bluuebunny/crossref_metadata_2025 huggingface dataset:
Appearance-based gaze estimation with feature fusion of multi-level information elements
Authors: Ren Zhonghe , Fang Fengzhou , Hou Gaofeng , Li Zihao , Niu Rui
Published: April 2023

Gaze estimation is a fundamental task in many applications of cognitive sciences, human–computer interaction, and robotics. The purely data-driven appearance-based gaze estimation methods may suffer from a lack of interpretability, which prevents their applicability to pervasive scenarios. In this study, a feature fusion method with multi-level information elements is proposed to improve the comprehensive performance of the appearance-based gaze estimation model. The multi-level feature extraction and expression are carried out from the originally captured images, and a multi-level information element matrix is established. A gaze conduction principle is formulated for reasonably fusing information elements from the established matrix. According to the gaze conduction principle along with the matrix, a multi-level information element fusion (MIEF) model for gaze estimation is proposed. Then, several input modes and network structures of the MIEF model are designed, and a series of grouping experiments are carried out on a small-scale sub-dataset. Furthermore, the optimized input modes and network structures of the MIEF model are selected for training and testing on the whole dataset to verify and compare model performance. Experimental results show that optimizing the feature combination in the input control module and fine-tuning the computational architecture in the feature extraction module can improve the performance of the gaze estimation model, which would enable the reduction of the model by incorporating the critical features and thus improve the performance and accessibility of the method. Compared with the reference baseline, the optimized model based on the proposed feature fusion method of multi-level information elements can achieve efficient training and improve the test accuracy in the verification experiment. The average error is 1.63 cm on phones on the GazeCapture dataset, which achieves comparable accuracy with state-of-the-art methods.
Proton beam therapy for muscle-invasive bladder cancer: A systematic review and analysis with Proton-Net, a multicenter prospective patient registry database
Authors: Araya Masayuki , Ishikawa Hitoshi , Nishioka Kentaro , Maruo Kazushi , Asakura Hirofumi , Iizumi Takashi , Takagi Masaru , Murakami Masao , Azuma Haruhito , Obara Wataru , Aoyama Hidefumi , Sakurai Hideyuki
Published: April 2023

To assess the safety and efficacy of proton beam therapy (PBT) for muscle-invasive bladder cancer (MIBC), we examined the outcomes of 36 patients with MIBC (cT2-4aN0M0) who were enrolled in the Proton-Net prospective registry study and received PBT with concurrent chemotherapy from May 2016 to June 2018. PBT was also compared with X-ray chemoradiotherapy in a systematic review (X-ray (photon) radiotherapy). The radiotherapy consisted of 40–41.4 Gy (relative biological effectiveness (RBE) delivered in 20–23 fractions to the pelvic cavity or the entire bladder using X-rays or proton beams, followed by a boost of 19.8–36.3 Gy (RBE) delivered in 10–14 fractions to all tumor sites in the bladder. Concurrently, radiotherapy was given with intra-arterial or systemic chemotherapy of cisplatin alone or in combination with methotrexate or gemcitabine. Overall survival (OS), progression-free survival (PFS) and local control (LC) rates were 90.8, 71.4 and 84.6%, respectively, after 3 years. Only one case (2.8%) experienced a treatment-related late adverse event of Grade 3 urinary tract obstruction, and no severe gastrointestinal adverse events occurred. According to the findings of the systematic review, the 3-year outcomes of XRT were 57–84.8% in OS, 39–78% in PFS and 51–68% in LC. The weighted mean frequency of adverse events of Grade 3 or higher in the gastrointestinal and genitourinary systems was 6.2 and 2.2%, respectively. More data from long-term follow-up will provide us with the appropriate use of PBT and validate its efficacy for MIBC.
Propyl-cyanide isomer formation on interstellar ices from radical association: a quantum theoretical study
Authors: Kerkeni Boutheïna , Gámez Victoria , Ouerfelli Ghofrane , Senent Maria Luisa , Feautrier Nicole
Published: April 2023

