bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen peroxide attenuates rhinovirus-induced anti-viral interferon secretion in sinonasal epithelial cells
Authors: Lee Sang Hag , Han Mun Soo , Lee Tae Hoon , Lee Da Bin , Park Jae Hyung , Lee Seung Hyeok , Kim Tae Hoon
Published: February 2023

Background

Altered innate defense mechanisms, including an imbalance between oxidants and antioxidants release, have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). The aim of this study is to investigate whether oxidative stress may attenuate the secretion of anti-viral interferons in human sinonasal mucosa.

Methods

The levels of H2O2 in nasal secretion were increased in patients with CRS with nasal polyps, compared with that of CRS patients without nasal polyps and control subjects. Normal sinonasal epithelial cells derived from healthy subjects were cultured under an air-liquid interface. The cultured cells were infected with rhinovirus 16 (RV 16) or treated with poly (I: C), TLR3 agonist, after being pretreated with an oxidative stressor, H2O2 or antioxidant, N-acetylcysteine (NAC). Thereafter, the expression levels of type I (IFN-β) and type III (IFN-λ1 and λ2) interferons and interferon-stimulated genes (ISGs) were evaluated with RT-qPCR, ELISA, and western blot.

Results

The data showed that the production of type I (IFN-β) and type III (IFN-λ1 and λ2) interferons and ISGs was upregulated in cells infected with RV 16 or treated with poly (I: C). However, their up-regulated expression was attenuated in cells pretreated with H2O2, but not inhibited in cells pretreated with NAC. In line with these data, the up-regulated expression of TLR3, RIG-1, MDA5, and IRF3 was reduced in cells pretreated with H2O2, but not attenuated in cells treated with NAC. Furthermore, cells transfected with Nrf2 siRNA showed decreased secretion of anti-viral interferons whereas sulforaphane treatment enhanced the secretory capacity of antiviral interferons.

Conclusions

These results suggest that the production of RV16-induced antiviral interferons may be attenuated by oxidative stress.
An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway
Authors: Trezise Stephanie , Kong Isabella Y. , Hawkins Edwin D. , Herold Marco J. , Willis Simon N. , Nutt Stephen L.
Published: February 2023

Background

Humoral immunity depends on the differentiation of B cells into antibody secreting cells (ASCs). Excess or inappropriate ASC differentiation can lead to antibody-mediated autoimmune diseases, while impaired differentiation results in immunodeficiency.

Methods

We have used CRISPR/Cas9 technology in primary B cells to screen for regulators of terminal differentiation and antibody production.

Results

We identified several new positive (Sec61a1, Hspa5) and negative (Arhgef18, Pold1, Pax5, Ets1) regulators that impacted on the differentiation process. Other genes limited the proliferative capacity of activated B cells (Sumo2, Vcp, Selk). The largest number of genes identified in this screen (35) were required for antibody secretion. These included genes involved in endoplasmic reticulum-associated degradation and the unfolded protein response, as well as post-translational protein modifications.

Discussion

The genes identified in this study represent weak links in the antibody-secretion pathway that are potential drug targets for antibody-mediated diseases, as well as candidates for genes whose mutation results in primary immune deficiency.
Preventive effects of Mycobacterium tuberculosis DNA vaccines on the mouse model with latent tuberculosis infection
Authors: Liang Yan , Li Xiaoping , Yang Yourong , Xiao Li , Liang Yumei , Mi Jie , Xue Yong , Gong Wenping , Wang Lan , Wang Jie , Zhang Junxian , Shi Yingchang , Peng Bizhen , Chen Xiaoyang , Zhao Weiguo , Wu Xueqiong
Published: February 2023

Background

About a quarter of the world’s population with latent tuberculosis infection (LTBI) are the main source of active tuberculosis. Bacillus Calmette Guerin (BCG) cannot effectively control LTBI individuals from developing diseases. Latency-related antigens can induce T lymphocytes of LTBI individuals to produce higher IFN-γ levels than tuberculosis patients and normal subjects. Herein, we firstly compared the effects of M. tuberculosis (MTB) ag85ab and 7 latent DNA vaccines on clearing latent MTB and preventing its activation in the mouse LTBI model.

Methods

A mouse LTBI model was established, and then immunized respectively with PBS, pVAX1 vector, Vaccae vaccine, ag85ab DNA and 7 kinds of latent DNAs (including rv1733c, rv2660c, rv1813c, rv2029c, rv2628, rv2659c and rv3407) for three times. The mice with LTBI were injected with hydroprednisone to activate the latent MTB. Then, the mice were sacrificed for the bacterial count, histopathological examination, and immunological evaluation.

Results

Using chemotherapy made the MTB latent in the infected mice, and then using hormone treatment reactivated the latent MTB, indicating that the mouse LTBI model was successfully established. After the mouse LTBI model was immunized with the vaccines, the lung colony-forming units (CFUs) and lesion degree of mice in all vaccines group were significantly decreased than those in the PBS group and vector group (P<0.0001, P<0.05). These vaccines could induce antigen-specific cellular immune responses. The number of IFN-γ effector T cells spots secreted by spleen lymphocytes in the ag85ab DNA group was significantly increased than those in the control groups (P<0.05). In the splenocyte culture supernatant, IFN-γ and IL-2 levels in the ag85ab, rv2029c, and rv2659c DNA groups significantly increased (P<0.05), and IL-17A levels in ag85ab and rv2659c DNA groups also significantly increased (P<0.05). Compared with the PBS and vector groups, the proportion of CD4+CD25+FOXP3+ regulatory T cells in spleen lymphocytes of ag85ab, rv2660c, rv2029c, and rv3407 DNA groups were significantly reduced (P<0.05).

