bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the reporting quality of pediatric neuro-oncology protocols, abstracts, and trials: Adherence to the SPIRIT and CONSORT statements
Authors: Suppree Joshua S , Hart Sophia , Keshwara Sumirat M , Trichinopoly Krishna Sandhya , Gillespie Conor S , Richardson George E , Mustafa Mohammad A , Mallucci Conor L , Pizer Barry , Hayden James , Islim Abdurrahman I , Jenkinson Michael D , Millward Christopher P
Published: May 2024

Background

It is of vital importance to comprehensively and transparently report clinical trial activity. The SPIRIT 2013 and CONSORT 2010 statements exist to define items to be reported in clinical trial protocols and randomized controlled trials, respectively. The aim of this methodological review was to assess the reporting quality of pediatric neuro-oncology trial protocols and trial result articles.

Methods

Published trial protocols and phase II/III trial result articles relating to pediatric brain tumors (published after the introduction of the SPIRIT 2013 statement), were identified through searches of 4 electronic bibliographic databases. The reporting quality of included trial protocols and result articles was assessed against the aforementioned statements. In addition, the CONSORT-A checklist was used to assess the abstracts of trial result articles. Percentage adherence was calculated for each article.

Results

Nine trial protocols, 68 phase II trials, and 8 phase III trial result articles were included. Mean adherence of trial protocols to the SPIRIT statement was 76.8% (SD: 0.09). Mean adherence of trial abstracts to CONSORT-A was 67.4% (SD: 0.13) for phase II abstracts and 47.5% (SD: 0.09) for phase III abstracts. Adherence of trial result articles to CONSORT was 71.3% (SD: 0.10) for phase II trials and 70.3% (SD: 0.13) for phase III trials.

Conclusions

The reporting quality of pediatric neuro-oncology trial protocols and trial result articles requires improvement, particularly in the areas of randomization and blinding. This is consistent with our previously published findings following similar assessment of reporting quality for adult neuro-oncology trial protocols and result articles.
Human Capital Reallocation across Firms: Evidence from Idiosyncratic Shocks
Authors: Gilje Erik P , Taillard Jérôme P , Zeng Linghang
Published: May 2024

We study human capital reallocation following firm-specific idiosyncratic shocks. We analyze relegation battles in the English Premier League, a setting that offers well-identified idiosyncratic shocks as well as both individual-level and firm-level productivity metrics. Following a negative idiosyncratic shock, we find that relatively more productive players move to more productive clubs and maintain their long-term productivity. They get replaced with lower productivity players. Overall, our results show that in a setting with highly transferable and observable skills, idiosyncratic shocks lead to a reallocation of human capital that moves the industry toward a better overall match between individual-level and firm-level productivity. (JEL G31, G32, G33, J24)
Risk of urolithiasis associated with allopurinol versus benzbromarone among patients with gout: a population-based cohort study
Authors: Kang Eun Ha , Shin Anna , Park Chang Soo , Lee Eun Bong , Lee Yun Jong , Curhan Gary , Choi Hyon K
Published: May 2024

Objectives

To compare the risk of urolithiasis in gout patients initiating allopurinol, a xanthine oxidase inhibitor, vs benzbromarone, a uricosuric.

Methods

Using the 2011–20 Korea National Health Insurance Service database, we conducted a cohort study on gout patients initiating allopurinol vs benzbromarone as the first-line urate-lowering treatment. The primary outcome was a new onset urinary stone. The secondary outcome was a stone requiring intervention. We estimated hazard ratios (HRs) and 95% CIs using Cox proportional hazard models with a 5:1 ratio propensity-score matching on >80 variables. Subgroup analyses were done by age, sex, thiazide use and cardiovascular risk.

Results

61 300 allopurinol initiators PS-matched on 12 260 benzbromarone initiators were included (mean age 59 years, 79% male). During a mean follow-up of 322 days, 619 urolithiasis cases occurred with an incidence rate of 0.87 per 100 person-years in allopurinol and 1.39 in benzbromarone initiators, showing a HR of 0.64 (95% CI, 0.51–0.80). Approximately 44% of urinary stones required intervention with a HR of 0.61 (95% CI, 0.43–0.88). The lower risk associated with allopurinol compared with benzbromarone persisted across subgroups but was greater in the high than non-high cardiovascular risk subgroup (P for interaction = 0.02)

Conclusion

This population-based cohort study found that allopurinol compared with benzbromarone was associated with a substantially lower risk of urolithiasis particularly in the presence of the high cardiovascular risk. This finding provides important safety information for clinicians’ decision-making on urate-lowering treatments of different mechanisms of action.
Validation of the Behçet’s Syndrome Overall Damage Index (BODI) for retrospective studies and a proposal for modification
Authors: Ozogul Yeliz Yagiz , Ozguler Yesim , Esatoglu Sinem N , Ucar Didar , Uygunoglu Ugur , Kutlubay Zekayi , Hamuryudan Vedat , Hatemi Gulen
Published: May 2024

Objective

Assessment of damage accrual over time is important for evaluating and comparing long-term results of treatment modalities and strategies. Retrospective studies may be useful for assessing long-term damage, especially in rare diseases. We aimed to validate Behçet’s Syndrome Overall Damage Index (BODI) for use in retrospective studies by evaluating its construct validity, reliability and feasibility in retrospectively collected data. Additionally, we aimed to determine missing items by evaluating Behçet’s syndrome patients with different types of organ involvement and long-term follow-up.

