bluuebunny/crossref_metadata_2025 huggingface dataset:
From images to features: unbiased morphology classification via variational auto-encoders and domain adaptation
Authors: Xu Quanfeng , Shen Shiyin , de Souza Rafael S , Chen Mi , Ye Renhao , She Yumei , Chen Zhu , Ishida Emille E O , Krone-Martins Alberto , Durgesh Rupesh
Published: October 2023

We present a novel approach for the dimensionality reduction of galaxy images by leveraging a combination of variational auto-encoders (VAEs) and domain adaptation (DA). We demonstrate the effectiveness of this approach using a sample of low-redshift galaxies with detailed morphological type labels from the Galaxy Zoo Dark Energy Camera Legacy Survey (DECaLS) project. We show that 40-dimensional latent variables can effectively reproduce most morphological features in galaxy images. To further validate the effectiveness of our approach, we utilized a classical random forest classifier on the 40-dimensional latent variables to make detailed morphology feature classifications. This approach performs similar to a direct neural network application on galaxy images. We further enhance our model by tuning the VAE network via DA using galaxies in the overlapping footprint of DECaLS and Beijing-Arizona Sky Survey + Mayall z-band Legacy Survey, enabling the unbiased application of our model to galaxy images in both surveys. We observed that DA led to even better morphological feature extraction and classification performance. Overall, this combination of VAE and DA can be applied to achieve image dimensionality reduction, defect image identification, and morphology classification in large optical surveys.
Rad53 regulates the lifetime of Rdh54 at homologous recombination intermediates
Authors: Hu Jingyi , Ferlez Bryan , Dau Jennifer , Crickard J Brooks
Published: October 2023

Rdh54 is a conserved DNA translocase that participates in homologous recombination (HR), DNA checkpoint adaptation, and chromosome segregation. Saccharomyces cerevisiae Rdh54 is a known target of the Mec1/Rad53 signaling axis, which globally protects genome integrity during DNA metabolism. While phosphorylation of DNA repair proteins by Mec1/Rad53 is critical for HR progression little is known about how specific post translational modifications alter HR reactions. Phosphorylation of Rdh54 is linked to protection of genomic integrity but the consequences of modification remain poorly understood. Here, we demonstrate that phosphorylation of the Rdh54 C-terminus by the effector kinase Rad53 regulates Rdh54 clustering activity as revealed by single molecule imaging. This stems from phosphorylation dependent and independent interactions between Rdh54 and Rad53. Genetic assays reveal that loss of phosphorylation leads to phenotypic changes resulting in loss-of-heterozygosity (LOH) outcomes. Our data highlight Rad53 as a key regulator of HR intermediates through activation and attenuation of Rdh54 motor function.
Sea-ATI unravels novel vocabularies of plant active cistrome
Authors: Wen Chenjin , Yuan Zhen , Zhang Xiaotian , Chen Hao , Luo Lin , Li Wanying , Li Tian , Ma Nana , Mao Fei , Lin Dongmei , Lin Zhanxi , Lin Chentao , Xu Tongda , Lü Peitao , Lin Juncheng , Zhu Fangjie
Published: October 2023

The cistrome consists of all cis-acting regulatory elements recognized by transcription factors (TFs). However, only a portion of the cistrome is active for TF binding in a specific tissue. Resolving the active cistrome in plants remains challenging. In this study, we report the assay sequential extraction assisted-active TF identification (sea-ATI), a low-input method that profiles the DNA sequences recognized by TFs in a target tissue. We applied sea-ATI to seven plant tissues to survey their active cistrome and generated 41 motif models, including 15 new models that represent previously unidentified cis-regulatory vocabularies. ATAC-seq and RNA-seq analyses confirmed the functionality of the cis-elements from the new models, in that they are actively bound in vivo, located near the transcription start site, and influence chromatin accessibility and transcription. Furthermore, comparing dimeric WRKY CREs between sea-ATI and DAP-seq libraries revealed that thermodynamics and genetic drifts cooperatively shaped their evolution. Notably, sea-ATI can identify not only positive but also negative regulatory cis-elements, thereby providing unique insights into the functional non-coding genome of plants.
mtFociCounter for automated single-cell mitochondrial nucleoid quantification and reproducible foci analysis
Authors: Rey Timo , Tábara Luis Carlos , Prudent Julien , Minczuk Michal
Published: October 2023

Mitochondrial DNA (mtDNA) encodes the core subunits for OXPHOS, essential in near-all eukaryotes. Packed into distinct foci (nucleoids) inside mitochondria, the number of mtDNA copies differs between cell-types and is affected in several human diseases. Currently, common protocols estimate per-cell mtDNA-molecule numbers by sequencing or qPCR from bulk samples. However, this does not allow insight into cell-to-cell heterogeneity and can mask phenotypical sub-populations. Here, we present mtFociCounter, a single-cell image analysis tool for reproducible quantification of nucleoids and other foci. mtFociCounter is a light-weight, open-source freeware and overcomes current limitations to reproducible single-cell analysis of mitochondrial foci. We demonstrate its use by analysing 2165 single fibroblasts, and observe a large cell-to-cell heterogeneity in nucleoid numbers. In addition, mtFociCounter quantifies mitochondrial content and our results show good correlation (R = 0.90) between nucleoid number and mitochondrial area, and we find nucleoid density is less variable than nucleoid numbers in wild-type cells. Finally, we demonstrate mtFociCounter readily detects differences in foci-numbers upon sample treatment, and applies to Mitochondrial RNA Granules and superresolution microscopy. mtFociCounter provides a versatile solution to reproducibly quantify cellular foci in single cells and our results highlight the importance of accounting for cell-to-cell variance and mitochondrial context in mitochondrial foci analysis.
Serologic immunogenicity and safety of herpes zoster subunit vaccine in patients with rheumatoid arthritis receiving Janus kinase inhibitors
Authors: Källmark Hanna , Bergström Tomas , Nagel Johanna , Gullstrand Birgitta , Einarsson Jon T , Bengtsson Anders A , Kapetanovic Meliha C
Published: October 2023

