bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for Three Subgroups of Female FMR1 Premutation Carriers Defined by Distinct Neuropsychiatric Features: A Pilot Study
Authors: Schmitt Lauren M. , Dominick Kelli C. , Liu Rui , Pedapati Ernest V. , Ethridge Lauren E. , Smith Elizabeth , Sweeney John A. , Erickson Craig A.
Published: January 2022

Over 200 Cytosine-guanine-guanine (CGG) trinucleotide repeats in the 5′ untranslated region of the Fragile X mental retardation 1 (FMR1) gene results in a “full mutation,” clinically Fragile X Syndrome (FXS), whereas 55 – 200 repeats result in a “premutation.”FMR1premutation carriers (PMC) are at an increased risk for a range of psychiatric, neurocognitive, and physical conditions. Few studies have examined the variable expression of neuropsychiatric features in female PMCs, and whether heterogeneous presentation among female PMCs may reflect differential presentation of features in unique subgroups. In the current pilot study, we examined 41 female PMCs (ages 17–78 years) and 15 age-, sex-, and IQ-matched typically developing controls (TDC) across a battery of self-report, eye tracking, expressive language, neurocognitive, and resting state EEG measures to determine the feasibility of identifying discrete clusters. Secondly, we sought to identify the key features that distinguished these clusters of female PMCs. We found a three cluster solution usingk-means clustering. Cluster 1 represented a psychiatric feature group (27% of our sample); cluster 2 represented a group with executive dysfunction and elevated high frequency neural oscillatory activity (32%); and cluster 3 represented a relatively unaffected group (41%). Our findings indicate the feasibility of using a data-driven approach to identify naturally occurring clusters in female PMCs using a multi-method assessment battery. CGG repeat count and its association with neuropsychiatric features differ across clusters. Together, our findings provide important insight into potential diverging pathophysiological mechanisms and risk factors for each female PMC cluster, which may ultimately help provide novel and individualized targets for treatment options.
Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function
Authors: Becic Amina , Leifeld Jennifer , Shaukat Javeria , Hollmann Michael
Published: January 2022

Tetraspanins (Tspans) comprise a membrane protein family structurally defined by four transmembrane domains and intracellular N and C termini that is found in almost all cell types and tissues of eukaryotes. Moreover, they are involved in a bewildering multitude of diverse biological processes such as cell adhesion, motility, protein trafficking, signaling, proliferation, and regulation of the immune system. Beside their physiological roles, they are linked to many pathophysiological phenomena, including tumor progression regulation, HIV-1 replication, diabetes, and hepatitis. Tetraspanins are involved in the formation of extensive protein networks, through interactions not only with themselves but also with numerous other specific proteins, including regulatory proteins in the central nervous system (CNS). Interestingly, recent studies showed that Tspan7 impacts dendritic spine formation, glutamatergic synaptic transmission and plasticity, and that Tspan6 is correlated with epilepsy and intellectual disability (formerly known as mental retardation), highlighting the importance of particular tetraspanins and their involvement in critical processes in the CNS. In this review, we summarize the current knowledge of tetraspanin functions in the brain, with a particular focus on their impact on glutamatergic neurotransmission. In addition, we compare available resolved structures of tetraspanin family members to those of auxiliary proteins of glutamate receptors that are known for their modulatory effects.
Modulation of Gut Microbiota and Immune System by Probiotics, Pre-biotics, and Post-biotics
Authors: Liu Yue , Wang Jiaqi , Wu Changxin
Published: January 2022

The human gastrointestinal tract harbours a complex microbial community, which interacts with the mucosal immune system closely. Gut microbiota plays a significant role in maintaining host health, which could supply various nutrients, regulate energy balance, modulate the immune response, and defence against pathogens. Therefore, maintaining a favourable equilibrium of gut microbiota through modulating bacteria composition, diversity, and their activity is beneficial to host health. Several studies have shown that probiotics and pre-biotics could directly and indirectly regulate microbiota and immune response. In addition, post-biotics, such as the bioactive metabolites, produced by gut microbiota, and/or cell-wall components released by probiotics, also have been shown to inhibit pathogen growth, maintain microbiota balance, and regulate an immune response. This review summarises the studies concerning the impact of probiotics, pre-biotics, and post-biotics on gut microbiota and immune systems and also describes the underlying mechanisms of beneficial effects of these substances. Finally, the future and challenges of probiotics, pre-biotics, and post-biotics are proposed.
High Precision Bone Cutting by Er: YAG Lasers Might Minimize the Invasiveness of Navigated Brain Biopsies
Authors: Ha Thanh Tu , Thieringer Florian M. , Bammerlin Martin , Cordier Dominik
Published: January 2022

