bluuebunny/crossref_metadata_2025 huggingface dataset:
Two protein disulfide isomerase subgroups work synergistically in catalyzing oxidative protein folding
Authors: Fan Fenggui , Zhang Qiao , Zhang Yini , Huang Guozhong , Liang Xuelian , Wang Chih-chen , Wang Lei , Lu Dongping
Published: September 2021

Disulfide bonds play essential roles in the folding of secretory and plasma membrane proteins in the endoplasmic reticulum (ER). In eukaryotes, protein disulfide isomerase (PDI) is an enzyme catalyzing the disulfide bond formation and isomerization in substrates. The Arabidopsis (Arabidopsis thaliana) genome encodes diverse PDIs including structurally distinct subgroups PDI-L and PDI-M/S. It remains unclear how these AtPDIs function to catalyze the correct disulfide formation. We found that one Arabidopsis ER oxidoreductin-1 (Ero1), AtERO1, can interact with multiple PDIs. PDI-L members AtPDI2/5/6 mainly serve as an isomerase, while PDI-M/S members AtPDI9/10/11 are more efficient in accepting oxidizing equivalents from AtERO1 and catalyzing disulfide bond formation. Accordingly, the pdi9/10/11 triple mutant exhibited much stronger inhibition than pdi1/2/5/6 quadruple mutant under dithiothreitol treatment, which caused disruption of disulfide bonds in plant proteins. Furthermore, AtPDI2/5 work synergistically with PDI-M/S members in relaying disulfide bonds from AtERO1 to substrates. Our findings reveal the distinct but overlapping roles played by two structurally different AtPDI subgroups in oxidative protein folding in the ER.
NtMYB305a binds to the jasmonate-responsive GAG region of NtPMT1a promoter to regulate nicotine biosynthesis
Authors: Bian Shiquan , Sui Xueyi , Wang Jiahao , Tian Tian , Wang Chunkai , Zhao Xue , Liu Xiaofeng , Fang Ning , Zhang Yu , Liu Yanhua , Du Yongmei , Wang Bingwu , Timko Michael P , Zhang Zhongfeng , Zhang Hongbo
Published: September 2021

MYB transcription factors play essential roles in regulating plant secondary metabolism and jasmonate (JA) signaling. Putrescine N-methyltransferase is a key JA-regulated step in the biosynthesis of nicotine, an alkaloidal compound highly accumulated in Nicotiana spp. Here we report the identification of NtMYB305a in tobacco (Nicotiana tabacum) as a regulatory component of nicotine biosynthesis and demonstrate that it binds to the JA-responsive GAG region, which comprises a G-box, an AT-rich motif, and a GCC-box-like element, in the NtPMT1a promoter. Yeast one-hybrid analysis, electrophoretic mobility shift assay and chromatin immunoprecipitation assays showed that NtMYB305a binds to the GAG region in vitro and in vivo. Binding specifically occurs at the ∼30-bp AT-rich motif in a G/C-base-independent manner, thus defining the AT-rich motif as previously unknown MYB-binding element. NtMYB305a localized in the nucleus of tobacco cells where it is capable of activating the expression of a 4×GAG-driven GUS reporter in an AT-rich motif-dependent manner. NtMYB305a positively regulates nicotine biosynthesis and the expression of NtPMT and other nicotine pathway genes. NtMYB305a acts synergistically with NtMYC2a to regulate nicotine biosynthesis, but no interaction between these two proteins was detected. This identification of NtMYB305a provides insights into the regulation of nicotine biosynthesis and extends the roles played by MYB transcription factors in plant secondary metabolism.
Concentration Bias in Intertemporal Choice
Authors: Dertwinkel-Kalt Markus , Gerhardt Holger , Riener Gerhard , Schwerter Frederik , Strang Louis
Published: September 2021

Many intertemporal trade-offs are unbalanced: while the advantages of options are concentrated in a few periods, the disadvantages are dispersed over numerous periods. We provide novel experimental evidence for “concentration bias,” the tendency to overweight advantages that are concentrated in time. Subjects commit to too much overtime work that is dispersed over multiple days in exchange for a bonus that is concentrated in time: concentration bias increases subjects’ willingness to work by 22.4% beyond what standard discounting models could account for. In additional conditions and a complementary experiment involving monetary payments, we study the mechanisms behind concentration bias and demonstrate the robustness of our findings.
Collateral Booms and Information Depletion
Authors: Asriyan Vladimir , Laeven Luc , Martín Alberto
Published: September 2021

We develop a new theory of information production during credit booms. Entrepreneurs need credit to undertake investment projects, some of which enable them to divert resources. Lenders can protect themselves from such diversion in two ways: collateralization, and costly screening that generates durable information about projects. In equilibrium, the collateralization-screening mix depends on the value of aggregate collateral. High collateral values make it possible to reallocate resources towards productive projects, but they also crowd out screening. This has important dynamic implications. During credit booms driven by high collateral values (e.g. real estate booms), economic activity expands but the economy’s stock of information on existing projects gets depleted. As a result, collateral-driven booms end in deep crises and slow recoveries: when booms end, investment is constrained both by the lack of collateral and by the lack of information on existing projects, which takes time to rebuild. We provide empirical support for the mechanism using US firm-level data.
Discordance in patient and physician global assessment in relapsing polychondritis
Authors: Rose Emily , Ferrada Marcela A , Quinn Kaitlin A , Arnaud Laurent , Goodspeed Wendy , Kim Jeff , Allen Clint , Sirajuddin Arlene , Chen Marcus , Grayson Peter C
Published: September 2021

Objectives

Relapsing polychondritis (RP) is a rare, heterogeneous, systemic inflammatory disease that targets cartilage. Patient-reported outcome measures may differ from physician assessment. This study compared patient global assessment (PtGA) and physician global assessment (PhGA) scores in a prospective cohort of patients with RP.