Objective

Patients with RA treated with Janus kinase inhibitors (JAKis) are at increased risk of herpes zoster (HZ). The objective of this study was to investigate the serological immunogenicity and safety of the HZ subunit (HZ/su) vaccine in RA patients treated with JAKi, for which little is known.

Methods

RA patients treated with JAKi (n = 82) at the Department of Rheumatology, Skåne University Hospital, Lund and Malmö, Sweden, and healthy controls (n = 51) received two doses of the HZ/su vaccine (Shingrix). Vaccine-specific antibody responses were analysed using indirect ELISA. Post-vaccination antibody levels were compared between patients and controls using analysis of covariance. Potential predictors for vaccine response were investigated using a multivariable linear regression analysis. Self-reported adverse events (AEs) and changes in RA disease activity were analysed.

Results

Following vaccination, vaccine-specific antibody levels increased significantly in both patients and controls (P < 0.0001). A total of 80.5% of patients and 98.0% of controls achieved a ≥4-fold increase in antibody levels. Post-vaccination antibody levels were lower in patients than controls [ratio 0.44 (95% CI 0.31, 0.63)] and lower in patients receiving JAKi + methotrexate than JAKi monotherapy [ratio 0.43 (95% CI 0.24, 0.79)]. AEs, mostly mild/moderate, were common. One patient developed HZ and six patients (6.5%) had increased RA disease activity following vaccination.

Conclusion

The HZ/su vaccine was serologically immunogenic in most RA patients treated with JAKi. Moreover, the vaccine had an acceptable safety profile. These results support recommendations for use of the HZ/su vaccine in this vulnerable population.

Trial registration

ClinicalTrials.gov (https://clinicaltrials.gov), NCT03886038.
A decade of progress in juvenile idiopathic arthritis treatments and outcomes in Canada: results from ReACCh-Out and the CAPRI registry
Authors: Nguyen Kelly , Barsalou Julie , Basodan Daniah , Batthish Michelle , Benseler Susanne M , Berard Roberta A , Blanchette Nicholas , Boire Gilles , Bolaria Roxana , Bruns Alessandra , Cabral David A , Cameron Bonnie , Campillo Sarah , Cellucci Tania , Chan Mercedes , Chédeville Gaëlle , Chetaille Anne-Laure , Chhabra Amieleena , Couture Julie , Dancey Paul , De Bruycker Jean-Jacques , Demirkaya Erkan , Dhalla Muhammed , Duffy Ciarán M , Feldman Brian M , Feldman Debbie E , Gerschman Tommy , Haddad Elie , Heale Liane , Herrington Julie , Houghton Kristin , Huber Adam M , Human Andrea , Johnson Nicole , Jurencak Roman , Lang Bianca , Larché Maggie , Laxer Ronald M , LeBlanc Claire M , Lee Jennifer J Y , Levy Deborah M , Lim Lillian , Lim Lily S H , Luca Nadia , McGrath Tara , McMillan Tamara , Miettunen Paivi M , Morishita Kimberly A , Ng Hon Yan , Oen Kiem , Park Jonathan , Petty Ross E , Proulx-Gauthier Jean-Philippe , Ramsey Suzanne , Roth Johannes , Rosenberg Alan M , Rozenblyum Evelyn , Rumsey Dax G , Schmeling Heinrike , Schneider Rayfel , Scuccimarri Rosie , Shiff Natalie J , Silverman Earl , Soon Gordon , Spiegel Lynn , Stringer Elizabeth , Tam Herman , Tse Shirley M , Tucker Lori B , Turvey Stuart , Twilt Marinka , Duffy Karen Watanabe , Yeung Rae S M , Guzman Jaime
Published: October 2023

Objective

To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005–2010 and 2017–2021 inception cohorts.

Methods

Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan–Meier survival analysis and multivariable Cox regression.

Results

The 2005–2010 and 2017–2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005–2010 and 26% (23, 30) in the 2017–2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10).

Conclusion

Although baseline disease characteristics were comparable in the 2005–2010 and 2017–2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity.
Acute inhibition of AMPA receptors by perampanel reduces amyloid β‐protein levels by suppressing β‐cleavage of APP in Alzheimer's disease models
Authors: Ueda Sakiho , Kuzuya Akira , Kawata Masayoshi , Okawa Kohei , Honjo Chika , Wada Takafumi , Matsumoto Mizuki , Goto Kazuya , Miyamoto Masakazu , Yonezawa Atsushi , Tanabe Yasuto , Ikeda Akio , Kinoshita Ayae , Takahashi Ryosuke
Published: October 2023