Methods

We included 300 patients who had at least two clinic visits at 1-year intervals. The construct validity for use in retrospective trials was assessed by comparing BODI scores calculated from patient charts and during face-to-face visits. BODI was additionally scored using retrospective chart data by two different observers and by the same observer six months apart, in a blinded manner. The time for filling BODI was evaluated to assess feasibility. Additionally, damaged items that were missing from BODI were identified.

Results

There was a good correlation between the retrospective and face-to-face evaluation of BODI (ICC 0.99; %95 CI 0.99–0.99). Inter-observer and intra-observer agreement were good (ICC 0.96 and 1, respectively). The main damage items that BODI did not capture were hypertension, liver failure, lung parenchymal involvement, glaucoma and lymphedema.

Conclusion

BODI seems to be a reliable and feasible instrument for assessing damage in retrospective studies. Modifying BODI using the additional damage items identified in this study may make it an even better scale.
Amphiregulin secreted by umbilical cord multipotent stromal cells protects against ferroptosis of macrophages via the activating transcription factor 3-CD36 axis to alleviate endometrial fibrosis
Authors: Wang Jiali , Li Jingman , Wang Shuangan , Pan Yuchen , Yang Jingjing , Yin Lijie , Dou Huan , Hou Yayi
Published: May 2024

Endometrium fibrosis is the leading cause of uterine infertility. Macrophages participated in the occurrence and development of endometrial fibrosis. We previously reported that human umbilical cord multipotent stromal cells (hUC-MSCs) exerted their therapeutic effect in a macrophage-dependent manner in endometrial fibrosis. However precise mechanisms by which hUC-MSCs may influence macrophages in endometrial fibrosis remain largely unexplored. Here, we demonstrated that abnormal iron and lipid metabolism occurred in patients with intrauterine adhesions (IUA) and murine models. Ferroptosis has been proven to contribute to the progression of fibrotic diseases. Our results revealed that pharmacological activation of ferroptosis by Erastin aggravated endometrial fibrosis, while inhibition of ferroptosis by Ferrostatin-1 ameliorated endometrial fibrosis in vivo. Moreover, ferroptosis of macrophages was significantly upregulated in endometria of IUA murine models. Of note, transcriptome profiles revealed that CD36 gene expression was significantly increased in patients with IUA and immunofluorescence analysis showed CD36 protein was mainly located in macrophages. Silencing CD36 in macrophages could reverse cell ferroptosis. Dual luciferase reporter assay revealed that CD36 was the direct target of activation transcription factor 3 (ATF3). Furthermore, through establishing coculture system and IUA murine models, we found that hUC-MSCs had a protective role against macrophage ferroptosis and alleviated endometrial fibrosis related to decreased CD36 and ATF3. The effect of hUC-MSCs on macrophage ferroptosis was attributed to the upregulation of amphiregulin (AREG). Our data highlighted that macrophage ferroptosis occurred in endometrial fibrosis via the ATF3-CD36 pathway and hUC-MSCs protected against macrophage ferroptosis to alleviate endometrial fibrosis via secreting AREG. These findings provided a potential target for therapeutic implications of endometrial fibrosis.
The Rediscovery of a Relict Unlocks the First Global Phylogeny of Whip Spiders (Amblypygi)
Authors: de Miranda Gustavo S , Kulkarni Siddharth S , Tagliatela Jéssica , Baker Caitlin M , Giupponi Alessandro P L , Labarque Facundo M , Gavish-Regev Efrat , Rix Michael G , Carvalho Leonardo S , Fusari Lívia Maria , Harvey Mark S , Wood Hannah M , Sharma Prashant P
Published: May 2024

Asymmetrical rates of cladogenesis and extinction abound in the tree of life, resulting in numerous minute clades that are dwarfed by larger sister groups. Such taxa are commonly regarded as phylogenetic relicts or “living fossils” when they exhibit an ancient first appearance in the fossil record and prolonged external morphological stasis, particularly in comparison to their more diversified sister groups. Due to their special status, various phylogenetic relicts tend to be well-studied and prioritized for conservation. A notable exception to this trend is found within Amblypygi (“whip spiders”), a visually striking order of functionally hexapodous arachnids that are notable for their antenniform first walking leg pair (the eponymous “whips”). Paleoamblypygi, the putative sister group to the remaining Amblypygi, is known from Late Carboniferous and Eocene deposits but is survived by a single living species, Paracharon caecusHansen (1921), that was last collected in 1899. Due to the absence of genomic sequence-grade tissue for this vital taxon, there is no global molecular phylogeny for Amblypygi to date, nor a fossil-calibrated estimation of divergences within the group. Here, we report a previously unknown species of Paleoamblypygi from a cave site in Colombia. Capitalizing upon this discovery, we generated the first molecular phylogeny of Amblypygi, integrating ultraconserved element sequencing with legacy Sanger datasets and including described extant genera. To quantify the impact of sampling Paleoamblypygi on divergence time estimation, we performed in silico experiments with pruning of Paracharon. We demonstrate that the omission of relicts has a significant impact on the accuracy of node dating approaches that outweighs the impact of excluding ingroup fossils, which bears upon the ancestral range reconstruction for the group. Our results underscore the imperative for biodiversity discovery efforts in elucidating the phylogenetic relationships of “dark taxa,” and especially phylogenetic relicts in tropical and subtropical habitats. The lack of reciprocal monophyly for Charontidae and Charinidae leads us to subsume them into one family, Charontidae, new synonymy.
Benefits and Limits of Phasing Alleles for Network Inference of Allopolyploid Complexes
Authors: Tiley George P , Crowl Andrew A , Manos Paul S , Sessa Emily B , Solís-Lemus Claudia , Yoder Anne D , Burleigh J Gordon
Published: May 2024

