influence of blade tip surface roughness on the tip leakage flow characteristics and hence the compressor performance. The studies were carried out at different tip clearance of 0.38τ, 0.77τ, 1.15τ, and 1.54τ and blade tip surface roughness of 0.31ε and 0.62ε. The tip clearance of 0.38τ with blade tip surface roughness of 0.62ε resulted in the highest stall margin and pressure rise of 20.3% and 4.3%, respectively. The compressor blade loading was found to be improved by 5.9% after incorporating the blade tip surface roughness. The isosurfaces of vorticity contour plotted using the Q-criterion showed the reduction in strength of the tip leakage vortex. The tip leakage trajectory was found to be shifted toward the suction surface of the blade for the blade tip with surface roughness. This positive alteration in the tip leakage flow structure led to the improved performance for the blade tip with surface roughness.
On microphone array beamforming and insights into the underlying signal models in the short-time-Fourier-transform domain
Authors: Pan Chao , Chen Jingdong , Shi Guangming , Benesty Jacob
Published: January 2021

This paper studies signal models for microphone array beamforming in the short-time-Fourier-transform (STFT) domain with long acoustic impulse responses. The major contributions are as follows. First, the signal modeling problem is investigated in the STFT domain and a general decomposition is proposed for the convolved source signal. Second, new insights into the array manifold are presented: the STFT of the windowed acoustic impulse response from the source to the sensors. Third, the structure of the reference signal is analyzed: it can be viewed as the output of a beamformer without considering the noise in the observation signal. Fourth, based on the new perspectives and decomposition, a signal model is derived based on the use of the superdirective beamformer. Finally, three performance measures are defined, based on which three optimal/suboptimal signal models are derived and their performance is assessed under different acoustic environments and analysis window lengths. The performance of the well-known minimum variance distortionless response (MVDR) beamformer is evaluated, which justifies the properties of the developed signal models.
Effects of Varying Overground Walking Speeds on Lower-Extremity Muscle Synergies in Healthy Individuals
Authors: Escalona Manuel J. , Bourbonnais Daniel , Goyette Michel , Le Flem Damien , Duclos Cyril , Gagnon Dany H.
Published: January 2021

The effects of walking speeds on lower-extremity muscle synergies (MSs) were investigated among 20 adults who walked 20 m at SLOW (0.6 ± 0.2 m/s), natural (NAT; 1.4 ± 0.1 m/s), and FAST (1.9 ± 0.1 m/s) speeds. Surface electromyography of eight lower-extremity muscles was recorded before extracting MSs using a nonnegative matrix factorization algorithm. Increasing walking speed tended to merge MSs associated with weight acceptance and limb deceleration, whereas reducing walking speed does not change the number and composition of MSs. Varying gait speed, particularly decreasing speed, may represent a gait training strategy needing additional attention given its effects on MSs.
Anti–Na
+
/K
+
-ATPase immunotherapy ameliorates α-synuclein pathology through activation of Na
+
/K
+
-ATPase α1–dependent autophagy
Authors: Cao Lei , Xiong Siping , Wu Zhiyuan , Ding Lei , Zhou Yebo , Sun Haijian , Zhu Mengyuan , Lee Wei Thye , Nie Xiaowei , Bian Jin-Song
Published: January 2021

Activation of NKAα1-dependent autophagy ameliorates α-synuclein pathology.
Structural basis for heme-dependent NCoR binding to the transcriptional repressor REV-ERBβ
Authors: Mosure Sarah A. , Strutzenberg Timothy S. , Shang Jinsai , Munoz-Tello Paola , Solt Laura A. , Griffin Patrick R. , Kojetin Douglas J.
Published: January 2021