Hippocampal hyperexcitability is a promising therapeutic target to prevent Aβ deposition in AD since enhanced neuronal activity promotes presynaptic Aβ production and release. This article highlights the potential application of perampanel (PER), an AMPA receptor (AMPAR) antagonist approved for partial seizures, as a therapeutic agent for AD. Using transgenic AD mice combined with in vivo brain microdialysis and primary neurons under oligomeric Aβ‐evoked neuronal hyperexcitability, the acute effects of PER on Aβ metabolism were investigated. A single oral administration of PER rapidly decreased ISF Aβ40 and Aβ42 levels in the hippocampus of J20, APP transgenic mice, without affecting the Aβ40/Aβ42 ratio; 5 mg/kg PER resulted in declines of 20% and 31%, respectively. Moreover, PER‐treated J20 manifested a marked decrease in hippocampal APP βCTF levels with increased FL‐APP levels. Consistently, acute treatment of PER reduced sAPPβ levels, a direct byproduct of β‐cleavage of APP, released to the medium in primary neuronal cultures under oligomeric Aβ‐induced neuronal hyperexcitability. To further evaluate the effect of PER on ISF Aβ clearance, a γ‐secretase inhibitor was administered to J20 1 h after PER treatment. PER did not influence the elimination of ISF Aβ, indicating that the acute effect of PER is predominantly on Aβ production. In conclusion, acute treatment of PER reduces Aβ production by suppressing β‐cleavage of amyloid‐β precursor protein effectively, indicating a potential effect of PER against Aβ pathology in AD.
One-stage Reconstruction with the Composite Anterolateral Thigh Flap for Skin and Extensor Tendon Defects of the Thumb by Snakebite
Authors: Sơn Trần Thiết , Chiến Vũ Hồng , Nghĩa Phan Tuấn , Trọng Nguyễn Hữu , Nhật Phạm Kiến , Thúy Tạ Thị Hồng , Dung Phạm Thị Việt
Published: October 2023

Venomous snakebites can cause severe injury. The loss of tendon and skin of the hand is incredibly challenging for the surgeon. A single-staged reconstruction with the free composite anterolateral thigh flap is an acceptable option for a complex thumb injury. In this case, reconstruction for a 23-year-old patient with a complex cobra-induced thumb injury had failed to cover the defect with a skin graft. There was a limitation in choice, and the patient was treated with the free composite anterolateral thigh (ALT) flap and fascia lata flap in one stage to reconstruct both the extensor tendon and the soft tissue coverage. The flap was well-vascularized, and no complications were reported. A single-stage reconstruction with a composite ALT flap with vascularized fascia was chosen as a suitable alternative. The result is satisfying both aesthetically and functionally. This technique can help shorten treatment time and restore function quickly, allowing patients to return to work in less time. The disadvantages of this technique are flap thickness, which can affect finger movement and aesthetics. The composite ALT flap with vascularized fascia lata shows that it is a reliable procedure for single-staged reconstruction, especially combined with the tendon preparation in the hand.
Comparison between visit-to-visit office and 24-h blood pressure variability in treated hypertensive patients
Authors: Mancia Giuseppe , Facchetti Rita , Quarti-Trevano Fosca , Dell’Oro Raffaella , Cuspidi Cesare , Grassi Guido
Published: October 2023

Objectives:

In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on visit-to-visit 24-h BPV.

Methods:

In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3–4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared.

Results:

Twenty-four-hour SBP-CV was about 20% less than office SBP-CV (P < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1–4% of 24-h SBP or DBP-CV values.

Conclusion:

Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability.
Association of serum uric acid levels with blood pressure and the incidence of hypertension in the middle-aged and elderly populations
Authors: Sasaki Nobuo , Ueno Yoshitaka , Ozono Ryoji , Yoshimura Kenichi , Nakano Yukiko , Higashi Yukihito
Published: October 2023

Objective:

This study aimed to investigate the relationship between serum uric acid (SUA) levels and hypertension in the middle-aged and elderly populations.

Methods:

The cross-sectional analysis included 13 349 middle-aged and elderly general health checkup examinees without cardiovascular disease. The retrospective cohort analysis included 6659 normotensive participants (mean age: 64.6 years). Participants were divided into three groups based on their SBP/DBP levels: normal (<120/<80 mmHg), high normal (120–129/<80 mmHg), and elevated (130–139/80–89 mmHg), and were classified into three groups based on the results of 75 g oral glucose tolerance test: normoglycemia, prediabetes, and diabetes.

Results:

SUA levels were significantly associated with SBP and DBP in this cross-sectional study. Over a mean 6.5-year follow-up period, 2038 participants developed hypertension. According to the SUA quartiles, the incidence of hypertension increased [26.1% in quartile (Q1) (≤4.1 mg/dl), 28.6% in Q2 (4.2–4.9 mg/dl), 32.6% in Q3 (5.0–5.8 mg/dl), 34.9% in Q4 (≥5.9 mg/dl); P for trend <0.001]. In multivariable analyses, SUA levels were positively associated with hypertension incidence only in the normal BP group [Q4 vs. Q1 odds ratio (OR): 1.64, 95% confidence intervals (CIs): 1.11–2.44; Q3 vs. Q1 OR: 1.69, 95% CI: 1.19–2.42] and in the normoglycemic group (Q4 vs. Q1 OR: 1.34, 95% CI: 1.02–1.76; Q3 vs. Q1 OR: 1.36, 95% CI: 1.07–1.74).