Biopsies of brain tissue are sampled and examined to establish a diagnosis and to plan further treatment, e.g. for brain tumors. The neurosurgical procedure of sampling brain tissue for histologic examination is still a relatively invasive procedure that carries several disadvantages. The “proof of concept”-objective of this study is to answer the question if laser technology might be a potential tool to make brain biopsies less invasive, faster and safer. Laser technology might carry the opportunity to miniaturize the necessary burr hole and also to angulate the burr hole much more tangential in relation to the bone surface in order to take biopsies from brain regions that are usually only difficult and hazardous to access. We examined if it is possible to miniaturize the hole in the skull bone to such a high extent that potentially the laser-created canal itself may guide the biopsy needle with sufficient accuracy. The 2-dimensional, i.e. radial tolerance of the tip of biopsy needles inserted in these canals was measured under defined lateral loads which mimic mechanical forces applied by a surgeon. The canals through the skull bones were planned in angles of 90° (perpendicular) and 45° relative to the bone surface. We created a total of 33 holes with an Er : YAG laser in human skull bones. We could demonstrate that the achievable radial tolerance concerning the guidance of a biopsy needle by a laser created bone canal is within the range of the actual accuracy of a usual navigated device if the canal is at least 4 mm in length. Lateral mechanical loads applied to the biopsy needle had only minor impact on the measurable radial tolerance. Furthermore, in contrast to mechanical drilling systems, laser technology enables the creation of bone canals in pointed angles to the skull bone surface. The latter opens the perspective to sample biopsies in brain areas that are usually not or only hazardous to access.
Patterns-of-Care Analysis for Radiotherapy of Elderly Head-and-Neck Cancer Patients: A Trinational Survey in Germany, Austria and Switzerland
Authors: Haehl Erik , Rühle Alexander , Spohn Simon , Sprave Tanja , Gkika Eleni , Zamboglou Constantinos , Grosu Anca-Ligia , Nicolay Nils H.
Published: January 2022

Objectives

The number of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing, and clinical trials defining the standard of care either excluded or underrepresented elderly patients. This leaves physicians with a challenging and highly individual treatment decision largely lacking clinical evidence.

Methods

A tri-national patterns-of-care survey was sent to all members of the German (DEGRO), Austrian (ÖGRO), and Swiss (SRO/SSRO) national societies of radiation oncology. The online questionnaire consisted of 27 questions on the treatment of elderly HNSCC patients, including 6 case-based questions. Frequency distributions and subgroup comparisons were calculated using SPSS statistics software.

Results

A total of 132 answers were collected, including 46(35%) form universities, 52(39%) from non-university-hospitals and 34(26%) from private practices. 83(63%) treat 1-5 and 42(32%) >5 elderly HNSCC patients per month. Target volumes are defined analog current guidelines by 65(50%) of responders and altered based on age/comorbidities or tumor stage by 36(28%) and 28(22%), respectively. Chemotherapy is routinely administered by 108(84%) if indicated, with weekly 40mg/m2 of cisplatin being the favored regimen by 68(53%) in the definitive situation and 60(47%) in the adjuvant setting. Hypofractionation and hyperfractionation/acceleration are used by 26(20%) and 11(9%), respectively. Only 7(5%) clinicians routinely recommend inpatient treatment for elderly HNSCC patients. In a typical definitive patient case, 73(63%) responders recommended chemoradiation with bilateral elective node irradiation analog current guidelines. In an adjuvant example case recommendations regarding elective volume and chemotherapy were heterogeneous. Differences between responders’ institutions concern the frequency of PET-CT in staging, preventive port-catheter and PEG implantation, the choice of chemotherapy regimens and the use of alternative fractionations.

Conclusion

Treatment of elderly HNSCC-patients in the German-speaking countries mainly follows guidelines established for younger patients. Algorithms for patient stratification and treatment de-escalation for “unfit” elderly patients are needed.
Clinical Status and Future Prospects of Transanal Total Mesorectal Excision
Authors: Guo Zichao , Ji Xiaopin , Wang Shaodong , Zhang Yaqi , Liu Kun , Wang Changgang , Deng Yang , Zhang Tao , Cheng Xi , Zhao Ren
Published: January 2022

Low rectal cancer has always posed surgical challenges to gastrointestinal surgeons. Transanal total mesorectal excision (taTME) is a novel approach to radical resection for low rectal cancer. Compared with conventional laparoscopic TME (laTME), taTME is relevant to the benefits of better vision of the mesorectal plane, feasibility of operating in a narrow pelvis, and exact definition of distal resection margin, which may lead to a higher possibility of free circumferential resection margin, better quality of TME specimen, and lower conversion rate. Although there are concerns about its long-term oncological outcomes and complex learning curve, taTME is a promising alternative for rectal cancer. In this review, we discuss the application status and prospects of taTME.
Long-Term Outcomes in Uveal Melanoma After Ruthenium-106 Brachytherapy
Authors: Cennamo Gilda , Montorio Daniela , D’ Andrea Luca , Farella Antonio , Matano Elide , Giuliano Mario , Liuzzi Raffaele , Breve Maria Angelica , De Placido Sabino , Cennamo Giovanni
Published: January 2022

Uveal melanoma is the most common primary intraocular malignancy. The aim of this retrospective study was to report the results after ruthenium-106 (Ru-106) plaque brachytherapy for uveal melanoma in terms of tumor control, visual acuity, radiation-related complications, tumor recurrence, metastases, and patients’ survival rate during 4 years’ follow-up. A total of 355 eyes from 355 patients have been treated with Ru-106 plaque brachytherapy for uveal melanoma between February 2011 and March 2020. Five patients were lost to follow-up, and then 350 eyes of 350 patients (mean age 58 ± 11 years) were enrolled in this retrospective study. All patients underwent a complete ophthalmic examination including echography and spectral domain–optical coherence tomography. The mean follow-up was 4 years (3 months to 9 years). After treatment, the mean tumor thickness was reduced to 1.75 ± 0.21 mm. Radiation complications were found in 63% of patients: 38% showed radiation maculopathy, 11% had optic neuropathy, and 14% developed cataracts. Cancer-free survival was 99%, 97%, and 85%, respectively, at 5, 7, and 9 years. Ru-106 plaque brachytherapy represents a reliable treatment of uveal melanoma. This technique is valid and safe with a low rate of ocular complications during a long-term follow-up.
Diagnostic Model of Superficial Lymph Nodes Based on Clinical History and Ultrasound Findings: A Prospective Cohort Study
Authors: Tan Xiao-Qu , Qian Lin-Xue , Zhao Jun-Feng , Sun Peng-Fei , Li Qing-Qing , Feng Ruo-Xuan
Published: January 2022

