bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and Efficacy of the Rechallenge of Immune Checkpoint Inhibitors After Immune-Related Adverse Events in Patients With Cancer: A Systemic Review and Meta-Analysis
Authors: Zhao Qing , Zhang Jianwei , Xu Lingyi , Yang Huaxia , Liang Naixin , Zhang Li , Zhang Fengchun , Zhang Xuan
Published: September 2021

Introduction

Little evidence exists on the safety and efficacy of the rechallenge of immune checkpoint inhibitors (ICIs) after immune-related adverse events (irAEs) in patients with cancer.

Methods

We searched PubMed, Web of Science, Embase, and Cochrane for articles on ICI rechallenge after irAEs for systemic review and meta-analysis. The outcomes included the incidence and associated factors for safety and objective response rate (ORR) and disease control rate (DCR) for efficacy.

Results

A total of 789 ICI rechallenge cases from 18 cohort studies, 5 case series studies, and 54 case reports were included. The pooled incidence of all-grade and high-grade irAEs after rechallenge in patients with cancer was 34.2% and 11.7%, respectively. Compared with initial ICI treatment, rechallenge showed a higher incidence for all-grade irAEs (OR, 3.81; 95% CI, 2.15–6.74; p < 0.0001), but similar incidence for high-grade irAEs (p > 0.05). Types of initial irAEs (pneumonitis and global irAEs) and cancer (non-small cell lung cancer and multiple cancer) recapitulated these findings. Gastrointestinal irAEs and time interval between initial irAEs and ICI rechallenge were associated with higher recurrence of high-grade irAEs (p < 0.05), whereas initial anti-PD-1/PD-L1 antibodies were associated with a lower recurrence (p < 0.05). Anti-PD-1/PD-L1 antibodies rechallenge was associated with a lower all-grade irAE recurrence (p < 0.05). The pooled ORR and DCR after rechallenge were 43.1% and 71.9%, respectively, showing no significant difference compared with initial ICI treatment (p > 0.05).

Conclusions

ICI rechallenge after irAEs showed lower safety and similar efficacy outcomes compared with initial ICI treatment.

Systematic Review Registration

PROSPERO, identifier CRD42020191405.
Plant-Morphing Strategies and Plant-Inspired Soft Actuators Fabricated by Biomimetic Four-Dimensional Printing: A Review
Authors: Ren Luquan , Li Bingqian , Wang Kunyang , Zhou Xueli , Song Zhengyi , Ren Lei , Liu Qingping
Published: September 2021

Graphical Abstract

The plant-morphing strategies, manufacturing methods, materials, stimuli and applications of biological and bioinspired material.
The Stress-Active Cell Division Protein ZapE Alters FtsZ Filament Architecture to Facilitate Division in Escherichia coli
Authors: DiBiasio Eric C. , Dickinson Rebecca A. , Trebino Catherine E. , Ferreira Colby N. , Morrison Josiah J. , Camberg Jodi L.
Published: September 2021

During pathogenic infections, bacterial cells experience environmental stress conditions, including low oxygen and thermal stress. Bacterial cells proliferate during infection and divide by a mechanism characterized by the assembly of a large cytoskeletal structure at the division site called the Z-ring. The major protein constituting the Z-ring is FtsZ, a tubulin homolog and GTPase that utilizes the nucleotide to assemble into dynamic polymers. In Escherichia coli, many cell division proteins interact with FtsZ and modulate Z-ring assembly, while others direct cell wall insertion and peptidoglycan remodeling. Here, we show that ZapE, an ATPase that accumulates during late constriction, directly interacts with FtsZ and phospholipids in vitro. In the presence of adenosine triphosphate (ATP), ZapE induces bundling of GTP-induced FtsZ polymers; however, ZapE also binds FtsZ in the absence of GTP. The ZapE mutant protein ZapE(K84A), which is defective for ATP hydrolysis, also interacts with FtsZ and induces FtsZ filament bundling. In vivo, cultures of zapE deletion cells contain a low percentage of filamentous cells, suggesting that they have a modest division defect; however, they are able to grow when exposed to stress, such as high temperature and limited oxygen. When combined with the chromosomal deletion of minC, which encodes an FtsZ disassembly factor, ΔzapE ΔminC cells experience growth delays that slow proliferation at high temperature and prevent recovery. This synthetic slow growth phenotype after exposure to stress suggests that ZapE may function to ensure proliferation during and after stress, and this is exacerbated when cells are also deleted for minC. Expression of either ZapE or ZapE(K84A) complements the aberrant growth phenotypes in vivo suggesting that the division-associated role of ZapE does not require ZapE ATP hydrolysis. These results support that ZapE is a stress-regulated cell division protein that interacts directly with FtsZ and phospholipids, promoting growth and division after exposure to environmental stress.
A Seed-Endophytic Bacillus safensis Strain With Antimicrobial Activity Has Genes for Novel Bacteriocin-Like Antimicrobial Peptides
Authors: Romero-Severson Jeanne , Moran Thomas E. , Shrader Donna G. , Fields Francisco R. , Pandey-Joshi Susan , Thomas Clayton L. , Palmer Emily C. , Shrout Joshua D. , Pfrender Michael E. , Lee Shaun W.
Published: September 2021

