bluuebunny/crossref_metadata_2025 huggingface dataset:
Appressed, directed and silicified trichomes of the kudzu climbing vine
Authors: Seo Dahye , Park Junhyung , Kim Ki Woo
Published: August 2022

Kudzu (Pueraria montana var. lobata) is becoming one of the most prevalent climbing vines in urban forests. Here, surface characteristics of kudzu leaves and stems are investigated using field-emission scanning electron microscopy and X-ray microanalysis. The leaf and stem surfaces were characterized by different types of trichomes. No adhesive pads, modified hooks or tendrils were found on kudzu vines. Trichomes on the leaves and stems of kudzu could be categorized into (i) complex bulbous glandular trichomes and (ii) needle-shaped nonglandular trichomes (NSNGTs). Two morphotypes of the nonglandular trichomes were present on the stems: (i) long hairy nonglandular trichomes and (ii) short NSNGTs. The leaf trichomes were appressed and oriented in an uphill direction, whereas the stem trichomes were appressed and oriented in a downhill direction. This opposite trichome orientation appears to facilitate climbing and prohibits slipping of kudzu vines through differential friction between the plants and the kudzu vines. X-ray microanalysis revealed a distinct accumulation of silicon in the leaf and stem trichomes. These results suggest that appressed, directed and silicified trichomes may contribute to the twining behavior of kudzu vines.
Theosis as Limitation: The Case of the Apocalypse and Martyrs
Authors: Azar Michael G
Published: August 2022

While a variety of scholars and theologians of the modern period have understood the doctrine of theosis as a Greek outgrowth of simpler Jewish seedlings, the apocalyptic and martyrological texts examined here suggest something of the opposite. In a theological environment when christological accuracy was in its infancy and polytheistic motifs and heavenly hierarchies were common and unremarkable, John’s Apocalypse and early martyrologies themselves blurred the distinction between Christ and the martyrs to such a degree that the language of theosis—particularly after the waning of regular martyrdom—arose alongside the language of christological accuracy as a means to reel in and clarify problematic claims in more taxonomically sound ways. In other words, what the stabilization of orthodox Christology did for early, controversial views of Jesus, the stabilization of the language of theosis did for early, controversial views of the martyrs, who had often been worshipped alongside, if not in lieu of, Christ himself. The doctrine of theosis thus came to serve chiefly as a limitation on, rather than a simple outgrowth of, earlier soteriological claims.
MIGHTEE: the nature of the radio-loud AGN population
Authors: Whittam I H , Jarvis M J , Hale C L , Prescott M , Morabito L K , Heywood I , Adams N J , Afonso J , An Fangxia , Ao Y , Bowler R A A , Collier J D , Deane R P , Delhaize J , Frank B , Glowacki M , Hatfield P W , Maddox N , Marchetti L , Matthews A M , Prandoni I , Randriamampandry S , Randriamanakoto Z , Smith D J B , Taylor A R , Thomas N L , Vaccari M
Published: August 2022

We study the nature of the faint radio source population detected in the MeerKAT International GHz Tiered Extragalactic Exploration (MIGHTEE) Early Science data in the COSMOS field, focusing on the properties of the radio-loud active galactic nuclei (AGNs). Using the extensive multiwavelength data available in the field, we are able to classify 88 per cent of the 5223 radio sources in the field with host galaxy identifications as AGNs (35 per cent) or star-forming galaxies (54 per cent). We select a sample of radio-loud AGNs with redshifts out to z ∼ 6 and radio luminosities 1020 < L1.4 GHz/W Hz−1 < 1027 and classify them as high-excitation and low-excitation radio galaxies (HERGs and LERGs). The classification catalogue is released with this work. We find no significant difference in the host galaxy properties of the HERGs and LERGs in our sample. In contrast to previous work, we find that the HERGs and LERGs have very similar Eddington-scaled accretion rates; in particular we identify a population of very slowly accreting AGNs that are formally classified as HERGs at these low radio luminosities, where separating into HERGs and LERGs possibly becomes redundant. We investigate how black hole mass affects jet power, and find that a black hole mass ≳ 107.8 M⊙ is required to power a jet with mechanical power greater than the radiative luminosity of the AGN (Lmech/Lbol > 1). We discuss that both a high black hole mass and black hole spin may be necessary to launch and sustain a dominant radio jet.
A search for period changes of eight short-period Type II Cepheids
Authors: Yacob Alemiye M , Berdnikov Leonid N , Pastukhova Elena N , Kniazev Alexei Y , Whitelock Patricia A
Published: August 2022

In this study, we investigate the period changes of eight short-period Type II Cepheids of the BL Her subtype, i.e. with periods in the 1–4 d range. The O − C diagrams for these stars are constructed using all suitable observational data from ground and space surveys. This spans a time interval of over one century and includes digitized photographic plates as well as photometry from the literature. The O − C diagrams show parabolic evolutionary trends, which indicate the presence of both increasing and decreasing periods for these eight short-period stars. These period changes are in good agreement with the recent theoretical evolutionary framework and stellar evolution models for BL Her stars. The pulsation stability test proposed by Lombard and Koen also suggests that the changes in the periods are real.
The long non-coding RNA SPRIGHTLY and its binding partner PTBP1 regulate exon 5 skipping of SMYD3 transcripts in group 4 medulloblastomas
Authors: Lee Bongyong , Katsushima Keisuke , Pokhrel Rudramani , Yuan Menglang , Stapleton Stacie , Jallo George , Wechsler-Reya Robert J , Eberhart Charles G , Ray Animesh , Perera Ranjan J
Published: August 2022

Background

Although some of the regulatory genes, signaling pathways, and gene regulatory networks altered in medulloblastomas (MB) are known, the roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs), are poorly described. Here we report that the lncRNA SPRIGHTLY (SPRY4-IT1) gene is upregulated in group 4 medulloblastoma (G4 MB).