Both linear and branched isomers of propyl cyanide (PrCN; C3H7CN) are ubiquitous in interstellar space. To date, PrCN is one of the most complex molecules found in the interstellar medium. Furthermore, it is the only one observed species to share the branched atomic backbone of amino acids, some of the building blocks of life. Radical–radical chemical reactions are examined in detail using density functional theory, ab initio methods, and the energy resolved master equation formalism to compute rate constants at a low pressure value prevalent in the ISM. Quantum chemical studies are reported for both isomers considering two possibilities: the gas phase association and the surface reactions of radicals on a 34-water amorphous ice model. The reaction mechanism involves the following radicals association: CH3CHCH3 + CN, CH3 + CH3CHCN and CH3CH2 + CH2CN, CH3 + CH2CH2CN, CN + CH3CH2CH2 for iso-PrCN and n-PrCN formation, respectively. Two DFT methods: M062X and ωB97XD with the 6-311++G(d,p) basis set were tested for reactions in gas phase and on the ice mantle. In the gas phase, MP2/aug-cc-pVTZ level of theory is also used, and the energetics of the five reactions are calculated using explicitly correlated coupled cluster (CCSD(T)-F12) method. All reaction paths are exoergic and barrierless in the gas phase and on the ice-model, suggesting that the formation of iso-PrCN and n-PrCN is efficient on the ice model adopted in this paper. The gas phase rate constants of formation of both isomers can be eventually used as a high limit for the solid state reactions.
The XMM cluster survey: exploring scaling relations and completeness of the dark energy survey year 3 redMaPPer cluster catalogue
Authors: Upsdell E W , Giles P A , Romer A K , Wilkinson R , Turner D J , Hilton M , Rykoff E , Farahi A , Bhargava S , Jeltema T , Klein M , Bermeo A , Collins C A , Ebrahimpour L , Hollowood D , Mann R G , Manolopoulou M , Miller C J , Rooney P J , Sahlén Martin , Stott J P , Viana P T P , Allam S , Alves O , Bacon D , Bertin E , Bocquet S , Brooks D , Burke D L , Carrasco Kind M , Carretero J , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Diehl H T , Dietrich J P , Everett S , Ferrero I , Frieman J , García-Bellido J , Gerdes D W , Gutierrez G , Hinton S R , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lima M , Marshall J L , Mena-Fernández J , Menanteau F , Miquel R , Mohr J J , Ogando R L C , Pieres A , Raveri M , Rodriguez-Monroy M , Sanchez E , Scarpine V , Sevilla-Noarbe I , Smith M , Suchyta E , Swanson M E C , Tarle G , To C , Weaverdyck N , Weller J , Wiseman P
Published: April 2023

We cross-match and compare characteristics of galaxy clusters identified in observations from two sky surveys using two completely different techniques. One sample is optically selected from the analysis of 3 years of Dark Energy Survey observations using the redMaPPer cluster detection algorithm. The second is X-ray selected from XMM observations analysed by the XMM Cluster Survey. The samples comprise a total area of 57.4 deg2, bounded by the area of four contiguous XMM survey regions that overlap the DES footprint. We find that the X-ray-selected sample is fully matched with entries in the redMaPPer catalogue, above λ > 20 and within 0.1 <$z$ <0.9. Conversely, only 38 per cent of the redMaPPer catalogue is matched to an X-ray extended source. Next, using 120 optically clusters and 184 X-ray-selected clusters, we investigate the form of the X-ray luminosity–temperature (LX –TX ), luminosity–richness (LX –λ), and temperature–richness (TX –λ) scaling relations. We find that the fitted forms of the LX –TX relations are consistent between the two selection methods and also with other studies in the literature. However, we find tentative evidence for a steepening of the slope of the relation for low richness systems in the X-ray-selected sample. When considering the scaling of richness with X-ray properties, we again find consistency in the relations (i.e. LX –λ and TX –λ) between the optical and X-ray-selected samples. This is contrary to previous similar works that find a significant increase in the scatter of the luminosity scaling relation for X-ray-selected samples compared to optically selected samples.
Large-scale density and velocity field reconstructions with neural networks
Authors: Ganeshaiah Veena Punyakoti , Lilow Robert , Nusser Adi
Published: April 2023

We assess a neural network (NN) method for reconstructing 3D cosmological density and velocity fields (target) from discrete and incomplete galaxy distributions (input). We employ second-order Lagrangian Perturbation Theory to generate a large ensemble of mock data to train an auto-encoder (AE) architecture with a Mean Squared Error (MSE) loss function. The AE successfully captures non-linear features arising from gravitational dynamics and the discreteness of the galaxy distribution. It preserves the positivity of the reconstructed density field and exhibits a weaker suppression of the power on small scales than the traditional linear Wiener filter (WF), which we use as a benchmark. In the density reconstruction, the reduction of the AE MSE relative to the WF is $\sim 15~{{\ \rm per\ cent}}$ , whereas for the velocity reconstruction a relative reduction of up to a factor of two can be achieved. The AE is advantageous to the WF at recovering the distribution of the target fields, especially at the tails. In fact, trained with an MSE loss, any NN estimate approaches the unbiased mean of the underlying target given the input. This implies a slope of unity in the linear regression of the true on the NN-reconstructed field. Only for the special case of Gaussian fields, the NN and WF estimates are equivalent. Nonetheless, we also recover a linear regression slope of unity for the WF with non-Gaussian fields.
A potential histone-chaperone activity for the MIER1 histone deacetylase complex
Authors: Wang Siyu , Fairall Louise , Pham Trong Khoa , Ragan Timothy J , Vashi Dipti , Collins Mark O , Dominguez Cyril , Schwabe John W R
Published: April 2023

Histone deacetylases 1 and 2 (HDAC1/2) serve as the catalytic subunit of six distinct families of nuclear complexes. These complexes repress gene transcription through removing acetyl groups from lysine residues in histone tails. In addition to the deacetylase subunit, these complexes typically contain transcription factor and/or chromatin binding activities. The MIER:HDAC complex has hitherto been poorly characterized. Here, we show that MIER1 unexpectedly co-purifies with an H2A:H2B histone dimer. We show that MIER1 is also able to bind a complete histone octamer. Intriguingly, we found that a larger MIER1:HDAC1:BAHD1:C1QBP complex additionally co-purifies with an intact nucleosome on which H3K27 is either di- or tri-methylated. Together this suggests that the MIER1 complex acts downstream of PRC2 to expand regions of repressed chromatin and could potentially deposit histone octamer onto nucleosome-depleted regions of DNA.
Co-activation for enhanced K-ion storage in battery anodes
Authors: Feng Yanhong , Lv Yawei , Fu Hongwei , Parekh Mihir , Rao Apparao M , Wang He , Tai Xiaolin , Yi Xianhui , Lin Yue , Zhou Jiang , Lu Bingan
Published: April 2023