Methods

Adult patients with RP underwent a standardized comprehensive evaluation at ∼6 month intervals. At each visit, three physicians scored PhGA by consensus. The patient independently completed four patient-reported outcomes: PtGA, 36-item Short Form Health Survey (SF-36), Brief Illness Perception Questionnaire (BIPQ) and Multidimensional Fatigue Inventory (MFI). Patient–physician discordance was defined as a difference between PtGA and PhGA of ≥3 on a 0–10 scale.

Results

A total of 76 patients were evaluated over 154 visits. The median PhGA was 3 [interquartile range (IQR) 2–3] and the median PtGA was 5 (IQR 4–7). PtGA and PhGA were concordant in 66 visits (42.9%) and patients scored disease severity ≥3 points higher than physicians scored disease activity (positive discordance) in 84 visits (54.5%). Compared with visits with concordance, visits with positive discordance were associated with significantly worse scores on the MFI, BIPQ, SF-36 physical component score and SF-36 mental component score.

Conclusion

Patients with RP typically self-report high PtGA that does not align with PhGA. Discordance is likely driven by the high physical and psychological burden of illness experienced by patients. Multifaceted treatment approaches that address the burden of disease in RP from the patient perspective are needed.
Burden of comorbid conditions in children and young people with juvenile idiopathic arthritis: a collaborative analysis of 3 JIA registries
Authors: Kearsley-Fleet Lianne , Klotsche Jens , van Straalen Joeri W , Costello Wendy , D’Angelo Gianfranco , Giancane Gabriella , Horneff Gerd , Klein Ariane , Láday Matilda , Lunt Mark , de Roock Sytze , Ruperto Nicolino , Schoemaker Casper , Vijatov-Djuric Gordana , Vojinovic Jelena , Vougiouka Olga , Wulffraat Nico M ,   UK JIA Biologics Registers Investigators Group; Paediatric Rheumatology International Trials Organisation (PRINTO), Hyrich Kimme L , Minden Kirsten , Swart Joost F
Published: September 2021

Objectives

Burden of comorbidities are largely unknown in JIA. From 2000, national and international patient registries were established to monitor biologic treatment, disease activity and adverse events in patients with JIA. The aim of this analysis was to investigate in parallel, for the first time, three of the largest JIA registries in Europe/internationally—UK JIA Biologic Registers (BCRD/BSPAR-ETN), German biologic registers (BiKeR/JuMBO), multinational Pharmachild—to quantify the occurrence of selected comorbidities in patients with JIA.

Methods

Information on which data the registers collect were compared. Patient characteristics and levels of comorbidity were presented, focussing on four key conditions: uveitis, MAS, varicella, and history of tuberculosis. Incidence rates of these on MTX/biologic therapy were determined.

Results

8066 patients were registered into the three JIA registers with similar history of the four comorbidities across the studies; however, varicella vaccination coverage was higher in Germany (56%) vs UK/Pharmachild (16%/13%). At final follow-up, prevalence of varicella infection was lower in Germany (15%) vs UK/Pharmachild (37%/50%). Prevalence of TB (0.1–1.8%) and uveitis (15–19%) was similar across all registers. The proportion of systemic-JIA patients who ever had MAS was lower in Germany (6%) vs UK (15%) and Pharmachild (17%).

Conclusion

This analysis is the first and largest to investigate the occurrence of four important comorbidities in three JIA registries in Europe and the role of anti-rheumatic drugs. Combined, these three registries represent one of the biggest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies.
The rise of UK–China research collaboration: Trends, opportunities and challenges
Authors: Adams Jonathan , Johnson Jo , Grant Jonathan
Published: September 2021

China has become an impactful science superpower, but it is asserted that its influence provides it with disproportionate benefits that some national research policies have not thus far appreciated. To create context, Web of Science data are used to analyse research collaborations between the UK and China: trends in volume of output between 1981 and 2019; citation impact; and comparative performance across research fields. UK–China collaboration increased from fewer than 100 co-authored papers before 1990, to 750 per year in 2000, 3,324 in 2010, and 16,267 papers (10.9 per cent of UK output) in 2019. UK–China collaboration is concentrated in technology-based fields: in some (e.g. telecommunication), over 30 per cent of UK papers are in collaboration with Chinese-based researchers. The paper discusses the policy consequences to the UK of this indicative dependency, arguing that exiting from such collaborations is ill advised, provided the risks, perceived or real, are mapped, managed, and mitigated.
The Silicon Valley imaginary: US corporate tax reform in the 1980s
Authors: Ergen Timur , Rademacher Inga
Published: September 2021