Methods

SPRIGHTLY expression was assessed in MB subgroup patient-derived xenografts, cell lines, and patient samples. The effect of SPRIGHTLY hemizygous deletion on proliferation, invasion, apoptosis, and colony formation were assessed in vitro and on tumor growth in vivo. dChIRP pull-down assays were used to assess SPRIGHTLY-binding partners, confirmed by immunoprecipitation. SMYD3 ΔE5 transcripts were examined in cell lines and publicly available RNA-seq data. Pathway analysis was performed by phospho-kinase profiling and RNA-seq.

Results

CRISPR/Cas9 deletion of SPRIGHTLY reduced cell viability and invasion and increased apoptosis in G4 MB cell lines in vitro. SPRIGHTLY hemizygous-deleted G4 MB cells injected into mouse cerebellums produced smaller tumors than those derived from parental cells expressing both copies of SPRIGHTLY. SPRIGHTLY lncRNA bound to the intronic region of the SMYD3 pre-mRNA transcript. SPRIGHTLY also interacted with PTPB1 protein to regulate SMYD3 exon skipping to produce an aberrant protein. SPRIGHTLY-driven SMYD3 regulation enhanced the expression of EGFR pathway genes in G4 MB cell lines and activated cell coagulation/hemostasis-related gene expression, suggesting a novel oncogenic role in G4 MB.

Conclusions

These results demonstrate the importance of SPRIGHTLY lncRNA as a promoter of G4 MB and the role of the SPRIGHTLY-SMYD3-PTPB1 axis as an important oncogenic regulator in MB.
Retina regeneration: lessons from vertebrates
Authors: Sharma Poonam , Ramachandran Rajesh
Published: August 2022

Unlike mammals, vertebrates such as fishes and frogs exhibit remarkable tissue regeneration including the central nervous system. Retina being part of the central nervous system has attracted the interest of several research groups to explore its regenerative ability in different vertebrate models including mice. Fishes and frogs completely restore the size, shape and tissue structure of an injured retina. Several studies have unraveled molecular mechanisms underlying retina regeneration. In teleosts, soon after injury, the Müller glial cells of the retina reprogram to form a proliferating population of Müller glia-derived progenitor cells capable of differentiating into various neural cell types and Müller glia. In amphibians, the transdifferentiation of retinal pigment epithelium and differentiation of ciliary marginal zone cells contribute to retina regeneration. In chicks and mice, supplementation with external growth factors or genetic modifications cause a partial regenerative response in the damaged retina. The initiation of retina regeneration is achieved through sequential orchestration of gene expression through controlled modulations in the genetic and epigenetic landscape of the progenitor cells. Several developmental biology pathways are turned on during the Müller glia reprogramming, retinal pigment epithelium transdifferentiation and ciliary marginal zone differentiation. Further, several tumorigenic pathways and gene expression events also contribute to the complete regeneration cascade of events. In this review, we address the various retinal injury paradigms and subsequent gene expression events governed in different vertebrate species. Further, we compared how vertebrates such as teleost fishes and amphibians can achieve excellent regenerative responses in the retina compared with their mammalian counterparts.
Laminin 332-functionalized coating to regulate the behavior of keratinocytes and gingival mesenchymal stem cells to enhance implant soft tissue sealing
Authors: Liu Lipeng , Wang Jing , Li Ying , Liu Bing , Zhang Wei , An Weikang , Wang Qing , Xu Boya , Zhao Lingzhou , Ma Chufan
Published: August 2022

Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli; hence, an essential process to prevent peri-implantitis. Laminin 332 (LN332) is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes (HDs) with integrin α6β4. In this work, poly (D, L-lactide) (PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly, displaying staged LN332 release for as long as 28 days. The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrin α6β4, which can promote adhesion, migration and proliferation of HaCaT cells and further enhance the expression of keratinocyte HD-related molecules, including integrin α6β4, LN332 and plectin. Furthermore, the PDLLA-LN332 composite coating can promote the adhesion, spreading and proliferation of gingival mesenchymal stem cells and accelerate their epithelial differentiation. Therefore, the PDLLA-LN332 composite coating can enhance implant soft tissue sealing, warranting further in vivo study.
Economic and Social Outsiders but Political Insiders: Sweden’s Populist Radical Right
Authors: Bo’ Ernesto Dal , Finan Frederico , Folke Olle , Persson Torsten , Rickne Johanna
Published: August 2022