The relative natural abundance of potassium and potentially high energy density has established potassium-ion batteries as a promising technology for future large-scale global energy storage. However, the anodes’ low capacity and high discharge platform lead to low energy density, which impedes their rapid development. Herein, we present a possible co-activation mechanism between bismuth (Bi) and tin (Sn) that enhances K-ion storage in battery anodes. The co-activated Bi-Sn anode delivered a high capacity of 634 mAh g–1, with a discharge plateau as low as 0.35 V, and operated continuously for 500 cycles at a current density of 50 mA g–1, with a high Coulombic efficiency of 99.2%. This possible co-activation strategy for high potassium storage may be extended to other Na/Zn/Ca/Mg/Al ion battery technologies, thus providing insights into how to improve their energy storage ability.
Culture-Positive and Culture-Negative Empyema After Thoracoscopic Decortication: A Comparison of Short-term and Long-term Outcomes
Authors: Cheng Ya-Fu , Chen Yi-Ling , Cheng Ching-Yuan , Huang Chang-Lun , Hung Wei-Heng , Wang Bing-Yen
Published: April 2023

Background

Empyema thoracis is a serious infectious disease and is associated with high morbidity and mortality. The perioperative outcomes between culture-positive and culture-negative empyema after thoracoscopic decortication remained controversial, especially since there were no studies that reported the survival outcomes between culture-positive and culture-negative empyema.

Methods

This single-institute study involved a retrospective analysis. Patients with empyema thoracis who underwent thoracoscopic decortication between January 2012 and December 2021 were included in the study. Patients were grouped into a culture-positive group and a culture-negative group according to culture results obtained no later than 2 weeks after surgery.

Results

A total of 1087 patients with empyema received surgery, and 824 were enrolled after exclusion. Among these, 366 patients showed positive culture results and 458 patients showed negative results. Longer intensive care unit stays (11.69 vs 5.64 days, P < .001), longer ventilator usage (24.70 vs 14.01 days, P = .002), and longer postoperative hospital stays (40.83 vs 28.37 days, P < .001) were observed in the culture-positive group. However, there was no significant difference in 30-day mortality between the 2 groups (5.2% in culture negative vs 5.0% in culture positive, P = .913). The 2-year survival was not significantly different between the 2 groups (P = .236).

Conclusions

Patients with culture-positive or culture-negative empyema who underwent thoracoscopic decortication showed similar short-term and long-term survival outcomes. A higher risk of death was associated with advanced age, a higher Charlson Comorbidity Index score, phase III empyema, and a cause other than pneumonia.
Glyceraldehyde-3-phosphate dehydrogenase subunits A and B are essential to maintain photosynthetic efficiency
Authors: Simkin Andrew J , Alqurashi Mohammed , Lopez-Calcagno Patricia E , Headland Lauren R , Raines Christine A
Published: April 2023

In plants, glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12) reversibly converts 1,3-bisphosphoglycerate to glyceraldehyde-3-phosphate coupled with the reduction of NADPH to NADP+. The GAPDH enzyme that functions in the Calvin–Benson cycle is assembled either from 4 glyceraldehyde-3-phosphate dehydrogenase A (GAPA) subunit proteins forming a homotetramer (A4) or from 2 GAPA and 2 glyceraldehyde-3-phosphate dehydrogenase B (GAPB) subunit proteins forming a heterotetramer (A2B2). The relative importance of these 2 forms of GAPDH in determining the rate of photosynthesis is unknown. To address this question, we measured the photosynthetic rates of Arabidopsis (Arabidopsis thaliana) plants containing reduced amounts of the GAPDH A and B subunits individually and jointly, using T-DNA insertion lines of GAPA and GAPB and transgenic GAPA and GAPB plants with reduced levels of these proteins. Here, we show that decreasing the levels of either the A or B subunits decreased the maximum efficiency of CO2 fixation, plant growth, and final biomass. Finally, these data showed that the reduction in GAPA protein to 9% wild-type levels resulted in a 73% decrease in carbon assimilation rates. In contrast, eliminating GAPB protein resulted in a 40% reduction in assimilation rates. This work demonstrates that the GAPA homotetramer can compensate for the loss of GAPB, whereas GAPB alone cannot compensate fully for the loss of the GAPA subunit.
Impact of the COVID-19 pandemic on patients with rheumatoid arthritis: data from the Ontario Best Practices Research Initiative (OBRI)
Authors: Wong-Pack Matthew , Hepworth Elliot , Movahedi Mohammad , Kuriya Bindee , Pope Janet , Keystone Edward , Thorne Carter , Ahluwalia Vandana , Cesta Angela , Mously Carol , Bombardier Claire , Lau Arthur , Aydin Sibel Zehra
Published: April 2023

Objective

The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic.

