bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-differences in the longitudinal recovery of neuromuscular function in COVID-19 associated acute respiratory distress syndrome survivors
Authors: Lulic-Kuryllo Tea , Benedini Marco , Cogliati Marta , Cudicio Alessandro , Guarneri Bruno , Gazzina Stefano , Piva Simone , Latronico Nicola , Orizio Claudio , Negro Francesco
Published: June 2023

Introduction

Patients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection.

Methods

We performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle.

Results

We found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes.

Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge.

Discussion

Females infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation.
Epidemiology and risk factors of respiratory syncytial virus associated acute respiratory tract infection in hospitalized children younger than 5 years from Sri Lanka
Authors: Divarathna Maduja V. M. , Rafeek Rukshan A. M. , Morel Adrian J. , Aththanayake Chathuri , Noordeen Faseeha
Published: June 2023

Background

Respiratory syncytial virus (RSV) is the leading cause of acute respiratory tract infections (ARTI) and a major cause of morbidity and mortality in children worldwide.

Aim

This study aimed to describe the prevalence and seasonal patterns of RSV and to determine the actual and predictive association of RSV-associated ARTI and clinical, socio-demographic, and climatic risk factors in children < 5 years.

Methods

Nasopharyngeal aspirates were collected from 500 children < 5 years admitted to the Kegalle General Hospital, Sri Lanka between May 2016 to July 2018. RSV and RSV subtypes were detected using immunofluorescence assay and real time RT-PCR, respectively. Descriptive and inferential statistics were done for the data analysis using Chi-square, Fisher’s exact, Kruskal–Wallis test, and multiple binary logistic regression in the statistical package for social sciences (SPSS), version 16.0.

Results

Prevalence of RSV-associated ARTI was 28% in children < 5 years. Both RSV subtypes were detected throughout the study period. RSV-B was the dominant subtype detected with a prevalence of 72.14%. RSV infection in general caused severe respiratory disease leading to hypoxemia. Compared to RSV-B, RSV-A infection had more symptoms leading to hypoxemia. Factors increasing the risk of contracting RSV infection included number of people living (n > 6), having pets at home and inhaling toxic fumes. The inferential analysis predicts RSV infection in children < 5 years with ARTI, with a 75.4% probability with clinical and socio-demographic characteristics like age < 1 year, fever for > 4 days, cough, conjunctivitis, stuffiness, fatigue, six or more people at home, having pets at home and inhaling toxic fumes. Climatic factors like increases in temperature (°C), wind speed (Km/h), wind gust (Km/h), rainfall (mm) and atmospheric pressure (mb) showed a strong correlation with the RSV infection in children.
N-terminal lid swapping contributes to the substrate specificity and activity of thermophilic lipase TrLipE
Authors: Fang Yakun , Liu Fan , Shi Yi , Yang Ting , Xin Yu , Gu Zhenghua , Shi Guiyang , Zhang Liang
Published: June 2023

TrLipE is a thermophilic lipase that has potential commercial applications because of its catalytic ability under extreme conditions. Consistent with most lipases, the lid of TrLipE is located over the catalytic pocket, controls the substrate channel to the active center, and regulates the substrate specificity, activity, and stability of the enzyme through conformational changes. TrLipE from Thermomicrobium roseum has potential industrial applications, which is hindered by its weak enzymatic activity. Here, 18 chimeras (TrL1-TrL18) were reconstructed by N-terminal lid swapping between TrLipE and structurally similar enzymes. The results showed that the chimeras had a similar pH range and optimum pH as wild TrLipE but a narrower temperature range of 40–80°C, and TrL17 and the other chimeras showed lower optimum temperatures of 70°C and 60°C, respectively. In addition, the half-lives of the chimeras were lower than those of TrLipE under optimum temperature conditions. Molecular dynamics simulations indicated that chimeras had high RMSD, RMSF, and B-factor values. When p-nitrophenol esters with different chains were used as substrates, compared with TrLipE, most of the chimeras had a low Km and high kcat value. The chimeras TrL2, TrL3, TrL17, and TrL18 could specifically catalyze the substrate 4-nitrophenyl benzoate, with TrL17 showing the highest kcat/Km value of 363.88 ± 15.83 L⋅min–1⋅mmol–1. Mutants were then designed by investigating the binding free energies of TrL17 and 4-nitrophenyl benzoate. The results indicated that single, double, and triple substitution variants (M89W and I206N; E33W/I206M and M89W/I206M; and M89W/I206M/L21I and M89W/I206N/L21I, respectively) presented approximately 2- to 3-fold faster catalysis of 4-nitrophenyl benzoate than the wild TrL17. Our observations will facilitate the development of the properties and industrial applications of TrLipE.
Whole-body microbiota of newborn calves and their response to prenatal vitamin and mineral supplementation
Authors: Luecke Sarah M. , Holman Devin B. , Schmidt Kaycie N. , Gzyl Katherine E. , Hurlbert Jennifer L. , Menezes Ana Clara B. , Bochantin Kerri A. , Kirsch James D. , Baumgaertner Friederike , Sedivec Kevin K. , Swanson Kendall C. , Dahlen Carl R. , Amat Samat
Published: June 2023

