bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial stewardship in veterinary medicine: a review of online resources
Authors: Allerton Fergus , Russell James
Published: May 2023

Background

An awareness of antimicrobial resistance and stewardship is important for all prescribers from a One-Health perspective. Educational resources have been created to help veterinary practitioners and encourage an optimized approach to their antimicrobial use.

Objectives

To support veterinarians to select the most appropriate educational resource to meet their personal learning goals in relation to veterinary antimicrobial stewardship (AMS).

Methods

Modular online platforms, developed to promote AMS in veterinary practice (farm and companion animal), were reviewed and key features highlighted, including the required time commitment, resource type, focus and source as well as a subjective evaluation of resource accessibility (according to prior knowledge base).

Results

Five different online courses are described in this educational resource review: Antimicrobial stewardship in veterinary practice; Farm Vet Champions; Farmed Animal Antimicrobial Stewardship Initiative (FAAST); the Pathway of antimicrobial resistance (AMR) for a veterinary services professional; and the VetAMS online learning program. Each of these tools introduces users to key themes of veterinary AMS. Upon completion of any of the courses practitioners should feel confident to assume an active role as proponents of rational antimicrobial use. Significant differences between resources, relating to the focus (companion or farm animal), scope and depth of material covered, are recognized reflecting their respective target audiences.

Conclusions

Several informative and accessible resources, centred on the core principles of veterinary AMS, were reviewed. Key features have been highlighted to inform and guide resource-users towards the most appropriate tool for them. Greater engagement with these educational resources will hopefully contribute to improved antimicrobial prescribing among veterinarians and greater awareness of the importance of stewardship for the profession.
Donor selection for fecal bacterial transplantation and its combined effects with inulin on early growth and ileal development in chicks
Authors: Song Yang , Cui Yibo , Wang Yumeng , Yu Jing , Wang Baolin , Wen Qiongyi , Zheng Xin
Published: May 2023

Aims

To select the best donor and investigate its combined effects with inulin on growth performance, and ileal health of chicks.

Methods and results

The chicks (Hy-line Brown) were treated with fecal microbiota suspension from different breeder hens to select the best donor. Treatment with fecal microbiota transplantation (FMT) alone or in combination with inulin resulted in improvement in gut microbiome in chicks. The organ indexes were improved on day 7, especially the bursa of fabricius index (P < 0.05). On day 14, immune performance, ileal morphology, and barrier were improved, and simultaneously, the concentration of short-chain fatty acids was also increased. In addition, for the expression of ileal barrier-related genes, Anaerofustis and Clostridium were positively correlated with them (P < 0.05), Blautia, Prevotella, Veillonella, and Weissella showed a negative correlation (P < 0.05), and RFN20 showed a positive correlation with gut morphology (P < 0.05).

Conclusion

Combination of homologous FMT and inulin promoted early growth and intestinal health of chicks.
Copper-inducible expression system for metabolic engineering of Escherichia coli
Authors: Liu Lingrui , Zhang Lu , Wang Junyi , Cao Mingfeng , Yuan Jifeng
Published: May 2023

Aims

The inducible expression system plays an important role in engineering Escherichia coli for chemical production. However, it still heavily relies on expensive chemical inducers, like IPTG. There is a pressing need to develop alternative expression systems with more affordable inducers.

Materials and results

We herein report a copper-inducible expression system in E. coli based on the two-component Cus system and T7 RNA polymerase (RNAP). By integrating the gene encoding T7 RNAP at the CusC locus, we managed to program eGFP expression under the T7 promoter in response to different concentrations of Cu2+ (0–20 μM). Subsequently, we demonstrated that the copper-inducible expression system was suitable for the metabolic engineering of E. coli toward protocatechuic acid overproduction, and the resulting strain with combined manipulation of the central metabolism via CRISPRi produced 4.12 g L−1 PCA under the optimal copper concentration and induction time.

Conclusions

We have established a copper-inducible T7 RNAP expression system in E. coli. The copper-inducible expression system could rationally control metabolic pathways in a temporal and dose-dependent manner. The gradient expression system based on copper inducer could be widely used in E. coli cell factories, and the design principle reported here would also be applicable in other prokaryotes.
The development and function of human monocyte-derived dendritic cells regulated by metabolic reprogramming
Authors: Zhao Ying , Gao Cuie , Liu Lu , Wang Li , Song Zhiqiang
Published: May 2023