Conclusions

MTB ag85ab and 7 kinds of latent DNA vaccines showed immune preventive efficacies on a mouse model of LTBI, especially the rv2659c, and rv1733c DNA. Our findings will provide candidates for the development of new multi-stage vaccines against TB.
Immune checkpoint inhibitors and Chimeric Antigen Receptor (CAR)-T cell therapy: Potential treatment options against Testicular Germ Cell Tumors
Authors: Schepisi Giuseppe , Gianni Caterina , Cursano Maria Concetta , Gallà Valentina , Menna Cecilia , Casadei Chiara , Bleve Sara , Lolli Cristian , Martinelli Giovanni , Rosti Giovanni , De Giorgi Ugo
Published: February 2023

Germ cell tumors (GCTs) represent a heterogeneous neoplasm family affecting gonads and rarely occurring in extragonadal areas. Most of patients have a good prognosis, often even in the presence of metastatic disease; however, in almost 15% of cases, tumor relapse and platinum resistance are the main challenges. Thus, novel treatment strategies with both improved antineoplastic activity and minor treatment-related adverse events compared with platinum are really expected. In this context, the development and the high activity demonstrated by immune checkpoint inhibitors in solid tumors and, subsequently, the interesting results obtained from the use of chimeric antigen receptor (CAR-) T cell therapy in hematological tumors, have stimulated research in this direction also in GCTs. In this article, we will analyze the molecular mechanisms underlying the immune action in the development of GCTs, and we will report the data from the studies that tested the new immunotherapeutic approaches in these neoplasms.
Moving away from lexicalism in psycho- and neuro-linguistics
Authors: Krauska Alexandra , Lau Ellen
Published: February 2023

In standard models of language production or comprehension, the elements which are retrieved from memory and combined into a syntactic structure are “lemmas” or “lexical items.” Such models implicitly take a “lexicalist” approach, which assumes that lexical items store meaning, syntax, and form together, that syntactic and lexical processes are distinct, and that syntactic structure does not extend below the word level. Across the last several decades, linguistic research examining a typologically diverse set of languages has provided strong evidence against this approach. These findings suggest that syntactic processes apply both above and below the “word” level, and that both meaning and form are partially determined by the syntactic context. This has significant implications for psychological and neurological models of language processing as well as for the way that we understand different types of aphasia and other language disorders. As a consequence of the lexicalist assumptions of these models, many kinds of sentences that speakers produce and comprehend—in a variety of languages, including English—are challenging for them to account for. Here we focus on language production as a case study. In order to move away from lexicalism in psycho- and neuro-linguistics, it is not enough to simply update the syntactic representations of words or phrases; the processing algorithms involved in language production are constrained by the lexicalist representations that they operate on, and thus also need to be reimagined. We provide an overview of the arguments against lexicalism, discuss how lexicalist assumptions are represented in models of language production, and examine the types of phenomena that they struggle to account for as a consequence. We also outline what a non-lexicalist alternative might look like, as a model that does not rely on a lemma representation, but instead represents that knowledge as separate mappings between (a) meaning and syntax and (b) syntax and form, with a single integrated stage for the retrieval and assembly of syntactic structure. By moving away from lexicalist assumptions, this kind of model provides better cross-linguistic coverage and aligns better with contemporary syntactic theory.
First insight into how stress exposure triggers Vibrio harveyi recipient successful conjugation
Authors: Deng Yiqin , Gao Si’ao , Xu Liwen , Cheng Changhong , Ma Hongling , Feng Juan
Published: February 2023

Conjugation is the most common horizontal gene transfer (HGT) process that can be affected by environmental change and promote bacterial virulence and drug resistance. However, it is unknown whether environmental changes can influence the conjugation ability of the marine fish pathogen Vibrio harveyi, thereby affecting its pathogenicity and drug resistance. This study systematically analyzes the effect of environmental stress on the ability of V. harveyi to obtain shuttle plasmids from Escherichia coli during conjugation. The results indicate that V. harveyi cannot receive shuttle plasmid pMMB207 without exposure to stress. However, certain stress exposure (37–46°C, 4%–16% ethanol, 0.14–0.56 mM SDS, 0.04~0.05 M NaOH, and 0.012–0.024 M HCl for 5–60 minutes) in the log phase of V. harveyi before conjugation successfully induces the fertility of the V. harveyi recipient in intergeneric mating with E. coli. In particular, ethanol and heat stress showed strong induction with up to 2.5 × 105 and 5.3 × 103 transconjugants when exposed to 16% ethanol for 10 minutes and 40°C for 60 minutes, respectively. Additionally, appropriate levels of NaOH (0.05 M, 10 minutes), SDS (0.42 mM, 5 minutes), and HCl (0.024 M, 5 minutes) lead to 2.3 × 103, 4.5 × 102, and 1.8 × 102 transconjugants, respectively. These results will help establish homologous recombination gene knockout technology and greatly advance molecular theoretical research on V. harveyi. They will also support the establishment of disease prevention and control strategies based on the interruption of the HGT process by environmental regulation.
Clinical spectrum and outcomes of idiopathic inflammatory myopathies in South Africans
Authors: Birch Candice , Tikly Mohammed , Govind Nimmisha
Published: February 2023

Background

Idiopathic inflammatory myopathies (IIM) are rare diseases for which there is a paucity of data in Africa. We undertook a retrospective records review of clinical and laboratory features of patients with IIM attending a tertiary service in Gauteng, South Africa.