Early life microbial colonization and factors affecting colonization patterns are gaining interest due to recent developments suggesting that early life microbiome may play a role in Developmental Origins of Health and Disease. In cattle, limited information exists on the early microbial colonization of anatomical sites involved in bovine health beyond the gastrointestinal tract. Here, we investigated 1) the initial microbial colonization of seven different anatomical locations in newborn calves and 2) whether these early life microbial communities and 3) serum cytokine profiles are influenced by prenatal vitamin and mineral (VTM) supplementation. Samples were collected from the hoof, liver, lung, nasal cavity, eye, rumen (tissue and fluid), and vagina of beef calves that were born from dams that either received or did not receive VTM supplementation throughout gestation (n = 7/group). Calves were separated from dams immediately after birth and fed commercial colostrum and milk replacer until euthanasia at 30 h post-initial colostrum feeding. The microbiota of all samples was assessed using 16S rRNA gene sequencing and qPCR. Calf serum was subjected to multiplex quantification of 15 bovine cytokines and chemokines. Our results indicated that the hoof, eye, liver, lung, nasal cavity, and vagina of newborn calves were colonized by site-specific microbiota, whose community structure differed from the ruminal-associated communities (0.64 ≥ R2 ≥ 0.12, p ≤ 0.003). The ruminal fluid microbial community was the only one that differed by treatment (p < 0.01). However, differences (p < 0.05) by treatment were detected in microbial richness (vagina); diversity (ruminal tissue, fluid, and eye); composition at the phylum and genus level (ruminal tissue, fluid, and vagina); and in total bacterial abundance (eye and vagina). From serum cytokines evaluated, concentration of chemokine IP-10 was greater (p = 0.02) in VTM calves compared to control calves. Overall, our results suggest that upon birth, the whole-body of newborn calves are colonized by relatively rich, diverse, and site-specific bacterial communities. Noticeable differences were observed in ruminal, vaginal, and ocular microbiota of newborn calves in response to prenatal VTM supplementation. These findings can derive future hypotheses regarding the initial microbial colonization of different body sites, and on maternal micronutrient consumption as a factor that may influence early life microbial colonization.
Identification of diagnostic biomarkers in Alzheimer’s disease by integrated bioinformatic analysis and machine learning strategies
Authors: Jin Boru , Cheng Xiaoqin , Fei Guoqiang , Sang Shaoming , Zhong Chunjiu
Published: June 2023

Background

Alzheimer’s disease (AD) is the most prevalent form of dementia, and is becoming one of the most burdening and lethal diseases. More useful biomarkers for diagnosing AD and reflecting the disease progression are in need and of significance.

Methods

The integrated bioinformatic analysis combined with machine-learning strategies was applied for exploring crucial functional pathways and identifying diagnostic biomarkers of AD. Four datasets (GSE5281, GSE131617, GSE48350, and GSE84422) with samples of AD frontal cortex are integrated as experimental datasets, and another two datasets (GSE33000 and GSE44772) with samples of AD frontal cortex were used to perform validation analyses. Functional Correlation enrichment analyses were conducted based on Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the Reactome database to reveal AD-associated biological functions and key pathways. Four models were employed to screen the potential diagnostic biomarkers, including one bioinformatic analysis of Weighted gene co-expression network analysis (WGCNA)and three machine-learning algorithms: Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE) and random forest (RF) analysis. The correlation analysis was performed to explore the correlation between the identified biomarkers with CDR scores and Braak staging.

Results

The pathways of the immune response and oxidative stress were identified as playing a crucial role during AD. Thioredoxin interacting protein (TXNIP), early growth response 1 (EGR1), and insulin-like growth factor binding protein 5 (IGFBP5) were screened as diagnostic markers of AD. The diagnostic efficacy of TXNIP, EGR1, and IGFBP5 was validated with corresponding AUCs of 0.857, 0.888, and 0.856 in dataset GSE33000, 0.867, 0.909, and 0.841 in dataset GSE44770. And the AUCs of the combination of these three biomarkers as a diagnostic tool for AD were 0.954 and 0.938 in the two verification datasets.

Conclusion

The pathways of immune response and oxidative stress can play a crucial role in the pathogenesis of AD. TXNIP, EGR1, and IGFBP5 are useful biomarkers for diagnosing AD and their mRNA level may reflect the development of the disease by correlation with the CDR scores and Breaking staging.
Case report: Anti septin-5-encephalitis as a treatable cause of cerebellar ataxia and psychiatric symptoms
Authors: Wischmann Johannes , Borowski Kathrin , Havla Joachim , Thaler Franziska S. , Winkler Tobias , Jung Tobias , Straube Andreas , Masouris Ilias
Published: June 2023

Objectives

Anti-septin-5 encephalitis is a rare disease with only few published cases, mainly based on retrospective CSF and serum analyses. Predominant symptoms are cerebellar ataxia and oculomotor abnormalities. Due to the rareness of the disease, treatment recommendations are scarce. Herein, we prospectively describe the clinical course of a female patient with anti-septin-5 encephalitis.