We study the politicians and voters of the Sweden Democrats, a major populist radical-right party. Based on detailed administrative data, we present the first comprehensive account of which politicians are selected into such a party. Surveys show that politicians and voters of the Sweden Democrats share strong anti-establishment and anti-immigration attitudes that drastically set them apart from Sweden’s other parties. Searching for individual traits that link naturally to these attitudes, we classify the universe of Swedish politicians and voters by social and economic marginalization and exposure to immigration. Politicians from the Sweden Democrats over-represent marginalized groups without strong attachments to the labour market or to traditional nuclear families, which instead are under-represented among politicians in all other parties. Among voters, the Sweden Democrats have higher electoral support in precincts with higher shares of the same marginalized groups. We see the mobilization of the marginalized as an important driver of the party’s success. Finally, we uncover that Sweden-Democrat politicians score lower on a number of valence traits than other-party politicians. In sum, the rise of the Sweden Democrats raised political representation for marginalized groups, but this came at a valence cost.
Variability in cell-free expression reactions can impact qualitative genetic circuit characterization
Authors: Rhea Katherine A , McDonald Nathan D , Cole Stephanie D , Noireaux Vincent , Lux Matthew W , Buckley Patricia E
Published: August 2022

Cell-free expression systems provide a suite of tools that are used in applications from sensing to biomanufacturing. One of these applications is genetic circuit prototyping, where the lack of cloning is required and a high degree of control over reaction components and conditions enables rapid testing of design candidates. Many studies have shown utility in the approach for characterizing genetic regulation elements, simple genetic circuit motifs, protein variants or metabolic pathways. However, variability in cell-free expression systems is a known challenge, whether between individuals, laboratories, instruments, or batches of materials. While the issue of variability has begun to be quantified and explored, little effort has been put into understanding the implications of this variability. For genetic circuit prototyping, it is unclear when and how significantly variability in reaction activity will impact qualitative assessments of genetic components, e.g. relative activity between promoters. Here, we explore this question by assessing DNA titrations of seven genetic circuits of increasing complexity using reaction conditions that ostensibly follow the same protocol but vary by person, instrument and material batch. Although the raw activities vary widely between the conditions, by normalizing within each circuit across conditions, reasonably consistent qualitative performance emerges for the simpler circuits. For the most complex case involving expression of three proteins, we observe a departure from this qualitative consistency, offering a provisional cautionary line where normal variability may disrupt reliable reuse of prototyping results. Our results also suggest that a previously described closed loop controller circuit may help to mitigate such variability, encouraging further work to design systems that are robust to variability.

Graphical Abstract
Neuropathic pain and itch: mechanisms in allergic conjunctivitis
Authors: Kalangara Jerry P. , Vanijcharoenkarn Kristine , Chisolm Sarah , Kuruvilla Merin E.
Published: August 2022

Purpose of review

Allergic conjunctivitis is highly prevalent and affects up to one third of the general population. The current understanding of the pathophysiology and therapeutic strategies center around the type 2 inflammatory pathway. However, there is an increasing body of evidence that suggests neurogenic mechanisms also play a role in allergic inflammation, with a substantial proportion of allergic conjunctivitis patients experiencing both ocular itch and pain.

Recent findings

Unmyelinated C fibres on the ocular surface transmit histaminergic itch and can be directly activated by mast cell mediators. The conjunctival mucosa also contains TRPV1+ (histamine-dependent) and TRPA1+ (histamine-independent) neurons that enhance ocular pain and itch in allergic conjunctivitis. Allergen-complexed IgE also binds directly to FcεRI expressed on peripheral neurons. Environmental aeroallergens can also directly stimulate neuronal nociceptors to release inflammatory substances. Allergic inflammation thus stimulates nerve terminals to release vasoactive and inflammatory neuropeptides, leading to a cyclical neuronal dysregulation that augments mast cell activity. These repetitive cycles lead to both peripheral and central sensitization and neuronal plasticity, resulting in decreased itch/pain thresholds and a heightened itch/pain response.

Neurogenic mechanisms including peripheral and central sensitization may drive chronic ocular itch and pain secondary to allergic inflammation. Research into these pathways may help to identify therapeutic targets in allergic conjunctivitis patients with refractory symptoms.
Multilevel Decompression Surgery for Degenerative Lumbar Spinal Canal Stenosis Is Similarly Effective With Single-level Decompression Surgery
Authors: Yamamoto Tatsuya , Yagi Mitsuru , Suzuki Satoshi , Takahashi Yohei , Nori Satoshi , Tsuji Osahiko , Nagoshi Narihito , Ogawa Jun , Matsumoto Morio , Nakamura Masaya , Watanabe Kota
Published: August 2022

Study Design.

Retrospective case series.

Objective.

The purpose of this study was to investigate the outcome of multilevel posterior decompression surgery for degenerative lumbar spinal stenosis compared with single-level surgery.

Summary of Background Data.

The clinical outcomes of multilevel decompression surgery are still controversial because previous studies have not been designed to randomize or adjust the patient background.

Materials and Methods.