Materials and methods

Case records of patients seen between January 1990 and December 2019 and fulfilling the Bohan and Peter criteria for IIM were reviewed for demographics, clinical features, special investigations and drug therapy.

Results

Of 94 patients included in the study, 65 (69.1%) had dermatomyositis (DM) and 29 (30.9%) had polymyositis (PM). Overall, the mean (SD) age at presentation and disease duration were 41.5 (13.6) and 5.9 (6.2) years, respectively. 88 (93.6%) were Black Africans. The most common cutaneous features in DM patients were Gottron’s lesions (72.3%) and abnormal cuticular overgrowth (67.7%). Dysphagia was the most common extra-muscular feature (31.9%), more so in PM than DM (p = 0.02). Creatine kinase, total leucocyte count and CRP were similarly higher in PM than DM patients (p = 0.006, 0.002, and 0.01, respectively). Anti-nuclear and anti-Jo-1 antibodies were positive in 62.2 and 20.4% of patients tested, respectively, the latter significantly more in PM than DM patients (OR = 5.1, p = 0.03) and more likely to be positive with ILD (p = 0.001). Corticosteroids were prescribed in all patients, 89.4% had additional immunosuppressive drugs and 6.4% required intensive/high care. Malignancies occurred in three patients, all of whom had DM. There were seven known deaths.

Conclusion

The present study provides further insights into the spectrum of clinical features of IIM, especially cutaneous features of DM, anti-Jo-1 antibodies and associated ILD, in a cohort of predominantly black African patients.
Post-operative gamma knife radiosurgery for WHO grade I intracranial meningiomas: A single-center, retrospective study
Authors: Yu Jinxiu , Zeng Jiamin , Hu Guanye , Wang Jing , Chen Guohao , Huang Minyi , Liang Shunyao , He Yong , Deng Yinhui , Gong Ye , Fu Junyi
Published: February 2023

Objective

To explore the results of the Gamma Knife radiosurgery (GKRS) for World Health Organization (WHO) grade I intracranial meningiomas after surgical resection.

Methods

A total of 130 patients who were pathologically diagnosed as having WHO grade I meningiomas and who underwent post-operative GKRS were retrospectively reviewed in a single center.

Results

Of the 130 patients, 51 patients (39.2%) presented with radiological tumor progression with a median follow-up time of 79.7 months (ranging from 24.0 to 291.3 months). The median time to radiological tumor progression was 73.4 months (ranging from 21.4 to 285.3 months), whereas 1-, 3-, 5-, and 10-year radiological progression-free survival (PFS) was 100, 90, 78, and 47%, respectively. Moreover, 36 patients (27.7%) presented with clinical tumor progression. Clinical PFS at 1, 3, 5, and 10 years was 96, 91, 84, and 67%, respectively. After GKRS, 25 patients (19.2%) developed adverse effects, including radiation-induced edema (n = 22). In a multivariate analysis, a tumor volume of ≥10 ml and falx/parasagittal/convexity/intraventricular location were significantly associated with radiological PFS [hazard ratio (HR) = 1.841, 95% confidence interval (CI) = 1.018–3.331, p = 0.044; HR = 1.761, 95% CI = 1.008–3.077, p = 0.047]. In a multivariate analysis, a tumor volume of ≥10 ml was associated with radiation-induced edema (HR = 2.418, 95% CI = 1.014–5.771, p = 0.047). Of patients who presented with radiological tumor progression, nine were diagnosed with malignant transformation. The median time to malignant transformation was 111.7 months (ranging from 35.0 to 177.2 months). Clinical PFS after repeat GKRS was 49 and 20% at 3 and 5 years, respectively. Secondary WHO grade II meningiomas were significantly associated with a shorter PFS (p = 0.026).

Conclusions

Post-operative GKRS is a safe and effective treatment for WHO grade I intracranial meningiomas. Large tumor volume and falx/parasagittal/convexity/intraventricular location were associated with radiological tumor progression. Malignant transformation was one of the main cause of tumor progression in WHO grade I meningiomas after GKRS.
Effects of regional brain volumes on cognition in sickle cell anemia: A developmental perspective
Authors: Hamdule Shifa , Kölbel Melanie , Stotesbury Hanne , Murdoch Russell , Clayden Jonathan D. , Sahota Sati , Hood Anna Marie , Clark Christopher A. , Kirkham Fenella Jane
Published: February 2023

Background and objectives

Cognitive difficulties in people with sickle cell anemia (SCA) are related to lower processing speed index (PSI) and working memory index (WMI). However, risk factors are poorly understood so preventative strategies have not been explored. Brain volumes, specifically white matter volumes (WMV) which increases through early adulthood, have been associated with better cognition in healthy typically developing individuals. In patients with SCA, the reduced WMV and total subcortical volumes noted could explain cognitive deficits. We therefore examined developmental trajectories for regional brain volumes and cognitive endpoints in patients with SCA.