Accurately reconstructing the reticulate histories of polyploids remains a central challenge for understanding plant evolution. Although phylogenetic networks can provide insights into relationships among polyploid lineages, inferring networks may be hindered by the complexities of homology determination in polyploid taxa. We use simulations to show that phasing alleles from allopolyploid individuals can improve phylogenetic network inference under the multispecies coalescent by obtaining the true network with fewer loci compared with haplotype consensus sequences or sequences with heterozygous bases represented as ambiguity codes. Phased allelic data can also improve divergence time estimates for networks, which is helpful for evaluating allopolyploid speciation hypotheses and proposing mechanisms of speciation. To achieve these outcomes in empirical data, we present a novel pipeline that leverages a recently developed phasing algorithm to reliably phase alleles from polyploids. This pipeline is especially appropriate for target enrichment data, where the depth of coverage is typically high enough to phase entire loci. We provide an empirical example in the North American Dryopteris fern complex that demonstrates insights from phased data as well as the challenges of network inference. We establish that our pipeline (PATÉ: Phased Alleles from Target Enrichment data) is capable of recovering a high proportion of phased loci from both diploids and polyploids. These data may improve network estimates compared with using haplotype consensus assemblies by accurately inferring the direction of gene flow, but statistical nonidentifiability of phylogenetic networks poses a barrier to inferring the evolutionary history of reticulate complexes.
Histone deacetylase‐3 regulates the expression of the amyloid precursor protein and its inhibition promotes neuroregenerative pathways in Alzheimer's disease models
Authors: Davis Nicola , Taylor Ben , Abelleira‐Hervas Laura , Karimian‐Marnani Najmeh , Aleksynas Robertas , Syed Nelofer , Di Giovanni Simone , Palmisano Ilaria , Sastre Magdalena
Published: May 2024

HDAC3 inhibition has been shown to improve memory and reduce amyloid‐β (Aβ) in Alzheimer's disease (AD) models, but the underlying mechanisms are unclear. We investigated the molecular effects of HDAC3 inhibition on AD pathology, using in vitro and ex vivo models of AD, based on our finding that HDAC3 expression is increased in AD brains. For this purpose, N2a mouse neuroblastoma cells as well as organotypic brain cultures (OBCSs) of 5XFAD and wild‐type mice were incubated with various concentrations of the HDAC3 selective inhibitor RGFP966 (0.1–10 μM) for 24 h. Treatment with RGFP966 or HDAC3 knockdown in N2a cells was associated with an increase on amyloid precursor protein (APP) and mRNA expressions, without alterations in Aβ42 secretion. In vitro chromatin immunoprecipitation analysis revealed enriched HDAC3 binding at APP promoter regions. The increase in APP expression was also detected in OBCSs from 5XFAD mice incubated with 1 μM RGFP966, without changes in Aβ. In addition, HDAC3 inhibition resulted in a reduction of activated Iba‐1‐positive microglia and astrocytes in 5XFAD slices, which was not observed in OBCSs from wild‐type mice. mRNA sequencing analysis revealed that HDAC3 inhibition modulated neuronal regenerative pathways related to neurogenesis, differentiation, axonogenesis, and dendritic spine density in OBCSs. Our findings highlight the complexity and diversity of the effects of HDAC3 inhibition on AD models and suggest that HDAC3 may have multiple roles in the regulation of APP expression and processing, as well as in the modulation of neuroinflammatory and neuroprotective genes.
A Systematic Review of Laser Treatment for Angiofibromas in Tuberous Sclerosis
Authors: Gu Yaron , Verheyden Matthew J. , Sebaratnam Deshan F. , Liu Rose C
Published: May 2024

BACKGROUND

While mammalian target of rapamycin inhibitors have revolutionized the management of angiofibroma in tuberous sclerosis complex (TS), physical modalities such as laser are still indicated for recalcitrant lesions.

OBJECTIVE

The authors performed a systematic review of the efficacy and safety of laser treatment for TS-related facial angiofibroma.

METHODS

The electronic databases such as MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to October 10, 2023, for eligible records.

RESULTS

Forty-seven articles met the inclusion criteria, representing a total of 217 patients with TS-related facial angiofibroma who received laser treatment. Several lasers have been trialed in patients including carbon dioxide (n= 95, 43.7%), pulsed dye (n= 21, 9.7%), argon (n= 16, 7.4%), neodymium-doped: yttrium aluminum garnet (n= 12, 5.5%), copper vapor (n= 9, 4.1%), potassium titanyl phosphate (n= 7, 3.2%), erbium: yttrium aluminum garnet (n= 2, 0.9%), lasers and various combination therapies (n= 55, 25.3%).