Objectives

Differentiation of benign and malignant changes in lymph nodes is extremely important. We aimed to identify the ultrasound and clinical diagnostic criteria permitting this differentiation.

Methods

Clinical and ultrasound data were collected at Beijing Friendship Hospital from May 2019 to November 2020. Univariate and multivariate analysis were performed using statistical methods, and a mathematical model was established to evaluate benign and malignant lymph nodes.

Results

A total of 1343 LNs (person) with US‐guided core needle or fine needle biopsy (CNB or FNB) were evaluated in the analysis. Variables with a high predictive power were sex (odds ratio, OR: 3.360, p<0.001), short diameter (OR: 4.660, p<0.001), short/long diameter (S/L) ratio (OR: 1.515, P=0.007), border (OR: 1.626, p=0.002), cortex echogenicity (OR: 2.089, P<0.001), fusion (OR: 2.313, p=0.002), vascularity (peripheral vascularity, OR: 3.424, p<0.001; mixed vascularity, OR: 4.127, p<0.001), and medical history (fever/local pain, OR: 0.316, p<0.001; tumor history in the drainage area, OR: 4.595, p<0.001; both, OR: 5.554, p<0.001). The cut-off score on receiver operating characteristic (ROC) curve analysis using these eight variables was 2.5. The largest area under the ROC curve (Az) value was 82.3% (95% confidence interval (CI), 0.805–0.851), and the sensitivity (79.4%), specificity (72.3%), and accuracy (74.8%) were higher than those for nearly all the single indices.

Conclusion

The model of combination of ultrasound and clinical symptoms can preliminarily evaluate the benign and malignant of lymph nodes.
Endoscopic Endonasal Intraconal Approach for Orbital Tumor Resection: Case Series and Systematic Review
Authors: Zhang Xin , Hua Wei , Quan Kai , Yu Guo , Du Zunguo , Yang Zixiao , Wang Xiaowen , Song Jianping , Chen Liang , Zhu Wei
Published: January 2022

Intraorbital tumor could be approached by numerous surgical methods. The neuroendoscopic endonasal approach could provide a feasible corridor for indicated tumors. Herein we present a series of 6 consecutive intraorbital tumors from April 2018 to October 2020, which received endonasal endoscopic resection. Cadaveric dissection was performed for the intraconal approach, and the literature was also reviewed. Five tumors were located intraconally, while one extraconally. The pathology revealed 1 angioleiomyoma, 1 cavernous hemangioma, 1 pilocytic astrocytoma, 1 meningioma, and 2 schwannomas. Five of the six achieved gross total resection, including 3 tumors with lateral extension beyond the optic nerve. Preoperative visual deterioration was observed in 4 of the 6 patients, and all got improvement postoperatively. Transient oculomotor nerve palsy was presented in one patient postoperatively. No cerebrospinal fluid leakage, enophthalmos, or strabismus was observed. The median follow-up time is 27 months (11~41 months). At the 6-month follow-up, the visual acuity remained unchanged compared with that at discharge. Proptosis was resolved in 2 of the 3 patients; diplopia was improved in one patient. In conclusion, endoscopic endonasal intraconal approach could be suitable for selected pathological conditions, and for both medial or beyond medial extraconal and intraconal orbital tumors.
Percutaneous Radiofrequency Ablation Combined With Chemotherapy Versus Chemotherapy Only for Ovarian Cancer Liver Metastasis
Authors: Wu Chun-Xue , Chen Miao-Ling , Zhang Hao , Han Jian-Jun
Published: January 2022

Purpose

To compare the feasibility and efficacy of radiofrequency ablation (RFA) combined with chemotherapy and chemotherapy alone in patients with ovarian cancer liver metastasis (OCLM).

Methods

In this retrospective study, a total of 60 patients diagnosed with OCLM between May 2015 to February 2017 were included. All patients with ovarian cancer received chemotherapy and primary cytoreductive surgery before. Thirty patients underwent RFA and chemotherapy, and thirty patients only took chemotherapy. The overall survival (OS), CA-125 levels, and serum AST and ALT levels were compared between the two groups.

Results

In the RFA group, the 1-,2-, and 3-year OS rates after RFA were 93.3%, 80.0%, and 53.3%, respectively. Serum AST and ALT levels were both elevated after RFA (p=0.0004, p<0.0001). In the chemotherapy group, the 1-,2-, and 3-year OS rates were 79.5%, 60.1%, and 42.1%, respectively. Levels of serum AST and ALT were stable. CA-125 levels for both groups were also available.