Methods

We describe diagnostic workup, treatment and follow-up of a 54-year-old patient presenting with vertigo, unsteady gait, lack of drive and behavioral changes.

Results

Clinical examination revealed severe cerebellar ataxia, saccadic smooth pursuit, upbeat-nystagmus, and dysarthria. Additionally, the patient presented with a depressive syndrome. MRI of the brain and spinal cord were normal. CSF analysis showed lymphocytic pleocytosis (11 cells/μl). Extensive antibody testing revealed anti septin-5 IgG in both CSF and serum without coexisting anti-neuronal antibodies. PET/CT detected no signs of malignancy. Corticosteroids, plasma exchange, and rituximab led to transient clinical improvement followed by relapse. Re-applied treatment with plasma exchange followed by bortezomib resulted in moderate but sustained clinical improvement.

Discussion

Anti septin-5 encephalitis represents a rare but treatable and therefore relevant differential diagnosis in patients with cerebellar ataxia. Psychiatric symptoms can be observed in anti septin-5 encephalitis. Immunosuppressive treatment including bortezomib is moderately effective.
Chromogranin B (CHGB) is dimorphic and responsible for dominant anion channels delivered to cell surface via regulated secretion
Authors: Yadav Gaya P. , Wang Haiyuan , Ouwendijk Joke , Cross Stephen , Wang Qiaochu , Qin Feng , Verkade Paul , Zhu Michael X. , Jiang Qiu-Xing
Published: June 2023

Regulated secretion is conserved in all eukaryotes. In vertebrates granin family proteins function in all key steps of regulated secretion. Phase separation and amyloid-based storage of proteins and small molecules in secretory granules require ion homeostasis to maintain their steady states, and thus need ion conductances in granule membranes. But granular ion channels are still elusive. Here we show that granule exocytosis in neuroendocrine cells delivers to cell surface dominant anion channels, to which chromogranin B (CHGB) is critical. Biochemical fractionation shows that native CHGB distributes nearly equally in soluble and membrane-bound forms, and both reconstitute highly selective anion channels in membrane. Confocal imaging resolves granular membrane components including proton pumps and CHGB in puncta on the cell surface after stimulated exocytosis. High pressure freezing immuno-EM reveals a major fraction of CHGB at granule membranes in rat pancreatic β-cells. A cryo-EM structure of bCHGB dimer of a nominal 3.5 Å resolution delineates a central pore with end openings, physically sufficient for membrane-spanning and large single channel conductance. Together our data support that CHGB-containing (CHGB+) channels are characteristic of regulated secretion, and function in granule ion homeostasis near the plasma membrane or possibly in other intracellular processes.
Ameliorative effects of Kyung-Ok-Ko and its mixture with Pueraria lobata Ohwi on postmenopausal osteoporosis by promoting phytoestrogenic activity in rats
Authors: Kim Minseo , Kim Hyun-Sook , Oh Joohee , Zhou Xiangqin , Ahn SongHee , Koo Youngtae , Kim Hyun-Jung , Jang Jiwon
Published: June 2023

Introduction

Kyung-Ok-Ko (KOK) is a popular traditional medicine used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms in Asia. Pueraria lobata Ohwi (P. lobata) is rich in isoflavones and has been traditionally used in combination with other herbs to produce synergistic and pharmaceutical effects via a multi-target approach for disease treatment. We aimed to investigate the phytoestrogenic effects of KOK extract against postmenopausal symptoms in ovariectomized (OVX) rats and confirm its efficacy by mixing KOK and P. lobata extracts.

Methods

OVX rats were daily oral administrated with KOK and KOK + P. lobata mixture extracts (300–400 mg/kg) and their body weight and tail temperature were monitored for 12 weeks. The biochemical parameters, estradiol levels, and bone turnover markers were measured in the serum samples. Moreover, the estrogen receptor, ER-α and ER-β expression in the uterus and the uterus morphology were evaluated. AMPK, ATG1/ULK1, and mTOR protein expression in the liver were assessed.

Results

The 12-week treatment with KOK and KOK + P. lobata mixture extracts did not cause liver damage or hormonal changes in the OVX rats. The treatments reduced the high lipid accumulation-related body weight gain and the tail temperature increase that was induced by ovariectomy. Further, it exhibited protective effects against hyperlipidemia and osteoporosis. No significant difference was observed in uterine weight compared to the OVX-treated group, while endometrial thickness reduction inhibition was observed due to ovariectomy. Bone mineral density (BMD) and serum osteocalcin levels, which decreased in OVX rats, increased with both treatments. Western blotting analysis showed that ER-α and ER-β were not expressed in the treated rats, whereas these proteins were expressed in Sham-operated rats. No significant differences in the phosphorylation of AMPK were observed; however, the ATG1/ULK1 and mTOR protein phosphorylation levels were upregulated and downregulated in the treated rats compared to those of OVX rats, respectively.