CONCLUSION

Potassium titanyl phosphate, pulsed dye, and neodymium-dopsed:yttrium aluminum garnet lasers are better suited to manage the vascular components of angiofibroma while ablative lasers such as erbium: yttrium aluminum garnet and carbon dioxide lasers may present better options for lesions with a prominent fibrous component. While several lasers have been trialed with broadly favorable results, the low level of evidence precludes definitive conclusions, and no single laser appears superior.
Targeting cellular cathepsins inhibits hepatitis E virus entry
Authors: Klöhn Mara , Burkard Thomas , Janzen Juliana , Haase Jil A. , Gömer André , Fu Rebecca , Ssebyatika George , Nocke Maximilian K. , Brown Richard J. P. , Krey Thomas , Dao Thi Viet Loan , Kinast Volker , Brüggemann Yannick , Todt Daniel , Steinmann Eike
Published: May 2024

Background and Aims:

HEV is estimated to be responsible for 70,000 deaths annually, yet therapy options remain limited. In the pursuit of effective antiviral therapies, targeting viral entry holds promise and has proven effective for other viruses. However, the precise mechanisms and host factors required during HEV entry remain unclear. Cellular proteases have emerged as host factors required for viral surface protein activation and productive cell entry by many viruses. Hence, we investigated the functional requirement and therapeutic potential of cellular protease during HEV infection.

Approach and Results:

Using our established HEV cell culture model and subgenomic HEV replicons, we found that blocking lysosomal cathepsins (CTS) with small molecule inhibitors impedes HEV infection without affecting replication. Most importantly, the pan-cathepsin inhibitor K11777 suppressed HEV infections with an EC50 of ~0.02 nM. Inhibition by K11777, devoid of notable toxicity in hepatoma cells, was also observed in HepaRG and primary human hepatocytes. Furthermore, through time-of-addition and RNAscope experiments, we confirmed that HEV entry is blocked by inhibition of cathepsins. Cathepsin L (CTSL) knockout cells were less permissive to HEV, suggesting that CTSL is critical for HEV infection. Finally, we observed cleavage of the glycosylated ORF2 protein and virus particles by recombinant CTSL.

Conclusions:

In summary, our study highlights the pivotal role of lysosomal cathepsins, especially CTSL, in the HEV entry process. The profound anti-HEV efficacy of the pan-cathepsin inhibitor K11777, especially with its notable safety profile in primary cells, further underscores its potential as a therapeutic candidate.
Peri-anesthetic Environmental and Occupational Exposure to Desflurane Waste Anesthetic Gas in a Large Animal Veterinary Hospital
Authors: Douglas Hope F. , Midon Monica , Floriano Dario , Hopster Klaus
Published: May 2024

Objectives

The goals were to determine the environmental levels of desflurane waste anesthetic gas and the desflurane occupational exposure of operating room staff during the anesthesia of large animal veterinary patients.

Methods

Active environmental sampling was performed using single-beam infrared spectrophotometry. Passive sampling with dosimeter badges was used to measure the occupational exposure of anesthesia and operating room staff.

Results

Higher concentrations of desflurane (n = 16) were measured at all recovery timepoints relative to the concentrations measured at all locations and timepoints at the start of anesthesia and surgery (P < 0.05). Time-weighted average desflurane concentrations from dosimeter badges (n = 310) were higher for anesthesia staff than for other operating room personnel (P < 0.0001).

Conclusions

The anesthetic recovery of large animal patients is a period of increased exposure to desflurane waste anesthetic gas for veterinary staff.
The Association of Physiotherapy and Opioid Use With Duration of Compensated Time Loss for Workers With Low Back Pain
Authors: Low Karyn K. X. , Di Donato Michael , Gray Shannon E.
Published: May 2024

Objective

To determine patterns of physiotherapy and opioid use among compensated workers with low back pain (LBP), factors associated with these, and their association with time loss.

Methods

Accepted Victorian and South Australian workers' compensation claims, services, and medicines data for LBP claims lodged June 30, 2010–July 1, 2015. Descriptive statistics, multinomial logistic, and Cox regression were used to determine usage groups, their predictors, and effect of these on time loss.

Results

Of 15,728 claims, 24.4% received no services, 3.6% received opioids only, 43.3% received physiotherapy only, and 28.8% received both opioids and physiotherapy. Sex, age, occupation, remoteness, jurisdiction, and socioeconomic status were significantly associated with usage groups. Using opioids and physiotherapy had the longest time loss.

Conclusions

Any services/medicine usage was associated with increased time loss and was longest for combined physiotherapy and opioids.
Mandated Rest Breaks and Occupational Injuries and Illnesses in Dallas County, Texas Construction Workers
Authors: Schinasi Leah H. , Williams Augusta , Schnake-Mahl Alina
Published: May 2024

Objective

We estimated associations of a rest break ordinance, implemented for construction workers in Dallas, Texas in 2016, with workplace injuries and illnesses.

Methods

We used workers’ compensation claims data to compare changes in rates of injuries and illnesses among Dallas County, Texas construction (ie, “treated”) workers with changes in untreated workers, before (2013–2015) and after (2016–2018) a rest break ordinance was implemented.

Results

Immediately after the ordinance was implemented, rates of injuries/illnesses among treated workers were modestly lower than in comparison workers (rate ratio comparing postmandate vs premandate rates, treated vs comparison workers: 0.89, 95% confidence interval: 0.72–1.11). Postordinance versus preordinance slope trends were similar in the treated versus the comparison group.