How do policy paradigms change? This article demonstrates that changing social imaginaries about economic growth enabled paradigmatic changes in USA corporate tax policy in the 1980s. Based on archival sources, it reconstructs how policy makers switched from focused support for capital-intensive smoke-stack industries towards support for emerging high tech-sectors between two major tax-bills in 1981 and 1986. This switch was made possible by the emergence of what we call the Silicon Valley imaginary—the idea that sound economic policies stimulate the reallocation of society’s resources towards new economic fields. The emergence of this social imaginary resulted from political realignments and changing notions of economic growth and justice. The search for sources of future economic growth and societal coalitions led policy-makers to appropriate ideas about the promises of new industries.
Prospective Study to Assess the Response to Therapy and Its Predictors in Children with Scrub Typhus
Authors: Arun Babu Thirunavukkarasu , Narayanasamy Dinesh Kumar , Jamir Limalemla
Published: September 2021

Doxycycline is the drug of choice for pediatric scrub typhus (ST) while azithromycin is considered as an equally effective alternative. This study was undertaken to assess the response to therapy and its predictors in pediatric ST cases treated with doxycycline and azithromycin. Children ≤12 year with fever ≥7 days were screened for ST by IgM ELISA (positive if optical density >0.5). All positive cases were divided into two groups based on whether treated with doxycycline or azithromycin. Fever clearance time (FCT), duration of hospitalization and other clinical characteristics of cases in both groups were compared. Out of 2710 children admitted with fever for more than 7 days, 660 cases (24.35%) tested positive for ST by IgM ELISA. Cases treated with azithromycin and doxycycline were 316 (47.87%) and 344 (52.12%), respectively. In our study, the FCT (p = 0.004), mean duration of hospital stay (p = 0.011), persistence of fever for >48 h after starting antibiotic therapy (p = 0.001) and severe ST requiring ICU admission (p = 0.046) were significantly lower in children who received doxycycline. The logistic regression analysis revealed that the presence of splenomegaly (Adjusted Odds Ratio (AOR) 2.60; 95% Confidence interval (CI) = 1.49–4.53; p = 0.001) and lung crepts (AOR 2.02; 95% CI = 1.06–3.85; p = 0.032) in azithromycin-treated group and presence of meningeal signs (AOR 16.11; 95% CI = 5.47–47.45; p < 0.001), anemia (AOR 2.28; 95% CI = 1.02–5.08; p = 0.044), lung crepts (AOR 2.66; 95% CI = 1.16–6.05; p = 0.020) and absence of eschar (AOR 3.48; 95% CI = 1.70–7.13; p = 0.001) in the doxycycline group was significantly associated with prolonged FCT (>48 h). Doxycycline is superior to azithromycin in defervescing fever, reducing hospital stay and preventing severity in pediatric ST.
Isolation and identification of potentially pathogenic free-living amoeba in dialysis fluid samples of hydraulic systems in hemodialysis units
Authors: Biglarnia Farzaneh , Solhjoo Kavous , Rezanezhad Hassan , Taghipour Ali , Armand Belal
Published: September 2021

Background

Free-living amoeba (FLA), including Acanthamoeba, Naegleria, Balamuthia and Vermamoeba, have been isolated from water, sand, soil, dust and air. Numerous studies considered that FLA are a significant cause of neurological and ocular complications in high-risk groups, including immunocompromised individuals. The present study aimed to identify morphological and molecular characteristics of FLA isolates in dialysis fluid samples of hydraulic systems in hemodialysis units in Iran.

Methods

A total of 328 dialysis fluid samples were collected from 16 dialysis machines, including 164 samples before hemodialysis sessions (after cleaning) and 164 samples after hemodialysis sessions (before cleaning). Filtration and cultivation were performed on non-nutrient agar medium. Also, PCR and sequencing were applied by using the genus-specific primers along with a common primer set on positive samples.

Results

Both morphology and molecular investigations showed that 22.5% (74/328) of dialysis fluid samples were positive for FLA. There was a positive relationship between the high frequency of FLA after hemodialysis sessions (before cleaning) compared with before hemodialysis sessions (after cleaning) (OR=2.86; 95% CI 1.5 to 5.45). Considering the PCR assay, 16.46% (54/328) samples were identified as Acanthamoeba spp. (belonging to T3 and T4 genotypes), 5.18% (17/328) as Vermamoeba vermiformis and 0.91% (3/328) as Vahlkampfiidae family (Naegleria australiensis, Naegleria pagei and Allovahlkampfia).

Conclusion

The present results support a need to improve filtration and purification methods for dialysis fluid of hydraulic systems in hemodialysis units. They also highlight the relevance of periodic screenings for FLA-related diseases in hemodialysis patients.
7Psychoanalysis
Authors: Vashisht Jivitesh
Published: September 2021

Psychoanalysis has served as a time-tested, albeit occasionally contentious, method for interpreting a range of literary and cultural works, but how might we account for its own textual cultures and practices? For that matter, are psychoanalytic and literary genres distinct entities, or is their interface significantly more porous than we might imagine at first? In what follows, I review four critical texts published in 2020 (a double issue of a journal and two monographs) that grapple with various aspects of these questions and offer rich, formally attentive studies of psychoanalytic writing and its entanglements with literary genres such as the novella, memoir, and autobiography. The review is organized into four sections: 1. Introduction. Psychoanalysis: A Writing Cure? 2. After John Forrester: Reopening the Psychoanalytic Case, which discusses Felicity Callard and Chris Millard’s guest-edited issue of History of the Human Sciences entitled Thinking In, With, Beyond, and Across Cases with John Forrester; 3. The Freudian Case History and its Literary Legacies, devoted to Arne Höcker’s The Case of Literature: Forensic Narratives from Goethe to Kafka; and 4. Recovering the Analysand’s Voice, which explores Anat Tzur Mahalel’s Reading Freud’s Patients: Memoir, Narrative, and the Analysand.
An Improved Assembly of theAlbugo candidaAc2V Genome Reveals the Expansion of the “CCG” Class of Effectors
Authors: Furzer Oliver J. , Cevik Volkan , Fairhead Sebastian , Bailey Kate , Redkar Amey , Schudoma Christian , MacLean Dan , Holub Eric B. , Jones Jonathan D. G.
Published: September 2021