Structural and biochemical evidence resolves previous contradictory findings for heme-dependent NCoR recruitment to REV-ERBβ.
Orographic evolution of northern Tibet shaped vegetation and plant diversity in eastern Asia
Authors: Li Shu-Feng , Valdes Paul J. , Farnsworth Alex , Davies-Barnard T. , Su Tao , Lunt Daniel J. , Spicer Robert A. , Liu Jia , Deng Wei-Yu-Dong , Huang Jian , Tang He , Ridgwell Andy , Chen Lin-Lin , Zhou Zhe-Kun
Published: January 2021

Orogenesis in northern Tibet determines the vegetation and plant diversity of eastern Asia by intensifying winter precipitation.
NOTCH1-driven UBR7 stimulates nucleotide biosynthesis to promote T cell acute lymphoblastic leukemia
Authors: Srivastava Shashank , Sahu Umakant , Zhou Yalu , Hogan Ann K. , Sathyan Kizhakke Mattada , Bodner Justin , Huang Jiehuan , Wong Kelvin A. , Khalatyan Natalia , Savas Jeffrey N. , Ntziachristos Panagiotis , Ben-Sahra Issam , Foltz Daniel R.
Published: January 2021

UBR7 supports nucleotide biosynthesis and NOTCH1-driven T cell acute lymphoblastic leukemia through regulation of PRPS enzymes.
A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action
Authors: Bai Silei , Wang Jianxue , Yang Kailing , Zhou Cailing , Xu Yangfan , Song Junfeng , Gu Yuanxin , Chen Zheng , Wang Min , Shoen Carolyn , Andrade Brenda , Cynamon Michael , Zhou Kai , Wang Hui , Cai Qingyun , Oldfield Eric , Zimmerman Steven C. , Bai Yugang , Feng Xinxin
Published: January 2021

An oligoamidine with two bacteria-specific mechanisms of action showed broad-spectrum, resistance-resistant antimicrobial effect.
The structure of the actin filament uncapping complex mediated by twinfilin
Authors: Mwangangi Dennis M. , Manser Edward , Robinson Robert C.
Published: January 2021

Competitive interactions between capping protein, twinfilin, and actin drive actin filament uncapping and recycling.
Architecture and regulation of an enterobacterial cellulose secretion system
Authors: Abidi Wiem , Zouhir Samira , Caleechurn Meryem , Roche Stéphane , Krasteva Petya Violinova
Published: January 2021

Structural snapshots decipher nucleotide dependence, asymmetry, and polymerization in the enterobacterial cellulose secretion.
Meta-optics achieves RGB-achromatic focusing for virtual reality
Authors: Li Zhaoyi , Lin Peng , Huang Yao-Wei , Park Joon-Suh , Chen Wei Ting , Shi Zhujun , Qiu Cheng-Wei , Cheng Ji-Xin , Capasso Federico
Published: January 2021

A large dispersion-engineered metalens achieves multicolor focusing and opens a path to a future virtual reality platform.
Engineering biopharmaceutical formulations to improve diabetes management
Authors: Maikawa Caitlin L. , d’Aquino Andrea I. , Lal Rayhan A. , Buckingham Bruce A. , Appel Eric A.
Published: January 2021

This Review provides an overview of developments in formulation engineering and delivery strategies of insulin for the treatment of diabetes.
Better together: Alveolar macrophage and memory T cell cosignaling in ex vivo human lungs
Authors: Keller Steven P.
Published: January 2021

Ex vivo lung perfusion enables assessment of the resident adaptive immune system and provides insight into the lung response to pathogen exposure.
Limited Utility of Procalcitonin in Identifying Community-Associated Bacterial Infections in Patients Presenting with Coronavirus Disease 2019
Authors: May Michael , Chang Michelle , Dietz Donald , Shoucri Sherif , Laracy Justin , Sobieszczyk Magdalena E. , Uhlemann Anne-Catrin , Zucker Jason , Kubin Christine J.
Published: January 2021