Conclusions

Ten-minute rest breaks were associated with modestly lower rates of workplace injury/illnesses. More comprehensive standards may be needed for protection.
The transition of surgical simulation training and its learning curve: a bibliometric analysis from 2000 to 2023
Authors: Zhang Jun , Luo Zai , Zhang Renchao , Ding Zehao , Fang Yuan , Han Chao , Wu Weidong , Cen Gang , Qiu Zhengjun , Huang Chen
Published: May 2024

Background:

Proficient surgical skills are essential for surgeons, making surgical training an important part of surgical education. The development of technology promotes the diversification of surgical training types. This study analyzes the changes in surgical training patterns from the perspective of bibliometrics, and applies the learning curves as a measure to demonstrate their teaching ability.

Method:

Related papers were searched in the Web of Science database using the following formula: TS=[(training OR simulation) AND (learning curve) AND (surgical)]. Two researchers browsed the papers to ensure that the topics of articles were focused on the impact of surgical simulation training on the learning curve. CiteSpace, VOSviewer, and R packages were applied to analyze the publication trends, countries, authors, keywords, and references of selected articles.

Result:

Ultimately, 2461 documents were screened and analyzed. The USA is the most productive and influential country in this field. Surgical endoscopy and other interventional techniques publish the most articles, while surgical endoscopy and other interventional techniques is the most cited journal. Aggarwal Rajesh is the most productive and influential author. Keyword and reference analyses reveal that laparoscopic surgery, robotic surgery, virtue reality, and artificial intelligence were the hotspots in the field.

Conclusion:

This study provided a global overview of the current state and future trend in the surgical education field. The study surmised the applicability of different surgical simulation types by comparing and analyzing the learning curves, which is helpful for the development of this field.
Transcutaneous auricular vagus nerve stimulation as a novel therapy connecting the central and peripheral systems: a review
Authors: Zou Ningyi , Zhou Qing , Zhang Yuzhengheng , Xin Chen , Wang Yifei , Claire-Marie Rangon , Rong Peijing , Gao Guojian , Li Shaoyuan
Published: May 2024

Currently, clinical practice and scientific research mostly revolve around a single disease or system, but the single disease-oriented diagnostic and therapeutic paradigm needs to be revised. This review describes how transcutaneous auricular vagus nerve stimulation (taVNS), a novel non-invasive neuromodulation approach, connects the central and peripheral systems of the body. Through stimulation of the widely distributed vagus nerve from the head to the abdominal cavity, this therapy can improve and treat central system disorders, peripheral system disorders, and central-peripheral comorbidities caused by autonomic dysfunction. In the past, research on taVNS has focused on the treatment of central system disorders by modulating this brain nerve. As the vagus nerve innervates the heart, lungs, liver, pancreas, gastrointestinal tract, spleen and other peripheral organs, taVNS could have an overall modulatory effect on the region of the body where the vagus nerve is widespread. Based on this physiological basis, the authors summarize the existing evidence of the taVNS ability to regulate cardiac function, adiposity, glucose levels, gastrointestinal function, and immune function, among others, to treat peripheral system diseases, and complex diseases with central and peripheral comorbidities. This review shows the successful examples and research progress of taVNS using peripheral neuromodulation mechanisms from more perspectives, demonstrating the expanded scope and value of taVNS to provide new ideas and approaches for holistic therapy from both central and peripheral perspectives.
The impact of frailty on clinical outcomes of older patients undergoing enhanced recovery after lumbar fusion surgery: a prospective cohort study
Authors: Wang Shuai-Kang , Wang Qi-Jun , Wang Peng , Li Xiang-Yu , Cui Peng , Wang Dong-Fan , Chen Xiao-Long , Kong Chao , Lu Shi-Bao
Published: May 2024

Background:

Frailty is recognized as a surrogate for physiological age and has been established as a valid and independent predictor of postoperative morbidity, mortality, and complications. Enhanced recovery after surgery (ERAS) can enhance surgical safety by minimizing stress responses in frail patients, enabling surgeons to discharge patients earlier. However, the question of whether and to what extent the frailty impacts the post-ERAS outcomes in older patients remains.

Materials and methods:

An evidence-based ERAS program was implemented in our center from January 2019. This is a prospective cohort study of patients aged ≥75 years who underwent open transforaminal lumbar interbody fusion (TLIF) for degenerative spine disease from April 2019 to October 2021. Frailty was assessed with the Fried frailty scale (FP scale), and patients were categorized as non/prefrail (FP 0-2) or frail (FP ≥ 3). The preoperative variables, operative data, postoperative outcomes, and follow-up information were compared between the two groups. Univariate and multivariate logistic regression analyses were used to identify risk factors for 90-day major complications and prolonged length of hospital stay after surgery.

Results:

A total of 245 patients (age of 79.8±3.4 year) who had a preoperative FP score recorded and underwent scheduled TLIF surgery were included in the final analysis. Comparisons between nonfrail and prefrail/frail patients revealed no significant difference in age, sex, and surgery-related variables. Even after adjusting for multiple comparisons, the association between Fried frailty and ADL-dependency, IADL-dependency, and malnutrition remained significant. Preoperative frailty was associated with increased rates of postoperative adverse events. A higher CCI grade was an independent predictor for 90-day major complications, while Fried frailty and MNA-SF scores <12 were predictive of poor postoperative recovery.