Albugo candida is an obligate oomycete pathogen that infects many plants in the Brassicaceae family. We resequenced the genome of isolate Ac2V using PacBio long reads and constructed an assembly augmented by Illumina reads. The Ac2VPB genome assembly is 10% larger and more contiguous compared with a previous version. Our annotation of the new assembly, aided by RNA-sequencing information, revealed a 175% expansion (40 to 110) in the CHxC effector class, which we redefined as “CCG” based on motif analysis. This class of effectors consist of arrays of phylogenetically related paralogs residing in gene sparse regions, and shows signatures of positive selection and presence/absence polymorphism. This work provides a resource that allows the dissection of the genomic components underlying A. candida adaptation and, particularly, the role of CCG effectors in virulence and avirulence on different hosts.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
An Advanced One-Step RT-LAMP for Rapid Detection ofLittle cherry virus 2Combined with High-Throughput Sequence-Based Phylogenomics Reveal Divergent Flowering Cherry Isolates
Authors: Tahzima Rachid , Foucart Yoika , Peusens Gertie , Reynard Jean-Sébastien , Massart Sébastien , Beliën Tim , De Jonghe Kris
Published: September 2021

Little cherry virus 2 (LChV-2, genus Ampelovirus) is considered to be the main causal agent of the economically damaging little cherry disease, which can only be controlled by removal of infected trees. The widespread viral disease of sweet cherry (Prunus avium L.) is affecting the survival of long-standing orchards in North America and Europe, hence the dire need for an early and accurate diagnosis to establish a sound disease control strategy. The endemic presence of LChV-2 is mainly confirmed using laborious time-consuming reverse-transcription (RT-PCR). A rapid reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay targeting a conserved region of the coat protein was developed and compared with conventional RT-PCR for the specific detection of LChV-2. This affordable assay, combined with a simple RNA extraction, deploys desirable characteristics such as higher ability for faster (<15 min), more analytically sensitive (100-fold), and robust broad-range diagnosis of LChV-2 isolates from sweet cherry, ornamental flowering cherry displaying heterogenous viral etiology and, for the first time, newly identified potential insect vectors. Moreover, use of Sanger and total RNA high-throughput sequencing as complementary metaviromics approaches confirmed the LChV-2 RT-LAMP detection of divergent LChV-2 isolates in new hosts and the relationship of their whole-genome was exhaustively inferred using maximum-likelihood phylogenomics. This entails unprecedented critical understanding of a novel evolutionary clade further expanding LChV-2 viral diversity. In conclusion, this highly effective diagnostic platform facilitates strategical support for early in-field testing to reliably prevent dissemination of new LChV-2 outbreaks from propagative plant stocks or newly postulated insect vectors. Validated results and major advantages are herein thoroughly discussed, in light of the knowledge required to increase the potential accuracy of future diagnostics and the essential epidemiological considerations to proactively safeguard cherries and Prunus horticultural crop systems from little cherry disease.
Stemphylium Leaf Blight: A Re-Emerging Threat to Onion Production in Eastern North America
Authors: Hay Frank , Stricker Sara , Gossen Bruce D. , McDonald Mary Ruth , Heck Daniel , Hoepting Christy , Sharma Sandeep , Pethybridge Sarah
Published: September 2021

Stemphylium leaf blight (SLB), caused by Stemphylium vesicarium, is a foliar disease of onion worldwide, and has recently become an important disease in the northeastern United States and Ontario, Canada. The symptoms begin as small, tan to brown lesions on the leaves that can progress to defoliate plants. Crop loss occurs through reduced photosynthetic area, resulting in smaller, lower-quality bulbs. Leaf necrosis caused by SLB also can compromise bulb storage, as green leaves are required for the uptake of sprout inhibitors applied prior to harvest. The pathogen can overwinter on infested onion residue and infected volunteer plants. Asymptomatic weedy hosts near onion fields may also be a source of inoculum. Production of ascospores of the teleomorph (Pleospora allii) peaks in early spring in northeastern North America, often before the crop is planted, and declines rapidly as daily mean air temperatures rise. Conidia are usually present throughout the growing season. Application of fungicides is a standard practice for management of the complex of fungi that can cause foliar diseases of onion in this region. Recent assessments have shown that populations of S. vesicarium in New York and Ontario are resistant to at least three single-site mode-of-action fungicides. Three disease prediction systems have been developed and evaluated that may enable growers to reduce the frequency and/or number of fungicide applications, but the loss of efficacious fungicides due to resistance development within S. vesicarium populations threatens sustainability. The lack of commercially acceptable onion cultivars with sufficient resistance to reduce the number of fungicides for SLB also limits the ability to manage SLB effectively. Integrated disease management strategies for SLB are essential to maintain profitable, sustainable onion production across eastern North America.
Efficacy of Disinfectants Against Tropical Race 4 Causing Fusarium Wilt in Cavendish Bananas
Authors: Salacinas Maricar , Meijer Harold J. G. , Mamora Samuel Herbert , Corcolon Benny , Mirzadi Gohari Amir , Ghimire Bikal , Kema Gerrit H. J.
Published: September 2021