Bacteriocins are a highly diverse group of antimicrobial peptides that have been identified in a wide range of commensal and probiotic organisms, especially those resident in host microbiomes. Rising antibiotic resistance have fueled renewed research into new drug scaffolds such as antimicrobial peptides for use in therapeutics. In this investigation, we examined mung bean seeds for endophytes possessing activity against human and plant pathogens. We isolated a novel strain of Bacillus safensis, from the contents of surface-sterilized mung bean seed, which we termed B. safensis C3. Genome sequencing of C3 identified three distinct biosynthetic systems that produce bacteriocin-based peptides. C3 exhibited antibacterial activity against Escherichia coli, Xanthomonas axonopodis, and Pseudomonas syringae. Robust antimicrobial activity of B. safensis C3 was observed when C3 was co-cultured with Bacillus subtilis. Using the cell-free supernatant of C3 and cation exchange chromatography, we enriched a product that retained antimicrobial activity against B. subtilis. The peptide was found to be approximately 3.3 kDa in size by mass spectrometry, and resistant to proteolysis by Carboxypeptidase Y and Endoproteinase GluC, suggesting that it is a modified variant of an AS-48 like bacteriocin. Our findings open new avenues into further development of novel bacteriocin-based scaffolds for therapeutic development, as well as further investigations into how our discoveries of bacteriocin-producing plant commensal microorganisms may have the potential for an immediate impact on the safety of food supplies.
The Ganglioside Monosialotetrahexosylganglioside Protects Auditory Hair Cells Against Neomycin-Induced Cytotoxicity Through Mitochondrial Antioxidation: An in vitro Study
Authors: Li Yujin , Li Ao , Wang Chao , Jin Xin , Zhang Yaoting , Lu Ling , Wang Shou-Lin , Gao Xia
Published: September 2021

Neomycin is a common ototoxic aminoglycoside antibiotic that causes sensory hearing disorders worldwide, and monosialotetrahexosylganglioside (GM1) is reported to have antioxidant effects that protect various cells. However, little is known about the effect of GM1 on neomycin-induced hair cell (HC) ototoxic damage and related mechanism. In this study, cochlear HC-like HEI-OC-1 cells along with whole-organ explant cultures were used to establish an in vitro neomycin-induced HC damage model, and then the apoptosis rate, the balance of oxidative and antioxidant gene expression, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were measured. GM1 could maintain the balance of oxidative and antioxidant gene expression, inhibit the accumulation of ROS and proapoptotic gene expression, promoted antioxidant gene expression, and reduce apoptosis after neomycin exposure in HEI-OC-1 cells and cultured cochlear HCs. These results suggested that GM1 could reduce ROS aggregation, maintain mitochondrial function, and improve HC viability in the presence of neomycin, possibly through mitochondrial antioxidation. Hence, GM1 may have potential clinical value in protecting against aminoglycoside-induced HC injury.
Recharging Difficulty With Pulse Generator After Deep Brain Stimulation: A Case Series of Five Patients
Authors: Li Hongyang , Su Daoqing , Lai Yijie , Xu Xinmeng , Zhang Chencheng , Sun Bomin , Li Dianyou , Pan Yixin
Published: September 2021

Background: Deep brain stimulation (DBS) is a well-established treatment for a variety of movement disorders. Rechargeable cell technology was introduced to pulse generator more than 10 years ago and brought great benefits to patients. However, with the widespread use of rechargeable implanted pulse generators (r-IPGs), a new hardware complication, when charging the r-IPG has been difficult, was encountered.