Conclusion:

Frail older patients had more adverse post-ERAS outcomes after TLIF compared to non/prefrail older patients. Continued research and multidisciplinary collaboration will be essential to refine and optimize protocols for surgical care in frail older adults.
Outflow Graft Obstruction due to Local Aortic Dissection After Implantation of Left Ventricle Assist Device (HeartMate 3)
Authors: Capek Lukas , Huber Adrian Thomas , Reineke David , Dobner Stephan , Hunziker Lukas Christoph , Schnegg Bruno
Published: May 2024

Left ventricular assist devices (LVADs) improve symptoms and outcomes in patients with advanced heart failure. We report the case of a patient with a freshly implanted HeartMate 3 LVAD, suffering abruptly on postoperative day 55 from pejoration of his heart failure with multiple episodes of low-flow alarm. Outflow graft obstruction (OGO) due to local aortic dissection was diagnosed with multimodality imaging. After a multidisciplinary discussion, a surgical approach was decided, and the patient benefited from a revision of his outflow graft.
External Validation of the PREdiction of Survival on Extracorporeal Membrane Oxygenation Therapy (PRESET) Score: A Single-Center Cohort Experience
Authors: Mazuru Vitalie , Mang Sebastian , Ajouri Jonas , Muellenbach Ralf M. , Bals Robert , Feth Maximilian , Zeiner Carsten , Wengenmayer Tobias , Lepper Philipp M. , Rixecker Torben M. , Seiler Frederik
Published: May 2024

Acute respiratory distress syndrome (ARDS) is a life-threatening condition affecting >10% of intensive care unit (ICU) patients worldwide with a mortality of up to 59% depending on severity. Extracorporeal membrane oxygenation (ECMO) is a potentially life-saving procedure in severe ARDS but is technically and financially challenging. In recent years, various scoring systems have been proposed to select patients most likely to benefit from ECMO, with the PREdiction of Survival on ECMO Therapy (PRESET) score being one of the most used. We collected data from 283 patients with ARDS of various etiology who underwent veno-venous (V-V) ECMO therapy at a German tertiary care ICU from January 2012 to December 2022. Median age in the cohort was 56 years, and 64.31% were males. The in-hospital mortality rate was 50.88% (n = 144). The median (25%; 75% quartile) severity scores were 38 (31; 49) for Simplified Acute Physiology Score (SAPS) II, 12 (10; 13) for Sequential Organ Failure Assessment (SOFA) and 7 (5; 8) for PRESET. Simplified Acute Physiology Score-II displayed the best prognostic value (area under the receiver operating characteristic [AUROC]: 0.665 [confidence interval (CI): 0.574–0.756; p = 0.046]). Prediction performance was weak in all analyzed scores despite good calibration. Simplified Acute Physiology Score-II had the best discrimination after adjustment of our original cohort. The use of scores explored in this study for patient selection for eligibility for V-V ECMO is not recommendable.
Hemocompatibility Evaluation of a Novel Ambulatory Pulmonary Assist System Using a Lightweight Axial-Flow Pump
Authors: Hong Yeahwa , Shin Suji , Nasim Umar , Roberts Kalliope G. , Potchernikov Alexander S. , Liu Kimberly Y. , Dufendach Keith A. , Skoog David J. , Bacchetta Matthew , Cook Keith E.
Published: May 2024

The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS’s axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each). Each sheep was supported on the PAS for 12 hours with two L/minute of blood flow and four L/minute of sweep gas. Hemolysis, coagulation, inflammation, and platelet activation and loss were compared among the groups. In this study, the plasma-free hemoglobin (pfHb) was less than 10 mg/dl in all groups. The pfHb was significantly lower in the AFP group compared to other groups. There was no significant clot formation in the pumps and oxygenators in all groups. Furthermore, no significant differences in coagulation (oxygenator resistance, fibrinopeptide A), inflammation (white blood cell counts, IL-8), and platelet activation and loss (p-selectin, platelet counts) were observed among the groups (all, p > 0.05). This study demonstrates equivalent hemocompatibility of the PAS’s AFP to other contemporary mechanical pumps with a reduced level of hemolysis on startup.
In dystrophicmdxhindlimb muscles where fibrosis is limited versican haploinsufficiency transiently improves contractile function without decreasing inflammation
Authors: Debruin Danielle , McRae Natasha L. , Addinsall Alex B. , McCulloch Daniel R. , Barker Robert G. , Hayes Alan , Murphy Robyn M. , Stupka Nicole
Published: May 2024

The provisional matrix protein versican is upregulated in Duchenne muscular dystrophy. Versican heightens inflammation in fibrotic diseases and is involved in myogenesis. In fibrotic diaphragm muscles from dystrophicmdxmice, versican reduction attenuated macrophage infiltration and improved contractile function. We investigated the association between versican andmdxhindlimb muscle pathology, where inflammation and regeneration are increased but fibrosis is minimal. Immunohistochemistry and qRT-PCR were used to assess how fiber type and glucocorticoids (α-methylprednisolone) modulate versican expression. Femalemdxand male versican haploinsufficient (hdf) mice were bred resulting in malemdx-hdf andmdx(control) pups. Versican expression, contractile function, and pathology were evaluated in fast extensor digitorum longus (EDL) and slow soleus muscles, excised under medetomidine-midazolam- fentanyl anesthesia.

Versican immunoreactivity was highest in soleus muscles.VersicanmRNA transcripts were reduced by α-methylprednisolone in soleus, but not EDL, muscles. Versican expression was decreased in soleus muscles from 6-week-oldmdx-hdf mice leading to increased force output and a modest reduction in fatiguability. These functional benefits were not accompanied by decreased inflammation; muscle architecture, regeneration markers, and fiber type also did not differ between genotypes. Improvements in soleus function were lost in adult (20-week-old)mdx-hdf mice with no significant effect of versican haploinsufficiency on macrophage infiltration and regeneration markers.