Fusarium wilt of banana (FWB), caused by a suite of Fusarium fungi, is among the most devastating plant diseases. The iconic FWB epidemic in the previous century lasted decades and was caused by so-called Race 1 strains that wiped out the dominant ‘Gros Michel’ banana plantations across Central America. Eventually, it was stopped because the Race 1-resistant ‘Cavendish’ banana variety replaced ‘Gros Michel’, which dominates global production (>50%) and trade (>95%). However, presently, the so-called Tropical Race 4 (TR4) threatens plantations of ‘Cavendish’ and many other banana varieties around the globe. Prevention is the first line of defense against the spread of TR4. Therefore, many disinfection units are installed to prevent the entry of TR4 in banana plantations. These foot and tire baths are filled with disinfectants, but limited knowledge is available on their efficacy. In this project, we evaluated 13 disinfectants commonly used in the Philippines. Our results show that the efficacy of these products depends on the type of fungal spores, the exposure time, and the replenishment frequency of the disinfection units. The resting spores of TR4 were resistant to all but one − unfortunately corrosive − disinfectant. Furthermore, we show that the actual contact time with disinfectants was far below the thresholds determined in laboratory experiments. Finally, muddy disinfection units reduced the efficacy of disinfectants. Taken together, we conclude that practices are inadequate to prevent the dissemination of TR4.
Factors Influencing Hypertrophic Scarring after Thyroidectomy
Authors: Xie Hang , Xiang Ying , Yang E. , Zhang HengShu
Published: September 2021

OBJECTIVE

To identify the risk factors of hypertrophic scarring (HS) after thyroidectomy and construct a risk prediction model.

METHODS

From November 2018 to March 2019, the clinical data of patients undergoing thyroidectomy were collected for retrospective analysis. According to the occurrence of HS, the patients were divided into an HS group and a non-HS group. Univariate analysis and binary logistic regression analysis were conducted to explore the independent risk factors for HS. Receiver operating characteristic analysis was also carried out.

RESULTS

In this sample, 121 of 385 patients developed HS, an incidence of 31.4%. Univariate analysis showed significant differences in sex, age, postoperative infection, history of abnormal wound healing, history of pathologic scar, family history of pathologic scar, and scar prevention measures between the two groups (P < .05). Binary logistic regression analysis indicated that age 45 years or younger (odds ratio [OR], 1.815), history of abnormal wound healing (OR, 4.247), history of pathologic scarring (OR, 9.840), family history of pathologic scarring (OR, 5.708), and absence of preventive scar measures (OR, 5.566) were independent factors for HS after thyroidectomy. The area under the receiver operating characteristic curve was 0.837. When the optimal diagnostic cutoff value was 0.206, the sensitivity was 0.661, and the specificity was 0.932.

CONCLUSIONS

The development of HS after thyroidectomy is related to many factors, and the proposed risk prediction model based on the combined risk factors shows a good predictive value for postoperative HS. When researchers consider the prevention and treatment of scarring in patients at risk, the incidence of HS in different populations can provide theoretical support for clinical decision-making.
Effectiveness of Ozone Therapy as an Adjunct Treatment for Lower-Limb Ulcers: A Systematic Review
Authors: Bomfim Tássia Lima , Gomes Isla Alcântara , Meneses Daniele de Vasconcelos Cerqueira , Araujo Adriano Antunes de Souza
Published: September 2021

OBJECTIVE

To evaluate the effectiveness of topical ozone therapy as an adjuvant treatment in the healing of lower limb ulcers through a systematic literature review.

DATA SOURCES

Three databases were used to search for studies conducted in the period up to and including September 2020: PubMed, Scopus, and the Web of Science.

STUDY SELECTION

The search identified 44 studies, 7 of which met the eligibility criteria and were evaluated.

DATA EXTRACTION

Study design, study location, number of patients, patient age, type of control, wound type, intervention type, equipment used to generate ozone (ozone generation), evaluation methodology, and main results were extracted from each study.

DATA SYNTHESIS

A total of 506 patients 18 years or older with chronic wounds, such as venous or diabetic ulcers, on the lower limbs were enrolled. The majority of studies addressed diabetic foot ulcers.

CONCLUSIONS

The ozone therapy protocols demonstrated a healing effect in all included studies, and none reported adverse effects. This reinforces the need for more controlled and randomized clinical trials to determine the effectiveness of this treatment and establish clinical criteria for its use.
Colocating Wound Care for Patients with Sickle Cell Ulcers in a Hematology Clinic
Authors: Flattau Anna , Vinces Giacomo , You Shuo , Crouch Andrew S. , Minniti Caterina P.
Published: September 2021

OBJECTIVE

Leg ulcers affect 15% of people with sickle cell disease. However, wound centers typically treat few people with this condition, which makes it difficult to concentrate clinical expertise or support the scientific study of this orphan disease. This article describes an initiative to increase engagement in care through a partnership between wound healing and hematology leadership that led to colocating wound services within a sickle cell clinic.

METHODS

Via a retrospective chart review, the authors collected records of all adult patients with sickle cell disease who received wound care in the last decade, including 7 years of wound center data and 3 years of data from the colocated services. Patient and visit characteristics were analyzed using descriptive analytics.