Conclusion:

In the middle-aged and elderly populations, normotensive or normoglycemic individuals with SUA levels at least 5 mg/dl may be potential targets for SUA management to prevent hypertension.
Influence of Job Burnout on Decision-Making and Coping With Stress Among Nurses
Authors: Gao Yana , Liu Jun , Liu Jie , Duan Ting
Published: October 2023

Job burnout is highly prevalent among health care workers. This study determined the effect of job burnout on decision-making and coping with stress among nurses. Two hundred seventy-seven nurses in Xijing Hospital were investigated using the Job Burnout Scale, Decision Scale, and Simple Stress Coping Style Scale. The total score of job burnout was 107.8 ± 16.479 (severe burnout) and clinical decision-making consciousness was 123.75 ± 16.094 (moderate decision-making consciousness). No statistical differences existed in different gender samples (P > .05). Burnout and clinical decision-making awareness of clinical nurses were stronger than nursing interns and regular trainee nurses, but the occupational pressure of nursing interns was the highest (P < .05). Marital status also showed significant differences in job burnout; unmarried nurses were more prone to burnout (P < .05). In conclusions, burnout is a serious issue among nurses, which is closely related with clinical decision-making awareness, negative coping, and occupational stress. Nurse identity and marital status had significant effects on burnout.
Dramatic Reduction in Corneal Transplants for Keratoconus 15 Years After the Introduction of Corneal Collagen Crosslinking
Authors: Hagem Anne Marie , Thorsrud Andreas , Sæthre Marit , Sandvik Gunhild , Kristianslund Olav , Drolsum Liv
Published: October 2023

Purpose:

The aim of this study was to investigate the effect of the implementation of corneal collagen crosslinking (CXL) on the frequency of corneal transplants among patients with keratoconus (KC) in the same region.

Methods:

Before the introduction of CXL in 2007, 55 primary corneal transplants had been conducted in patients with KC (2005 and 2006) at the Department of Ophthalmology, Oslo University Hospital, Norway. We collected data from our corneal transplant registry for 2021 and 2022. The primary outcome was the number of corneal transplants performed in patients with KC. Age, sex, visual acuity (logarithm of the minimal angle of resolution), KC stage according to the Amsler–Krumeich classification system, and steepest keratometry reading (maximum keratometry, Pentacam, HR) were recorded. Furthermore, we registered the annual number of CXL treatments conducted from 2007 to 2022.

Results:

A total of 352 corneal transplants were performed in 2021 and 2022. Among them, 11 (3.1%) were transplants for patients with KC. All included patients were male; further, 90.1% and 9.1% of the patients were graded stages 4 and 3, respectively. The mean maximum keratometry was 79.0 diopter (range 61.0–109). The mean best-corrected visual acuity (logarithm of the minimal angle of resolution) was 1.3 (range 0.2–3.0). In 2021 to 2022, 431 CXL treatments were performed.

Conclusions:

There was a significant decrease in the number of corneal transplants performed in patients with KC 15 years after the introduction of CXL. This indicates that the availability of CXL treatment over many years may considerably reduce the need for keratoplasties in this group of patients.
Immunogenicity of COVID-19 Vaccination in People Living with HIV: Progress and Challenges
Authors: Song Jin-Wen , Shen Lili , Wang Fu-Sheng
Published: October 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has resulted in numerous confirmed cases and deaths worldwide. Recent studies have shown that people living with HIV (PLWH) are prone to develop severe illness and poor outcomes if they experience coronavirus disease 2019 (COVID-19), especially those with uncontrolled viremia and low CD4 T-cell count. Therefore, many countries prioritized PLWH for COVID-19 vaccination. However, lower magnitude or faster waning humoral immune responses elicited by other vaccines have been documented in PLWH, raising concerns regarding the efficacy of the COVID-19 vaccine in these specific populations. Here, we summarize the current progress in the immunogenicity and efficacy of different types of SARS-CoV-2 vaccinations in PLWH and highlight several challenges faced by PLWH in the current COVID-19 pandemics.
Effect of Different Factors on the Quality of Life and Sequelae of COVID-19 Patients After Discharge
Authors: Guo Nan , Yao Ya-Ping , Song Le , Wang Guan-Zhen , He Jun-Li , Zheng Ning , Mo Qiong , Ni Wen-Xu , Zhang Bo , Wang Fu-Sheng , Huang Lei
Published: October 2023

Background

The continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an international public health emergency, resulting in a significant global disease burden. The long-term effects of SARS-CoV-2 infection in humans and the long-term prognosis of patients with coronavirus disease 2019 (COVID-19) after discharge remain unclear. We aimed to assess the quality of life (QoL) and sequelae in patients with COVID-19 after discharge from the hospital by conducting multiple follow-up visits to understand the long-term effects of SARS-CoV-2 on patients' health and its possible influencing factors.

Methods

COVID-19 patients discharged from Huoshenshan Hospital (Wuhan, China) between February 15 and April 5, 2020, were followed up at 6, 9, and 12 months after discharge. They completed questionnaires on postdischarge QoL and sequelae under the guidance of medical staff with professional training. The demographic and clinical characteristics of the COVID-19 patients were analyzed using descriptive statistics. A generalized estimating equation model was used to analyze the QoL-related factors. The χ
2 test (or Fisher exact test) and multivariate logistic regression analysis were used to analyze the sequelae and influencing factors.