Human monocyte-derived dendritic cells (moDCs) that develop from monocytes play a key role in innate inflammatory responses as well as T cell priming. Steady-state moDCs regulate immunogenicity and tolerogenicity by changing metabolic patterns to participate in the body's immune response. Increased glycolytic metabolism after danger signal induction may strengthen moDC immunogenicity, whereas high levels of mitochondrial oxidative phosphorylation were associated with the immaturity and tolerogenicity of moDCs. In this review, we discuss what is currently known about differential metabolic reprogramming of human moDC development and distinct functional properties.
Impact of jets on kilonova photometric and polarimetric emission from binary neutron star mergers
Authors: Shrestha Manisha , Bulla Mattia , Nativi Lorenzo , Markin Ivan , Rosswog Stephan , Dietrich Tim
Published: May 2023

A merger of binary neutron stars creates heavy unstable elements whose radioactive decay produces a thermal emission known as a kilonova. In this paper, we predict the photometric and polarimetric behaviour of this emission by performing 3D Monte Carlo radiative transfer simulations. In particular, we choose three hydrodynamical models for merger ejecta, two including jets with different luminosities and one without a jet structure, to help decipher the impact of jets on the light curve and polarimetric behaviour. In terms of photometry, we find distinct colour evolutions across the three models. Models without a jet show the highest variation in light curves for different viewing angles. In contrast to previous studies, we find models with a jet to produce fainter kilonovae when viewed from orientations close to the jet axis, compared to a model without a jet. In terms of polarimetry, we predict relatively low levels (≲0.3–0.4 per cent) at all orientations that, however, remain non-negligible until a few days after the merger and longer than previously found. Despite the low levels, we find that the presence of a jet enhances the degree of polarization at wavelengths ranging from 0.25 to $2.5\rm{\mu m}$, an effect that is found to increase with the jet luminosity. Thus, future photometric and polarimetric campaigns should observe kilonovae in blue and red filters for a few days after the merger to help constrain the properties of the ejecta (e.g. composition) and jet.
Tidal capture of an asteroid by a magnetar: FRB-like bursts, glitch, and antiglitch
Authors: Wu Qin , Zhao Zhen-Yin , Wang Fa-Yin
Published: May 2023

Recently, remarkable antiglitch and glitch accompanied by bright radio bursts of the Galactic magnetar SGR J1935+2154 were discovered. These two infrequent temporal coincidences between the glitch/antiglitch and the fast radio burst (FRB)-like bursts reveal their physical connection of them. Here, we propose that the antiglitch/glitch and FRB-like bursts can be well understood by an asteroid tidally captured by a magnetar. In this model, an asteroid is tidally captured and disrupted by a magnetar. Then, the disrupted asteroid will transfer the angular momentum to the magnetar producing a sudden change in the magnetar rotational frequency at the magnetosphere radius. If the orbital angular momentum of the asteroid is parallel (or antiparallel) to that of the spinning magnetar, a glitch (or antiglitch) will occur. Subsequently, the bound asteroid materials fall back to the pericentre and eventually are accreted to the surface of the magnetar. Massive fragments of the asteroid cross magnetic field lines and produce bright radio bursts through coherent curvature radiation. Our model can explain the sudden magnetar spin changes and FRB-like bursts in a unified way.
Protection of Catalytic Cofactors by Polypeptides as a Driver for the Emergence of Primordial Enzymes
Authors: Gutierrez-Rus Luis I , Gamiz-Arco Gloria , Gavira J A , Gaucher Eric A , Risso Valeria A , Sanchez-Ruiz Jose M
Published: May 2023

Enzymes catalyze the chemical reactions of life. For nearly half of known enzymes, catalysis requires the binding of small molecules known as cofactors. Polypeptide-cofactor complexes likely formed at a primordial stage and became starting points for the evolution of many efficient enzymes. Yet, evolution has no foresight so the driver for the primordial complex formation is unknown. Here, we use a resurrected ancestral TIM-barrel protein to identify one potential driver. Heme binding at a flexible region of the ancestral structure yields a peroxidation catalyst with enhanced efficiency when compared to free heme. This enhancement, however, does not arise from protein-mediated promotion of catalysis. Rather, it reflects the protection of bound heme from common degradation processes and a resulting longer lifetime and higher effective concentration for the catalyst. Protection of catalytic cofactors by polypeptides emerges as a general mechanism to enhance catalysis and may have plausibly benefited primordial polypeptide-cofactor associations.
Systematic assessment of hexavalent chromium-induced damage to male fertility and the preventive role of melatonin: a longitudinal study from the translational point of view
Authors: Li Tianjiao , Lv Yinghua , Wu Zhili , Guo Ming , Liu Ruifang , Zeng Wenxian , Zheng Yi
Published: May 2023