Methods

Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student’s paired two-sample t-tests and McNamar’s tests were performed for continuous and categorical variables between time periods.

Results

The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7 (12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P < 0.0001) and increased Janus kinase inhibitor usage (P = 0.0002). Biologic DMARD use remained stable throughout the pandemic.

Conclusion

In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.
AKEBIA THERAPEUTICS INC v FIBROGEN, INC
Authors:   Court of Appeal
Published: April 2023

H1 Patents — European Patents — Infringement — Validity — Pharmaceuticals — Treatment of anaemia — Revocation — Construction — Novelty — Obviousness — Obvious to try — Reasonable expectation of success — Sufficiency — Claims with both structural and functional features — Excessive claim breadth — Whether the skilled person had to be able to identify substantially all compounds covered by the claim without undue burden — Uncertainty — Identification of technical contribution — Plausibility — Reasonable prediction — Agrevo obviousness — Process limited product claims — Appeal to Court of Appeal
Characteristics and Outcomes of Squamous Cell Carcinoma and Other Cutaneous Malignancies in Epidermolysis Bullosa: A Systematic Review
Authors: Kim Patrick Jinhyung , Abduelmula Abrahim , Mistry Jenna , Mufti Asfandyar , Sibbald R. Gary
Published: April 2023

OBJECTIVE

To identify cases and summarize outcomes of cutaneous malignancies in patients with epidermolysis bullosa (EB).

DATA SOURCES

MEDLINE and EMBASE databases were searched on February 8, 2022.

STUDY SELECTION

Original observational or experimental studies with cases of cutaneous malignancy in patients with inherited EB were included.

DATA EXTRACTION

Data were extracted by two reviewers in duplicate.

DATA SYNTHESIS

A total of 87 articles with 367 patients were included in this systematic review. Squamous cell carcinomas were the most common malignancy (94.3%) with a median survival of 60 months. The presence of metastasis was investigated at diagnosis in 77 patients; 18.8% of patients had detectable metastasis. Patients with squamous cell carcinoma with metastasis at diagnosis had significantly shorter median survival (16.8 months) than those without (72 months; P = .027). The remission rate was 47.6%. At the end of follow-up, 15.1% were alive with disease, and 41.6% were deceased. Other malignancies included malignant melanoma and basal cell carcinoma. The most common initial modes of management were excisions (71.9%) and amputations (17.6%). Other modes included chemotherapy (4.6%), radiation (3.9%), and no treatment (2.6%). The overall rate of recurrence or new lesions was 38.8%, with a median time of 16 months to recurrence or new lesions. Immediate recurrence was lowest following amputation (4.3%). There were no statistically significant differences in median survival among initial excision, amputation, and all other modes combined (P = .30).

CONCLUSIONS

Squamous cell carcinomas in patients with EB have a high likelihood of metastasis and mortality. Surgical excision is the most common intervention. There are no significant differences in survival among different initial management options. There is a need for research that documents and monitors outcomes of the treatment options.
Type-2-low severe asthma endotypes for new treatments: the new asthma frontier
Authors: Chung Kian Fan
Published: April 2023

Purpose of review

Type-2 (T2)-high asthma represents a well defined group of severe eosinophilic asthma for which there are now effective biologic therapies targetting the interleukins (ILs) 4, 5 and 13, and Immunoglobulin E. T2-low asthma detected in the clinic by a low blood eosinophil count remains ill-defined and is the focus of this review.

Recent findings

By analysing transcriptomic and proteomic expression in sputum samples in U-BIOPRED cohort, both T2-high and -low molecular phenotypes have been described. Using clustering approaches, a neutrophilic-predominant cluster associated with activation markers of neutrophilic and inflammasome activation with interferon and tumour necrosis factor expression, together with a cluster of paucigranulocytic inflammation linked to oxidative phosphorylation and senescence pathways have been described. Using gene set variation analysis, specific molecular phenotypes driven by IL-6 trans-signalling pathway, or those by IL-6, IL-17 and IL-22 pathways were identified linked to a mixed granulocytic or neutrophilic inflammation.

Previous trials of antineutrophilic agents in asthma have failed because enrolled patients were not specifically chosen for these targeted treatments. Although the T2-low molecular pathways should be validated in other cohorts, the availability of targeted therapies indicated for other autoimmune conditions should encourage a trial of these respective biological therapies for these specific molecular phenotypes.
Strategies to Counteract Impact of Harmful Bias in Selection of Medical Residents
Authors: Edje Louito , Casillas Carlos , O’Toole Jennifer K.
Published: April 2023

Human biases impact medical care in ways that perpetuate health disparities. Research has demonstrated that biases negatively affect patient outcomes and stifle diversity across the physician workforce, further compounding health disparities by worsening patient–physician concordance. Taken as one, the application, interview, recruitment, and selection processes employed by residency programs has been one of the critical junctures where bias has exacerbated inequities among future physicians. In this article, the authors define diversity and bias, review the history of bias in residency programs’ processes for selecting residents, explore the impact of this history on workforce demographics, and discuss ways to optimize and work toward equity in the practices used by residency programs to select residents.
Postoperative delirium: identifying the patient at risk and altering the course
Authors: Hoogma Danny Feike , Milisen Koen , Rex Steffen , Al tmimi Layth
Published: April 2023