Methods

Data from two cohorts, the Sleep and Asthma Cohort and Prevention of Morbidity in SCA, were available. MRI data included T1-weighted axial images, pre-processed before regional volumes were extracted using Free-surfer. PSI and WMI from the Weschler scales of intelligence were used to test neurocognitive performance. Hemoglobin, oxygen saturation, hydroxyurea treatment and socioeconomic status from education deciles were available.

Results

One hundred and twenty nine patients (66 male) and 50 controls (21 male) aged 8–64 years were included. Brain volumes did not significantly differ between patients and controls. Compared with controls, PSI and WMI were significantly lower in patients with SCA, predicted by increasing age and male sex, with lower hemoglobin in the model for PSI but no effect of hydroxyurea treatment. In male patients with SCA only, WMV, age and socioeconomic status predicted PSI, while total subcortical volumes predicted WMI. Age positively and significantly predicted WMV in the whole group (patients + controls). There was a trend for age to negatively predict PSI in the whole group. For total subcortical volume and WMI, age predicted decrease only in the patient group. Developmental trajectory analysis revealed that PSI only was significantly delayed in patients at 8 years of age; the rate of development for the cognitive and brain volume data did not differ significantly from controls.

Discussion

Increasing age and male sex negatively impact cognition in SCA, with processing speed, also predicted by hemoglobin, delayed by mid childhood. Associations with brain volumes were seen in males with SCA. Brain endpoints, calibrated against large control datasets, should be considered for randomized treatment trials.
A systematic framework for predictive biomarkers in immune effector cell-associated neurotoxicity syndrome
Authors: Butt Omar H. , Zhou Alice Y. , Ances Beau M. , DiPersio John F. , Ghobadi Armin
Published: February 2023

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the management of several life-threatening malignancies, often achieving durable sustained responses. The number of patients treated with this new class of cell-based therapy, along with the number of Food and Drug Association (FDA) approved indications, are growing significantly. Unfortunately Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) can often occur after treatment with CAR-T cells, and severe ICANS can be associated with significant morbidity and mortality. Current standard treatments are mainly steroids and supportive care, highlighting the need for early identification. In the last several years, a range of predictive biomarkers have been proposed to distinguish patients at increased risk for developing ICANS. In this review, we discuss a systematic framework to organize potential predictive biomarkers that builds on our current understanding of ICANS.
Blood flow perfusion in visual pathway detected by arterial spin labeling magnetic resonance imaging for differential diagnosis of ocular ischemic syndrome
Authors: Chen Yanan , Feng Xue , Huang Yingxiang , Zhao Lu , Chen Xi , Qin Shuqi , Sun Jiao , Jing Jing , Zhang Xiaolei , Wang Yanling
Published: February 2023

Background

Ocular ischemic syndrome (OIS), attributable to chronic hypoperfusion caused by marked carotid stenosis, is one of the important factors that cause ocular neurodegenerative diseases such as optic atrophy. The current study aimed to detect blood flow perfusion in a visual pathway by arterial spin labeling (ASL) and magnetic resonance imaging (MRI) for the differential diagnosis of OIS.

Methods

This diagnostic, cross-sectional study at a single institution was performed to detect blood flow perfusion in a visual pathway based on 3D pseudocontinuous ASL (3D-pCASL) using 3.0T MRI. A total of 91 participants (91 eyes) consisting of 30 eyes with OIS and 61 eyes with noncarotid artery stenosis-related retinal vascular diseases (39 eyes with diabetic retinopathy and 22 eyes with high myopic retinopathy) were consecutively included. Blood flow perfusion values in visual pathways derived from regions of interest in ASL images, including the retinal-choroidal complex, the intraorbital segments of the optic nerve, the tractus optics, and the visual center, were obtained and compared with arm-retinal circulation time and retinal circulation time derived from fundus fluorescein angiography (FFA). Receiver operating characteristic (ROC) curve analyses and the intraclass correlation coefficient (ICC) were performed to evaluate the accuracy and consistency.

Results

Patients with OIS had the lowest blood flow perfusion values in the visual pathway (all p < 0.05). The relative intraorbital segments of optic nerve blood flow values at post-labeling delays (PLDs) of 1.5 s (area under the curve, AUC = 0.832) and the relative retinal–choroidal complex blood flow values at PLDs of 2.5 s (AUC = 0.805) were effective for the differential diagnosis of OIS. The ICC of the blood flow values derived from the retinal–choroidal complex and the intraorbital segments of the optic nerve between the two observers showed satisfactory concordance (all ICC > 0.932, p < 0.001). The adverse reaction rates of ASL and FFA were 2.20 and 3.30%, respectively.

Conclusion

3D-pCASL showed that the participants with OIS had lower blood flow perfusion values in the visual pathway, which presented satisfactory accuracy, reproducibility, and safety. It is a noninvasive and comprehensive differential diagnostic tool to assess blood flow perfusion in a visual pathway for the differential diagnosis of OIS.
Efficacy of acupuncture for the treatment of Parkinson’s disease-related constipation (PDC): A randomized controlled trial
Authors: Li Ying-Jia , Leong Ian-I , Fan Jing-Qi , Yan Ming-Yue , Liu Xin , Lu Wei-Jing , Chen Yuan-Yuan , Tan Wei-Qiang , Wang Yu-Ting , Zhuang Li-Xing
Published: February 2023

Objective

To evaluate the efficacy of acupuncture in treating Parkinson’s disease-related constipation (PDC).