Chromium (Cr) and its compounds are closely associated with individuals’ lives and extensively used in industry. Excessive exposure to hexavalent chromium (Cr(VI)) induces oxidative damage of various organs including the testes, posing a serious threat to male reproductive fitness. As an endogenous antioxidant, melatonin holds potent antioxidative and anti-inflammatory properties, becoming a potential candidate for treatment of a variety of diseases, including reproductive disorders. Here, by using a mouse model, we systematically assessed Cr(VI)-induced damage to male fertility as well as the preventive role of melatonin. We analyzed the histology and pathology of the testis and epididymis, the density, viability, and malformation of caudal epididymal sperm, the proliferative activity and apoptosis of various spermatogenic subtypes and Sertoli cells, as well as the fertility of mice at five timepoints within one cycle of spermatogenesis (Days 0, 14, 21, 28, and 35) post 14 days of Cr(VI) and/or melatonin intraperitoneal injection. We identified that the testicular damage caused by Cr(VI) persisted to Day 21 after administration and then started to be alleviated, with clear alleviation on Day 35. Pretreatment with melatonin evidently reduced Cr(VI)-induced testicular damage and accelerated spermatogenic restoration, generating an almost normal phenotype on Day 35. Melatonin pretreatment also retained the sperm quality at all time points investigated. Moreover, melatonin to some extent preserved the fertility of Cr(VI)-treated mice without apparent side effects. The findings shed light on the future clinical application of melatonin as a therapeutic agent for environmental heavy metal toxicant-induced male subfertility or infertility.
Colchicine-responsive chronic recurrent multifocal osteomyelitis associated with familial Mediterranean fever in the presence of MEFV mutation: A case report
Authors: Izumikawa Miharu , Kato Mikiya , Wakiya Risa , Kameda Tomohiro , Nakashima Shusaku , Shimada Hiromi , Miyagi Taichi , Sugihara Koichi , Ushio Yusuke , Mino Rina , Mizusaki Mao , Chujo Kanako , Hiraishi Takashi , Kadowaki Norimitsu , Dobashi Hiroaki
Published: May 2023

A 38-year-old female was referred with a history of fever, polyarthralgia, and bone pain. She was diagnosed with chronic recurrent multifocal osteomyelitis based on imaging and biopsy findings. Non-steroidal anti-inflammatory drugs and bisphosphonate caused no improvement. Then, she developed recurrent diarrhoea and abdominal pain. Genetic testing revealed MEFV mutation. Based on the symptoms and genetic mutation results that emerged during the course of these events, she was diagnosed with familial Mediterranean fever. All symptoms, including bone pain, improved with daily colchicine administration. This case was considered familial Mediterranean fever complicated with a clinical diagnosis of chronic recurrent multifocal osteomyelitis, which is included in the spectrum of pyrine autoinflammatory diseases. Considering this case, patients with chronic recurrent multifocal osteomyelitis with MEFV gene variants may respond to colchicine.
Visual comet scoring revisited: a guide to scoring comet assay slides and obtaining reliable results
Authors: Møller Peter , Azqueta Amaya , Sanz-Serrano Julen , Bakuradze Tamara , Richling Elke , Eyluel Bankoglu Ezgi , Stopper Helga , Claudino Bastos Victoria , Langie Sabine A S , Jensen Annie , Scavone Francesca , Giovannelli Lisa , Wojewódzka Maria , Kruszewski Marcin , Valdiglesias Vanessa , Laffon Blanca , Costa Carla , Costa Solange , Teixeira João Paulo , Marino Mirko , Del Bo Cristian , Riso Patrizia , Zheng Congying , Shaposhnikov Sergey , Collins Andrew
Published: May 2023

Measurement of DNA migration in the comet assay can be done by image analysis or visual scoring. The latter accounts for 20%–25% of the published comet assay results. Here we assess the intra- and inter-investigator variability in visual scoring of comets. We include three training sets of comet images, which can be used as reference for researchers who wish to use visual scoring of comets. Investigators in 11 different laboratories scored the comet images using a five-class scoring system. There is inter-investigator variation in the three training sets of comets (i.e. coefficient of variation (CV) = 9.7%, 19.8%, and 15.2% in training sets I–III, respectively). However, there is also a positive correlation of inter-investigator scoring in the three training sets (r = 0.60). Overall, 36% of the variation is attributed to inter-investigator variation and 64% stems from intra-investigator variation in scoring between comets (i.e. the comets in training sets I–III look slightly different and this gives rise to heterogeneity in scoring). Intra-investigator variation in scoring was also assessed by repeated analysis of the training sets by the same investigator. There was larger variation when the training sets were scored over a period of six months (CV = 5.9%–9.6%) as compared to 1 week (CV = 1.3%–6.1%). A subsequent study revealed a high inter-investigator variation when premade slides, prepared in a central laboratory, were stained and scored by investigators in different laboratories (CV = 105% and 18%–20% in premade slides with comets from unexposed and hydrogen peroxide-exposed cells, respectively). The results indicate that further standardization of visual scoring is desirable. Nevertheless, the analysis demonstrates that visual scoring is a reliable way of analysing DNA migration in comets.
Association between CKD-MBD and mortality in older patients with advanced CKD—results from the EQUAL study
Authors: Magagnoli Lorenza , Cozzolino Mario , Caskey Fergus J , Evans Marie , Torino Claudia , Porto Gaetana , Szymczak Maciej , Krajewska Magdalena , Drechsler Christiane , Stenvinkel Peter , Pippias Maria , Dekker Friedo W , de Rooij Esther N M , Wanner Christoph , Chesnaye Nicholas C , Jager Kitty J ,   the EQUAL study investigators
Published: May 2023