Conclusion

Based on our analysis of a single institution’s series of patients with OCLM, RFA could be a feasibly effective option in the management of OCLM.
Radiomics Study for Discriminating Second Primary Lung Cancers From Pulmonary Metastases in Pulmonary Solid Lesions
Authors: Zhong Feiyang , Liu Zhenxing , An Wenting , Wang Binchen , Zhang Hanfei , Liu Yumin , Liao Meiyan
Published: January 2022

Background

The objective of this study was to assess the value of quantitative radiomics features in discriminating second primary lung cancers (SPLCs) from pulmonary metastases (PMs).

Methods

This retrospective study enrolled 252 malignant pulmonary nodules with histopathologically confirmed SPLCs or PMs and randomly assigned them to a training or validation cohort. Clinical data were collected from the electronic medical records system. The imaging and radiomics features of each nodule were extracted from CT images.

Results

A rad-score was generated from the training cohort using the least absolute shrinkage and selection operator regression. A clinical and radiographic model was constructed using the clinical and imaging features selected by univariate and multivariate regression. A nomogram composed of clinical-radiographic factors and a rad-score were developed to validate the discriminative ability. The rad-scores differed significantly between the SPLC and PM groups. Sixteen radiomics features and four clinical-radiographic features were selected to build the final model to differentiate between SPLCs and PMs. The comprehensive clinical radiographic–radiomics model demonstrated good discriminative capacity with an area under the curve of the receiver operating characteristic curve of 0.9421 and 0.9041 in the respective training and validation cohorts. The decision curve analysis demonstrated that the comprehensive model showed a higher clinical value than the model without the rad-score.

Conclusion

The proposed model based on clinical data, imaging features, and radiomics features could accurately discriminate SPLCs from PMs. The model thus has the potential to support clinicians in improving decision-making in a noninvasive manner.
Case Report: Japanese Siblings of Cystic Fibrosis With a Novel Large Heterozygous Deletion in the CFTR Gene
Authors: Kawase Mayumi , Ogawa Masato , Hoshina Takayuki , Kojiro Masumi , Nakakuki Miyuki , Naruse Satoru , Ishiguro Hiroshi , Kusuhara Koichi
Published: January 2022

Cystic fibrosis (CF) is a rare disease in the Japanese. The most common CFTR variant in Japanese CF patients is a large heterozygous deletion that can easily avoid detection by standard gene sequencing methods. We herein report a novel large heterozygous deletion in the CFTR gene in Japanese siblings with CF. A genetic analysis was performed in two patients (9-year-old boy and 5-month-old girl) who were clinically diagnosed with CF because of the positive result for the rapid fecal pancreatic elastase antigen test and the elevation of the sweat chloride concentration. In addition to conventional polymerase chain reaction (PCR) and direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was performed to check for a large deletion and duplication of the CFTR gene. Based on MLPA findings, the breakpoint of heterozygous deletion was identified by real-time quantitative PCR followed by the sequence of the amplified junction fragment. In MLPA, the numbers of the fragments corresponding to exons 1, 16, 17a, and 17b and 234 nt and 747 nt upstream from the translation initiation codon of exon 1 in the CFTR gene and exon 3 in the ASZ1 gene were reduced by almost half. The c.2908+1085_3367+260del7201 variant (exon 16-17b deletion) was identified in one allele. The other allele had a large 137,567-bp deletion from g.117,361,112 (ASZ1 3′ flanking region) to g.117,498,678 (CFTR intron 1) on chromosome 7. Since the deletion variant lacked the entire promoter region of CFTR, CFTR mRNA would not be transcribed from the allele, indicating it to be a novel pathogenic variant causing CF. As large mutations are frequently detected in Japanese CF patients, MPLA can be useful when searching for variants.
Combining a Pharmacological Network Model with a Bayesian Signal Detection Algorithm to Improve the Detection of Adverse Drug Events
Authors: Ji Xiangmin , Cui Guimei , Xu Chengzhen , Hou Jie , Zhang Yunfei , Ren Yan
Published: January 2022

Introduction: Improving adverse drug event (ADE) detection is important for post-marketing drug safety surveillance. Existing statistical approaches can be further optimized owing to their high efficiency and low cost.

Objective: The objective of this study was to evaluate the proposed approach for use in pharmacovigilance, the early detection of potential ADEs, and the improvement of drug safety.

Methods: We developed a novel integrated approach, the Bayesian signal detection algorithm, based on the pharmacological network model (ICPNM) using the FDA Adverse Event Reporting System (FAERS) data published from 2004 to 2009 and from 2014 to 2019Q2, PubChem, and DrugBank database. First, we used a pharmacological network model to generate the probabilities for drug-ADE associations, which comprised the proper prior information component (IC). We then defined the probability of the propensity score adjustment based on a logistic regression model to control for the confounding bias. Finally, we chose the Side Effect Resource (SIDER) and the Observational Medical Outcomes Partnership (OMOP) data to evaluate the detection performance and robustness of the ICPNM compared with the statistical approaches [disproportionality analysis (DPA)] by using the area under the receiver operator characteristics curve (AUC) and Youden’s index.

Results: Of the statistical approaches implemented, the ICPNM showed the best performance (AUC, 0.8291; Youden’s index, 0.5836). Meanwhile, the AUCs of the IC, EBGM, ROR, and PRR were 0.7343, 0.7231, 0.6828, and 0.6721, respectively.