Postoperative delirium (POD) is a common neurocognitive syndrome seen in older patients after major surgery. POD is linked to longer stays in hospital and intensive care, a greater incidence of postoperative complications, worse functional outcome, and higher mortality. Researchers have not yet fully elucidated the exact pathophysiology of POD. Several risk factors that contribute to the development of POD have been identified, such as advanced age, cardiac or hip surgery, preoperative cognitive decline or delirium, disturbances in brain levels of neurotransmitters and information processing, oxidative stress and neuro-inflammation.

Identifying patients at risk for POD enables a more precise and efficient allocation of medical resources and facilitates POD prevention and management.

The present review addresses how to identify patients at risk of POD and summarizes the currently available evidence and best-practice recommendations for peri-operative management and prevention of POD.
Matrisome gene-based subclassification of patients with liver fibrosis identifies clinical and molecular heterogeneities
Authors: Chen Wei , Sun Yameng , Chen Shuyan , Ge Xiaodong , Zhang Wen , Zhang Ning , Wu Xiaoning , Song Zhuolun , Han Hui , Desert Romain , Yan Xuzhen , Yang Aiting , Das Sukanta , Athavale Dipti , Nieto Natalia , You Hong
Published: April 2023

Background & Aims:

Excessive deposition and crosslinking of extracellular matrix increases liver density and stiffness, promotes fibrogenesis, and increases resistance to fibrinolysis. An emerging therapeutic opportunity in liver fibrosis is to target the composition of the extracellular matrix or block pathogenic communication with surrounding cells. However, the type and extent of extracellular changes triggering liver fibrosis depend on the underlying etiology. Our aim was to unveil matrisome genes not dependent on etiology, which are clinically relevant to liver fibrosis.

Approach & Results:

We used transcriptomic profiles from liver fibrosis cases of different etiologies to identify and validate liver fibrosis-specific matrisome genes (LFMGs) and their clinical and biological relevance. Dysregulation patterns and cellular landscapes of LFMGs were further explored in mouse models of liver fibrosis progression and regression by bulk and single-cell RNA sequencing. We identified 35 LFMGs, independent of etiology, representing an LFMG signature defining liver fibrosis. Expression of the LFMG signature depended on histological severity and was reduced in regressive livers. Patients with liver fibrosis, even with identical pathological scores, could be subclassified into LFMGLow and LFMGHigh, with distinguishable clinical, cellular, and molecular features. Single-cell RNA sequencing revealed that microfibrillar-associated protein 4+ activated HSC increased in LFMGHigh patients and were primarily responsible for the LFMG signature expression and dysregulation.

Conclusions:

The microfibrillar-associated protein 4+ -activated HSC-derived LFMG signature classifies patients with liver fibrosis with distinct clinical and biological characteristics. Our findings unveil hidden information from liver biopsies undetectable using traditional histologic assessments.
Valproic Acid–Associated Hyperammonemia
Authors: Wong Yiu-Ching Jennifer , Fan Julia , Wan Andrea , Mihic Tamara , Gnyra Michelle
Published: April 2023

Background

Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA–induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management.

Methods

An electronic search was performed through Ovid MEDLINE, Ovid Embase, Web of Science, and PsycINFO using search terms that identified hyperammonemia in patients receiving VPA. Two reviewers independently performed primary title and abstract screening with a third reviewer resolving conflicting screening results. This process was repeated during the full-text review process.

Results

A total of 240 articles were included. Prevalence of asymptomatic hyperammonemia (5%–73%) was higher than symptomatic hyperammonemia (0.7%–22.2%) and occurred within the therapeutic range of VPA serum concentration. Various risk factors were identified, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. There was insufficient data to support routine monitoring of ammonia level for VPA-associated hyperammonemia.

Conclusions

Valproic acid–associated hyperammonemia is a common adverse effect that may occur within therapeutic range of VPA. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.
Recurrent Swelling in Pediatric Cochlear Implant Patients
Authors: Shaida Zara , Magos Tiarnan , Kanona Hala , Shaida Azhar
Published: April 2023

Objective

To determine the prevalence, characteristics, and outcomes of pediatric patients with recurrent swelling over their cochlear implant receiver package.

Study Design

Retrospective case review.

Setting

Tertiary referral center.

Patients

A total of 332 bilateral cochlear implant patients under the age of 18 years were reviewed. Twelve patients with more than one episode of swelling around their cochlear implant receiver package were isolated. Patients with clinical evidence of infection were excluded from the study. The etiology of hearing loss was heterogeneous.

Intervention

Three patients underwent ultrasound, and three patients underwent bedside aspiration. Most patients were treated with 7 days of oral broad-spectrum antibiotics.

Main Outcome Measure

Incidence, frequency, and course of recurrent swelling around cochlear implant receiver packages.