Background

Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD.

Methods

We used data from the European Quality study, which includes patients aged ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.73 m2 from six European countries. Sequentially adjusted Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV and non-CV mortality. Effect modification between biomarkers was also assessed.

Results

In 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH [adjusted hazard ratio (aHR) 1.12, 95% confidence interval (CI) 1.03–1.23, P = .01] and phosphate (aHR 1.35, 95% CI 1.00–1.84, P = .05), but not calcium (aHR 1.11, 95% CI 0.57–2.17, P = .76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality in most models.

Conclusions

CKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality.
Plasma arginine metabolites in health and chronic kidney disease
Authors: Au Amy Y M , Mantik Kevin , Bahadory Forough , Stathakis Paul , Guiney Hayley , Erlich Jonathan , Walker Robert , Poulton Richie , Horvath Andrea Rita , Endre Zoltan H
Published: May 2023

Background

Elevated plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) are risk factors for chronic kidney disease (CKD) and cardiovascular disease. Using plasma cystatin C (pCYSC)-based estimated glomerular filtration rate (eGFR) trajectories, we identified a cohort at high risk of poor kidney-related health outcomes amongst members of the Dunedin Multidisciplinary Health and Development Study (DMHDS). We therefore examined associations between methylarginine metabolites and kidney function in this cohort.

Methods

ADMA, SDMA, L-arginine and L-citrulline were measured in plasma samples from 45-year-olds in the DMHDS cohort by liquid chromatography–tandem mass spectrometry.

Results

In a healthy DMHDS subset (n = 376), mean concentrations were: ADMA (0.40 ± 0.06 µmol/L), SDMA (0.42 ± 0.06 µmol/L), L-arginine (93.5 ± 23.1 µmol/L) and L-citrulline (24.0 ± 5.4 µmol/L). In the total cohort (n = 857), SDMA correlated positively with serum creatinine (Pearson's r = 0.55) and pCYSC (r = 0.55), and negatively with eGFR (r = 0.52). A separate cohort of 38 patients with stage 3–4 CKD (eGFR 15–60 mL/min/1.73 m2) confirmed significantly higher mean ADMA (0.61 ± 0.11 µmol/L), SDMA (0.65 ± 0.25 µmol/L) and L-citrulline (42.7 ± 11.8 µmol/L) concentrations. DMHDS members classified as high-risk of poor kidney health outcomes had significantly higher mean concentrations of all four metabolites compared with individuals not at risk. ADMA and SDMA individually predicted high-risk of poor kidney health outcomes with areas under the ROC curves (AUCs) of 0.83 and 0.84, and together with an AUC of 0.90.

Conclusions

Plasma methylarginine concentrations facilitate stratification for risk of CKD progression.
Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD)
Authors: Taal Maarten W , Lucas Bethany , Roderick Paul , Cockwell Paul , Wheeler David C , Saleem Moin A , Fraser Simon D S , Banks Rosamonde E , Johnson Tim , Hale Lorna J , Andag Uwe , Skroblin Philipp , Bayerlova Michaela , Unwin Robert , Vuilleumier Nicolas , Dusaulcy Rodolphe , Robertson Fiona , Colby Elizabeth , Pitcher David , Braddon Fiona , Benavente Melissa , Davies Elaine , Nation Michael , Kalra Philip A
Published: May 2023

Background

Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care.

Methods

Eligible participants with CKD stages G3–4 or stages G1–2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated glomerular filtration rate (eGFR).

Results

A total of 2996 participants was enrolled. Median (interquartile range) age was 66 (54–74) years, eGFR 33.8 (24.0–46.6) mL/min/1.73 m2 and urine albumin to creatinine ratio 209 (33–926) mg/g; 58.5% were male. Of these participants, 1883 (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin–angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin.