Materials and methods

This was a randomized, controlled trial in which patients, outcome assessors, and statisticians were all blinded. Seventy-eight eligible patients were randomly assigned to either the manual acupuncture (MA) or sham acupuncture (SA) groups and received 12 sessions of treatment over a 4-week period. Following treatment, patients were monitored until the eighth week. The primary outcome was the change in weekly complete spontaneous bowel movements (CSBMs) from baseline after treatment and follow-up. The Constipation Symptom and Efficacy Assessment Scale (CSEAS), the Patient-Assessment of Constipation Quality of Life questionnaire (PAC-QOL), and the Unified Parkinson’s Disease Rating Scale (UPDRS) were used as secondary outcomes.

Results

In the intention-to-treat analysis, 78 patients with PDC were included, with 71 completing the 4-week intervention and 4-week follow-up. When compared to the SA group, weekly CSBMs were significantly increased after treatment with the MA group (P < 0.001). Weekly CSBMs in the MA group were 3.36 [standard deviation (SD) 1.44] at baseline and increased to 4.62 (SD, 1.84) after treatment (week 4). The SA group’s weekly CSBMs were 3.10 (SD, 1.45) at baseline and 3.03 (SD, 1.25) after treatment, with no significant change from baseline. The effect on weekly CSBMs improvement in the MA group lasted through the follow-up period (P < 0.001).

Conclusion

Acupuncture was found to be effective and safe in treating PDC in this study, and the treatment effect lasted up to 4 weeks.

Clinical trial registration

http://www.chictr.org.cn/index.aspx, identifier ChiCTR2200059979
Lentilactobacillus kefiri SGL 13 and Andrographis paniculata alleviate dextran sulfate sodium induced colitis in mice
Authors: Manna Laura , Rizzi Eleonora , Bafile Eleonora , Cappelleri Andrea , Ruscica Massimiliano , Macchi Chiara , Podaliri Vulpiani Michele , Salini Romolo , Rossi Emanuela , Panebianco Concetta , Perri Francesco , Pazienza Valerio , Federici Federica
Published: February 2023

Introduction

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions that typically involve diarrhea, abdominal pain, fatigue, and weight loss, with a dramatic impact on patients’ quality of life. Standard medications are often associated with adverse side effects. Thus, alternative treatments such as probiotics are of great interest. The purpose of the present study was to evaluate the effects of oral administration of Lentilactobacillus kefiri (basonym: Lactobacillus kefiri) SGL 13 and Andrographis paniculata, namely, Paniculin 13™, on dextran sodium sulfate (DSS)- treated C57BL/6J mice.

Methods

Colitis was induced by administering 1.5% DSS in drinking water for 9 days. Forty male mice were divided into four groups, receiving PBS (control), 1.5% DSS, Paniculin 13™ and 1.5% DSS + Paniculin 13™.

Results

The results showed that body weight loss and Disease Activity Index (DAI) score were improved by Paniculin 13™. Moreover, Paniculin 13™ ameliorated DSS-induced dysbiosis, by modulating the gut microbiota composition. The gene expression of MPO, TNFα and iNOS in colon tissue was reduced and these data matched with the histological results, supporting the efficacy of Paniculin 13™ in reducing the inflammatory response. No adverse effects were associated to Paniculin 13™ administration.

Discussion

In conclusion, Paniculin 13™ could be an effective add-on approach to conventional therapies for IBD.
Exploring women's experiences with persistent pain and pain management following breast cancer treatment: A qualitative study
Authors: Smith Michelle D. , Manning Joanne , Nielsen Mandy , Hayes Sandra C. , Plinsinga Melanie L. , Coppieters Michel W.
Published: February 2023

This qualitative study aimed to explore experiences of women with persistent pain following breast cancer treatment, including their perceptions about the cause of their pain, how they manage their pain and their interactions with healthcare providers related to their pain during and following breast cancer treatment. Fourteen women who experienced pain for more than 3 months following breast cancer treatment were recruited from the general breast cancer survivorship community. Focus groups and in-depth, semi-structured interviews were conducted by one interviewer, audio-recorded, and transcribed verbatim. Transcripts were coded and analysed using Framework Analysis. Three main descriptive themes emerged from the interview transcripts: (1) characteristics of pain, (2) interactions with healthcare providers and (3) pain management. Women had various types and degrees of persistent pain, all of which they believed were related to breast cancer treatment. Most felt like they were not given enough information pre- or post-treatment and believed their experience and ability to cope with pain would have been better if they were given accurate information and advice about (the possibility of) experiencing persistent pain. Pain management strategies ranged from trial and error approaches, to pharmacotherapy, and to ‘just coping with the pain”. These findings highlight the importance of the provision of empathetic supportive care before, during and after cancer treatment that can facilitate access to relevant information, multidisciplinary care teams (including allied health professionals) and consumer support.
Management challenges in the treatment of severe hyperbilirubinemia in low- and middle-income countries: Encouraging advancements, remaining gaps, and future opportunities
Authors: Satrom Katherine M. , Farouk Zubaida L. , Slusher Tina M.
Published: February 2023