Objective: The aims of this study were to report five cases confronted with r-IPG charging difficulty postoperatively and to explore the predisposing factors and treatment strategies for this rare complication.

Methods: We retrospectively reviewed our DBS patient database for those who were implanted with r-IPGs. From 2012, we identified a total of 1,226 patients, with five of them experiencing charging difficulties after surgery. Detailed patient profiles and clinical procedures were scrutinized and reviewed.

Results: All the charging problems were resolved by reoperation. Cases 1 and 2 required their r-IPGs to be anchored to the muscle and fascia. Cases 3 and 4 had their r-IPGs inserted in the wrong orientation at the initial surgery, which was resolved by turning around the r-IPGs at the revision surgery. Case 5, in which we propose that the thick subcutaneous fat layer blocked the connection between the r-IPG and the recharger, required a second operation to reposition the r-IPG in a shallow layer underneath the skin. For all cases, the charging problems were resolved without reoccurrences to date.

Conclusion: Our case series indicates a novel hardware complication of DBS surgery, which had been rarely reported before. In this preliminary study, we describe several underlying causes of this complication and treatment methods.
PRDM12 Is Transcriptionally Active and Required for Nociceptor Function Throughout Life
Authors: Kokotović Tomislav , Langeslag Michiel , Lenartowicz Ewelina M. , Manion John , Fell Christopher W. , Alehabib Elham , Tafakhori Abbas , Darvish Hossein , Bellefroid Eric J. , Neely G. Gregory , Kress Michaela , Penninger Josef M. , Nagy Vanja
Published: September 2021

PR domain-containing member 12 (PRDM12) is a key developmental transcription factor in sensory neuronal specification and survival. Patients with rare deleterious variants in PRDM12 are born with congenital insensitivity to pain (CIP) due to the complete absence of a subtype of peripheral neurons that detect pain. In this paper, we report two additional CIP cases with a novel homozygous PRDM12 variant. To elucidate the function of PRDM12 during mammalian development and adulthood, we generated temporal and spatial conditional mouse models. We find that PRDM12 is expressed throughout the adult nervous system. We observed that loss of PRDM12 during mid-sensory neurogenesis but not in the adult leads to reduced survival. Comparing cellular biophysical nociceptive properties in developmental and adult-onset PRDM12 deletion mouse models, we find that PRDM12 is necessary for proper nociceptive responses throughout life. However, we find that PRDM12 regulates distinct age-dependent transcriptional programs. Together, our results implicate PRDM12 as a viable therapeutic target for specific pain therapies even in adults.
Prediction Model of Pathologic Central Lymph Node Negativity in cN0 Papillary Thyroid Carcinoma
Authors: Shu Xiujie , Tang Lingfeng , Hu Daixing , Wang Yuanyuan , Yu Ping , Yang Zhixin , Deng Chang , Wang Denghui , Su Xinliang
Published: September 2021

Background

Most patients with papillary thyroid carcinoma (PTC) have an excellent prognosis. Although central lymph node invasion is frequent, management via central lymph node dissection (CLND) remains controversial. The present study retrospectively investigated independent predictors of pathologic central lymph node negativity (pCLN-) and established a prediction model for pCLN- in clinical lymph node negativity (cN0) PTC.

Methods

A total of 2,687 patients underwent thyroid surgery for cN0 PTC from 2013 to 2018 at the First Affiliated Hospital of Chongqing Medical University, and lobectomy plus ipsilateral CLND was the basic surgical extent. Clinicopathological characteristics were reviewed and analyzed. Univariate and multivariate analyses were performed to identify factors related to pCLN-. A prediction model was established based on the results of multivariate analyses.

Results

The pCLN- rate was 51.5% (1,383/2,687). Multivariate analysis revealed that sex, age, thyroid stimulating hormone (TSH), size, location, laterality, unifocality and extrathyroidal extension negativity (ETE-) were independent predictors of pCLN-. The nomogram showed good discriminative ability (C-index: 0.784 and 0.787 in derivation and validation groups, respectively) and was well calibrated. We quantified the clinical usefulness of the nomogram by decision curve analysis. The median length of follow-up was 30 (range 12– 83) months, and 190 cases were lost, with a follow-up rate of 92.9% (2,497/2,687). Of the 2,687 patients included, 21 (0.8%) experienced recurrence.