Conclusions

NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and to investigate underlying mechanisms to inform new treatment development.
Significant increase of high-risk chromosome 1q gain and 6q loss at recurrence in posterior fossa group A ependymoma: A multicenter study
Authors: Donson Andrew M , Bertrand Kelsey C , Riemondy Kent A , Gao Dexiang , Zhuang Yonghua , Sanford Bridget , Norris Gregory A , Chapman Rebecca J , Fu Rui , Willard Nicholas , Griesinger Andrea M , Ribeiro de Sousa Graziella , Amani Vladimir , Grimaldo Enrique , Hankinson Todd C , Booker Ffyona , Sill Martin , Grundy Richard G , Pajtler Kristian W , Ellison David W , Foreman Nicholas K , Ritzmann Timothy A
Published: May 2023

Background

Ependymoma (EPN) posterior fossa group A (PFA) has the highest rate of recurrence and the worst prognosis of all EPN molecular groups. At relapse, it is typically incurable even with re-resection and re-irradiation. The biology of recurrent PFA remains largely unknown; however, the increasing use of surgery at first recurrence has now provided access to clinical samples to facilitate a better understanding of this.

Methods

In this large longitudinal international multicenter study, we examined matched samples of primary and recurrent disease from PFA patients to investigate the biology of recurrence.

Results

DNA methylome derived copy number variants (CNVs) revealed large-scale chromosome gains and losses at recurrence in PFA. CNV changes were dominated by chromosome 1q gain and/or 6q loss, both previously identified as high-risk factors in PFA, which were present in 23% at presentation but increased to 61% at first recurrence. Multivariate survival analyses of this cohort showed that cases with 1q gain or 6q loss at first recurrence were significantly more likely to recur again. Predisposition to 1q+/6q− CNV changes at recurrence correlated with hypomethylation of heterochromatin-associated DNA at presentation. Cellular and molecular analyses revealed that 1q+/6q− PFA had significantly higher proportions of proliferative neuroepithelial undifferentiated progenitors and decreased differentiated neoplastic subpopulations.

Conclusions

This study provides clinically and preclinically actionable insights into the biology of PFA recurrence. The hypomethylation predisposition signature in PFA is a potential risk-classifier for trial stratification. We show that the cellular heterogeneity of PFAs evolves largely because of genetic evolution of neoplastic cells.
Stepwise changes in flavonoids in spores/pollen contributed to terrestrial adaptation of plants
Authors: Xue Jing-Shi , Qiu Shi , Jia Xin-Lei , Shen Shi-Yi , Shen Chong-Wen , Wang Shui , Xu Ping , Tong Qi , Lou Yu-Xia , Yang Nai-Ying , Cao Jian-Guo , Hu Jin-Feng , Shen Hui , Zhu Rui-Liang , Murray Jeremy D , Chen Wan-Sheng , Yang Zhong-Nan
Published: May 2023

Protecting haploid pollen and spores against UV-B light and high temperature, 2 major stresses inherent to the terrestrial environment, is critical for plant reproduction and dispersal. Here, we show flavonoids play an indispensable role in this process. First, we identified the flavanone naringenin, which serves to defend against UV-B damage, in the sporopollenin wall of all vascular plants tested. Second, we found that flavonols are present in the spore/pollen protoplasm of all euphyllophyte plants tested and that these flavonols scavenge reactive oxygen species to protect against environmental stresses, particularly heat. Genetic and biochemical analyses showed that these flavonoids are sequentially synthesized in both the tapetum and microspores during pollen ontogeny in Arabidopsis (Arabidopsis thaliana). We show that stepwise increases in the complexity of flavonoids in spores/pollen during plant evolution mirror their progressive adaptation to terrestrial environments. The close relationship between flavonoid complexity and phylogeny and its strong association with pollen survival phenotypes suggest that flavonoids played a central role in the progression of plants from aquatic environments into progressively dry land habitats.
How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies
Authors: Boyadzhieva Zhivana , Ruffer Nikolas , Kötter Ina , Krusche Martin
Published: May 2023

Objectives

To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.

Methods

A protocolized systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analysed.

Results

We identified 36 publications with a total of 116 patients; 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), Janus kinase inhibitors (JAKi) (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR 1/2, 50%; PR 1/2, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF inhibitors, rituximab and MTX. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (6/67, 8.9%), cytopenias (4/67, 5.9%), and acute (4/67, 5.9%) and chronic graft-vs-host-disease (2/67, 2.9%).

Conclusion

Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. Adverse events remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.
Sociodemographic Trends in Telemedicine Visit Completion in Spine Patients During the COVID-19 Pandemic
Authors: Owolo Edwin , Petitt Zoey , Rowe Dana , Luo Emily , Bishop Brandon , Poehlein Emily , Green Cynthia L. , Cook Chad , Erickson Melissa , Goodwin C. Rory
Published: May 2023

Study Design:

Retrospective cohort study

Objective:

This study identifies potential disparities in telemedicine utilization in the wake of the COVID-19 pandemic and its aftermath in patients receiving spine surgery.