Results

The first swelling appeared between 0.86 and 9.95 years after surgery (mean, 3.38), and the occurrence of the last episode ranged from 0.06 to 3.42 years from the current date (mean, 1.04). The total number of episodes ranged from 2 to 18 (mean, 6). Seven patients had unilateral swellings, and five had bilateral swellings. Swellings were associated with upper respiratory tract infection or minor trauma, or had no identifiable cause. Aspiration in three cases showed evidence of altered blood.

Conclusions

Recurrent otherwise asymptomatic swelling over cochlear implant receiver packages in children is more common than initially thought. Possible causes include hematoma and seroma secondary to upper respiratory tract infection. The incidence and the timing of swelling are variable. There were no swelling-related device failures or reimplantations so patients and parents can be reassured about the long-term outcome.
Long Noncoding RNA MIR600HG Binds to MicroRNA-125a-5p to Prevent Pancreatic Cancer Progression Via Mitochondrial Tumor Suppressor 1–Dependent Suppression of Extracellular Regulated Protein Kinases Signaling Pathway
Authors: Chen Fang , Zheng Xiang , Liang Wenmei , Jiang Chunxia , Su De , Fu Bao
Published: April 2023

Objectives

Significance of long noncoding RNAs in pancreatic cancer (PC) progression has been documented. Here, we identified a novel long noncoding RNA MIR600HG in PC and its underlying mechanism during PC progression.

Methods

Through bioinformatics analysis, we selected MIR600HG, microRNA-125a-5p (miR-125a-5p), and mitochondrial tumor suppressor 1 (MTUS1) as objects with their expression patterns assayed in the collected PC tissues and PC cells. Pancreatic cancer cells were manipulated with ectopic expression and deficiency of MIR600HG, miR-125a-5p, and/or MTUS1 for assaying cell biological processes in vitro and tumorigenesis in vivo.

Results

MIR600HG and MTUS1 levels were downregulated and miR-125a-5p was upregulated in PC tissues and cells. MIR600HG could bind to miR-125a-5p, while miR-125a-5p negatively targeted MTUS1. MIR600HG resulted in suppression in malignant properties of PCs. All these changes could be reversed by miR-125a-5p elevation. In addition, miR-125a-5p targeted MTUS1 to activate the extracellular regulated protein kinases signaling pathway. In vivo experiment also verified the inhibitory role of MIR600HG in PC.

Conclusions

Taken together, MIR600HG acts as an inhibitor for PC progression by upregulating miR-125a-5p–mediated MTUS1 through extracellular regulated protein kinases pathway.
Role of Immunohistochemistry in Suspected Pancreatic Ductal Adenocarcinoma
Authors: Valentini Anna M. , Savino Maria T. , Donghia Rossella , Schena Nicolò , Arborea Graziana
Published: April 2023

Objectives

Differential diagnosis between pancreatic ductal adenocarcinoma (PDAC) and benign mimickers can be very difficult on small histological samples, such as fine needle aspiration biopsies (FNAB). We aimed to investigate the diagnostic value of immunostaining for IMP3, Maspin, S100A4, S100P, TFF2, and TFF3 in FNAB pancreatic lesions.

Methods

We prospectively enrolled 20 consecutive patients with suspected PDAC, collecting FNABs at our department between 2019 and 2021.

Results

Three of the 20 enrolled patients resulted negative for all immunohistochemical markers, while all the others were positive for Maspin. All other immunohistochemistry (IHC) markers had sensitivity and accuracy of less than 100%. On the basis of the IHC, the preoperative diagnosis on FNAB was nonmalignant lesions in the IHC negative cases and PDAC in the others. All patients subsequently underwent surgery for the pancreatic solid mass demonstrated by imaging techniques. The concordance between the preoperative and postoperative diagnosis was 100%; all IHC negative samples were diagnosed on surgical specimens as chronic pancreatitis and Maspin-positive samples as PDAC.

Conclusions

Our results demonstrate that even in the presence of little histological material, such as FNAB, the use of Maspin alone is sufficient to discriminate between PDAC and nonmalignant pancreatic lesions, with 100% accuracy.
The Clinical Characteristics and Outcome of Elderly Patients With Acute Pancreatitis
Authors: Wang Qiu , Chen Yiqiu , Huang Ping , Su De , Gao Fei , Fu Xiaoyun , Fu Bao
Published: April 2023

Objectives

This study aimed to identify the risk factors for the progression of acute pancreatitis (AP) to severe acute pancreatitis (SAP) and death in elderly patients.

Methods

This was a single-center retrospective study conducted in a tertiary teaching hospital. Data on patient demographics, comorbidities, duration of hospitalization, complications, interventions, and mortality rates were collected.

Results

Between January 2010 and January 2021, 2084 elderly patients with AP were included in this study. The mean age of the patients was 70.0 years (standard deviation, 7.1 years). Among them, 324 (15.5%) had SAP and 105 died (5.0%). The 90-day mortality rate in the SAP group was significantly higher than that in the AP group (P < 0.0001). Multivariate regression analysis revealed that trauma, hypertension, and smoking were risk factors for SAP. After multivariate adjustment, acute respiratory distress syndrome, acute kidney injury, sepsis, organ perforation, and abdominal hemorrhage were associated with higher 90-day mortality.