A retrospective review of prospectively collected data from 659 surgically treated lumbar spinal stenosis patients with a minimum 2-year follow-up was performed. Among them, we compared baseline and 2-year postoperative patient-reported outcomes (PROs) including the Visual Analog Scale and Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores of 122 patients who underwent three or more levels of surgery (M group) and 304 patients who underwent single-level surgery (S group). Further analyses were performed of 116 paired patients from both groups who were propensity score matched by age and baseline PROs.

Results.

The number of perioperative complications including extradural hematoma, surgical site infection, and spinal fluid leakage [M vs. S: 10 (8%) vs. 19 (6%), P=0.47], and frequency of revision surgery [5 (4%) vs. 23 (8%), P=0.10] were similar between the two groups. In the analysis of propensity score–matched patients, there were comparable improvements in the Visual Analog Scale score for lower back pain (2.6 vs. 2.4, P=0.55), buttock-leg pain (3.1 vs. 3.4, P=0.48), and buttock-leg numbness (2.9 vs. 2.9, P=0.77) in both groups. There were also similar improvements in the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire scores including lower back pain, lumbar function, walking ability, and mental health domains, except for the social life function domain (20.7±26.5 vs. 28.0±27.5, P=0.04).

Conclusions.

Despite the longer surgical time and a larger volume of estimated blood loss, multilevel decompression surgery showed similar improvement to that of single-level surgery in terms of recovery of PROs and frequency of revision surgery. Multilevel decompression surgery provides good clinical outcomes with acceptable complication and revision rates when selecting appropriate patient and spinal levels.
Treatment of Self-Harm Scars: A Scoping Review
Authors: Edriss Manar , Monconduit Rachel , St Claire Kayla , Akers Katherine G. , Mehregan Darius
Published: August 2022

BACKGROUND

Self-harm scars are a consequence of deliberate self-injury, serving as a visual reminder for involved individuals. Patients often reach out to their providers seeking treatment for their scars. However, there is currently no standard for treating self-harm scars, because multiple options are being explored.

OBJECTIVE

A scoping review was conducted to identify and characterize the body of literature on different treatments for self-harm scars, including surgical, laser, and vitamin A management.

METHODS

Thorough literature searches were conducted in PubMed/MEDLINE, EMBASE, and CINAHL Complete. The search strategy was designed and implemented by a medical librarian.

RESULTS

Of 510 retrieved articles, 4 described laser treatments, 8 described surgical treatments, and 2 described vitamin A treatments.

CONCLUSION

A multidisciplinary approach is critical for the selection and outcome of the treatment of self-harm scars.
2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia
Authors: Farmakis Dimitrios , Porter John , Taher Ali , Domenica Cappellini Maria , Angastiniotis Michael , Eleftheriou Androulla ,   for the 2021 TIF Guidelines Taskforce
Published: August 2022

Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care and follow-up, ideally in specialized centers and by multidisciplinary teams of experts. Despite the significant progress in TDT diagnosis and treatment over the past decades that has dramatically improved patients’ prognosis, its management remains challenging. On one hand, diagnostic and therapeutic advances are not equally applied to all patients across the world, particularly in several high-prevalence eastern regions. On the other, healthcare systems in low-prevalence western countries that have recently received large numbers of migrant thalassemia patients, were not ready to address patients’ special needs. Thalassaemia International Federation (TIF), a global patient-driven umbrella federation with 232 member-associations in 62 countries, strives for equal access to quality care for all patients suffering from thalassemia or other hemoglobinopathies in every part of the world by promoting education, research, awareness, and advocacy. One of TIF’s main actions is the development and dissemination of clinical practice guidelines for the management of these patients. In 2021, the fourth edition of TIF’s guidelines for the management of TDT was published. The full text provides detailed information on the management of TDT patients and the clinical presentation, pathophysiology, diagnostic approach, and treatment of disease complications or other clinical entities that may occur in these patients, while also covering relevant psychosocial and organizational issues. The present document is a summary of the 2021 TIF guidelines for TDT that focuses mainly on clinical practice issues and recommendations.
Five Percent Variant Allele Frequency Is a Reliable Reporting Threshold for TP53 Variants Detected by Next Generation Sequencing in Chronic Lymphocytic Leukemia in the Clinical Setting
Authors: Pandzic Tatjana , Ladenvall Claes , Engvall Marie , Mattsson Mattias , Hermanson Monica , Cavelier Lucia , Ljungström Viktor , Baliakas Panagiotis
Published: August 2022