RESULTS

The general wound center had previously treated 35 patients with sickle cell ulcers over 7 years. In contrast, colocated services engaged 56 patients within 3 years, including 20 who transferred care and 36 new patients. The majority of patients at the colocated site were women, unlike at the wound center (58% vs 47%, P = .07). Results indicated that 36% of patients healed initial wounds, and 45% had new wound occurrences.

CONCLUSIONS

Colocation successfully increases the number of patients with sickle cell ulcers who will engage in wound care at a single site, laying the foundation for clinical studies to improve the evidence base for this difficult-to-treat condition.
Biological therapies, asthma and coronavirus disease 2019
Authors: Ribeiro Amélia , Aguiar Rita , Morais-Almeida Mário
Published: September 2021

Purpose of review

As of June 2021, coronavirus disease 2019 (COVID-19) exceeded 180 million reported cases and was responsible for almost 4 million deaths globally. Asthma affects approximately 262 million people worldwide and is an important cause of morbidity and mortality. Presently, it appears asthma is neither associated with an increased risk of contracting COVID-19 nor with a risk of severe COVID-19 or COVID-19 related death. Regarding the severe asthma patients on biologics, questions remain. The purpose of this review is to discuss the evidence regarding the relationship between asthma, biologics and COVID-19.

Recent findings

The available evidence does not suggest that severe asthmatics on treatment with biologics have a higher risk of severe acute respiratory syndrome coronavirus 2 infection compared to the general population. It does not appear that they have a higher risk of severe disease or COVID-19 related death either.

This review suggests that treatment with biologics for severe asthma is safe and should be maintained during the COVID-19 pandemic. However, more studies are needed to address this question and the role of biological therapy on different asthma phenotypes.
Expect postoperative care disruptions for orthopaedic trauma patients during the COVID-19 pandemic: a retrospective review of patient care trends
Authors: Christiano Anthony V. , Xiao Ryan C. , Barbera Joseph P. , Selverian Stephen R. , Podolnick Jeremy D. , Forsh David A.
Published: September 2021

Background:

With the global COVID-19 pandemic arriving in New York City (NYC) public health measures were instituted to prevent disease spread. Orthopaedic trauma continued despite the pandemic, and patients were left attempting to obtain postoperative care while the city’s focus shifted to the pandemic. The purpose of this study was to evaluate postoperative care of patients treated for orthopaedic trauma during the COVID-19 pandemic in NYC and identify areas for improvement in the event of an expected second wave.

Methods:

All patients who received operative care for orthopaedic trauma during the pandemic time period by two fellowship-trained orthopaedic traumatologists were identified, and their records were reviewed.

Results:

Forty-nine patients were included for analysis. Six patients (12%) tested positive for COVID-19. Six of 24 patients (25%) who were recommended to be discharged to inpatient rehabilitation refused. Of the 31 patients discharged home, nine patients (29%) refused in-home services. Thirteen of 31 patients (42%) reported a delay in receiving outpatient physical therapy, and five patients (16%) reported difficulty filling prescriptions. There were 1,814 scheduled visits in the orthopaedic trauma clinic from March to May 2019 with 1,126 attended visits (62%). During the pandemic there were 295 scheduled visits with 175 attended visits (59%, P=0.367). At the peak of the pandemic in April 2020 there were 58 scheduled visits with 27 attended visits (47%, P=0.017).

Conclusions:

Patients treated for orthopaedic trauma during the COVID-19 pandemic were at increased risk of improper discharge, delay in outpatient services, and absent follow-up, which may together pose an increased risk of adverse events.

Level of Evidence:

Level IV.
Distribution and Polarization of Hematogenous Macrophages Associated with the Progression of Intervertebral Disc Degeneration
Authors: Yamamoto Yusuke , Kokubo Yasuo , Nakajima Hideaki , Honjoh Kazuya , Watanabe Shuji , Matsumine Akihiko
Published: September 2021

Study Design.

In vivo study using immunostaining and immunoblot analysis.

Objective.

To determine the distribution of bone marrow-derived macrophages (BMDMs), macrophage polarization and cytokine expression in the process of intervertebral disc (IVD) degeneration.

Summary of Background Data.

Knowledge of the detailed distribution of exogeneous macrophages in the disc degeneration process is important for understanding the pathomechanisms and establishing novel therapeutic targets.

Methods.

To distinguish BMDMs, GFP-labeled bone marrow chimeric rats (n = 12) were generated. The degenerative process of the intervertebral disc was reproduced in a rat caudal disc puncture model (n = 49). Immunofluorescence staining was performed to observe the distribution of BMDMs, Iba-1 and GFP double-positive cells, and Iba-1 and iNOS (M1 macrophage) or arginase-1 (M2 macrophage) double-positive cells. Immunoblot analysis was used to evaluate differences in cytokines (TNF-α, IL-1β, IL-6, TGF-β, IL-4, and IL-10) depending on the distribution of BMDMs.

Results.

BMDMs infiltrated into the outer annulus fibrosus and endplate, while increasing tissue-resident macrophage was observed inside the annulus fibrosus/nucleus pulposus. The ratio of BMDMs and the polarity change differed among the regions. Especially in the endplate, BMDMs increased gradually and the macrophage phenotype was M2 dominant. Expression of IL-1β decreased gradually at endplate, and that of IL-4 increased early after disc puncture at inside of the annulus fibrosus.