Neonatal jaundice (NJ) is common in newborn infants. Severe NJ (SNJ) has potentially negative neurological sequelae that are largely preventable in high resource settings if timely diagnosis and treatment are provided. Advancements in NJ care in low- and middle-income countries (LMIC) have been made over recent years, especially with respect to an emphasis on parental education about the disease and technological advancements for improved diagnosis and treatment. Challenges remain, however, due to lack of routine screening for SNJ risk factors, fragmented medical infrastructure, and lack of culturally appropriate and regionally specific treatment guidelines. This article highlights both encouraging advancements in NJ care as well as remaining gaps. Opportunities are identified for future work in eliminating the gaps in NJ care and preventing death and disability related to SNJ around the globe.
Establishment and external verification of an oxidative stress-related gene signature to predict clinical outcomes and therapeutic responses of colorectal cancer
Authors: Cao Sha , Chen Cheng , Gu Dezhi , Wang Zhengdong , Xu Guanghui
Published: February 2023

Objective: Accumulated evidence highlights the biological significance of oxidative stress in tumorigenicity and progression of colorectal cancer (CRC). Our study aimed to establish a reliable oxidative stress-related signature to predict patients’ clinical outcomes and therapeutic responses.

Methods: Transcriptome profiles and clinical features of CRC patients were retrospectively analyzed from public datasets. LASSO analysis was used to construct an oxidative stress-related signature to predict overall survival, disease-free survival, disease-specific survival, and progression-free survival. Additionally, antitumor immunity, drug sensitivity, signaling pathways, and molecular subtypes were analyzed between different risk subsets through TIP, CIBERSORT, oncoPredict, etc. approaches. The genes in the signature were experimentally verified in the human colorectal mucosal cell line (FHC) along with CRC cell lines (SW-480 and HCT-116) through RT-qPCR or Western blot.

Results: An oxidative stress-related signature was established, composed of ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CDKN2A, CRYAB, NGFR, and UCN. The signature displayed an excellent capacity for survival prediction and was linked to worse clinicopathological features. Moreover, the signature correlated with antitumor immunity, drug sensitivity, and CRC-related pathways. Among molecular subtypes, the CSC subtype had the highest risk score. Experiments demonstrated that CDKN2A and UCN were up-regulated and ACOX1, CPT2, NAT2, NRG1, PPARGC1A, CRYAB, and NGFR were down-regulated in CRC than normal cells. In H2O2-induced CRC cells, their expression was notably altered.

Conclusion: Altogether, our findings constructed an oxidative stress-related signature that can predict survival outcomes and therapeutic response in CRC patients, thus potentially assisting prognosis prediction and adjuvant therapy decisions.
Differences in right ventricular function and response to targeted therapy between patients with IPAH and PAH-CHD
Authors: Zhu Tengteng , Wu Panyun , Tan Zhen , Jin Quan , Chen Yusi , Li Lian , Chen Zewei , Tang Yirui , Li Jiang , Fang Zhenfei
Published: February 2023

Background and aims: Pulmonary arterial hypertension (PAH) is a chronic pulmonary vascular disorder characterized by elevated pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP). Right heart failure is a life-threatening complication of PAH and predicts a poor prognosis. PAH associated with congenital heart disease (PAH-CHD) and idiopathic PAH (IPAH) are two prevalent PAH subtypes in China. In this section, we set out to explore baseline right ventricular (RV) function and its response to targeted agents between IPAH and PAH-CHD.

Methods and results: Consecutive patients diagnosed with IPAH or PAH-CHD by right heart catheterization (RHC) in the Second Xiangya Hospital from November 2011 to June 2020 were included. All patients received PAH-targeted therapy and the RV function was assessed by echocardiography at baseline and during follow-up. A total of 303 patients (age, 36.23 ± 13.10 years; women, 213 (70.3%); mean PAP [mPAP], 63.54 ± 16.12 mmHg; PVR, 14.74 ± 7.61 WU) with IPAH (n = 121) or PAH-CHD (n = 182) were included in this study. Compared with PAH-CHD, patients with IPAH had worse baseline RV function. As of the latest follow-up, forty-nine patients with IPAH and six patients with PAH-CHD died. Kaplan-Meier analyses showed better survival in PAH-CHD versus IPAH. After PAH-targeted therapy, patients with IPAH had less improvement in 6 MWD, World Health Organization functional class, and RV functional parameters compared with patients with PAH-CHD.

Conclusion: Compared with patients with PAH-CHD, patients with IPAH had worse baseline RV function, unfavourable prognosis, and inadequate response to targeted treatment.
What is the need and why is it time for innovative models for understanding lung repair and regeneration?
Authors: Weiss Daniel J.
Published: February 2023

Advances in tissue engineering continue at a rapid pace and have provided novel methodologies and insights into normal cell and tissue homeostasis, disease pathogenesis, and new potential therapeutic strategies. The evolution of new techniques has particularly invigorated the field and span a range from novel organ and organoid technologies to increasingly sophisticated imaging modalities. This is particularly relevant for the field of lung biology and diseases as many lung diseases, including chronic obstructive pulmonary disease (COPD) and idiopathic fibrosis (IPF), among others, remain incurable with significant morbidity and mortality. Advances in lung regenerative medicine and engineering also offer new potential avenues for critical illnesses such as the acute respiratory distress syndrome (ARDS) which also continue to have significant morbidity and mortality. In this review, an overview of lung regenerative medicine with focus on current status of both structural and functional repair will be presented. This will serve as a platform for surveying innovative models and techniques for study, highlighting the need and timeliness for these approaches.
Speed, agility, and musculoskeletal fitness are independently associated with areal bone mineral density in children
Authors: Mello Júlio B. , Rodríguez-Rodríguez Fernando , Gracia-Marco Luis , Teodoro Juliana L. , Gaya Anelise R. , Gaya Adroaldo C. A.
Published: February 2023

Background: There is still little understanding of the associations between physical fitness variables and bone health in children taking into account key confounders.