The clinical significance of small TP53 clones detected with next generation sequencing (NGS) in chronic lymphocytic leukemia is an issue of active debate. According to the official guidelines, treatment decisions should be guided only by variants with variant allele frequency (VAF) ≥10%. We present data on 325 consecutive patients with chronic lymphocytic leukemia analyzed with NGS. In total 47 pathogenic/likely pathogenic (P/LP), TP53 variants were detected in 26 patients (8%). Eleven of these (23%) were in the 5% to 10% VAF range and reported according to our institutional policy. All TP53 variants in the 5% to 10% VAF range were confirmed (100% concordance) with a second NGS panel. Our results where further validated with the performance of Sanger sequencing and digital droplet PCR (ddPCR). In 12 patients with available fluorescence in situ hybridization data and TP53 mutations within 5% to 10% VAF, deletion of chromosome 17p (del(17p)) was detectable in only 1 patient. We propose a robust diagnostic algorithm, which allows the safe detection and reporting of TP53 variants with VAF down to 5% in the clinical setting. Our study provides evidence that NGS is equally potent to detect variants with VAF 5% to 10% compared to those with VAF 10% to 15%, highlighting the urgent need for harmonization of NGS methodologies across diagnostic laboratories.
Ocular Impression-Based Scleral Lens With Wavefront-Guided Optics for Visual Improvement in Keratoconus
Authors: Gelles John D. , Cheung Brian , Akilov Sarah , Krisa Sydney , Trieu Gina , Greenstein Steven A. , Chung Daniel , Hersh Peter S.
Published: August 2022

This case reports on the use of wavefront-guided (wfg) optics on custom ocular impression-based scleral lenses (IBSLs) for visual improvement in a patient with keratoconus (KC). A 28-year-old man with KC, who had previously failed a traditional, diagnostically fit scleral lens (tSL), was fit with IBSLs with traditional optics. Using a system that included a dot matrix on the IBSL and a wavefront aberrometer with pupil and dot registration software, a wfgIBSL was created. When compared with the IBSL, the wfgIBSL reduced the total higher-order root mean square (HORMS) 67% and 64% in the right and left eye, respectively, resulting in a 2-line improvement in best-contact lens visual acuity (BCLVA) for both eyes. This case demonstrates the successful creation and application of a wfgIBSL resulting in a stable lens, a reduction in HORMS, and an improvement in BCLVA, after failure with a diagnostically fit tSL.
Private equity in ophthalmology: lessons from other specialties
Authors: Brill Daniel , Luo Shiming , Sridhar Jayanth , Williams Basil K.
Published: August 2022

Purpose of review

In the absence of long-term data of the effects of private equity in ophthalmology, this article reviews the role of private equity in other medical specialties as a guide to the future for ophthalmology.

Recent findings

Across an array of medical specialties, including anesthesiology, dermatology, emergency medicine, ophthalmology/optometry, radiology, and urology, medical practices are being consolidated into a few larger platform groups. Although there has been a short-term financial success for both private equity firms and senior medical practice partners, there exists broad skepticism from peer-reviewed publications and the national media.

Although the impact of private equity on ophthalmology is largely speculative, ophthalmology may follow some of the trends observed in other medical specialties. These trends include increased volume of services, increased profits, improved payer mix, increased payment per patient visit, increased use of midlevel practitioners, decreased physician autonomy, and decreased physician salaries.
Artificial intelligence in retinal imaging for cardiovascular disease prediction: current trends and future directions
Authors: Wong Dragon Y.L. , Lam Mary C. , Ran Anran , Cheung Carol Y.
Published: August 2022

Purpose of review

Retinal microvasculature assessment has shown promise to enhance cardiovascular disease (CVD) risk stratification. Integrating artificial intelligence into retinal microvasculature analysis may increase the screening capacity of CVD risks compared with risk score calculation through blood-taking. This review summarizes recent advancements in artificial intelligence based retinal photograph analysis for CVD prediction, and suggests challenges and future prospects for translation into a clinical setting.

Recent findings

Artificial intelligence based retinal microvasculature analyses potentially predict CVD risk factors (e.g. blood pressure, diabetes), direct CVD events (e.g. CVD mortality), retinal features (e.g. retinal vessel calibre) and CVD biomarkers (e.g. coronary artery calcium score). However, challenges such as handling photographs with concurrent retinal diseases, limited diverse data from other populations or clinical settings, insufficient interpretability and generalizability, concerns on cost-effectiveness and social acceptance may impede the dissemination of these artificial intelligence algorithms into clinical practice.

Artificial intelligence based retinal microvasculature analysis may supplement existing CVD risk stratification approach. Although technical and socioeconomic challenges remain, we envision artificial intelligence based microvasculature analysis to have major clinical and research impacts in the future, through screening for high-risk individuals especially in less-developed areas and identifying new retinal biomarkers for CVD research.
Multisite chronic pain as a causal risk factor for coronary artery disease: findings from Mendelian randomization
Authors: Zhu Jiahao , Wang Nini , Liu Houpu , Jiang Han , Cai Bingyue , Chen Dingwan , Li Yingjun
Published: August 2022

The potential consequences of the number of chronic pain sites (referred to multisite chronic pain) on the risk of cardiovascular diseases (CVDs) remain unclear. We attempted to investigate the causality of multisite chronic pain with CVDs and its possible causal mediators. Using summary genome-wide association statistics, two-sample Mendelian randomization (MR) analyses were performed to assess whether multisite chronic pain has a causal effect on the 3 CVDs including coronary artery disease, atrial fibrillation, and stroke. We then conducted MR mediation analyses to establish whether body mass index (BMI), smoking, and depression causally mediate any association. Genetic liability to multisite chronic pain was associated with increased risk of coronary artery disease (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.19-1.95 per one increase in the number of pain locations) but not with atrial fibrillation or stroke. We also found positive causal effects of multisite chronic pain on BMI, smoking, and depression and causal effects of BMI, smoking, and depression on coronary artery disease. In multivariable MR analyses, the excess risk of coronary artery disease was attenuated after adjusting for BMI (OR 1.43, 95% CI 1.05-1.93), smoking (OR 1.49, 95% CI 1.11-2.00), depression (OR 1.44, 95% CI 1.03-2.01), and 3 risk factors combined (OR 1.34, 95% CI 0.88-2.05). Our findings demonstrated that multisite chronic pain led to higher risk of coronary artery disease, which is partly mediated through BMI, smoking, and depression.
Implementing a standardized protocol to improve cervical cancer screening rates in primary care
Authors: Luckett Kathryn Lea
Published: August 2022