Conclusion

This is the first in vivo study observing the efficacy and synergistic effects of the mixture of KOK and P. lobata. Our results suggest the potential of KOK and KOK + P. lobata mixture as an alternative therapy for alleviating menopausal symptoms.
Thermal ablation as an alternative to liver transplantation for hepatocellular carcinoma with clinically significant portal hypertension: propensity score matching study
Authors: Long Yinglin , Yang Zhou , Zeng Qingjing , Liu Zhongqi , Xu Erjiao , He Xuqi , Yuan Lianxiong , Fu Binsheng , Li Kai
Published: June 2023

Purpose

The objectives were to investigate the safety and efficacy of thermal ablation as an alternative to liver transplantation for hepatocellular carcinoma patients with clinically significant portal hypertension (CSPH).

Materials and Methods

From July 2016 to September 2019, hepatocellular carcinoma patients with CSPH treated by liver transplantation (N=37) or thermal ablation (N=114) were enrolled. Cumulative intrahepatic recurrence, overall survival and major complications were compared by propensity score matching.

Results

In the two matched groups, the 1-, 2-, and 3-year intrahepatic recurrence rates for the ablation group (22.3%, 50.0%, and 50.0%, respectively) were significantly higher than those for the transplantation group (4.5%, 4.5%, and 4.5%, respectively) (P=0.016). The 1-, 2-, and 3-year overall survival rates were comparable between the two groups [96.1%, 88.7%, and 88.7%, respectively (ablation group) vs. 84.6%, 76.2%, and 76.2%, respectively (transplantation group)] (P=0.07). The major complication rate for the ablation group [4.8% (3/62)] was significantly lower than that for the transplantation group [36.0% (9/25)] (P<0.001).

Conclusions

Thermal ablation is a safe and effective alternative for hepatocellular carcinoma patients with CSPH.
Individual risk and prognostic value prediction by machine learning for distant metastasis in pulmonary sarcomatoid carcinoma: a large cohort study based on the SEER database and the Chinese population
Authors: Yi Xinglin , Xu Wenhao , Tang Guihua , Zhang Lingye , Wang Kaishan , Luo Hu , Zhou Xiangdong
Published: June 2023

Background

This study aimed to develop diagnostic and prognostic models for patients with pulmonary sarcomatoid carcinoma (PSC) and distant metastasis (DM).

Methods

Patients from the Surveillance, Epidemiology, and End Results (SEER) database were divided into a training set and internal test set at a ratio of 7 to 3, while those from the Chinese hospital were assigned to the external test set, to develop the diagnostic model for DM. Univariate logistic regression was employed in the training set to screen for DM-related risk factors, which were included into six machine learning (ML) models. Furthermore, patients from the SEER database were randomly divided into a training set and validation set at a ratio of 7 to 3 to develop the prognostic model which predicts survival of patients PSC with DM. Univariate and multivariate Cox regression analyses have also been performed in the training set to identify independent factors, and a prognostic nomogram for cancer-specific survival (CSS) for PSC patients with DM.

Results

For the diagnostic model for DM, 589 patients with PSC in the training set, 255 patients in the internal and 94 patients in the external test set were eventually enrolled. The extreme gradient boosting (XGB) algorithm performed best on the external test set with an area under the curve (AUC) of 0.821. For the prognostic model, 270 PSC patients with DM in the training and 117 patients in the test set were enrolled. The nomogram displayed precise accuracy with AUC of 0.803 for 3-month CSS and 0.869 for 6-month CSS in the test set.

Conclusion

The ML model accurately identified individuals at high risk for DM who needed more careful follow-up, including appropriate preventative therapeutic strategies. The prognostic nomogram accurately predicted CSS in PSC patients with DM.
Impact of DNA damage repair alterations on prostate cancer progression and metastasis
Authors: Lukashchuk Natalia , Barnicle Alan , Adelman Carrie A. , Armenia Joshua , Kang Jinyu , Barrett J. Carl , Harrington Elizabeth A.
Published: June 2023

Prostate cancer is among the most common diseases worldwide. Despite recent progress with treatments, patients with advanced prostate cancer have poor outcomes and there is a high unmet need in this population. Understanding molecular determinants underlying prostate cancer and the aggressive phenotype of disease can help with design of better clinical trials and improve treatments for these patients. One of the pathways often altered in advanced prostate cancer is DNA damage response (DDR), including alterations in BRCA1/2 and other homologous recombination repair (HRR) genes. Alterations in the DDR pathway are particularly prevalent in metastatic prostate cancer. In this review, we summarise the prevalence of DDR alterations in primary and advanced prostate cancer and discuss the impact of alterations in the DDR pathway on aggressive disease phenotype, prognosis and the association of germline pathogenic1 alterations in DDR genes with risk of developing prostate cancer.
Modality-based attention and dual-stream multiple instance convolutional neural network for predicting microvascular invasion of hepatocellular carcinoma
Authors: Li Zhi , Wang Yutao , Zhu Yuzhao , Xu Jiafeng , Wei Jinzhu , Xie Jiang , Zhang Jian
Published: June 2023

Background and purpose

The presence of microvascular invasion (MVI) is a crucial indicator of postoperative recurrence in patients with hepatocellular carcinoma (HCC). Detecting MVI before surgery can improve personalized surgical planning and enhance patient survival. However, existing automatic diagnosis methods for MVI have certain limitations. Some methods only analyze information from a single slice and overlook the context of the entire lesion, while others require high computational resources to process the entire tumor with a three-dimension (3D) convolutional neural network (CNN), which could be challenging to train. To address these limitations, this paper proposes a modality-based attention and dual-stream multiple instance learning(MIL) CNN.