Conclusions

Traumatic pancreatitis, hypertension, and smoking are independent risk factors for SAP in elderly patients. Acute respiratory distress syndrome, acute kidney injury, sepsis, organ perforation, and abdominal hemorrhage are independent risk factors for death in elderly patients with AP.
Risk Factors for Relapse and/or Prolonged Glucocorticoid Therapy in Polymyalgia Rheumatica
Authors: Vinicki Juan Pablo , Gut Oscar , Maliandi María del Rosario , Velasco Zamora Jose Luis , Linarez Miguel , Cusa Maria Alejandra , Got Julio , Spinetto Maria Andrea , Estevez Adrian Jorge , Brigante Alejandro , Curti Ana Carolina , Costi Ana Carolina , Cavallasca Javier
Published: April 2023

Background

In polymyalgia rheumatica (PMR) relapses and long-term GC dependency are common. We assessed risk factors for higher relapse rate and/or prolonged glucocorticoid therapy in PMR patients.

Methods

A multicenter and observational study (chart review) of PMR patients seen between 2006 and 2021 who had at least a 3-month follow-up period after starting GCs was performed. Results were expressed as median and interquartile range 25th–75th or mean ± standard deviation for numerical variables and percentage for categorical ones. Relapse versus nonrelapse groups were compared using Cox proportional analysis. Hazards ratios (HRs) with 95% confidence intervals (CIs) are reported. In all cases, a p value <0.05 was considered to indicate statistical significance.

Results

We included 185 patients (69.1% female). The median follow-up time was 17.1 months (interquartile range, 6.8–34.7). Incidence of relapses was 1.2 per 100 persons/month. In univariate analysis, PMR patients with a previous history of dyslipidemia had a lower risk of relapse (HR, 0.55; 95% CI, 0.33–0.94; p = 0.03); high-dose GC (HR, 2.35; 95% CI, 1.42–3.87; p = 0.001) and faster GC dose reduction had higher risk of relapse (HR, 3.04; 95% CI, 1.77–5.21; p = 0.001). In multivariate analysis, a previous history of dyslipidemia had a lower risk of relapse (HR, 0.54; 95% CI, 0.32–0.92; p = 0.023), and high dose of GC (HR, 2.46; 95% CI, 1.49–4.08; p = 0.001) remained the only risk factors for relapse.

Conclusions

Lower doses of corticosteroids and a slow rate of reduction are critical to avoid relapse in PMR. Risk factors for higher relapse rate rely on therapy more than clinical characteristics of the patients at the time of diagnosis of PMR.
Technical Basics and Clinical Benefits of Photon-Counting CT
Authors: Flohr Thomas , Schmidt Bernhard
Published: April 2023

Novel photon-counting detector CT (PCD-CT) has the potential to address the limitations of previous CT systems, such as insufficient spatial resolution, limited accuracy in detecting small low-contrast structures, or missing routine availability of spectral information. In this review article, we explain the basic principles and potential clinical benefits of PCD-CT, with a focus on recent literature that has grown rapidly since the commercial introduction of a clinically approved PCD-CT.
Multi-Site Implementation of an American College of Surgeons Geriatric Surgery Quality Improvement Initiative
Authors: Ma Meixi , Peters Xane D , Zhang Lindsey M , Hornor Melissa , Christensen Kataryna , Coleman JoAnn , Finlayson Emily , Flood Kellie L , Katlic Mark , Lagoo-Deenadayalan Sandhya , Robinson Thomas N , Rosenthal Ronnie A , Tang Victoria L , Ko Clifford Y , Russell Marcia M
Published: April 2023

Background:

The American College of Surgeons (ACS) Coalition for Quality in Geriatric Surgery (CQGS) identified standards of surgical care for the growing, vulnerable population of aging adults in the United States. The aims of this study were to 1) determine implementation feasibility for 30 selected standards, 2) identify barriers and best practices in their implementation, and 3) further refine these geriatric standards and verification process.

Study Design:

The CQGS requested participation from hospitals involved in the ACS National Surgical Quality Improvement Project (NSQIP) Geriatric Surgery Pilot Project, prior CQGS feasibility analyses, and hospitals affiliated with a core development team member. 30 standards were selected for implementation. Following implementation, site visits were conducted, and post-visit surveys were distributed.

Results :

Eight hospitals were chosen to participate. Program management (55%), immediate preoperative and intraoperative clinical care (62.5%), and postoperative clinical care (58%) had the highest mean percentage of “Fully Compliant” standards. Goals and decision making (30%), preoperative optimization (28%), and transitions of care (12.5%) had the lowest mean percentage of “Fully Compliant” standards. Best practices and barriers to implementation were identified across 13 of the 30 standards. Over 80% of the institutions reported that participation changed the surgical care provided for older adults.