Background:

Routine cervical cancer screening for women aged 21–65 is a recommended standard practice. Early identification and treatment of cervical cancer improves patient outcomes.

Local Problem:

Cervical cancer screening rates at the primary care project site were 51%, well below the national benchmark of 87%. The purpose of this quality improvement project was to increase cervical cancer screening rates by implementing a standardized eligibility assessment protocol.

Methods:

This initiative took place at an outpatient family practice site over 7.5 months and included 2,018 eligible patients.

Interventions:

Evidence-based interventions included a standardized process change that shifted eligibility assessment from an opportunistic screening by providers to a proactive screening by clinical staff. Using a system reminder prompt, clinical staff began assessing all eligible patients during rooming and proactively scheduling future Pap appointments in office or placing OBGYN referrals, per patient preference.

Results:

A statistically significant increase in cervical cancer screening rates occurred, 33% (p < .001). The rate of scheduled Pap appointments increased by 124% (p < .001), the rate of OBGYN referrals increased by 300% (p < .001), and the rate of completed Pap tests in office increased by 280% (p < .001).

Conclusion:

The results suggest that implementing a proactive, standardized screening process can increase cervical cancer screening rates in primary care.
Optimizing nutrition in chronic pancreatitis
Authors: Talukdar Rupjyoti , Unnisa Misbah
Published: August 2022

Purpose of review

This review aims to discuss recent developments in the nutritional management in chronic pancreatitis.

Recent findings

Nutritional assessment should be comprehensive and include dietary history, anthropometry, and biochemical nutritional parameters. Micronutrients should be evaluated at least yearly and dual-energy X-ray absorptiometry (DEXA) at every 2-yearly intervals. Studies on pancreatic enzyme replacement therapy (PERT) have primarily evaluated coefficient of fat excretion (CFA), coefficient of nitrogen excretion (CNA), and stool weight. Two RCTs, in which patients were treated with PERT for 7 days in a blinded manner and subsequently extended for 6–12 months in an open-label manner, showed improvement in nutritional parameters. However, two subsequent RCTs failed to show any benefit, and the most recent observational study demonstrated persistence of malnutrition even after PERT. The reason for the latter findings were nonadherence to PERT and poor oral intake of calories. Therefore, it is essential to educate the patients on adherence, counsel on taking high-protein, high-calorie diet, and supplement nutrients in those with inadequate oral intake. Other associated manifestations, such as diabetes and related complications, and anxiety/depression could also contribute to malnutrition directly or indirectly, and should, therefore, be adequately managed.

Nutritional assessment should be performed meticulously. Nutritional therapy should not be restricted to only PERT and nutritional supplementation, but should also include dietary counselling and disease related education.
RNA-based urinary assays for non-muscle invasive bladder cancer
Authors: Pijpers Olga M. , de Jong Joep J. , Zuiverloon Tahlita C.M. , Boormans Joost L.
Published: August 2022

Purpose of review

To provide an overview of the recent literature on RNA-based molecular urine assays for the diagnosis and surveillance of non-muscle invasive bladder cancer (NMIBC).

Recent findings

Articles were eligible for inclusion if performance metrics sensitivity, specificity, and negative-predictive value (NPV) were reported or could be calculated. Only prospective studies published between 2020–2022 were included. Five out of fourteen studies addressed the primary diagnostic setting; the proportion of gross hematuria patients in all study populations was >50%. Only one study reported performance metrics within a microscopic hematuria subgroup. This study evaluated Xpert Bladder and reported a sensitivity: 73%, specificity: 84%, NPV: 99%, and PPV: 12%. Ten studies assessed test performance during surveillance for NMIBC. For the detection of high-grade (HG) and high-risk (HR) NMIBC, sensitivity, specificity, NPV, and PPV varied between 78–100%, 64–89%, 97.0–99.7%, and 9.2–39%.

Multiple RNA-based urine assays have been investigated for the detection of urothelial cancer in the primary or surveillance setting. However, studies included within this review have important limitations, hampering the interpretation of study results. As such, performance metrics should be interpreted with caution and further research is required to evaluate the clinical impact of RNA-based urine assays in daily practice.
Molecular uropathology and cancer genetics for the urologist: key findings for classification and diagnosis
Authors: Compérat Eva , Oszwald André , Wasinger Gabriel , Kläger Johannes , Hassler Melanie R. , Shariat Shahrokh F.
Published: August 2022

Purpose of review

To highlight the latest changes in prostate cancer (PCa), urothelial carcinoma, upper tract urothelial carcinoma (UTUC) and renal cell carcinoma (RCC) diagnosis and the impact of genetics in this field.