Materials and methods

In this retrospective study, 283 patients with histologically confirmed HCC who underwent surgical resection between April 2017 and September 2019 were included. Five magnetic resonance (MR) modalities including T2-weighted, arterial phase, venous phase, delay phase and apparent diffusion coefficient images were used in image acquisition of each patient. Firstly, Each two-dimension (2D) slice of HCC magnetic resonance image (MRI) was converted into an instance embedding. Secondly, modality attention module was designed to emulates the decision-making process of doctors and helped the model to focus on the important MRI sequences. Thirdly, instance embeddings of 3D scans were aggregated into a bag embedding by a dual-stream MIL aggregator, in which the critical slices were given greater consideration. The dataset was split into a training set and a testing set in a 4:1 ratio, and model performance was evaluated using five-fold cross-validation.

Results

Using the proposed method, the prediction of MVI achieved an accuracy of 76.43% and an AUC of 74.22%, significantly surpassing the performance of the baseline methods.

Conclusion

Our modality-based attention and dual-stream MIL CNN can achieve outstanding results for MVI prediction.
Case Report: Longitudinal monitoring of clonal evolution by circulating tumor DNA for resistance to anti-EGFR antibody in a case of metastatic colorectal cancer
Authors: Sagawa Tamotsu , Sato Yasushi , Hirakawa Masahiro , Hamaguchi Kyoko , Tamura Fumito , Nagashima Hiroyuki , Fujikawa Koshi , Okamoto Koichi , Kawano Yutaka , Sogabe Masahiro , Miyamoto Hiroshi , Takayama Tetsuji
Published: June 2023

Background

Treatment with anti-EGFR antibody has been shown to prolong survival in patients with RAS wild-type metastatic colorectal cancer (mCRC). However, even patients who initially respond to anti-EGFR antibody therapy, almost without exception, develop resistance to the therapy and then fail to respond. Secondary mutations in the mitogen-activated protein (MAPK) signaling pathway (mainly in NRAS and BRAF) have been implicated in anti-EGFR resistance. However, the process by which resistant clones develop during therapy has not been elucidated, and considerable intrapatient and interpatient heterogeneity exists. Circulating tumor DNA (ctDNA) testing has recently allowed the noninvasive detection of heterogeneous molecular alterations that underlie the evolution of resistance to anti-EGFR. In this report, we describe our observation of genomic alterations in KRAS and NRAS in a patient with acquired resistance to anti-EGFR antibody drugs by tracking clonal evolution using serial ctDNA anaylsis.

Case presentation

A 54-year-old woman was initially diagnosed with sigmoid colon cancer with multiple liver metastases. After receiving first-line mFOLFOX + cetuximab, second-line FOLFIRI + ramucirumab, third-line trifluridine/tipiracil + bevacizumab, fourth-line regorafenib, and fifth-line CAPOX + bevacizumab, she was rechallenged with CPT-11 + cetuximab. The best response to anti-EGFR rechallenge therapy was a partial response. RAS in the ctDNA was assessed during treatment. The RAS status changed from wild type to mutant type, back to wild type, and again to mutant type (NRAS/KRAS codon 61) during the course of treatment.

Conclusion

In this report, tracking of ctDNA allowed us to describe clonal evolution in a case in which we observed genomic alterations in KRAS and NRAS in a patient who acquired resistance to anti-EGFR antibody drugs during treatment. It is reasonable to consider repeat molecular interrogation during progression in patients with mCRC by using ctDNA analysis, which could help to identify patients who may benefit from a rechallenge strategy.
Pain sensitivity differs between dog breeds but not in the way veterinarians believe
Authors: Caddiell Rachel M. P. , Cunningham Rachael M. , White Philip A. , Lascelles B. Duncan X. , Gruen Margaret E.
Published: June 2023

Background

Veterinarians hold distinct breed-specific pain sensitivity beliefs that differ from the general public but are highly consistent with one another. This is remarkable as there is no current scientific evidence for biological differences in pain sensitivity across dog breeds. Therefore, the present study evaluated whether pain sensitivity thresholds differ across a set of dog breeds and, if so, whether veterinarians’ pain sensitivity ratings explain these differences or whether these ratings are attributed to behavioral characteristics.

Methods

Pain sensitivity thresholds [using quantitative sensory testing (QST) methods] and canine behaviors (using owner questionnaires and emotional reactivity tests) were prospectively measured across selected dog breeds. Adult, healthy dogs from 10 dog breeds/breed types were recruited, representing breeds subjectively rated by veterinarians as high (chihuahua, German shepherd, Maltese, Siberian husky), average (border collie, Boston terrier, Jack Russell terrier), or low (golden retriever, pitbull, Labrador retriever) pain sensitivity. A final sample of 149 dogs was included in statistical analyses.