Conclusion: The proposed ICPNM combined the strengths of the pharmacological network model and the Bayesian signal detection algorithm and performed better in detecting true drug-ADE associations. It also detected newer ADE signals than a DPA and may be complementary to the existing statistical approaches.
Transcriptomic Profiling in Mice With CB1 receptor Deletion in Primary Sensory Neurons Suggests New Analgesic Targets for Neuropathic Pain
Authors: Liu Yongmin , Jia Min , Wu Caihua , Zhang Hong , Chen Chao , Ge Wenqiang , Wan Kexing , Lan Yuye , Liu Shiya , Li Yuanheng , Fang Mengyue , He Jiexi , Pan Hui-Lin , Si Jun-Qiang , Li Man
Published: January 2022

Type 1 and type 2 cannabinoid receptors (CB1 and CB2, respectively) mediate cannabinoid-induced analgesia. Loss of endogenous CB1 is associated with hyperalgesia. However, the downstream targets affected by ablation of CB1 in primary sensory neurons remain unknown. In the present study, we hypothesized that conditional knockout of CB1 in primary sensory neurons (CB1cKO) alters downstream gene expression in the dorsal root ganglion (DRG) and that targeting these pathways alleviates neuropathic pain. We found that CB1cKO in primary sensory neurons induced by tamoxifen in adult Advillin-Cre:CB1-floxed mice showed persistent hyperalgesia. Transcriptome/RNA sequencing analysis of the DRG indicated that differentially expressed genes were enriched in energy regulation and complement and coagulation cascades at the early phase of CB1cKO, whereas pain regulation and nerve conduction pathways were affected at the late phase of CB1cKO. Chronic constriction injury in mice induced neuropathic pain and changed transcriptome expression in the DRG of CB1cKO mice, and differentially expressed genes were mainly associated with inflammatory and immune-related pathways. Nerve injury caused a much larger increase in CB2 expression in the DRG in CB1cKO than in wildtype mice. Interfering with downstream target genes of CB1, such as antagonizing CB2, inhibited activation of astrocytes, reduced neuroinflammation, and alleviated neuropathic pain. Our results demonstrate that CB1 in primary sensory neurons functions as an endogenous analgesic mediator. CB2 expression is regulated by CB1 and may be targeted for the treatment of neuropathic pain.
Caenorhabditis Elegans Exhibits Morphine Addiction-like Behavior via the Opioid-like Receptor NPR-17
Authors: Ide Soichiro , Kunitomo Hirofumi , Iino Yuichi , Ikeda Kazutaka
Published: January 2022

Addiction has become a profound societal problem worldwide, and few effective treatments are available. The nematode Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study neurobiological disease states. C. elegans reportedly developed a preference for cues that had previously been paired with addictive drugs, similar to place conditioning findings in rodents. Moreover, several recent studies discovered and reported the existence of an opioid-like system in C. elegans. Still unclear, however, is whether C. elegans exhibits addictive-like behaviors for opioids, such as morphine. In the present study, we found that C. elegans exhibited dose-dependent preference for morphine using the conditioned chemosensory-cue preference (CCP) test. This preference was blocked by co-treatment with the opioid receptor antagonist naloxone. C. elegans also exhibited aversion to naloxone-precipitated withdrawal from chronic morphine exposure. The expression of morphine-induced CCP and morphine withdrawal were abolished in worms that lacked the opioid-like receptor NPR-17. Dopamine-deficient mutant (cat-2 (e1112)) worms also did not exhibit morphine-induced CCP. These results indicate that the addictive function of the opioid system exists in C. elegans, which may serve as a useful model of opioid addiction.
Human Arylamine N-Acetyltransferase 1 (NAT1) Knockout in MDA-MB-231 Breast Cancer Cell Lines Leads to Transcription of NAT2
Authors: Carlisle Samantha M. , Trainor Patrick J. , Doll Mark A. , Hein David W.
Published: January 2022

Many cancers, including breast cancer, have shown differential expression of human arylamine N-acetyltransferase 1 (NAT1). The exact effect this differential expression has on disease risk and progression remains unclear. While NAT1 is classically defined as a xenobiotic metabolizing enzyme, other functions and roles in endogenous metabolism have recently been described providing additional impetus for investigating the effects of varying levels of NAT1 on global gene expression. Our objective is to further evaluate the role of NAT1 in breast cancer by determining the effect of NAT1 overexpression, knockdown, and knockout on global gene expression in MDA-MB-231 cell lines. RNA-seq was utilized to interrogate differential gene expression (genes correlated with NAT1 activity) across three biological replicates of previously constructed and characterized MDA-MB-231 breast cancer cell lines expressing parental (Scrambled), increased (Up), decreased (Down, CRISPR 2–12), or knockout (CRISPR 2–19, CRISPR 5–50) levels of NAT1. 3,889 genes were significantly associated with the NAT1 N-acetylation activity of the cell lines (adjusted p ≤ 0.05); of those 3,889 genes, 1,756 were positively associated with NAT1 N-acetylation activity and 2,133 were negatively associated with NAT1 N-acetylation activity. An enrichment of genes involved in cell adhesion was observed. Additionally, human arylamine N-acetyltransferase 2 (NAT2) transcripts were observed in the complete NAT1 knockout cell lines (CRISPR 2–19 and CRISPR 5–50). This study provides further evidence that NAT1 functions as more than just a drug metabolizing enzyme given the observation that differences in NAT1 activity have significant impacts on global gene expression. Additionally, our data suggests the knockout of NAT1 results in transcription of its isozyme NAT2.
Numerical Study on the Influence of the Plasma Properties on the Keyhole Geometry in Laser Beam Welding
Authors: Coviello Donato , D’Angola Antonio , Sorgente Donato
Published: January 2022