The role of procalcitonin in identifying community-associated bacterial infections among patients with coronavirus disease 2019 is not yet established. In 2,443 patients with 148 bacterial coinfections, mean procalcitonin levels were significantly higher with any bacterial infection (13.16 ± 51.19 ng/ml;
P
= 0.0091) and with bacteremia (34.25 ± 85.01 ng/ml;
P
= 0.0125) than without infection (2.00 ± 15.26 ng/ml).
Laboratory Diagnosis of Lyme Borreliosis
Authors: Branda John A. , Steere Allen C.
Published: January 2021

Lyme borreliosis is caused by a growing list of related, yet distinct, spirochetes with complex biology and sophisticated immune evasion mechanisms.
Is the Patient Infected with SARS-CoV-2?
Authors: Klausner Jeffrey D. , Kojima Noah , Butler-Wu Susan M.
Published: January 2021

The U.S. Food and Drug Administration currently uses the nasopharyngeal swab specimen as the reference standard for evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. We propose that the patient-infected status algorithm is a superior way to classify whether an individual is infected or not infected.
Draft Genome Sequences of the Black Truffles Tuber brumale Vittad. and Tuber indicum Cook & Massee
Authors: Morin Emmanuelle , Murat Claude , Cichocki Nicolas , De la Varga Herminia , Kohler Annegret , Xu Jianping , Grigoriev Igor V. , Martin Francis M.
Published: January 2021

Tuber brumale
and
Tuber indicum
(Pezizomycetes) are two edible black truffles establishing ectomycorrhizal symbiosis with trees and shrubs.
T. brumale
is ubiquitous in Europe, and
T. indicum
is mainly found in China. Here, we present the draft genome sequences of
T. brumale
and
T. indicum
.
Draft Genome Sequences of a Bacillus subtilis Strain, a Bacillus velezensis Strain, a
Paenibacillus
Strain, and an Acinetobacter baumannii Strain, All Isolated from the Phyllosphere of Lactuca sativa or Solanum lycopersicum
Authors: Muñoz Claudia Y. , de Jong Anne , Kuipers Oscar P.
Published: January 2021

Four strains isolated from tomato and lettuce phyllosphere were sequenced in order to investigate the presence of novel antimicrobial gene clusters and to get a better understanding of plant microbe interactions. These strains comprise two
Bacillus
strains, one
Paenibacillus
strain, and one
Acinetobacter
strain.
Complete Genome Sequences of Two Environmental
Legionella
Isolates Obtained from Potable Water Sourced in a First Nation Community
Authors: MacMartin Teassa L. , Graham Christopher I. , Farenhorst Annemieke , Brassinga Ann Karen C.
Published: January 2021

Here, we report the complete genome sequences of two distinct isolates of
Legionella
that were obtained from potable water sourced from cistern-bearing homes within a First Nation community in Manitoba, Canada.
Genome Sequences of 10 SARS-CoV-2 Viral Strains Obtained by Nanopore Sequencing of Nasopharyngeal Swabs in Malta
Authors: Biazzo Manuele , Madeddu Silvia , Elnifro Elfath , Sultana Tessabella , Muscat Josie , Scerri Christian A. , Santoro Francesco , Pinzauti David
Published: January 2021

The genome sequences of 10 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains from Sliema, Malta, were obtained by Nanopore sequencing using the amplicon sequencing approach developed by the Artic Network. The assembled genomes were analyzed with Pangolin software and assigned to the B.1 lineage, which is widely circulating in Europe.
Draft Genome Sequences of
Dysgonomonas
sp. Strains BGC7 and HGC4, Isolated from the Hindgut of a Lower Termite
Authors: Bridges Charles M. , Nelson Michael C. , Graf Joerg , Gage Daniel J.
Published: January 2021

Dysgonomonas
spp. are facultative heterotrophs which colonize diverse environments, including the hindgut of the lower termite
Reticulitermes flavipes
.
Dysgonomonas
genomes are enriched for genes involving oligo- and polysaccharide utilization, enabling modification of a wide array of complex glycans. Here, we report draft genome sequences for
Dysgonomonas
sp. strains BGC7 and HGC4.
mSphere of Influence: Apoptotic Mimicry and Virus Entry
Authors: Brindley Melinda A.
Published: January 2021