Results

Veterinarians’ pain sensitivity ratings provided a minimal explanation for pain sensitivity thresholds measured using QST in dogs; however, dog breeds did differ in their pain sensitivity thresholds across the QST methods evaluated. Breed differences were observed for some aspects of emotional reactivity tests; however, these behavioral differences did not explain the differences in pain sensitivity thresholds found. Veterinarians’ pain sensitivity ratings were positively associated with dog approach scores for the disgruntled stranger test suggesting that the way dogs greet strangers may be a factor influencing veterinarians’ ratings of pain sensitivity across dog breeds.

Conclusions and clinical relevance

Overall, these findings highlight a need to investigate biological mechanisms that may explain breed differences in pain sensitivity because this may inform pain management recommendations. Further, future research should focus on when and how these breed-specific pain sensitivity beliefs developed in veterinarians, as veterinarians’ beliefs could impact the recognition and treatment of pain for canine patients.
Long-term follow-up in common variable immunodeficiency: the pediatric-onset and adult-onset landscape
Authors: Carrabba Maria , Salvi Marco , Baselli Lucia Augusta , Serafino Serena , Zarantonello Marina , Trombetta Elena , Pietrogrande Maria Cristina , Fabio Giovanna , Dellepiane Rosa Maria
Published: June 2023

Introduction

The primary aim of this study is to investigate the evolution of the clinical and laboratory characteristics during the time in a longitudinal cohort of pediatric-onset and adult-onset Common Variable Immunodeficiency (CVID) patients in order to identify early predictive features of the disease and immune dysregulation complications.

Methods

This is a retrospective-prospective monocentric longitudinal study spanning from 1984 to the end of 2021. The data of pediatric-onset vs. adult-onset patients have been compared for immunological features and for infectious and non-infectious complications assessed at diagnosis and follow-up.

Results

Seventy-three CVID patients have been enrolled, with a mean of 10.0 years (SD ± 8.17) of prospective follow-up. At diagnosis, infections were observed in 89.0% of patients and immune dysregulation in 42.5% of patients. At diagnosis, 38.6% of pediatric-onset and 20.7% of adult-onset patients presented with only infections. Polyclonal lymphoid proliferation (62.1%) and autoimmunity (51.7%) were more prevalent in the adult-onset than in the pediatric-onset group (polyclonal lymphoid proliferation 52.3% and autoimmunity 31.8%, respectively). Enteropathy was present in 9.1% of pediatric-onset and 17.2% of adult-onset patients. The prevalence of polyclonal lymphoid proliferation increased during follow-up more in pediatric-onset patients (diagnosis 52.3%—follow-up 72.7%) than in adult-onset patients (diagnosis 62.1%—follow-up 72.7%). The cumulative risk to develop immune dysregulation increases according to the time of disease and the time of diagnostic delay. At the same age, pediatric-onset patients have roughly double the risk of having a complication due to immune dysregulation than adult-onset patients, and it increases with diagnostic delay. The analysis of lymphocyte subsets in the pediatric-onset group showed that CD21 low B cells at diagnosis may be a reliable prognostic marker for the development of immune dysregulation during follow-up, as the ROC curve analysis showed (AUC = 0.796). In the adult-onset group, the percentage of transitional B cells measured at diagnosis showed a significant accuracy (ROC AUC = 0.625) in identifying patients at risk of developing immune dysregulation.

Discussion

The longitudinal evaluation of lymphocyte subsets combined with clinical phenotype can improve the prediction of lymphoid proliferation and allow experts to achieve early detection and better management of such complex disorder.
Improving localization accuracy for non-invasive automated early left ventricular origin localization approach
Authors: Zhou Shijie , Wang Raymond , Seagren Avery , Emmert Noah , Warren James W. , MacInnis Paul J. , AbdelWahab Amir , Sapp John L.
Published: June 2023

Background: We previously developed a non-invasive approach to localize the site of early left ventricular activation origin in real time using 12-lead ECG, and to project the predicted site onto a generic LV endocardial surface using the smallest angle between two vectors algorithm (SA).

Objectives: To improve the localization accuracy of the non-invasive approach by utilizing the K-nearest neighbors algorithm (KNN) to reduce projection errors.

Methods: Two datasets were used. Dataset #1 had 1012 LV endocardial pacing sites with known coordinates on the generic LV surface and corresponding ECGs, while dataset #2 included 25 clinically-identified VT exit sites and corresponding ECGs. The non-invasive approach used “population” regression coefficients to predict the target coordinates of a pacing site or VT exit site from the initial 120-m QRS integrals of the pacing site/VT ECG. The predicted site coordinates were then projected onto the generic LV surface using either the KNN or SA projection algorithm.

Results: The non-invasive approach using the KNN had a significantly lower mean localization error than the SA in both dataset #1 (9.4 vs. 12.5 mm, p < 0.05) and dataset #2 (7.2 vs. 9.5 mm, p < 0.05). The bootstrap method with 1,000 trials confirmed that using KNN had significantly higher predictive accuracy than using the SA in the bootstrap assessment with the left-out sample (p < 0.05).