Summary of Background Data:

COVID-19 led to the rapid uptake of telemedicine in the spine surgery patient population. While previous studies in other medical subspecialties have identified sociodemographic disparities in telemedicine uptake, this is the first study to identify disparities in patients undergoing spine surgery.

Materials and Methods:

This study included patients who underwent spine surgery between June 12, 2018 and July 19, 2021. Patients were required to have at least one scheduled patient visit, either virtual (video or telephone visit) or in-person. Binary socioeconomic variables used for modeling included: urbanicity, age at the time of the procedure, sex, race, ethnicity, language, primary insurer, and patient portal utilization. Analyses were conducted for the entire cohort and separately for cohorts of patients who had visits scheduled within specific timeframes: Pre–COVID-19 surge, initial COVID-19 surge, and post–COVID-19 surge.

Results:

After adjusting for all variables in our multivariable analysis, patients who utilized the patient portal had higher odds of completing a video visit compared with those who did not (OR: 5.21; 95% CI: 1.28, 21.23). Hispanic patients (OR: 0.44; 95% CI: 0.2, 0.98) or those living in rural areas (OR: 0.58; 95% CI: 0.36, 0.93) had lower odds of completing a telephone visit. Patients with no insurance or on public insurance had higher odds of completing a virtual visit of either type (OR: 1.88; 95% CI: 1.10, 3.23).

Conclusion:

This study demonstrates the disparity in telemedicine utilization across different populations within the surgical spine patient population. Surgeons may use this information to guide interventions aimed at reducing existing disparities and work with certain patient populations to find a solution.
Assessment of the External Validity of Dialogue Support for Predicting Lumbar Spine Surgery Outcomes in a US Cohort
Authors: Carreon Leah Y. , Glassman Steven D. , Mummaneni Praveen , Bydon Mohamad , Chan Andrew K. , Asher Anthony
Published: May 2023

Study Design.

External validation using prospectively collected data.

Objectives.

To determine the model performance of “Dialogue Support” (DS) in predicting outcomes after lumbar spine surgery.

Summary of Background Data.

To help clinicians discuss risk versus benefit with patients considering lumbar fusion surgery, DS has been made available online. As DS was created using a Swedish sample, there is a need to study how well DS performs in alternative populations.

Patients and Methods.

Preoperative data from patients enrolled in the Quality Outcomes Database were entered into DS. The probability for each patient to report satisfaction, achieve success (leg pain improvement ≥3), or have no leg pain 12 months after surgery was extracted and compared with their actual 12-month postoperative data. The ability of DS to identify patients in the Quality Outcomes Database who report satisfaction, achieve success, or have no leg pain 12 months after surgery was determined using Receiver operating characteristic curve analysis, goodness-of-fit tests, and calibration plots.

Results.

There was a significant improvement in all outcomes in 23,928 cases included in the analysis from baseline to 12 months postoperative. Most (84%) reported satisfaction, 67% achieved success, and 44% were pain-free 12 months postoperative. Receiver operating characteristic analysis showed that DS had a low ability to predict satisfaction [area under the curve (AUC) = 0.606], success (AUC = 0.546), and being pain-free (AUC = 0.578) at 12 months postoperative; poor fit for satisfaction (<0.001) and being pain-free (P = 0.004), but acceptable fit for success (P = 0.052). Calibration plots showed underestimation for satisfaction and success, but acceptable estimates for being pain-free.

Conclusion.

DS is not directly transferable to predict satisfaction and success after lumbar surgery in a US population. This may be due to differences in patient characteristics, weights of the variables included, or the exclusion of unknown variables associated with outcomes. Future studies to better understand and improve the transferability of these models are needed.
Percutaneous Transforaminal Endoscopic Discectomy Learning Curve
Authors: Maayan Omri , Pajak Anthony , Shahi Pratyush , Asada Tomoyuki , Subramanian Tejas , Araghi Kasra , Singh Nishtha , Korsun Maximillian K. , Singh Sumedha , Tuma Olivia C. , Sheha Evan D. , Dowdell James E. , Qureshi Sheeraz A. , Iyer Sravisht
Published: May 2023

Study Design.

Retrospective review of prospectively collected data.

Objective.

To describe the learning curve for percutaneous transforaminal endoscopic discectomy (PTED) and demonstrate its efficacy in treating lumbar disc herniation.

Summary of Background Data.

The learning curve for PTED has not yet been standardized in the literature.

Patients and Methods.