Melinda A. Brindley works in the field of virology with specific interests in understanding how viruses enter cells. In this mSphere of Influence article, she reflects on how the paper “Vaccinia virus uses macropinocytosis and apoptotic mimicry to enter host cells” by J. Mercer and A. Helenius (Science 320:531–535, 2008,
https://doi.org/10.1126/science.1155164
) made an impact on her by expanding our understanding of virus-host interactions and virus-cell binding.
Primary amenorrhoea as a manifestation of coeliac disease
Authors: Costa Sara Todo Bom , Sanmarful Inês Salas
Published: January 2021

Coeliac disease is a systemic autoimmune disorder that has a wide range of clinical manifestations that include abdominal pain, diarrhoea, obstipation, weight loss, short stature and even primary amenorrhoea. It can be asymptomatic, which makes it an underdiagnosed disease. We present a case report of a 15-year-old girl who was referred to a paediatric consultation due to primary amenorrhoea. A detailed clinical history revealed poor weight gain. Physical examination showed that secondary sexual characteristics were present and there was a low body mass index. Ultrasonography images and laboratory tests revealed a normal urogenital system and an adequate gonadal function. Coeliac disease antibodies were positive and the diagnosis was confirmed through duodenal biopsy. The symptom resolved with a gluten-free diet. An approach to primary amenorrhoea should always include investigation of a systemic illness as it is a rare but treatable diagnosis.
Neglected Achilles tendon rupture associated with rheumatoid arthritis: a case report and a brief review of the literature
Authors: Moreira Flávia Pinto , Sousa António , Machado Sara
Published: January 2021

We report a case about a 69-year-old man, suffering from rheumatoid arthritis, diagnosed with a neglected Achilles tendon rupture. Considering the large Achilles tendon gap and the bad quality of the autologous tendons caused by rheumatoid disease, a reconstruction using an Achilles tendon with calcaneus bone block allograft was performed, with excellent clinical and functional outcomes.
Management of bilateral osteochondritis dissecans of the trochlea in a skeletally immature patient
Authors: Eichman Elizabeth A , Harris Benjamin T , Burrus M Tyrrell
Published: January 2021

Osteochondritis dissecans (OCD) lesions are injuries that occur more commonly in the skeletally immature population. In most cases, the aetiology is not well understood, but fortunately, many OCD lesions may heal on their own over time, particularly in skeletally immature patients with open physes. Conversely, if the lesion is considered unstable, surgical intervention may be required. This case demonstrates an especially rare presentation of bilateral OCD lesions within the lateral femoral trochlear facet. The lesions became symptomatic approximately 1 year apart without a specific injury. Non-operative treatment was not recommended in either case due to the size and instability of each lesion. The surgical treatment used an augmented microfracture technique. At 12 and 23 months after surgery, both knees remain asymptomatic and the patient has returned to their desired activities.
IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy
Authors: Chen Tianyue , Ding Xiangqing , Liao Qibin , Gao Nan , Chen Ye , Zhao Chen , Zhang Xiaoyan , Xu Jianqing
Published: January 2021

Background

Oncolytic viruses (OVs) have shown promise in containing cancer progression in both animal models and clinical trials. How to further improve the efficacy of OVs are intensively explored. Arming OVs with immunoregulatory molecules has emerged as an important means to enhance their oncolytic activities majorly based on the mechanism of reverting the immunosuppressive nature of tumor environment. In this study, we aimed to identify the optimal combination of different OVs and immunomodulatory molecules for solid tumor treatment as well as the underlying mechanism, and subsequently evaluated its potential synergy with other immunotherapies.