Conclusion: The KNN significantly reduces the projection error and improves the localization accuracy of the non-invasive approach, which shows promise as a tool to identify the site of origin of ventricular arrhythmia in non-invasive clinical modalities.
Hibernation and hemostasis
Authors: De Vrij Edwin L. , Bouma Hjalmar R. , Henning Robert H. , Cooper Scott T.
Published: June 2023

Hibernating mammals have developed many physiological adaptations to accommodate their decreased metabolism, body temperature, heart rate and prolonged immobility without suffering organ injury. During hibernation, the animals must suppress blood clotting to survive prolonged periods of immobility and decreased blood flow that could otherwise lead to the formation of potentially lethal clots. Conversely, upon arousal hibernators must be able to quickly restore normal clotting activity to avoid bleeding. Studies in multiple species of hibernating mammals have shown reversible decreases in circulating platelets, cells involved in hemostasis, as well as in protein coagulation factors during torpor. Hibernator platelets themselves also have adaptations that allow them to survive in the cold, while those from non-hibernating mammals undergo lesions during cold exposure that lead to their rapid clearance from circulation when re-transfused. While platelets lack a nucleus with DNA, they contain RNA and other organelles including mitochondria, in which metabolic adaptations may play a role in hibernator’s platelet resistance to cold induced lesions. Finally, the breakdown of clots, fibrinolysis, is accelerated during torpor. Collectively, these reversible physiological and metabolic adaptations allow hibernating mammals to survive low blood flow, low body temperature, and immobility without the formation of clots during torpor, yet have normal hemostasis when not hibernating. In this review we summarize blood clotting changes and the underlying mechanisms in multiple species of hibernating mammals. We also discuss possible medical applications to improve cold preservation of platelets and antithrombotic therapy.
Role of autophagy-related proteins ATG8f and ATG8h in the maintenance of autophagic activity in Arabidopsis roots under phosphate starvation
Authors: Lin Li-Yen , Chow Hong-Xuan , Chen Chih-Hao , Mitsuda Nobutaka , Chou Wen-Chun , Liu Tzu-Yin
Published: June 2023

Nutrient starvation-induced autophagy is a conserved process in eukaryotes. Plants defective in autophagy show hypersensitivity to carbon and nitrogen limitation. However, the role of autophagy in plant phosphate (Pi) starvation response is relatively less explored. Among the core autophagy-related (ATG) genes, ATG8 encodes a ubiquitin-like protein involved in autophagosome formation and selective cargo recruitment. The Arabidopsis thaliana ATG8 genes, AtATG8f and AtATG8h, are notably induced in roots under low Pi. In this study, we show that such upregulation correlates with their promoter activities and can be suppressed in the phosphate response 1 (phr1) mutant. Yeast one-hybrid analysis failed to attest the binding of the AtPHR1 transcription factor to the promoter regions of AtATG8f and AtATG8h. Dual luciferase reporter assays in Arabidopsis mesophyll protoplasts also indicated that AtPHR1 could not transactivate the expression of both genes. Loss of AtATG8f and AtATG8h leads to decreased root microsomal-enriched ATG8 but increased ATG8 lipidation. Moreover, atg8f/atg8h mutants exhibit reduced autophagic flux estimated by the vacuolar degradation of ATG8 in the Pi-limited root but maintain normal cellular Pi homeostasis with reduced number of lateral roots. While the expression patterns of AtATG8f and AtATG8h overlap in the root stele, AtATG8f is more strongly expressed in the root apex and root hair and remarkably at sites where lateral root primordia develop. We hypothesize that Pi starvation-induction of AtATG8f and AtATG8h may not directly contribute to Pi recycling but rely on a second wave of transcriptional activation triggered by PHR1 that fine-tunes cell type-specific autophagic activity.
A fast phenotype approach of 3D point clouds of Pinus massoniana seedlings
Authors: Zhou Honghao , Zhou Yang , Long Wei , Wang Bin , Zhou Zhichun , Chen Yue
Published: June 2023

The phenotyping of Pinus massoniana seedlings is essential for breeding, vegetation protection, resource investigation, and so on. Few reports regarding estimating phenotypic parameters accurately in the seeding stage of Pinus massoniana plants using 3D point clouds exist. In this study, seedlings with heights of approximately 15-30 cm were taken as the research object, and an improved approach was proposed to automatically calculate five key parameters. The key procedure of our proposed method includes point cloud preprocessing, stem and leaf segmentation, and morphological trait extraction steps. In the skeletonization step, the cloud points were sliced in vertical and horizontal directions, gray value clustering was performed, the centroid of the slice was regarded as the skeleton point, and the alternative skeleton point of the main stem was determined by the DAG single source shortest path algorithm. Then, the skeleton points of the canopy in the alternative skeleton point were removed, and the skeleton point of the main stem was obtained. Last, the main stem skeleton point after linear interpolation was restored, while stem and leaf segmentation was achieved. Because of the leaf morphological characteristics of Pinus massoniana, its leaves are large and dense. Even using a high-precision industrial digital readout, it is impossible to obtain a 3D model of Pinus massoniana leaves. In this study, an improved algorithm based on density and projection is proposed to estimate the relevant parameters of Pinus massoniana leaves. Finally, five important phenotypic parameters, namely plant height, stem diameter, main stem length, regional leaf length, and total leaf number, are obtained from the skeleton and the point cloud after separation and reconstruction. The experimental results showed that there was a high correlation between the actual value from manual measurement and the predicted value from the algorithm output. The accuracies of the main stem diameter, main stem length, and leaf length were 93.5%, 95.7%, and 83.8%, respectively, which meet the requirements of real applications.
Do the emotions of tourist agents contribute to improving the sustainable planning of a territory?
Authors: Robina-Ramírez Rafael , Leal-Solís Ana , Gallardo-Vázquez Dolores , Cabezas-Hernández Teresa
Published: June 2023