Soleus muscles from juvenilemdxmice were most responsive to pharmacological or genetic approaches targeting versican; however, the benefits of versican reduction were limited due to low fibrosis. Pre-clinical matrix research in dystrophy should account for muscle phenotype and the interdependence between the fibrosis and inflammation.

NEW & NOTEWORTHY

The proteoglycan versican is upregulated in muscular dystrophy. In fibrotic diaphragm muscles frommdxmice, versican reduction attenuated macrophage infiltration and improved performance. Here, in hindlimb muscles from 6- and 20-week-oldmdxmice, where pathology is mild, versican reduction did not decrease inflammation and contractile function improvements were limited to juvenile mice. In dystrophicmdxmuscles, the association between versican and inflammation is mediated by fibrosis, demonstrating interdependence between the immune system and extracellular matrix.
Polygenic prediction and gene regulation networks
Authors: Poyatos Juan F
Published: May 2024

Exploring the degree to which phenotypic variation, influenced by intrinsic nonlinear biological mechanisms, can be accurately captured using statistical methods is essential for advancing our comprehension of complex biological systems and predicting their functionality. Here, we examine this issue by combining a computational model of gene regulation networks with a linear additive prediction model, akin to polygenic scores utilized in genetic analyses. Inspired by the variational framework of quantitative genetics, we create a population of individual networks possessing identical topology yet showcasing diversity in regulatory strengths. By discerning which regulatory connections determine the prediction of phenotypes, we contextualize our findings within the framework of core and peripheral causal determinants, as proposed by the omnigenic model of complex traits. We establish connections between our results and concepts such as global sensitivity and local stability in dynamical systems, alongside the notion of sloppy parameters in biological models. Furthermore, we explore the implications of our investigation for the broader discourse surrounding the role of epistatic interactions in the prediction of complex phenotypes.

Author Summary

This research delves into how well statistical methods can capture phenotypic variation influenced by nonlinear biological mechanisms. The study combines a computational model of gene regulation networks with a linear additive prediction model, similar to polygenic scores used in genetic analysis. By creating a population of individual networks with identical topology but varying regulatory strengths, the research identifies key regulatory connections that predict phenotypes. The findings are framed within the omnigenic model of complex traits, distinguishing core and peripheral causal determinants. The study also links its results to concepts like global sensitivity and local stability in dynamical systems, as well as sloppy parameters in biological models. Additionally, it examines the implications for understanding the role of epistatic interactions in predicting complex phenotypes. This work enhances our understanding of complex biological systems and their functionality.
EFFECT OF AYAHUASCA ON EXPERIMENTAL MODELS OF ETHANOL ADDICTION AND IMMUNOHISTOCHEMISTRY ANALYSIS IN RODENTS
Authors: Distefano Wiltenburg Victor , Morales-Lima Gabriela , Sousa Santos Aline Valéria , Bermúdez Echeverry Marcela , Cardoso Cruz Fábio , de Oliveira Silveira Gabriela , Yonamine Maurício , Ayako Tiba Paula , Rieli Mendes Fúlvio
Published: May 2024

Ayahuasca, a psychoactive brew originally used ritually and therapeutically by various traditional peoples in the Amazon, is receiving special attention for its potential therapeutic effects on addiction. This study investigates the effects of lyophilized ayahuasca in alcohol-induced animal model, examining behavioral, pharmacological, and neurobiological aspects. Phytochemical analysis confirmed the presence of β-carbolines and dimethyltryptamine, with all compound’s levels within literature ranges. Pharmacological screening revealed dose-dependent behavioral changes, with the highest dose inducing transient effects. Motor coordination deficits were observed at the highest dose, consistent with pharmacological screening. Pretreatment with ayahuasca prevented ethanol-induced conditioned place preference, suggesting anti-addictive potential. Immunoreactivity analysis revealed no significant changes in DeltaFosB and c-Fos expression in the nucleus accumbens core and shell subsections. This study suggests low acute toxicity of ayahuasca, motor coordination impairment at high doses, and potential anti-addictive effects in preventing ethanol-induced conditioned place preference. These findings contribute to the understanding of the pharmacological and behavioral effects of ayahuasca and highlight the need for further research and clinical studies to elucidate its therapeutic potential in substance use disorders.
Effects of longitudinal bending stiffness and midsole foam on running energetics
Authors: Perry Damion , Lino Herlandt , Bertschy Montgomery , Hoogkamer Wouter
Published: May 2024

Background

Advanced footwear technology has become commonplace in the competitive running world. However, a systematic exploration of the effects of each of the primary components has not yet been presented.

Purpose

To quantify running economy and step parameters in four different shoe conditions: PEBA shoes with plate, PEBA shoes without plate, EVA shoes with plate and EVA shoes without plate.

Methods

Participants ran at 14 km/h (n = 8 males) or 12 km/h (n = 6 females) on a treadmill. The shoe order was randomly assigned for the four shoe conditions, where the participants wore each shoe twice in a mirrored order.

Results

There was a significant reduction in metabolic power (1.0%) associated with the presence of a plate, as well as a similar reduction based on foam type (1.0%). However, there was no significant interaction between presence of plate and foam type. Adding a plate significantly reduced metabolic power for EVA by 1.3% but not for PEBA. PEBA foam significantly reduced metabolic power by 1.3% in shoes without a plate, but not for the shoes with a plate. Step frequency and contact time were similar between shoes and not correlated to running economy improvements.