Recent findings

Breast cancer1/2 mutations start to play a major role in PCa treatment with regard to personalized medicine. In urothelial carcinoma an overlap between histological pathological and molecular findings exists, fibroblast growth factor receptor alteration are starting to play a major role, programmed death-ligand 1 although problematic is still important in the treatment setting. UTUC is rare, but genetically different from urothelial carcinoma. In the development of RCC, different genetic pathways such as Von Hippel–Lindau, but also tuberous sclerosis 1/2 and others play a major role in tumor development.

Over the last years, genetics has become increasingly important role in the diagnosis and the treatment of patients with urological malignancies. The upcoming 5th edition (1) of the WHO still considers conventional surgical pathology as the diagnostic gold standard, but molecular pathology is gaining importance not only for diagnosis, but also in personalized treatment, of prostate, kidney cancer and urothelial carcinomas. Therefore, a close collaboration between surgical urology, pathology and oncology departments is mandatory. In this review, we will discuss the latest evolutions in PCa, urothelial carcinoma, upper urinary tract carcinomas and RCC s in the field of genetics in urology.
Evaluation of the Attitude of Parents in Pediatric Oncology Towards COVID-19 Vaccine
Authors: Kilci Ceren , Fettah Ali , Çapkinoğlu Emre , Kurucu Burçak , Ünüvar Gök Şeyma , Yeşil Şule , Berber Hamamci Melda , Şahin Gürses
Published: August 2022

Severe acute respiratory syndrome, coronavirus (SARS, COVID-19) has been declared a pandemic by the World Health Organization since March 2020. Patients with active cancer should be considered especially for priority access to the COVID-19 vaccine. Therefore, our study aimed to learn parents’ opinions of cancer-diagnosed patients about the COVID-19 vaccine. Between December 2021 and January 2022, 76 people were willing to answer the questionnaire from the parents of outpatient/inpatient patients at the Pediatric Hematology and Oncology Clinic of Dr. Sami Ulus Obstetrics, Child Health and Diseases Education Research Hospital were included. In our study, 18 parents (23.7%) did not get vaccinated. Among the reasons for not getting vaccinated, the most common answer for “I fear from the vaccine’s side effects.”, “Do you think oncology patients are at risk for COVID-19?”, “Do you think the COVID-19 pandemic affects cancer treatment?” were 90.7%, 89.5% and 21% yes, respectively. Would your opinion of the vaccine be positive if the domestic vaccine was produced?”—67.4% answered yes. Vaccine hesitation and public misinformation put cancer patients at risk. Increasing awareness of the rejection of COVID-19 vaccines is important for public health and the fight against the pandemic. In addition, the doctors’ recommendations for conducting oncology treatment will significantly impact parents’ compliance with the COVID-19 vaccine.
Diffuse Large B-Cell Lymphoma in the Public-Sector of Johannesburg, South Africa, in the Era of Widescale Antiretroviral Therapy Use
Authors: Vaughan Jenifer , Perner Yvonne , Wiggill Tracey
Published: August 2022

Background:

Diffuse large B-cell lymphoma (DLBCL) is a high-grade non-Hodgkin lymphoma with increased incidence among people living with HIV-infection (PLWH). Although its frequency is reportedly attenuated by antiretroviral therapy (ART), we have previously shown a similar rate of DLBCL in the post-ART era (2017) in Johannesburg, South Africa compared with that observed when ART had only limited availability in the South Africa state-sector (2007). Here, we present a more detailed analysis of DLBCL in the pre-and post-ART eras in Johannesburg.

Methods and Results:

All cases of DLBCL diagnosed in the state-sector hospitals of Johannesburg in 2007 and 2017 were extracted from the laboratory information system, and factors of interest compared. Most (>85%) were observed among PLWH at both time-points; ART-coverage was significantly higher in 2017 compared with 2007, but with failed immunological recovery in 50% of cases. The immunohistochemically-defined cell of origin differed according to HIV-status; the germinal center (GC) and non-GC subtypes predominating in the PLWH and the HIV-negative group, respectively. MYC-gene rearrangement was more common than is reported elsewhere (22.1%), whereas BCL6 and BCL2 gene rearrangements were less so (14.6% and 0%, respectively). Slight improvement in survival was noted in the post-ART era, but remained poor, with bone marrow involvement and albumin levels ≤30 g/L independently associated with mortality.

Conclusions:

Although the frequency of DLBCL in Johannesburg has not dropped significantly in the post-ART era, a slight improvement in survival is observed. However, outcomes remain poor, indicating a need for further improvements in care.
Pregnancy and malaria: the perfect storm
Authors: Rogerson Stephen J. , Unger Holger W.
Published: August 2022

Purpose of review

Malaria in pregnancy continues to exert a toll on pregnant women and their offspring.