Results

A total of 175 patients participated in at least 1 follow-up visit, and 120 completed all 3 follow-up visits. Patients diagnosed with severe and critically ill COVID-19 had worse mental conditions (χ
2 = 7.653, P = 0.022) than those with the nonsevere type (not severe or critical) and were more likely to feel fatigued (χ
2 = 4.836, P = 0.028). Female patients had a higher risk of sleep disturbance (χ
2 = 10.026, P = 0.002) and dyspnea (χ
2 = 5.672, P = 0.017) and had more difficulty returning to their original work and life (χ
2 = 8.922, P = 0.003) than male patients. Patients with diabetes had a worse appetite (χ
2 = 4.669, P = 0.031) and were more prone to sleep disturbance (χ
2 = 4.417, P = 0.036) after discharge. The proportion of patients with at least 1 sequela increased from 29.76% (50/168) at 6 months to 51.11% (69/135) at 9 months (χ
2 = 14.305, P < 0.001). Compared with the nonsevere type, patients diagnosed with severe and critically ill COVID-19 had an odds ratio (OR) of 4.325 (95% confidence interval [CI], 1.215–15.401) for memory decline. Female patients had an OR of 4.632 (95% CI, 1.716–12.501) for joint or muscle pain. Patients with hypertension had an OR of 3.014 (95% CI, 1.193–7.615) for joint or muscle pain.

Conclusion

One year after discharge, there were still some patients with varying degrees of decline in QoL and sequelae, which occurred in all follow-up visits. Moreover, QoL and sequelae after discharge were related to sex, clinical classification of COVID-19, and underlying diseases.
Lack of Correlation Between Segmental Trabecular Meshwork Pigmentation and Angiographically Determined Outflow in Ex Vivo Human Eyes
Authors: Strohmaier Clemens A. , Wanderer Daniel , Zhang Xiaowei , Zhang Hao F. , Strohmaier Susanne , Weinreb Robert N. , Huang Alex S.
Published: October 2023

Précis:

Trabecular meshwork (TM) pigmentation is not correlated with angiographically determined aqueous humor outflow (AHO) in an ex vivo perfusion model using human eyes.

Purpose:

To evaluate whether segmental TM pigmentation is correlated to segmental AHO in human eyes.

Methods:

Postmortem human eyes were acquired, and anterior segments were dissected. TM pigmentation was photographed 360-degrees around the eye. The anterior segments were then mounted onto a perfusion apparatus and perfused with Dulbecco’s phosphate buffered saline (DPBS) until a stabile baseline outflow facility was achieved. Aqueous angiography (AHO angiography) was performed using fluorescein (2%), and segmental AHO was documented around the limbus using an angiographic camera (Spectralis HRA+OCT). Circumferential and nasal TM pigmentation were compared with respective angiographic outflow imaging using a Pearson correlation analysis.

Results:

Segmental TM pigment distribution and segmental AHO were seen. TM pigment was statistically greatest in the inferior quadrant. AHO angiographic outflow was numerically greatest in the nasal quadrant, but this was not statistically significant. No statistically significant correlation was observed (r=−0.083, P=0.06) between segmental TM pigmentation and segmental AHO angiographic signal. Analyzing just the nasal quadrant, a significant weak negative correlation was found (r=−0.296, P=0.001).

Discussion:

Segmental TM pigmentation circumferentially around the eye is not a good proxy for segmental AHO circumferentially around the eye and should not be used to guide trabecular minimally invasive glaucoma surgeries.
Human Rhinovirus as a Cause of Fever in Neonates and Young Infants During the COVID-19 Pandemic, 2020–2022
Authors: Aizawa Yuta , Ikuse Tatsuki , Izumita Ryohei , Habuka Rie , Yamanaka Takayuki , Saitoh Akihiko
Published: October 2023

Background:

Human rhinovirus (HRV) was predominant and persistent during the coronavirus disease 2019 (COVID-19) pandemic despite nonpharmaceutical interventions. The data whether HRV persistence also occurred in neonates and young infants were very limited.

Methods:

This prospective observational study was conducted in Niigata, Japan, between January 2020 and September 2022. The participants were hospitalized neonates and infants less than 4 months of age with fever. We excluded patients with evidence of bacterial infection or obvious sick contact with influenza or respiratory syncytial virus infection, as confirmed by rapid antigen detection tests. COVID-19 diagnosed by polymerase chain reaction (PCR) or rapid antigen detection tests were also excluded. Parechovirus and enterovirus were examined by PCR using serum and/or cerebrospinal fluid. FilmArray Respiratory Panel v1.7 was conducted on nasopharyngeal swabs. If HRV was positive, the genotype was identified.

Results:

We included 72 patients (median age, 54 days; interquartile range, 28.5–79 days), and sepsis was diagnosed in 31 (43.1%) patients. In total, 27 (37.5%) patients had had positive multiplex PCR tests. These patients were more likely to have rhinorrhea (P = 0.004), cough (P = 0.01), and sick contact (P < 0.001) than those who with negative multiplex PCR. HRV was the most frequently detected virus (n = 23, 85.2%), and species A (n = 15, 71.4%) and C (n = 6, 28.6%) were genotyped. No seasonality or monthly predominance of the specific HRV types was observed.

Conclusions:

HRV was an important cause of fever in neonates and young infants during the COVID-19 pandemic, 2020 to 2022.
Toward targeted treatments for silicosis
Authors: Barnes Hayley , Lam Maggie , Tate Michelle D. , Hoy Ryan
Published: October 2023

Purpose of review

There has been a rapid increase in silicosis cases, particularly related to artificial stone. The key to management is avoidance of silica exposure. Despite this, many develop progressive disease and there are no routinely recommended treatments. This review provides a summary of the literature pertaining to pharmacological therapies for silicosis and examines the plausibility of success of such treatments given the disease pathogenesis.