Keyhole laser welding is the benchmark for deep-penetration joining processes. It needs high incident laser beam power densities at the workpiece surface to take place. The gaseous phase plays a fundamental role to keep the deep and narrow keyhole cavity open during the process. The plasma created in this process is a mixture of ionized metal vapors and the environmental gas and it develops inside the keyhole (keyhole plasma) and above the workpiece surface (plasma plume). The presence of plasma implicates absorption, scattering, and refraction of laser beam rays. These phenomena alter the power density of the laser beam irradiating the workpiece surface and thus affect the resulting welding process. In this work, a mathematical and numerical model has been developed to calculate the keyhole shape taking into account the plasma absorption effects. The model considers the keyhole walls as the liquid-vapor interface and computes the keyhole geometry applying a local energy balance at this interface. In addition, the model takes into account the multiple reflections effects inside the cavity through an iterative ray-tracing technique, and calculates the absorption mechanism due to inverse Bremsstrahlung for each ray along its segmented path inside the keyhole. Results show the effect of plasma properties on the keyhole shape and depth.
Safety of Bottle-Feeding Under Nasal Respiratory Support in Preterm Lambs With and Without Tachypnoea
Authors: Elsedawi Basma Fathi , Samson Nathalie , Nadeau Charlène , Vanhaverbeke Kristien , Nguyen Nam , Alain Charles , Fortin-Pellerin Etienne , Praud Jean-Paul
Published: January 2022

Aim: Convalescing preterm infants often require non-invasive respiratory support, such as nasal continuous positive airway pressure or high-flow nasal cannulas. One challenging milestone for preterm infants is achieving full oral feeding. Some teams fear nasal respiratory support might disrupt sucking–swallowing–breathing coordination and induce severe cardiorespiratory events. The main objective of this study was to assess the safety of oral feeding of preterm lambs on nasal respiratory support, with or without tachypnoea.

Methods: Sucking, swallowing and breathing functions, as well as electrocardiogram, oxygen haemoglobin saturation, arterial blood gases and videofluoroscopic swallowing study were recorded in 15 preterm lambs during bottle-feeding. Four randomly ordered conditions were studied: control, nasal continuous positive airway pressure (6 cmH2O), high-flow nasal cannulas (7 L•min–1), and high-flow nasal cannulas at 7 L•min–1 at a tracheal pressure of 6 cmH2O. The recordings were repeated on days 7–8 and 13–14 to assess the effect of maturation.

Results: None of the respiratory support impaired the safety or efficiency of oral feeding, even with tachypnoea. No respiratory support systematically impacted sucking–swallowing–breathing coordination, with or without tachypnoea. No effect of maturation was found.

Conclusion: This translational physiology study, uniquely conducted in a relevant animal model of preterm infant with respiratory impairment, shows that nasal respiratory support does not impact the safety or efficiency of bottle-feeding or sucking–swallowing–breathing coordination. These results suggest that clinical studies on bottle-feeding in preterm infants under nasal continuous positive airway pressure and/or high-flow nasal cannulas can be safely undertaken.
Effects of Food and Temperature on Drosophila melanogaster Reproductive Dormancy as Revealed by Quantification of a GFP-Tagged Yolk Protein in the Ovary
Authors: Hara Yusuke , Yamamoto Daisuke
Published: January 2022

When exposed to harsh environmental conditions, such as food scarcity and/or low temperature, Drosophila melanogaster females enter reproductive dormancy, a metabolic state that enhances stress resistance for survival at the expense of reproduction. Although the absence of egg chambers carrying yolk from the ovary has been used to define reproductive dormancy in this species, this definition is susceptible to false judgements of dormancy events: e.g. a trace amount of yolk could escape visual detection; a fly is judged to be in the non-dormancy state if it has a single yolk-containing egg chamber even when other egg chambers are devoid of yolk. In this study, we propose an alternative method for describing the maturation state of oocytes, in which the amount of yolk in the entire ovary is quantified by the fluorescence intensity derived from GFP, which is expressed as a fusion with the major yolk protein Yp1. We show that yolk deposition increases with temperature with a sigmoidal function, and the quality of food substantially alters the maximum accumulation of yolk attainable at a given temperature. The Yp1::GFP reporter will serve as a reliable tool for quantifying the amount of yolk and provides a new means for defining the dormancy state in D. melanogaster.
Divergent Abiotic Stressors Drive Grassland Community Assembly of Tibet and Mongolia Plateau
Authors: Wang Jianming , Li Mingxu , Xu Li , Liu Congcong , Yan Pu , He Nianpeng
Published: January 2022