Conclusion.

During the disc degeneration process, BMDMs were observed mainly around the endplate and outside area of the annulus fibrosus, with few in the inside area of annulus fibrosus and nucleus pulposus. Compared to other IVD area, macrophage polarity and cytokine expression is concomitantly M2-dominant in endplate. Increased hematogenous M2-phenotype macrophages in endplate with progression of IVD degeneration could enhance our understanding of the underlying mechanisms of disc degeneration.

Level of Evidence: N/A
Intraoperative Cone Beam CT in Hybrid Operation Room for Pediatric Scoliosis Patients
Authors: Tanikawa Yusuke , Oba Hiroki , Fujii Masahiro , Ikegami Shota , Uehara Masashi , Mimura Tetsuhiko , Miyagawa Jun , Hatakenaka Terue , Kuraishi Shugo , Takizawa Takashi , Munakata Ryo , Kamanaka Takayuki , Miyaoka Yoshinari , Michihiko Koseki , Takahashi Jun
Published: September 2021

Study Design.

Retrospective observational study.

Objective.

This study aimed to determine the effect of reducing the radiation dose of intraoperative cone beam computed tomography (CBCT) during posterior spinal fusion (PSF) for pediatric scoliosis on the rate of pedicle screw (PS) violation.

Summary of Background Data.

Intraoperative CBCT for pediatric scoliosis improves the accuracy of PS insertion in PSF. However, few reports have addressed the PS perforation rate from reduced radiation doses in hybrid navigation.

Methods.

We evaluated 855 PSs inserted into 58 pediatric scoliosis patients (11 male and 47 female, mean age: 16.6 yr) who underwent PSF using CBCT. A radiation dose of 1/3 or 1/5 of the normal dose (ND) was defined as a low dose (LD). After PS insertion, intraoperative CBCT images were reviewed to assess the degree of PS perforation. G2–3 (i.e., perforations of 4 mm or more) was defined as a violation. The PS violation rate was compared between the groups, and factors associated with violations were examined.

Results.

A total of 567 and 288 screws were inserted in the ND group and LD group, respectively. The PS violation rate was comparable at 1.8% in the ND group and 1.7% in the LD group. Multiple logistic regression analysis showed that distance from the upper instrumented vertebra (UIV) was an independently associated factor of PS violation (+1 vertebra, operation room 0.73, P 
= 0.038). In addition, the mean height of patients with PS violations (148.8 ± 3.6 cm) was significantly shorter than that of patients without violations (157.9 ± 1.2 cm) (P = 0.034).

Conclusion.

There was no increase in PS violation rate with lower doses of radiation for intraoperative navigation CBCT. Extra care is warranted for vertebrae close to the UIV and patients of shorter stature.

Level of Evidence: 3
Hepatotoxicity of contemporary antiretroviral drugs
Authors: Rivera Christina G. , Otto Ashley O. , Zeuli John D. , Temesgen Zelalem
Published: September 2021

Purpose of review

To date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years.

Recent findings

Although less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents.

Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.
Characterization of Morphologic and Cytochemical Staining Properties of Exogenous Materials Mimicking Fungal Organisms Encountered in Skin Biopsies
Authors: Lindsey Miki , Vishal Sagar , Gardner Jerad M. , Shalin Sara C.
Published: September 2021

Background:

Exogenous materials may be encountered in skin biopsies as contamination. Contamination may occur during the biopsy procedure in the clinic or during tissue processing in the laboratory. Although the experienced pathologist may often instinctively ignore clear examples of contamination, such tissue may be a source of confusion for young pathologists and those in training. Foreign materials can typically be recognized as exogenous by morphology, polarizability, and the presence or absence of a tissue reaction, but we have rarely encountered situations in which exogenous materials could be misinterpreted as organisms, either by their morphologic appearance or staining properties.

Methods:

Exogenous materials used during skin biopsy and grossing were embedded in a nonhuman tissue scaffold and prepared into histologic slides. Hematoxylin and eosin (H&E), periodic acid-Schiff with diastase, and Grocott methenamine silver stains were performed, and each material was evaluated under polarized microscopy.

Results:

Exogenous materials were divided into the following 3 categories with shared morphologic appearances and staining properties: suture materials, plant-based materials, and synthetic materials.

Conclusion:

We present a comprehensive characterization of the morphologic and cytochemical staining properties of multiple exogenous materials that may contaminate a skin biopsy. This characterization will aid the pathologist by providing a mechanism to identify potential contaminants in skin biopsies.
Updates on treating ductal carcinoma in situ: what's to know in 2021
Authors: Haji Farnaz , Baker Jennifer L. , DiNome Maggie L.
Published: September 2021

Purpose of review

Ductal carcinoma in situ (DCIS) is a noninvasive stage of disease but understood to be a nonobligate precursor to invasive breast cancer. As such, women with DCIS are routinely recommended for standard breast cancer treatment to prevent progression to invasive disease. DCIS, however, represents a heterogeneous group of lesions that differs in its biologic behavior and risk of progression. Thus, optimal treatment is unclear. This review presents the clinical trials evaluating the de-escalation of therapy, attempts at risk stratification, and future directions in the management of this disease.