Aim: The aim of this study was to analyze the associations between performance in tests of speed, agility, and musculoskeletal fitness (power of the upper and lower limbs) with bone mass of different regions in children, considering the adjustment to maturity-offset, lean percentage, and sex.

Methods: Cross-sectional study design: the sample consisted of 160 children aged 6–11 years. The physical fitness variables tested were 1) speed, assessed with the running test at a maximum speed of 20 m; 2) agility, assessed through the 4×4-m square test; 3) lower limb power, assessed using the standing long jump test, and 4) upper limb power, assessed using the 2-kg medicine ball throw test. Areal bone mineral density (aBMD) was obtained from the analysis of body composition by dual-energy X-ray absorptiometry (DXA). Simple and multiple linear regression models were performed using the SPSS software.

Results: In the crude regression analyses, the results indicated a linear relationship between all the physical fitness variables and aBMD in all body segments, but maturity-offset, sex, and lean mass percentage seemed to have an effect on these relationships. Except for the upper limb power, the other physical capacities (speed, agility, and lower limb power) were associated with aBMD in at least three body regions in the adjusted analyses. These associations occurred in the spine, hip, and leg regions, and the aBMD of the legs presented the best association magnitude (R2).

Conclusion: There is a significant association between speed, agility, and musculoskeletal fitness, specifically the lower limb power and aBMD. That is, the aBMD is a good indicator of the relationship between fitness and bone mass in children, but it is essential to consider specific fitness variables and skeletal regions.
A need for exhaustive and standardized characterization of ion channels activity. The case of KV11.1
Authors: Alameh Malak , Oliveira-Mendes Barbara Ribeiro , Kyndt Florence , Rivron Jordan , Denjoy Isabelle , Lesage Florian , Schott Jean-Jacques , De Waard Michel , Loussouarn Gildas
Published: February 2023

hERG, the pore-forming subunit of the rapid component of the delayed rectifier K+ current, plays a key role in ventricular repolarization. Mutations in the KCNH2 gene encoding hERG are associated with several cardiac rhythmic disorders, mainly the Long QT syndrome (LQTS) characterized by prolonged ventricular repolarization, leading to ventricular tachyarrhythmias, sometimes progressing to ventricular fibrillation and sudden death. Over the past few years, the emergence of next-generation sequencing has revealed an increasing number of genetic variants including KCNH2 variants. However, the potential pathogenicity of the majority of the variants remains unknown, thus classifying them as variants of uncertain significance or VUS. With diseases such as LQTS being associated with sudden death, identifying patients at risk by determining the variant pathogenicity, is crucial. The purpose of this review is to describe, on the basis of an exhaustive examination of the 1322 missense variants, the nature of the functional assays undertaken so far and their limitations. A detailed analysis of 38 hERG missense variants identified in Long QT French patients and studied in electrophysiology also underlies the incomplete characterization of the biophysical properties for each variant. These analyses lead to two conclusions: first, the function of many hERG variants has never been looked at and, second, the functional studies done so far are excessively heterogeneous regarding the stimulation protocols, cellular models, experimental temperatures, homozygous and/or the heterozygous condition under study, a context that may lead to conflicting conclusions. The state of the literature emphasizes how necessary and important it is to perform an exhaustive functional characterization of hERG variants and to standardize this effort for meaningful comparison among variants. The review ends with suggestions to create a unique homogeneous protocol that could be shared and adopted among scientists and that would facilitate cardiologists and geneticists in patient counseling and management.
Emergent molecular traits of lettuce and tomato grown under wavelength-selective solar cells
Authors: Charles Melodi , Edwards Brianne , Ravishankar Eshwar , Calero John , Henry Reece , Rech Jeromy , Saravitz Carole , You Wei , Ade Harald , O’Connor Brendan , Sederoff Heike
Published: February 2023

The integration of semi-transparent organic solar cells (ST-OSCs) in greenhouses offers new agrivoltaic opportunities to meet the growing demands for sustainable food production. The tailored absorption/transmission spectra of ST-OSCs impacts the power generated as well as crop growth, development and responses to the biotic and abiotic environments. To characterize crop responses to ST-OSCs, we grew lettuce and tomato, traditional greenhouse crops, under three ST-OSC filters that create different light spectra. Lettuce yield and early tomato development are not negatively affected by the modified light environment. Our genomic analysis reveals that lettuce production exhibits beneficial traits involving nutrient content and nitrogen utilization while select ST-OSCs impact regulation of flowering initiation in tomato. These results suggest that ST-OSCs integrated into greenhouses are not only a promising technology for energy-neutral, sustainable and climate-change protected crop production, but can deliver benefits beyond energy considerations.
Genome-wide identification and expression analysis of the HD2 protein family and its response to drought and salt stress in Gossypium species
Authors: Bano Nasreen , Fakhrah Shafquat , Lone Rayees Ahmad , Mohanty Chandra Sekhar , Bag Sumit Kumar
Published: February 2023