Recent findings

In-vitro and in-vivo models demonstrate potential efficacy for drugs, which target inflammasomes, cytokines, effector cells, fibrosis, autophagy, and oxidation.

There is some evidence for potential therapeutic targets in silicosis but limited translation into human studies. Treatment of silicosis likely requires a multimodal approach, and there is considerable cross-talk between pathways; agents that modulate both inflammation, fibrosis, autophagy, and ROS production are likely to be most efficacious.
Efficacy of Lactococcus lactis strain Plasma on clearance of anal HPV infection in men who have sex with men: A single-center, double-blinded, randomized placebo-controlled trial (CLEAR HPV study)
Authors: Mizushima Daisuke , Takano Misao , Ando Naokatsu , Kitamura Hiroshi , Shiojiri Daisuke , Nakamoto Takato , Aoki Takahiro , Watanabe Koji , Shimizu Yosuke , Uemura Yukari , Gatanaga Hiroyuki , Oka Shinichi
Published: October 2023

Background:

Anal cancer is a human papillomavirus-related cancer; specifically, it is preceded by high-grade squamous intraepithelial lesions, which are less likely to regress spontaneously than low-grade intraepithelial lesions. Although most human papillomavirus (HPV) infections are thought to clear spontaneously, anal HPV infection persists, especially in people living with HIV. Preliminary results from a recent small randomized placebo-controlled trial of oral bacteriotherapy using a high dose of probiotics demonstrated clearance of anal high-risk HPV (hr-HPV) infection and lower onset of new high-grade squamous intraepithelial lesions among people living with HIV. Lactococcus lactis strain Plasma is a lactic acid bacterium directly activating plasmacytoid dendritic cells and inducing release of type I and III interferons via Toll-like receptor 9 stimulation. Based on these findings, oral bacteriotherapy with LC-plasma may contribute to clearing anal hr-HPV infection and reducing anal precancerous lesions by activating innate and acquired immune responses. This randomized placebo-controlled trial aims to investigate the efficacy and safety of LC-plasma therapy in clearing anal hr-HPV infection and reducing anal precancerous lesions among men who have sex with men with or without HIV infection.

Methods:

Participants with anal hr-HPV infection will be included and receive test capsules. A total of 150 patients will be included in the intervention group with follow-up, which will consist of HPV genotype test, cytology by anal pap smear, and biopsy with high-resolution anoscopy. The primary endpoint will be the clearance rate of the hr-HPV genotype infection at the anal site at 180 days. The secondary endpoints will be changes in anal epithelial neoplasia detected using high-resolution anoscopy at 180 days; change in abnormal cytology by anal pap smear at 180 days; change in hr-HPV genotype at the anal site at 180 days; change or percentage change in peripheral blood CD4 positive T-lymphocyte numbers in HIV-infected participants at 180 days; changes in quantitative hepatitis B surface antigen levels at 180 days in the HBV-infected participants; and adherence to the study drugs.

Conclusion:

This randomized controlled study will provide data on the efficacy and safety of LC-plasma as a treatment for anal HPV infection and grade 2 or 3 anal intraepithelial neoplasia.
Treating rare tumors with liver transplantation
Authors: Melehy Andrew , Agopian Vatche
Published: October 2023

Purpose of review

The success of liver transplantation (LT) in treating unresectable hepatocellular carcinoma (HCC) has resulted in interest in LT for other oncologic conditions. Here, we discuss the role of LT for rare oncologic indications including metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs), hepatic epitheliod hemangioendothelioma (HEHE), fibrolamellar hepatocellular carcinoma (FLC), and hepatic angiosarcoma (HAS).

Recent findings

Conditions reviewed have been documented indications for LT in the available literature. We summarize the experience of LT for these indications and proposed management guidelines.

GEP-NETs with isolated metastases to the liver can be treated with LT with excellent long-term outcomes (10-year survival 88%) if strict selection criteria are used (low-intermediate grade, Ki-67% < 20%, complete resection of primary tumor, stable disease for 6 months, <50% hepatic involvement). HEHE is a rare hepatic tumor for which LT can be performed with reported 10-year survival around 70%. FLC is a distinct clinical entity to HCC and is optimally treated with surgical resection though experience with LT is described in observational series (5-year survival 50%, recurrence in 10%). HAS is a rapidly progressive tumor with a dismal prognosis with or without treatment, including LT.
Assessment of a Novel, Adjustable Task Trainer for Cardiac Surgical Skills
Authors: White Abigail , Turner Simon R. , Moon Michael C. , Zheng Bin
Published: October 2023

Introduction

A recent needs assessment in Canadian cardiac surgery programs identified the desire for a coronary artery bypass (CABG) and aortic valve replacement (AVR) simulation model for home practice. We aimed to develop and assess a portable, adjustable task trainer for cardiac surgical skills with high functional task alignment.

Methods

Intraoperative measurements were taken from patients undergoing elective CABG and AVR (N = 30). Measurements were taken in 3 axes and used to create a chest cavity that resembles the mediastinal constraints of a patient undergoing CABG and AVR. The task trainer is adjustable on the following 3 levels: (1) size of the incision, (2) depth of the chest, and (3) relative position of coronary artery or aortic valve model within the chest. Three groups (novices, intermediates, and experts) of cardiac surgery members evaluated the task trainer for functional task alignment and construct validity.