Multiple ecological processes simultaneously govern community assembly, but it remains unclear how abiotic stressors regulate the relative importance of these processes among different biogeographic regions. Therefore, we conducted a comprehensive study on the responses of community assembly to varying environmental gradients, using the mean, variance, skewness, and kurtosis of plant height (height), specific leaf area (SLA) and leaf dry matter content (LDMC) distributions on the Tibetan Plateau (TP) and the Mongolian Plateau (MP). Our results showed that the prevalence of trait convergence across all grasslands in both TP and MP seem to be the result of abiotic filtering or weaker competitive exclusion etc. These trait-convergence assembly processes decrease the functional dispersion but increase the evenness of the trait frequency distribution. The mean, variance, skewness, and kurtosis responses of grassland communities to abiotic stress varied between the TP and MP. On average, plant trait distribution was mainly driven by temperature on the TP, and low-temperature stress altered the community assembly rules. In contrast, water availability shaped plant trait frequency distributions on the MP, and drought stress mediated the balance between different assembly processes. Our results provide empirical evidence that divergent abiotic stressors regulate the grassland community assembly on the TP and MP. Together, our study speculates that different aspects of future climate change, such as climate warming and changing precipitation patterns, on community assembly are dependent on regional climatic regimes.
Selenium Supplementation and Crop Plant Tolerance to Metal/Metalloid Toxicity
Authors: Hasanuzzaman Mirza , Nahar Kamrun , García-Caparrós Pedro , Parvin Khursheda , Zulfiqar Faisal , Ahmed Naznin , Fujita Masayuki
Published: January 2022

Selenium (Se) supplementation can restrict metal uptake by roots and translocation to shoots, which is one of the vital stress tolerance mechanisms. Selenium can also enhance cellular functions like membrane stability, mineral nutrition homeostasis, antioxidant response, photosynthesis, and thus improve plant growth and development under metal/metalloid stress. Metal/metalloid toxicity decreases crop productivity and uptake of metal/metalloid through food chain causes health hazards. Selenium has been recognized as an element essential for the functioning of the human physiology and is a beneficial element for plants. Low concentrations of Se can mitigate metal/metalloid toxicity in plants and improve tolerance in various ways. Selenium stimulates the biosynthesis of hormones for remodeling the root architecture that decreases metal uptake. Growth enhancing function of Se has been reported in a number of studies, which is the outcome of improvement of various physiological features. Photosynthesis has been improved by Se supplementation under metal/metalloid stress due to the prevention of pigment destruction, sustained enzymatic activity, improved stomatal function, and photosystem activity. By modulating the antioxidant defense system Se mitigates oxidative stress. Selenium improves the yield and quality of plants. However, excessive concentration of Se exerts toxic effects on plants. This review presents the role of Se for improving plant tolerance to metal/metalloid stress.
Disruption of the Nα-Acetyltransferase NatB Causes Sensitivity to Reductive Stress in Arabidopsis thaliana
Authors: Huber Monika , Armbruster Laura , Etherington Ross D. , De La Torre Carolina , Hawkesford Malcolm J. , Sticht Carsten , Gibbs Daniel J. , Hell Rüdiger , Wirtz Markus
Published: January 2022

In Arabidopsis thaliana, the evolutionary conserved N-terminal acetyltransferase (Nat) complexes NatA and NatB co-translationally acetylate 60% of the proteome. Both have recently been implicated in the regulation of plant stress responses. While NatA mediates drought tolerance, NatB is required for pathogen resistance and the adaptation to high salinity and high osmolarity. Salt and osmotic stress impair protein folding and result in the accumulation of misfolded proteins in the endoplasmic reticulum (ER). The ER-membrane resident E3 ubiquitin ligase DOA10 targets misfolded proteins for degradation during ER stress and is conserved among eukaryotes. In yeast, DOA10 recognizes conditional degradation signals (Ac/N-degrons) created by NatA and NatB. Assuming that this mechanism is preserved in plants, the lack of Ac/N-degrons required for efficient removal of misfolded proteins might explain the sensitivity of NatB mutants to protein harming conditions. In this study, we investigate the response of NatB mutants to dithiothreitol (DTT) and tunicamycin (TM)-induced ER stress. We report that NatB mutants are hypersensitive to DTT but not TM, suggesting that the DTT hypersensitivity is caused by an over-reduction of the cytosol rather than an accumulation of unfolded proteins in the ER. In line with this hypothesis, the cytosol of NatB depleted plants is constitutively over-reduced and a global transcriptome analysis reveals that their reductive stress response is permanently activated. Moreover, we demonstrate that doa10 mutants are susceptible to neither DTT nor TM, ruling out a substantial role of DOA10 in ER-associated protein degradation (ERAD) in plants. Contrary to previous findings in yeast, our data indicate that N-terminal acetylation (NTA) does not inhibit ER targeting of a substantial amount of proteins in plants. In summary, we provide further evidence that NatB-mediated imprinting of the proteome is vital for the response to protein harming stress and rule out DOA10 as the sole recognin for substrates in the plant ERAD pathway, leaving the role of DOA10 in plants ambiguous.
Mothers’ Experience of Social Change and Individualistic Parenting Goals Over Two Generations in Urban China
Authors: Bian Qinglin , Chen Yuyan , Greenfield Patricia M. , Yuan Qinyi
Published: January 2022