The sustainability of a territory is achieved through orderly, balanced and harmonious planning over time. Sustainable tourism planning must incorporate the emotions of interest groups. Based on a scale of negative and positive emotions that has already been validated, a participatory study of a qualitative nature has been developed with 118 hotel managers from the region of Extremadura, in the south-west of Spain. In addition, another quantitative research study has been carried out, using a longitudinal exploratory model analyzed in three phases throughout the years 2021 and 2022, using the SEM-PLS methodology. The objective is to detect if the II Tourism Plan (2021–2023) can influence the willingness of hotel managers to participate, and if this participation generates emotions that enrich the planning process of the tourist authorities. The results highlight the importance of completing decision making (cognitive part) with the measurement of emotions (sensitive part) of private agents to involve them in the planning process.
The effect of credibility assessment techniques on consistency and subsequent memory for the truth
Authors: Dianiska Rachel E. , Meissner Christian A.
Published: June 2023

Repeated interviews are common during an investigation, and perceived consistency between multiple statements is associated with an interviewee’s credibility. Furthermore, research has shown that the act of lying can affect a person’s memory for what truthfully occurred. The current study assessed the influence of lying on memory during initial and repeated interviews, as well as how an interviewer’s approach might affect between-statement consistency for true and false statements. Participants performed a scavenger hunt at two sets of buildings on a university campus and then were either dismissed or interviewed (with a Reverse Order instruction or a Structured Interview) about their activities. Participants chose one set to tell the truth about and then created a lie about activities in another area of campus that had not been visited. One week later, all participants provided a second free recall statement about their activities during the scavenger hunt, and then a final truthful description of both areas that were visited during the scavenger hunt. Truthfully rehearsed experiences were associated with more accurate recall of information learned during the scavenger hunt as well as more consistent and more detailed statements. The Structured Interview led to initially more detailed statements, but more inconsistencies in the form of omissions.
The relationship between underage initiation of selling sex and depression among female sex workers in Eswatini
Authors: Grosso Ashley , Fielding-Miller Rebecca , Matse Sindy , Sithole Bhekie , Baral Stefan
Published: June 2023

Background

Minors who sell sex are likely to have complex mental health needs that may persist into adulthood. This topic is understudied in sub-Saharan Africa. This study hypothesized that adult female sex workers in Eswatini who started selling sex as minors have a higher prevalence of depression than those who started as adults. We also examined correlates of depression and underage initiation of selling sex, including stigma and condom-related behaviors.

Methods

From October–December 2014, women aged 18 or older who sold sex in the past 12 months in Eswatini were recruited through venue-based sampling. Participants completed a survey including the 9-item Patient Health Questionnaire (PHQ-9) and a question about the age at which they first sold sex for money. T-tests, χ2 tests and multivariable logistic regression were used to assess associations.

Results

Overall, 43.1% of participants (332/770) had probable depression, and 16.6% (128/770) started selling sex as minors under the age of 18. Over half (55.5%, 71/128) of those who started selling sex as minors had depression. This was significantly higher than the 40.7% (261/642) prevalence of depression among participants who started selling sex as adults (p = 0.002). After adjusting for confounders, female sex workers who started selling sex as minors had higher odds of depression than those who started as adults (adjusted odds ratio [aOR] 1.70, 95% confidence interval 1.11–2.60).

Conclusion

Results highlight the need for trauma-informed and adolescent-friendly mental health services in settings free of stigma toward female sex workers in Eswatini.
The Agile Co-production and Evaluation framework for developing public health interventions, messaging and guidance
Authors: Yardley Lucy , Denford Sarah , Kamal Atiya , May Tom , Kesten Jo M. , French Clare E , Weston Dale , Rubin G. James , Horwood Jeremy , Hickman Matthew , Amlôt Richard , Oliver Isabel
Published: June 2023

A lesson identified from the COVID-19 pandemic is that we need to extend existing best practice for intervention development. In particular, we need to integrate (a) state-of-the-art methods of rapidly coproducing public health interventions and messaging to support all population groups to protect themselves and their communities with (b) methods of rapidly evaluating co-produced interventions to determine which are acceptable and effective. This paper describes the Agile Co-production and Evaluation (ACE) framework, which is intended to provide a focus for investigating new ways of rapidly developing effective interventions and messaging by combining co-production methods with large-scale testing and/or real-world evaluation. We briefly review some of the participatory, qualitative and quantitative methods that could potentially be combined and propose a research agenda to further develop, refine and validate packages of methods in a variety of public health contexts to determine which combinations are feasible, cost-effective and achieve the goal of improving health and reducing health inequalities.