Recent findings

The burden of Plasmodium falciparum infection is especially large in Africa, and new data show lasting effects of maternal infection on the infant's neurocognitive development. Elsewhere, P. vivax infection causes relapsing infections that are challenging to prevent. Infection in first trimester of pregnancy is an area of increasing focus, and its adverse effects on pregnancy outcome are increasingly recognised. First-trimester infection is common and frequently acquired prior to conception. Although newer rapid diagnostic tests still have limited sensitivity, they may be useful in detection of early pregnancy malaria for treatment. Artemisinin-based combination therapies are efficacious in later pregnancy but have yet to be recommended in first trimester because of limited safety data. In Africa, intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine improves pregnancy outcomes, but sulfadoxine-pyrimethamine resistance is worsening. The alternative, IPTp with dihydroartemisinin-piperaquine, has greater antimalarial efficacy, but does not appear to improve pregnancy outcomes, because sulfadoxine-pyrimethamine has poorly understood nonmalarial benefits on birthweight.

Novel IPTp regimens must be combined with interventions to strengthen protection from malaria infection acquired before and in early pregnancy.
Systematic literature review and network meta-analysis of lurasidone, brexpiprazole and cariprazine for schizophrenia
Authors: Phalguni Angaja , McCool Rachael , Wood Hannah , Sanderson Alice , Rydevik Gustaf , Franklin Brooke , James Daniel
Published: August 2022

A systematic review was undertaken to identify randomized controlled trials (RCTs) comparing the efficacy and safety of lurasidone, brexpiprazole and cariprazine (selected because of a shared safety profile) with each other or placebo in adult patients with schizophrenia. Key outcomes included: Positive and Negative Syndrome Scales (PANSS), Clinical Global Impression-Severity (CGI-S) scores and cardiovascular and metabolic parameters. A feasibility assessment evaluated the trials’ suitability for inclusion in a Bayesian network meta-analysis (NMA). Random effects models were used. In total, 1138 records were identified and 19 RCTs contributed to the NMA. Lurasidone doses of 160 mg performed best in terms of change in PANSS and CGI-S scores at 6 weeks, with stronger evidence when compared with brexpiprazole than cariprazine. The safety outcomes were variable; for all treatments, the 95% credible intervals usually contained ‘no difference’. Active treatments were associated with lower odds of discontinuation due to any cause, and higher odds of experiencing any adverse event. Lurasidone was comparable to brexpiprazole and cariprazine for efficacy and safety outcomes assessed at 6 weeks, with the 160 mg dose being superior for the change in PANSS and CGI-S outcomes. The lurasidone results were relatively consistent across doses compared with brexpiprazole and cariprazine.
Namco: a microbiome explorer
Authors: Dietrich Alexander , Matchado Monica Steffi , Zwiebel Maximilian , Ölke Benjamin , Lauber Michael , Lagkouvardos Ilias , Baumbach Jan , Haller Dirk , Brandl Beate , Skurk Thomas , Hauner Hans , Reitmeier Sandra , List Markus
Published: August 2022

16S rRNA gene profiling is currently the most widely used technique in microbiome research and allows the study of microbial diversity, taxonomic profiling, phylogenetics, functional and network analysis. While a plethora of tools have been developed for the analysis of 16S rRNA gene data, only a few platforms offer a user-friendly interface and none comprehensively covers the whole analysis pipeline from raw data processing down to complex analysis. We introduce Namco, an R shiny application that offers a streamlined interface and serves as a one-stop solution for microbiome analysis. We demonstrate Namco’s capabilities by studying the association between a rich fibre diet and the gut microbiota composition. Namco helped to prove the hypothesis that butyrate-producing bacteria are prompted by fibre-enriched intervention. Namco provides a broad range of features from raw data processing and basic statistics down to machine learning and network analysis, thus covering complex data analysis tasks that are not comprehensively covered elsewhere. Namco is freely available at https://exbio.wzw.tum.de/namco/.
Spermidine promotes lysozyme tolerance and acid stress resistance in Streptococcus pyogenes M3
Authors: Banerji Rajashri , Iyer Parvati , Bhagwat Amrita , Saroj Sunil D.
Published: August 2022

Streptococcus pyogenes

are Gram-positive opportunistic pathogens residing in the human nasopharynx and skin. Changes in environmental conditions, such as pH, temperature and availability of essential ions, can stimulate the expression of

S. pyogenes

virulence factors. One such factor could be the availability of an extracellular pool of polyamines. Polyamines are synthesized from amino acids, and are universally present in the environment. Polyamines have been implicated in the ecology of pathogenesis by modulating quorum sensing, host adaptation and virulence. Polyamines mediate pathogenesis and help the pathogen resist environmental stress. In this study, we investigated the ability of the polyamine, spermidine, to promote acid stress survival of S. pyogenes. S. pyogenes does not synthesize spermidine, but the extracellular pool of spermidine constituted by the host and microbiome could be utilized as a signalling molecule. We report that spermidine promotes acid stress resistance in

S. pyogenes

. Moreover, spermidine affects the morphology of

S. pyogenes

by decreasing the cell size and increasing the dltA gene expression. Along with dltA, spermidine upregulated the gene expression of cell wall-modifying genes such as mur, pgdA, pepO and srtA, which might help the bacteria to resist acidic stress.