Consecutive patients who underwent lumbar PTED by a single surgeon between December 2020 and 2022 were included. Cumulative sum analysis was applied to operative and fluoroscopy time to assess the learning curve. Inflection points were used to divide cases into early and late phases. The 2 phases were analyzed for differences in operative and fluoroscopy time, length of stay, complications, and patient-reported outcome measures (PROMs). Patient characteristics and operative levels were also compared. PROMs entailed the Oswestry Disability Index, Patient-Reported Outcomes Measurement Information System, Visual Analog Scale Back/Leg, and 12-item Short Form Survey at preoperative, early postoperative (<6 mo), and late postoperative (≥6 mo) time points. PROMs between PTED cases and a comparable cohort of tubular microdiscectomy cases, performed by the same surgeon, were compared.

Results.

Fifty-five patients were included. Cumulative sum analysis indicated that both operative and fluoroscopy time diminished rapidly after case 31, suggesting a learning curve of 31 cases (early phase: n = 31; late phase: n = 24). Late-phase cases exhibited significantly lower operative times (85.7 vs. 62.2 min, P = 0.001) and fluoroscopy times (131.0 vs. 97.2 s, P = 0.001) compared with the early-phase cases. Both early and late-phase cases showed significant improvement in all PROMs. There were no differences in PROMs between the patients who underwent PTED and tubular microdiscectomy.

Conclusion.

The PTED learning curve was found to be 31 cases and did not impact PROMs or complication rates. Although this learning curve reflects the experiences of a single surgeon and may not be broadly applicable, PTED can serve as an effective modality for the treatment of lumbar disc herniation.
Hippo (YAP)–autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling
Authors: Zhu Shuguang , Wang Xiaowen , Chen Haoqi , Zhu Wenfeng , Li Xuejiao , Cui Ruiwen , Yi Xiaomeng , Chen Xiaolong , Li Hua , Wang Genshu
Published: May 2023

Background:

Hepatic ischemia-reperfusion injury (HIRI) remains a common complication during liver transplantation (LT) in patients. As a key downstream effector of the Hippo pathway, Yes-associated protein (YAP) has been reported to be involved in various physiological and pathological processes. However, it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.

Methods:

Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation. Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation.

Results:

Autophagy was activated in the post-perfusion liver grafts during LT in patients, and the expression of YAP positively correlated with the autophagic level of hepatocytes. Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI (P <0.05). YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models (P <0.05). Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine. In addition, inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species (P <0.05). Moreover, the regulation of autophagy by YAP during HIRI was mediated by AP1 (c-Jun) N-terminal kinase (JNK) signaling through binding to the transcriptional enhanced associate domain (TEAD).

Conclusions:

YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes. Targeting Hippo (YAP)–JNK–autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.
Regional analgesia for lung transplantation
Authors: Azem Karam , Mangoubi Eitan , Zribi Benjamin , Fein Shai
Published: May 2023

Lung transplantation (LTx) is the definitive treatment for end-stage pulmonary disease. About 4500 LTxs are performed annually worldwide.

It is considered challenging and complex surgery regarding anaesthesia and pain management. While providing adequate analgesia is crucial for patient comfort, early mobilisation and prevention of postoperative pulmonary complications, standardising an analgesic protocol is challenging due to the diversity of aetiologies, surgical approaches and the potential use of extracorporeal life support (ECLS).

Although thoracic epidural analgesia is commonly considered the gold standard, concerns regarding procedural safety and its potential for devastating consequences have led physicians to seek safer analgesic modalities such as thoracic nerve blocks.

The advantages of thoracic nerve blocks for general thoracic surgery are well established. However, their utility in LTx remains unclear.

Considering paucity of relevant literature, this review aims to raise awareness about the literature gap in the field and highlight the need for further high-quality studies determining the effectiveness of available techniques.
IncobotulinumtoxinA for Glabellar Frown Lines in Chinese Subjects: A Randomized, Double-blind, Active-Controlled Phase-3 Study
Authors: Wu Yan , Roll Susanna , Klein Gudrun , Geister Thorin L. , Makara Michael A. , Li Bi
Published: May 2023

Background:

This study evaluated the efficacy and safety of IncobotulinumtoxinA 20 U for treatment of glabellar frown lines in Chinese subjects.

Methods:

This was a prospective, randomized, double-blind, active-controlled, phase-3 study conducted in China. Subjects with moderate to severe glabellar frown lines at maximum frown were randomized to receive IncobotulinumtoxinA (N = 336) or OnabotulinumtoxinA (N = 167).