Methods

Panels of oncolytic viruses and cells stably expressing immunoregulatory molecules were separately evaluated for treating solid tumors in mouse model. A tumor-targeted replicating vaccinia virus Tian Tan strain with deletion of TK gene (TTVΔTK) was armed rationally with IL-21 to create rTTVΔTK-IL21 through recombination. CAR-T cells and iNKT cells were generated from human peripheral blood mononuclear cells. The impact of rTTVΔTK-IL21 on tumor-infiltrating lymphocytes was assessed by flow cytometry, and its therapeutic efficacy as monotherapy or in combination with CAR-T and iNKT therapy was assessed in mouse tumor models.

Results

IL-21 and TTV was respectively identified as most potent immunomodulatory molecule and oncolytic virus for solid tumor suppression in mouse models. A novel recombinant oncolytic virus that resulted from their combination, namely rTTVΔTK-mIL21, led to significant tumor regression in mice, even for noninjected distant tumor. Mechanistically, rTTV∆TK-mIL21 induced a selective enrichment of immune effector cells over Treg cells and engage a systemic response of therapeutic effect. Moreover, its human form showed a notable synergy with CAR-T or iNKT therapy for tumor treatment when coupled in humanized mice.

Conclusion

With a strong potency of shaping tumor microenvironment toward favoring TIL activities, rTTVΔTK-IL21 represents a new opportunity worthy of further exploration in clinical settings for solid tumor control, particularly in combinatorial strategies with other immunotherapies.

One sentence summary

IL21-armed recombinant oncolytic vaccinia virus has potent anti-tumor activities as monotherapy and in combination with other immunotherapies.
Rapid sequence induction
Authors: Fry R , Scott T
Published: January 2021

Emergency tracheal intubation undertaken by Rapid sequence induction (RSI) is a fundamental component of military anaesthesia. This common emergency procedure has evolved in both civilian and military practice, since it was first described, as new drugs have become available. Current practice now differs significantly from that undertaken by the procedure’s initial advocates. This is particularly the case in the deployed military environment. As military medicine continues to improve injury survivability, RSI will be undertaken in increasingly unstable casualties, requiring a bespoke emergency induction not commonly practised in the civilian setting.

This article will discuss RSI as first described, explore how this technique has been modified in domestic practice and describe how it can be adapted for use in austere environments for our most severely injured personnel.
An overview of common diseases of the nasal cavity and paranasal sinuses
Authors: Easto R , Shukla R , Williams R
Published: January 2021

Diseases of the nasal cavity and paranasal sinuses are a common complaint amongst the general population and service personnel. Chronic rhinosinusitis, with or without nasal polyps, and nasal deformity leading to airway obstruction are some of the commonest ear, nose and throat (ENT) conditions encountered. However, hidden within this generally benign group of conditions are some potentially lethal problems that clinicians need to be able to recognise.

This article aims to provide an overview of common conditions affecting the nose and paranasal sinuses, including fractured nasal bones, acute rhinosinusitis and its complications, and chronic rhinosinusitis. Epistaxis and sinonasal malignancies are largely outside the scope of this paper. Background information on pathogenesis will be described, along with guidance on diagnosis and management with particular stress on emergency pre-hospital treatment and indications for referral to an ENT specialist.
The management of acute hip pain in the military
Authors: Green NM , Matthews JJ
Published: January 2021

Acute hip pain is a common presenting complaint amongst the military population. It can present in a variety of ways, with a broad range of differential diagnoses to consider. Most cases of acute hip pain in military patients tend to be traumatic in origin. Pathology within the hip can be a diagnostic challenge, as symptoms often overlap between differential diagnoses and examination findings are not always sensitive or specific. Any hip injury will potentially downgrade a military patient and can also be a significant cause of long-term morbidity. Being able to manage the patient with acute hip pain effectively will ensure that patients spend less time in the diagnostic chain and reach the definitive treatment they require to continue to carry out their primary role.