Results

The CABG and AVR model had high functional task alignment. There was a high satisfaction for both models and all participants would recommend the AVR and CABG model as an educational tool. Performance time significantly differed between the groups for both models (CABG: P = 0.032 and AVR: P = 0.001), as well as number of errors (CABG: P = 0.04 and AVR: P = 0.043).

Conclusions

Using real patient data, we were able to develop an adjustable task trainer for training principles of CABG and AVR. Our pilot study provides preliminary sources of evidence for validity and future study will look to assess transferability of skill to the operating room.
Total flavonoids of Cynomorium songaricum attenuates cognitive defects in an Aβ1-42-induced Alzheimer’s disease rat model by activating BDNF/TrkB signaling transduction
Authors: Gu Zhirong , Lv Xin , Guo Yan , Qi Mei , Ge Bin
Published: October 2023

Alzheimer’s disease (AD) is a degenerative disorder characterized by cognitive dysfunction and BDNF/TrkB is a well-conceived anti-AD signaling. Cynomorium songaricum Rupr. (C. songaricum) is a herb with promising neuroprotective effects and the function is majorly attributed to flavonoids. The current study attempted to explore the effects of total flavonoids of C. songaricum (CS) on AD model by focusing on changes in BDNF/TrkB axis. AD model was induced in rats via transcranial injection of Aβ1-42 and AD symptoms treated with CS of three doses. Donepezil was used as the positive control. Changes in rat memory and learning abilities, brain histological, apoptosis, production of neurotransmitters, BDNF/TrkB axis, and apoptosis-related markers were measured. The injection of Aβ1-42 induced cognitive dysfunction in AD rats. The integrity of brain tissue structure was destructed and apoptosis was induced in AD rats, in which was found the increased production of AChE and Aβ1-42, and decreased production of ChAT, ACH. At the molecular level, the expression of BDNF, TrkB, and Bcl-2 was suppressed, while the expression of Bax, caspase-3, and caspase-9 was induced. After the administration of CS, the memory and learning abilities of rats were improved, the production of neurotransmitter was restored, ordered arrangement of pyramidal cells was retained, and neuron apoptosis was inhibited. The attenuation of Aβ1-42-indcued impairments was associated with the activation of BDNF/TrkB axis and blockade of apoptosis-related pathways. Collectively, CS can improve learning and memory abilities in Aβ1-42-induced AD model rats. which may depend on the activation of the hippocampal BDNF/TrkB signaling pathway.
Hydrothermal carbonization of vegetable-tanned leather shavings (HTC-VTS) for environmental remediation: optimization of process conditions
Authors: Debina Baissassou , Baçaoui Abdelaziz , Tamafo Fouégué Aymard Didier , Kouotou Daouda , Rahman Abdoul Ntieche , Yaacoubi Abdelrani , Benoît Loura Benguellah
Published: October 2023

Herein, the response surface methodology (RSM) has been used to study simultaneously the effects of carbonization temperature, residence time and moisture content on the activated hydrochar preparation-based vegetable-tanned leather shavings (VTS) using hydrothermal carbonization method (HTC). Owing to the desirability chosen, three responses were analysed, namely: the hydrochar yield, iodine and methylene blue numbers. The analysis of experimental results revealed that the hydrochar yield was decreased with increase in carbonization temperature which led to micropores formation inside the hydrochar network. The optimal preparation conditions retained were: 83.10%, 390.44 mg g
−1
and 259.63 mg g
−1
for the hydrochar yield, iodine and methylene blue number respectively. The hydrochar micrograph showed the presence of external pores, whereas the FTIR analysis recorded the presence of acidic functional groups found on hydrochar surface. The findings revealed that the VTS is a good precursor for the hydrochar preparation useful in the removal of organic and inorganic pollutants in aqueous media.
A blue-shifted genetically encoded Ca2+indicator with enhanced two-photon absorption
Authors: Aggarwal Abhi , Sunil Smrithi , Bendifallah Imane , Moon Michael , Drobizhev Mikhail , Zarowny Landon , Zheng Jihong , Wu Sheng-Yi , Lohman Alexander W. , Tebo Alison G. , Emiliani Valentina , Podgorski Kaspar , Shen Yi , Campbell Robert E.
Published: October 2023

Significance

Genetically encoded calcium ion (Ca2+) indicators (GECIs) are powerful tools for monitoring intracellular Ca2+concentration changes in living cells and model organisms. In particular, GECIs have found particular utility for monitoring the transient increase of Ca2+concentration that is associated with the neuronal action potential. However, the palette of highly optimized GECIs for imaging of neuronal activity remains relatively limited. Expanding the selection of available GECIs to include new colors and distinct photophysical properties could create new opportunities forin vitroandin vivofluorescence imaging of neuronal activity. In particular, blue-shifted variants of GECIs are expected to have enhanced two-photon brightness, which would facilitate multiphoton microscopy.

Aim

We describe the development and applications of T-GECO1 – a high-performance blue-shifted GECI based on theClavularia sp.-derived mTFP1.

Approach

We used protein engineering and extensive directed evolution to develop T-GECO1. We characterize the purified protein and assess its performancein vitrousing one-photon excitation in cultured rat hippocampal neurons,in vivousing one-photon excitation fiber photometry in mice, andex vivousing two-photon Ca2+imaging in hippocampal slices.