Conclusion:

This study represents the first national implementation assessment undertaken by the ACS for one of its quality programs. The CQGS pilot testing was able to demonstrate implementation feasibility for 30 standards, identify challenges and best practices, and further inform dissemination of the ACS Geriatric Surgery Verification Program.
Polysubstance use in South Asia
Authors: Mandal Piyali , Mittal Sumegha , Chadda Rakesh Kumar
Published: April 2023

Purpose of review

Polysubstance use is very common in the world, but there has been limited research in this area. South Asia is sandwiched between two of the world's largest heroin producing areas: the Golden Crescent and the Golden Triangle. The burden and prevalence of polysubstance use have not been estimated in this region of the world. We review the research findings on polysubstance use in different South Asian countries. The review also comments on the gaps in knowledge regarding polysubstance use in this region of the world.

Recent findings

The available literature on polysubstance use from South Asia suggests its widespread presence in the region, ranging from 20 to 90%, more commonly among illicit opioid drug users and injection drug users. Most of the available data is from epidemiological studies. There are few studies on the adverse effects of polysubstance use, but the limited data clearly suggests an elevated risk of comorbid psychopathology and health problems.

Polysubstance use still lacks a consensus definition. There is a need of more research on its prevalence, effects on health, and prevention and treatment.
Visual spatial location influences selection of instinctive behaviours in mouse
Authors: Solomon Samuel G. , Janbon Hadrien , Bimson Adam , Wheatcroft Thomas
Published: April 2023

Visual stimuli can elicit instinctive approach and avoidance behaviours. In mouse, vision is known to be important for both avoidance of an overhead threat and approach toward a potential terrestrial prey. The stimuli used to characterize these behaviours, however, vary in both spatial location (overhead or near the ground plane) and visual feature (rapidly expanding disc or slowly moving disc). We therefore asked how mice responded to the same visual features presented in each location. We found that a looming black disc induced escape behaviour when presented overhead or to the side of the animal, but the escapes produced by side-looms were less vigorous and often preceded by freezing behaviour. Similarly, small moving discs induced freezing behaviour when presented overhead or to the side of the animal, but side sweeps also elicited approach behaviours, such that mice explored the area of the arena near where the stimulus had been presented. Our observations therefore show that mice combine cues to the location and features of visual stimuli when selecting among potential behaviours.
Inertial wave attractors in rapidly rotating tilted cuboids
Authors: Welfert Bruno D. , Lopez Juan M. , Wu Ke
Published: April 2023

Flows in rapidly rotating fluid-filled containers are strongly constrained by the restorative Coriolis force. Their responses to small amplitude perturbations may result in the excitation of regular modes of the container for some very selective geometries, but in general the response is a network of inertial wave beams. Due to the peculiar laws governing how these beams reflect, the network of reflected beams may focus onto highly localized regions of the container, where the beam energy and wavenumber become unbounded in the absence of viscous and nonlinear processes. Here, we explore in detail this focusing of wave beams in cuboids, enabling a comprehensive analysis of this intriguing process.
Rethinking same-sex sexual behaviour: male field crickets have broad mating filters
Authors: Richardson Jon , Zuk Marlene
Published: April 2023

Same-sex sexual behaviour (SSB) occurs in many animals and is often treated as an anomaly requiring special explanation. One common explanation for SSB is mistaken identity. However, animals make similar ‘mistakes’ in other contexts—such as attempting to mate with immature individuals or inanimate objects. Framing such behaviours as ‘mistakes’ risks misinterpreting how animals make flexible mating decisions. Here we make a case for an alternative approach to thinking about SSB by instead considering an individual's mating filter. A broad filter means directing courtship toward anything that resembles a potential mate, whilst a narrow filter means only courting with receptive targets. We illustrate this approach by examining the mating filters of male Pacific field crickets (
Teleogryllus oceanicus
). We find that males engage in SSB but also misdirect courtship toward juveniles (but not plastic crickets). This finding suggests that SSB is not an anomaly and is better considered alongside other misdirected behaviours. We argue that by viewing misdirected behaviours through the lens of mating filters rather than as ‘mistakes’ we can build a more nuanced understanding of reproductive behaviour and begin to determine when having a broader mating filter can be advantageous.
Tsetse flies (
Glossina morsitans morsitans
) choose birthing sites guided by substrate cues with no evidence for a role of pheromones
Authors: Adden Andrea K. , Haines Lee R. , Acosta-Serrano Álvaro , Prieto-Godino Lucia L.
Published: April 2023

Tsetse flies significantly impact public health and economic development in sub-Saharan African countries by transmitting the fatal disease African trypanosomiasis. Unusually, instead of laying eggs, tsetse birth a single larva that immediately burrows into the soil to pupate. Where the female chooses to larviposit is, therefore, crucial for offspring survival. Previous laboratory studies suggested that a putative larval pheromone,
n
-pentadecane, attracts gravid female
Glossina morsitans morsitans
to appropriate larviposition sites. However, this attraction could not be reproduced in field experiments. Here, we resolve this disparity by designing naturalistic laboratory experiments that closely mimic the physical characteristics found in the wild. We show that gravid
G. m. morsitans
were neither attracted to the putative pheromone nor, interestingly, to pupae placed in the soil. By contrast, females appear to choose larviposition sites based on environmental substrate cues. We conclude that, among the many cues that likely contribute to larviposition choice in nature, substrate features are a main determinant, while we failed to find evidence for a role of pheromones.