Histone deacetylase 2 (HD2) proteins play an important role in the regulation of gene expression. This helps with the growth and development of plants and also plays a crucial role in responses to biotic and abiotic stress es. HD2s comprise a C2H2-type Zn2+ finger at their C-terminal and an HD2 label, deacetylation and phosphorylation sites, and NLS motifs at their N-terminal. In this study, a total of 27 HD2 members were identified, using Hidden Markov model profiles, in two diploid cotton genomes (Gossypium raimondii and Gossypium arboretum) and two tetraploid cotton genomes (Gossypium hirsutum and Gossypium barbadense). These cotton HD2 members were classified into 10 major phylogenetic groups (I-X), of which group III was found to be the largest with 13 cotton HD2 members. An evolutionary investigation showed that the expansion of HD2 members primarily occurred as a result of segmental duplication in paralogous gene pairs. Further qRT-PCR validation of nine putative genes using RNA-Seq data suggested that GhHDT3D.2 exhibits significantly higher levels of expression at 12h, 24h, 48h, and 72h of exposure to both drought and salt stress conditions compared to a control measure at 0h. Furthermore, gene ontology, pathways, and co-expression network study of GhHDT3D.2 gene affirmed their significance in drought and salt stress responses.
Testosterone, oxytocin and co-operation: A hypothesis for the origin and function of music
Authors: Fukui Hajime , Toyoshima Kumiko
Published: February 2023

Since the time of Darwin, theories have been proposed on the origin and functions of music; however, the subject remains enigmatic. The literature shows that music is closely related to important human behaviours and abilities, namely, cognition, emotion, reward and sociality (co-operation, entrainment, empathy and altruism). Notably, studies have deduced that these behaviours are closely related to testosterone (T) and oxytocin (OXT). The association of music with important human behaviours and neurochemicals is closely related to the understanding of reproductive and social behaviours being unclear. In this paper, we describe the endocrinological functions of human social and musical behaviour and demonstrate its relationship to T and OXT. We then hypothesised that the emergence of music is associated with behavioural adaptations and emerged as humans socialised to ensure survival. Moreover, the proximal factor in the emergence of music is behavioural control (social tolerance) through the regulation of T and OXT, and the ultimate factor is group survival through co-operation. The “survival value” of music has rarely been approached from the perspective of musical behavioural endocrinology. This paper provides a new perspective on the origin and functions of music.
Dinos and GoPros: Children’s exploratory behaviors in a museum and their reflections on their learning
Authors: Weisberg Deena Skolnick , Dunlap Lucretia C. , Sobel David M.
Published: February 2023

Research in both laboratory and museum settings suggests that children’s exploration and caregiver–child interaction relate to children’s learning and engagement. Most of this work, however, takes a third-person perspective on children’s exploration of a single activity or exhibit, and does not consider children’s perspectives on their own exploration. In contrast, the current study recruited 6-to 10-year-olds (N = 52) to wear GoPro cameras, which recorded their first-person perspectives as they explored a dinosaur exhibition in a natural history museum. During a 10-min period, children were allowed to interact with 34 different exhibits, their caregivers and families, and museum staff however they wished. Following their exploration, children were asked to reflect on their exploration while watching the video they created and to report on whether they had learned anything. Children were rated as more engaged when they explored collaboratively with their caregivers. Children were more likely to report that they learned something when they were more engaged, and when they spent more time at exhibits that presented information didactically rather than being interactive. These results suggest that static exhibits have an important role to play in fostering learning experiences in museums, potentially because such exhibits allow for more caregiver–child interaction.
The mediating role of coping strategies between depression and social support and the moderating effect of the parent–child relationship in college students returning to school: During the period of the regular prevention and control of COVID-19
Authors: Wang Jing , Chen Yu , Chen Huimin , Hua Long , Wang Jun , Jin Yuelong , He Lianping , Chen Yan , Yao Yingshui
Published: February 2023

Objective

According to the WHO, compared to before the COVID-19 pandemic, young people showed a significant increase in depressive symptoms. In light of the recent coronavirus pneumonia pandemic, this study was conducted to determine how social support, coping style, parent-child relationships, and depression are associated. We investigated how these factors interacted and affected the prevalence of depression during this challenging and unheard-of time. Our research may help both individuals and healthcare professionals better comprehend and assist those who are coping with the pandemic’s psychological effects.

Design and main outcome measures

3,763 students from a medical college in Anhui Province were investigated with Social Support Rate Scale, Trait Coping Style Questionnaire, and Self-rating Depression Scale.

Results

When the pandemic situation was normalizing, social support was associated with depression and the coping style of college students (p < 0.01). During the period of pandemic normalization, the parent–child relationship moderated the relationship between social support and positive coping (t = −2.45, p < 0.05); the parent–child relationship moderated the relationship between social support and negative coping (t = −4.29, p < 0.01); and the parent–child relationship moderated the association between negative coping and depression (t = 2.08, p < 0.05).

Conclusion

Social support has an impact on depression in the period of the regular prevention and control of COVID-19 through the mediating role of coping style and the moderating effect of the parent–child relationship.