Results

The Ca2+-bound state of T-GECO1 has an excitation peak maximum of 468 nm, an emission peak maximum of 500 nm, an extinction coefficient of 49,300 M-1cm-1, a quantum yield of 0.83, and two-photon brightness approximately double that of EGFP. The Ca2+-dependent fluorescence increase is 15-fold and the apparentKdfor Ca2+is 82 nM. With two-photon excitation conditions at 850 nm, T-GECO1 consistently enabled detection of action potentials with higher signal-to-noise (SNR) than a late generation GCaMP variant.

Conclusion

T-GECO1 is a high performance blue-shifted GECI that, under two-photon excitation conditions, provides advantages relative to late generation GCaMP variants.
Automated and Interpretable Detection of Hippocampal Sclerosis in temporal lobe epilepsy: AID-HS
Authors: Ripart Mathilde , DeKraker Jordan , Eriksson Maria H , Piper Rory J. , Mo Jia-Jie , Su Ting-Yu , Kochi Ryuzaburo , Wang Irene , Winston Gavin P , Clark Chris A , D’Arco Felice , Mankad Kshitij , Khan Ali R. , Baldeweg Torsten , Adler Sophie , Wagstyl Konrad
Published: October 2023

Hippocampal Sclerosis (HS) can elude visual detection on MRI scans of patients with temporal lobe epilepsy (TLE), causing delays in surgical treatment and reducing the likelihood of postsurgical seizure-freedom. We developed an open-source software that (1) detects HS from structural MRI scans, (2) generalises across a heterogeneous multicentre cohort of children and adults, and (3) generates individualised predictions for clinical evaluation.

We included a cohort of 363 participants (152 patients with HS, 90 disease controls with focal cortical dysplasia, and 121 healthy controls) from four epilepsy centres in the UK, North America, and China. We used the open-source software HippUnfold to extract morphological surface-based features and volumes of the hippocampus from T1w MRI scans. We compared pathological hippocampal morphology in patients with HS to normative growth charts generated from healthy controls, and to the contralateral hippocampi in patients with HS. HS was characterised by decreased volume, thickness and gyrification as well as increased mean and intrinsic curvature. A logistic regression classifier trained on these features detected 90.1% of HS patients, and accurately lateralised 97.4% of the HS cohort. Crucially, in patients with MRI-negative histopathologically confirmed HS, the classifier detected HS in 79.2% (19/24) and accurately lateralised the lesions in 91.7% (22/24). The Automated and Interpretable Detection of Hippocampal Sclerosis classifier (AID-HS) was packaged into an open-source pipeline, which detects and lateralises HS and generates individualised patient reports that characterise hippocampal developmental abnormalities.

AID-HS is capable of accurately detecting and lateralising HS in a large, heterogeneous, multi-centre, cohort of paediatric and adult patients with diagnostically challenging HS. Moreover, by offering transparent, robust and interpretable results, AID-HS can support the presurgical evaluation of patients with suspected TLE.
Generalized Reporter Score-based Enrichment Analysis for Omics Data
Authors: Peng Chen , Chen Qiong , Tan Shangjin , Shen Xiaotao , Jiang Chao
Published: October 2023

Enrichment analysis contextualizes biological features in pathways to facilitate a systematic understanding of high-dimensional data and is widely used in biomedical research. The emerging reporter score-based analysis (RSA) method shows more promising sensitivity, as it relies onp-valuesinstead of raw values of features. However, RSA cannot be directly applied to multi-group experimental designs and is often misused due to the lack of a proper tool. Here, we propose the Generalized Reporter Score-based Analysis (GRSA) method for multi-group and longitudinal omics data. A comparison with other popular enrichment analysis methods demonstrated that GRSA had increased sensitivity across multiple benchmark datasets. We applied GRSA to microbiome, transcriptome, and metabolome data and discovered new biological insights in omics studies. Finally, we demonstrated the application of GRSA beyond functional enrichment using a taxonomy database. We implemented GRSA in an R package, ReporterScore, integrating with a powerful visualization module and updatable pathway databases (https://github.com/Asa12138/ReporterScore). We believe the ReporterScore package will be a valuable asset for broad biomedical research fields.
Glomerular immune injury promotes anti-tumor activity
Authors: Avraham Shimrit , Korin Ben , Lo Jerry Hung-Hao , Cruz-Tleugabulova Mayra , Menon Hari , Darmanis Spyros , Liang Yuxin , Modrusan Zora , Durinck Steffen , Webster Joshua D , Shaw Andrey S
Published: October 2023

Recent evidence suggests that the interaction between the tumor microenvironment (TME) and systemic host environment can alter the host immune system to promote anti-tumor activity. Here, we investigated whether glomerular immune injury affects cancer progression. We used nephrotoxic serum nephritis (NTN), a model for glomerular immune injury, and followed it by cancer cell implantation. NTS-injected mice developed smaller primary tumors compared with controls. Tumors of NTS-injected mice had more activated CD8 T cells, suggesting a role for the immune system in the anti-tumor phenotype. Using RNA-seq data, we identified transcriptomic alterations in the bone marrow following NTN. Moreover, using scRNA-seq of white blood cells following NTN we found these transcriptomic alterations were reflected in γδ T cells and neutrophils. This is the first study to show that glomerular immune injury changes the transcription of cells in the bone marrow to advance anti-tumor activity. Our study highlights the pivotal role of BM-mediated transcriptional alterations underlying the enhanced host immunity to tumor growth.