This paper describes how best to manage military patients who present with acute hip pain. It covers the diagnostic challenges faced by clinicians, the differential diagnoses of acute hip pain and describes the management of some common injuries of the hip: tears of the acetabular labrum and femoral neck stress fractures.
Sir Gilbert Blane FRS: the man and his legacy
Authors: Penn-Barwell Jowan G
Published: January 2021

Sir Gilbert Blane (1749-1834) was a Medical Officer in the Royal Navy who saw action against both the French and Spanish fleets, and later served as a Commissioner on the Sick and Wounded Board of the Admiralty. His work to improve the living conditions and health of sailors, and the significant reductions in sickness rates this achieved, brought him national recognition and honours

In 1830, Sir Gilbert Blane established a legacy with the Royal College of Surgeons of England for the award of a Gold Medal in his name to be awarded to medical officers‘who have brought about an advancement….or improvement in any matter affecting the health or living conditions of Naval personnel’. The first two Gilbert Blane medals were awarded in 1832, and the eponymous award continues to this day, 182 years after his death.
Algorithm for cavo-tricuspid isthmus flutter on surface ECGs: the ACTIONS study
Authors: Frisch Daniel R , Frankel Eitan , Gill Deanna , Danaf Jad Al
Published: January 2021

Objective

Cavo-tricuspid isthmus atrial flutter (CTI-AFL) is an important arrhythmia to recognise because there is a highly effective and relatively low-risk ablation strategy. However, clinical experience has demonstrated that providers often have difficulty distinguishing AFL from atrial fibrillation.

Methods

We developed a novel ECG-based three-step algorithm to identify CTI-AFL based on established CTI flutter characteristics and verified on consecutive ablation cases of typical flutter, atypical flutter and atrial fibrillation. The algorithm assesses V1/inferior lead F-wave concordance, consistency of P-wave morphology and the presence of isoelectric intervals in the inferior leads. In this observation study, the algorithm was validated on a cohort of 50 second-year medical students. Students were paired in a control and experimental group, and each pair received 10 randomly selected ECGs (from a pool of 50 intracardiac electrogram-proven CTI-AFL and 50 AF or atypical AFL cases). The experimental group received a cover sheet with the CTI algorithm, and the control group received no additional guidance.

Results

There was a statistically significant difference in the mean number of correctly identified ECGs among the students in the experimental and control groups (8.12 vs 5.68, p<0.001). Students who used the algorithm correctly identified 2.44 more ECGs as being CTI-AFL or not CTI-AFL. Using the electrophysiology study as the gold standard, the algorithm had an accuracy of 81%, sensitivity of 81%, specificity of 82%, positive predictive value of 78% and negative predictive value of 84% in identifying CTI-AFL.

Conclusion

We developed a three-step ECG algorithm that provides a simple, sensitive, specific and accurate tool to identify CTI-AFL.
Effect of significant weight loss on disease activity: reason to implement this non-pharmaceutical intervention in daily clinical practice
Authors: Weijers Julia M , Müskens Wieland D , van Riel Piet L C M
Published: January 2021

Obesity is very common in patients with inflammatory rheumatic diseases (IRDs), of which between 27% and 37% of patients have a body mass index ≥30 kg/m2. In addition to further increasing the risk of developing cardiovascular diseases (CVDs) in this group of patients, obesity is associated with higher disease activity and a lower response to drug therapy. This case series showed that in those patients with rheumatoid arthritis or psoriatic arthritis with a substantial weight loss of >10% of body mass, median Disease Activity Score 28 joints score decreased with 0.9. This reduction in disease activity resulted in an increase in the percentage of patients achieving remission from 6% to 63%. This reduction in disease activity was obtained without intensification of medical treatment in 87% of the patients. This case series supports the current evidence that weight reduction has positive effects on the course of the disease and thus also on the CVD risk profile in these patients. Therefore, weight loss can serve as a non-pharmacological treatment option in obese patients with IRDs.