Conclusions

Starting from a baseline condition with traditional foam without a plate, either adding a plate or using PEBA foam improved running economy with a similar amount (1.3%). Adding the alternate second feature non-significantly improved running economy with an additional 0.6%. The benefit of both technologies combined (1.9%) was smaller than the sum of its parts (1.3% each).

Key points

The use of a PEBA foam midsole or the addition of a carbon fiber plate improves running economy a similar amount when compared to a traditional EVA running shoe without a plate.

Contrary to our hypothesis, the benefit of both technologies combined (1.9%) was smaller than the sum of its parts (1.3% each).
A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis
Authors: Ediriwickrema Asiri , Nakauchi Yusuke , Fan Amy C. , Köhnke Thomas , Hu Xiaoyi , Luca Bogdan A. , Kim YeEun , Ramakrishnan Sreejith , Nakamoto Margaret , Karigane Daiki , Linde Miles H. , Azizi Armon , Newman Aaron M. , Gentles Andrew J. , Majeti Ravindra
Published: May 2024

Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to appropriately meet the biological demands of the human body. Human MPPs remain ill-defined whereas mouse MPPs have been well characterized with distinct immunophenotypes and lineage potencies. Using multiomic single cell analyses and complementary functional assays, we identified new human MPPs and oligopotent progenitor populations within Lin-CD34+CD38dim/lo adult bone marrow with distinct biomolecular and functional properties. These populations were prospectively isolated based on expression of CD69, CLL1, and CD2 in addition to classical markers like CD90 and CD45RA. We show that within the canonical Lin-CD34+CD38dim/loCD90CD45RA-MPP population, there is a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69-erythroid-biased MPP. We also show that the canonical Lin-CD34+CD38dim/loCD90-CD45RA+ LMPP population can be separated into a CD2+ LMPP with lymphoid and myeloid potential, a CD2-LMPP with high lymphoid potential, and a CLL1+ GMP with minimal lymphoid potential. We used these new HSPC profiles to study human and mouse bone marrow cells and observe limited cell type specific homology between humans and mice and cell type specific changes associated with aging. By identifying and functionally characterizing new adult MPP sub-populations, we provide an updated reference and framework for future studies in human hematopoiesis.
Unequal genetic redundancies among MYC bHLH transcription factors underlie seedling photomorphogenesis in Arabidopsis
Authors: Garhwal Vikas , Das Sreya , Gangappa Sreeramaiah N.
Published: May 2024

Light is one of the most critical ecological cues controlling plant growth and development. Plants have evolved complex mechanisms to cope with fluctuating light signals. In Arabidopsis, bHLH transcription factors MYC2, MYC3, and MYC4 have been shown to play a vital role in protecting plants against herbivory and necrotrophic pathogens. While the role of MYC2 in light-mediated seedling development has been studied in some detail, the role of MYC3 and MYC4 still needs to be discovered. Here, we show that MYC4 negatively regulates seedling photomorphogenesis, while the MYC3 function seems redundant. However, the genetic analysis reveals that MYC3/MYC4 together act as positive regulators of seedling photomorphogenic growth as themyc3myc4double mutants showed exaggerated hypocotyl growth compared tomyc4single mutants and Col-0. Intriguingly, the loss ofMYC2function in themyc3myc4double mutant background (myc2myc3myc4) resulted in further enhancement in the hypocotyl growth thanmyc3myc4double mutants in WL, BL and FRL, suggesting that MYC2/3/4 together play an essential and positive role in meditating optimal seedling photomorphogenesis. Besides, MYC3/MYC4 genetically and physically interact with HY5 to partially inhibit its function in controlling hypocotyl and photo-pigment accumulation. Moreover, our results suggest that COP1 physically interacts and degrades MYC3 and MYC4 through the 26S proteasomal pathway and controls their response to dark and light for fine-tuning HY5 function and seedling photomorphogenesis.
Optimized Dosing and Delivery of Bacteriophage Therapy for Wound Infections
Authors: Lin Yung-Hao , Dharmaraj Tejas , Chen Qingquan , Echterhof Arne , Manasherob Robert , Zhang Lucy J. , de Leeuw Cas , Peterson Nana A. , Stannard Whitney , Li Zhiwei , Hajfathalian Maryam , Hargil Aviv , Martinez Hunter A. , Pourtois Julie , Chang Tony H. W. , Blankenberg Francis G. , Amanatullah Derek , Chaudhuri Ovijit , Bollyky Paul L.
Published: May 2024

Lytic bacteriophages, viruses that lyse (kill) bacteria, hold great promise for treating infections, including wound infections caused by antimicrobial-resistantPseudomonas aeruginosa.However, the optimal dosing and delivery strategies for phage therapy remain unclear. In a mouse wound infection model, we investigated the impact of dose, frequency, and administration route on the efficacy of phage therapy. We find that topical but not intravenous delivery is effective in this model. High-doses of phage reduces bacterial burden more effectively than low-doses, and repeated dosing achieves the highest eradication rates. Building on these insights, we developed “HydroPhage”, a hyaluronan-based hydrogel system that uses dynamic covalent crosslinking to deliver high-titre phages over one week. HydroPhage eradicates infections five times more effectively than intravenous injection. We conclude that hydrogel-based sustained phage delivery enhances the efficacy of phage therapy and offers a practical, well-tolerated option for topical application.