Results:

For the primary efficacy endpoint at day 30, response rates at maximum frown (score “none” or “mild”) on the Merz Aesthetic Scales Glabella Lines – Dynamic were comparable between IncobotulinumtoxinA (92.5%) and OnabotulinumtoxinA (95.1%) per investigator’s live rating. Noninferiority of IncobotulinumtoxinA versus OnabotulinumtoxinA was successfully demonstrated, as the two-sided 95% confidence interval of −0.97% to 0.43% for the difference in Merz Aesthetic Scales-based response rates (−0.27%) lay completely above the predefined noninferiority margin of −15%. For the secondary efficacy endpoints assessed at day 30, Merz Aesthetic Scales-based response rates (score “none” or “mild”) at maximum frown were similarly comparable between both groups per subject (>85%) and independent review panel (>96%) rating. Per Global Impression of Change Scales, greater than 80% of subjects and greater than 90% of investigators in both groups rated treatment results as at least “much improved” at day 30 compared with baseline. Safety profiles were consistent between groups; IncobotulinumtoxinA was well tolerated, and no new safety concerns were identified in Chinese subjects.

Conclusion:

IncobotulinumtoxinA 20 U is safe and effective for treatment of moderate to severe glabellar frown lines at maximum frown in Chinese subjects and is noninferior to OnabotulinumtoxinA 20 U.
Artificial or Augmented Authorship? A Conversation with a Chatbot on Base of Thumb Arthritis
Authors: Seth Ishith , Sinkjær Kenney Peter , Bulloch Gabriella , Hunter-Smith David J. , Bo Thomsen Jørn , Rozen Warren M.
Published: May 2023

ChatGPT is an open artificial intelligence chat box that could revolutionize academia and augment research writing. This study had an open conversation with ChatGPT and invited the platform to evaluate this article through series of five questions on base of thumb arthritis to test if its contributions and contents merely add artificial unusable input or help us augment the quality of the article. The information ChatGPT-3 provided was accurate, albeit surface-level, and lacks analytical ability to dissect for important limitations about base of thumb arthritis, which would not be conducive to potentiating creative ideas and solutions in plastic surgery. ChatGPT failed to provide relevant references and even “created” references instead of indicating its inability to perform the task. This highlights that as an AI-generator for medical publishing text, ChatGPT-3 should be used cautiously.
Reductions in Childhood Pneumonia Mortality After Vaccination in the United States
Authors: Paternina-Caicedo Angel , Smith Adrian D , Buchanich Jeanine , Garcia-Calavaro Christian , Alvis-Guzman Nelson , Narvaez Javier , de Oliveira Lucia Helena , De la Hoz-Restrepo Fernando
Published: May 2023

Background:

We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States.

Methods:

We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs).

Results:

Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0–1-month-old children was 2.55 per 100,00 pop., whereas for 2–11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0–59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4–21) and 19% (95% CI: 0–33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4–35) for all-cause pneumonia mortality and 22% (95% CI: −19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6–11-month-old infants.

Conclusions:

The universal introduction of PCV7, and later PCV13, for children 0–59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia.
Mental Health Matters: A Cross-Sectional Survey on Depression and Anxiety Symptoms and the Female and Male Athlete Triad
Authors: Olson Emily Miller , Miro Emily , Roche Megan , Mehta Shayna , Sainani Kristin , Kraus Emily
Published: May 2023

Objective:

To determine the relationship between the female and male athlete triad with depression and anxiety symptoms.

Design:

Cross-sectional survey.

Setting:

Survey distributed online through social media to participants.

Participants:

Male and female high school, collegiate, and postcollegiate athletes.

Interventions:

Participants completed a survey assessing components of the female athlete triad and the Patient-Reported Outcomes Measurement Information System depression and anxiety short-form questionnaires.

Main Outcome Measures:

Participants were classified into those with no, mild, moderate, or severe depression symptoms or anxiety symptoms. A female athlete triad (Triad) cumulative risk score was calculated. Multinomial logistic regressions were used to assess the relationship between triad score and depression/anxiety.

Results:

Two hundred fifty-four men and 780 women completed the survey; 66.6% of women and 41.3% of men reported at least mild anxiety symptoms; 54.2% of women and 38.7% of men reported at least mild depression symptoms. Triad risk score was significantly related to moderate and severe depression symptoms (P < 0 .0001) and moderate (P = 0.003) and severe (P < 0 .0001) anxiety symptoms in women. We found no significant associations between Triad risk score and depression or anxiety symptoms in men.

Conclusions:

We found a correlation between the female athlete triad and moderate and severe depression and anxiety symptoms in women. Depression and anxiety symptoms were most strongly related to the low energy availability component of the Triad risk score and to the presence of eating disorders/disordered eating. This suggests that mental health illness is most tied to the behavioral aspects of the Triad.

Clinical Relevance:

This study demonstrates the importance of screening for and treating mental health illness in those diagnosed with low energy availability, disordered eating, and/or the female athlete triad in addition to focusing on a nutrition intervention.