Recent findings

The de-escalation of therapy for patients with DCIS is being actively explored. Although no group of patients based on clinicopathologic features has yet been identified as suitable for omission of therapy, molecular tests appear better able to stratify patients at low risk for whom omission of radiation may be considered. Trials considering omission of surgery are ongoing, and the use of Herceptin and vaccine therapy are also being explored.

The current review provides a centralized summary enabling the clinician to better understand the complexity of DCIS and the controversies over the optimal management of this disease. It highlights the need for better risk stratification to individualize patient care.

Video abstract

http://links.lww.com/COOG/A77.
Addressing intimate partner violence with midlife women: awareness, support, empowerment
Authors: Chang Judy C. , Miller Elizabeth , Thurston Rebecca C.
Published: September 2021

Intimate partner violence (IPV) is a prevalent women's health problem that affects the health and well-being of midlife women. Clinicians who provide care to women have a responsibility to address IPV with their patients. Given the complexities surrounding IPV disclosure, the latest recommendations for IPV move beyond prior approaches that emphasize IPV screening and identification to that of universal education about IPV. Women experiencing IPV have indicated the utility of receipt of IPV information and resources regardless of disclosure. Further, a universal-education approach raises awareness about IPV for all patients to understand that IPV is prevalent, that IPV is associated with numerous negative health consequences, and that help is available.
Evaluation of Radiation-induced Pleural Effusions after Radiotherapy to Support Development of Animal Models of Radiation Pneumonitis
Authors: Aqeel Masooma , Medhora Meetha , Gore Elizabeth , Borkenhagen Jenna , Klawikowski Slade , Eastwood Daniel , Banerjee Anjishnu , Jacobs Elizabeth R.
Published: September 2021

Not all animal models develop radiation-induced pleural effusions (RIPEs) as a form of radiation-induced lung injury (RILI). Such effusions are also not well characterized in humans. The purpose of this study is to identify occurrences of RIPE in humans, provide justification for development of relevant animal models, and further characterize its risk factors in cancer patients. We also aim to identify dose thresholds for cardiopulmonary toxicity in humans to shed light on possible pathogenic mechanisms for RIPEs. We carried out a retrospective review of medical records of 96 cancer patients receiving thoracic irradiation (TRT) at our institution. Fifty-three (53%) patients developed a new pleural effusion post TRT; 18 (19%) had RIPE; and 67% developed RIPE ipsilateral to the site irradiated. None developed “contralateral only” effusions. Median time to development was 6 mo (IQR; 4–8 mo). Of 18, 8 patients (44%) had concomitant asymptomatic (radiographic only) or symptomatic radiation pneumonitis and pericardial effusion. Dosimetric factors, including combined and ipsilateral mean lung dose (MLD), were significantly associated with increased risk of RIPE. Angiotensin converting enzyme inhibition, steroids, or concurrent chemotherapy did not modify incidence of RIPE. Our results substantiate the occurrence and incidence of RIPEs in humans. In cancer patients, a median time to development of effusions around 6 mo also supports the onset of RIPEs concurrent with radiation pneumonitis. Future work needs to include large populations of cancer survivors in whom delayed RIPEs can be tracked and correlated with cardiovascular changes in the context of injury to multiple organs.
The role of biomarker in pancreatic neuroendocrine tumor: a narrative review
Authors: Guo Xiaofan , Gao Song , Li Zekun , Hao Jihui
Published: September 2021

Pancreatic neuroendocrine tumors (pNET) are heterogenous tumors originated from the diffuse neuroendocrine cells of pancreas, which show the function of synthesis, storage and secretion of peptide hormones and biomimetic amines. Biomarkers play a crucial role in the diagnosing, evaluating prognosis and predicting treatment response for pNET patients. Traditional NET markers such as chromogranin A and Neuron Specific Enolase, as a diagnostic biomarker, have relatively low sensitivity and specificity in pNET patients. The emergence of new types of biomarkers provides more reliable indicators for diagnosis and prognosis evaluation. Among them, NETest score is a promising biomarker with the highest diagnostic sensitivity (80%) and specificity (94%). In addition, this molecule can be also used as a prognostic biomarker, which can predict disease progression and shorter overall survival. Biomarkers related to therapeutic targets, such as vascular endothelial growth factor, vascular endothelial growth factor receptor, and key molecules of mTOR signaling pathway, have capability to predict response of treatment. With the development of next-generation sequencing, chip array, and digital droplet PCR, novel biomarkers such as circulating tumor cells, tumor-derived exosomes, and circulating tumor DNA and mRNA are expected to provide more accurate diagnosis, prognostic information, and prospective therapeutic targets. In this paper, biomarkers of pancreatic neuroendocrine tumor and their role in diagnosis, prognosis, diagnosis, treatment and monitoring are systematically introduced. Our conclusions can provide new basis for clinicians in the diagnosis and treatment process.
Menstrual cycle length and modern living: a review
Authors: Campbell Lily R. , Scalise Ariel L. , DiBenedictis Brett T. , Mahalingaiah Shruthi
Published: September 2021

Purpose of review

The aim of this review is to evaluate biological, life history, environmental, and lifestyle factors and exposures that cause variability in menstrual cycle length (MCL).

Recent findings

Recent literature has detailed a number of factors that influence MCL, with particular emphasis placed on novel environmental exposures, such as air pollution and endocrine disrupting chemicals.

MCL varies widely in response to intrinsic and extrinsic inputs and is a useful predictor of reproductive health and fecundability.

Video abstract

http://links.lww.com/COE/A28