During the past four decades, China has gone through rapid urbanization and modernization. As people adapt to dramatic sociodemographic shifts from rural communities to urban centers and as economic level rises, individualistic cultural values in China have increased. Meanwhile, parent and child behavior in early childhood has also evolved accordingly to match a more individualistic society. This mixed-method study investigated how social change in China may have impacted parenting goals and child development in middle childhood, as seen through the eyes of the current generation of mothers. Thirty mothers of fifth-grade elementary school students from Shenzhen, China were recruited and took part in semi-structured interviews. Participants answered questions and provided examples about their children’s life, their own childhood, and the perceived differences between the two generations. Participating mothers were also asked to rate which generation, themselves or their parents, cared more about the childrearing goals of academic competitiveness and socioemotional well-being. Using both qualitative and quantitative analysis, we expected and found an intergenerational increase in the perceived value mothers placed on individualistic traits: current mothers care more about their children’s academic competitiveness, personal happiness, and social adjustment, compared to their experience of their own mothers’ attitudes during their childhood a generation earlier. They also experience conflict between their children’s academic competitiveness and socioemotional well-being. As a function of both urbanization and increased economic means, children’s collectivistic family responsibilities for essential household chores have declined as the importance of schoolwork has increased.
PRO-Mueve Relaciones Sanas – A Gender-Based Violence Prevention Program for Adolescents: Assessment of Its Efficacy in the First Year of Intervention
Authors: Velasco Lilian , Thomas-Currás Helena , Pastor-Ruiz Yolanda , Arcos-Rodríguez Aroa
Published: January 2022

PRO-Mueve Relaciones Sanas(PRO-Mote Healthy Relationships) is a gender-based violence and dating violence prevention program targeted at adolescents. The program has been designed to be implemented during three consecutive courses [from the first to third year of Spanish mandatory secondary education (ESO)] in 8 annual sessions, imparted by university students who have been previously trained and supervised by university professors. The present study evaluates the effects of the program after the first year of implementation through a quasi-experimental design (Intervention GroupN= 181; Quasi-control groupN= 62;Mage= 12.11; SDage= 0.57; 54.7% girls) and assesses whether there are gender differences in the outcomes. The results obtained evidenced a significant reduction in benevolent sexism in the intervention group compared to the quasi-control group. Regarding hostile sexism, it was found to increase significantly in the quasi-control group, while it remained stable in the intervention group. Thus, there were significant differences between both groups after the intervention. Likewise, romantic love myths were found to decrease significantly, and knowledge about gender-based violence increased significantly in the intervention group between the two time points assessed, although there were no significant differences with the quasi-control group. No gender differences in the outcomes of the program were observed. The obtained results supported the efficacy of the program during the first year of intervention in the first course of the ESO and laid the foundation for the following phases of intervention.
When Fathers Feel Socially Constrained to Assume a Role: A Negative Predictor of the Coparental Relationship in Switzerland
Authors: Favez Nicolas , Max Aline , Bader Michel , Tissot Hervé
Published: January 2022

Role distribution is a central issue for parents in the transition to parenthood, but little is known about the motivations in fathers to assume a specific role. Differences in work-family balance in each parent may be motivated by an individual choice mutually shared by both partners; however, in many couples, the parents may feel forced to adopt a traditional role distribution, either for financial reasons, or to comply with social expectations about what men and women should do when they are parents. This feeling of being socially constrained to adopt a role distribution that is not congruent with intrinsic motivations can generate dissatisfaction and may jeopardize the development of the interparental relationship. Coparenting refers to the emotional and instrumental support parents bring to each other in their parental tasks. It has been shown to be central in family functioning and a powerful predictor of children’s emotional and cognitive development. In this study, we aimed to assess the extent to which different motivations for role distribution in fathers are predictive of the quality of the coparental relationship. A convenience sample of 144 fathers from the French-speaking part of Switzerland completed online questionnaires about their motivations, coparental relationship, and sociodemographic characteristics. Results showed that the reasons for role distribution were mainly economical, practical, and in order to meet personal expectations. Multivariate general linear modeling showed that role distribution that is constrained to meet social expectations and age were predictive of a less cohesive coparental relationship, whereas a deliberate choice in role distribution was linked to a more cohesive coparental relationship.
Peer Relationships and Depressive Symptoms Among Adolescents: Results From the German BELLA Study
Authors: Adedeji Adekunle , Otto Christiane , Kaman Anne , Reiss Franziska , Devine Janine , Ravens-Sieberer Ulrike
Published: January 2022

Background: Poor mental health affects adolescent development and is associated with health and social outcomes in later life. The current study uses cross-sectional data to explore the understudied aspects of peer relationships as a predictor of depressive symptom severity of adolescents in Germany.

Method: Data from the German BELLA study were analyzed. We focused on the most recent measurement point of the BELLA study and analyzed data of 446 adolescents (aged 14–17 years). Peer relationship was measured using four items from the internationally established Patient-Reported Outcome Measurement Information System (PROMIS). Depressive symptoms were assessed via seven items of the German version of the Centre for Epidemiological Studies Short Depression Scale (CES-D). Hierarchical linear regression models were computed to explore the association between depressive symptoms and peer relationships. Hierarchical linear regression models served to determine the added predictive effects of each aspect of peer relationships.

Result: The regression model showed that 22% of the variance of the severity of depressive symptoms could be explained by the quality of adolescents’ peer relationships (F(1,444) = 125.65, p < 0.001). Peer acceptance has the most substantial unique contribution to peer relationship as a predictor of depressive symptom severity (Change in R2 = 0.05; Change in F = 27.01, p < 0.001). The gender-specific analysis shows different trends for boys and girls.

Conclusion: The quality of peer relationships is a significant predictor of adolescents’ depressive symptoms severity. Improved peer acceptance, dependability, and ease of making new friends are significantly associated with reduced depression symptoms for Germany’s adolescent population.