Conclusion

This nomogram, which integrates available preoperative clinicopathological features and intraoperative frozen biopsy outcomes, is a reliable tool with high accuracy to predict pCLN- in cN0 PTC.
The Evolving Clinical Management of Genitourinary Cancers Amid the COVID-19 Pandemic
Authors: Izadmehr Sudeh , Lundon Dara J. , Mohamed Nihal , Katims Andrew , Patel Vaibhav , Eilender Benjamin , Mehrazin Reza , Badani Ketan K. , Sfakianos John P. , Tsao Che-Kai , Wiklund Peter , Oh William K. , Cordon-Cardo Carlos , Tewari Ashutosh K. , Galsky Matthew D. , Kyprianou Natasha
Published: September 2021

Coronavirus disease–2019 (COVID-19), a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has become an unprecedented global health emergency, with fatal outcomes among adults of all ages throughout the world. There is a high incidence of infection and mortality among cancer patients with evidence to support that patients diagnosed with cancer and SARS-CoV-2 have an increased likelihood of a poor outcome. Clinically relevant changes imposed as a result of the pandemic, are either primary, due to changes in timing or therapeutic modality; or secondary, due to altered cooperative effects on disease progression or therapeutic outcomes. However, studies on the clinical management of patients with genitourinary cancers during the COVID-19 pandemic are limited and do little to differentiate primary or secondary impacts of COVID-19. Here, we provide a review of the epidemiology and biological consequences of SARS-CoV-2 infection in GU cancer patients as well as the impact of COVID-19 on the diagnosis and management of these patients, and the use and development of novel and innovative diagnostic tests, therapies, and technology. This article also discusses the biomedical advances to control the virus and evolving challenges in the management of prostate, bladder, kidney, testicular, and penile cancers at all stages of the patient journey during the first year of the COVID-19 pandemic.
Extracellular Matrix Characterization in Gastric Cancer Helps to Predict Prognosis and Chemotherapy Response
Authors: Yang Zhi , Xue Feifei , Li Minhuan , Zhu Xingya , Lu Xiaofeng , Wang Chao , Xu En , Wang Xingzhou , Zhang Liang , Yu Heng , Ren Chuanfu , Wang Hao , Wang Yizhou , Chen Jie , Guan Wenxian , Xia Xuefeng
Published: September 2021

The extracellular matrix (ECM) plays a central role in the formation of the tumor microenvironment. The deposition of the ECM is associated with poor prognosis in a variety of tumors. Aberrant ECM deposition could undermine the effect of chemotherapy and immunotherapy. However, there is no systematic analysis on the relationship between the ECM and prognosis or chemotherapy effect. In the present study, we applied the gene set variation analysis (GSVA) algorithm to score 2199 canonical pathways in 2125 cases of probe or sequencing data and identified the core matrisome as the driving factor in gastric cancer progression. We classified gastric cancer samples into three clusters according to the composition of the ECM and evaluated clinical and multi-omics characterization of ECM phenotypes. The ECM score was evaluated by GSVA score of core matrisome and a higher ECM score predicted poor prognosis of gastric cancer [Hazard Ratio (HR), 2.084; p-value < 2 × 10−16]. In The Cancer Genome Atlas (TCGA) cohort and KUGH, YUSH, and KUCM cohorts, we verified that patients with a low ECM score could benefit from chemotherapy. By contrast, patients with a high ECM score did not achieve satisfactory response from chemotherapy. Determining the characteristics of the ECM microenvironment might help to predict the prognosis and chemotherapy response of patients with gastric cancer, and help to resolve the enigma of chemoresistance acquisition, as well as providing inspiration to develop combination therapy.
Resting Tendon Cross-Sectional Area Underestimates Biceps Brachii Tendon Stress: Importance of Measuring During a Contraction
Authors: Smart Rowan R. , O'Connor Brian , Jakobi Jennifer M.
Published: September 2021

Force produced by the muscle during contraction is applied to the tendon and distributed through the cross-sectional area (CSA) of the tendon. This ratio of force to the tendon CSA is quantified as the tendon mechanical property of stress. Stress is traditionally calculated using the resting tendon CSA; however, this does not take into account the reductions in the CSA resulting from tendon elongation during the contraction. It is unknown if calculating the tendon stress using instantaneous CSA during a contraction significantly increases the values of in vivo distal biceps brachii (BB) tendon stress in humans compared to stress calculated with the resting CSA. Nine young (22 ± 1 years) and nine old (76 ± 4 years) males, and eight young females (21 ± 1 years) performed submaximal isometric elbow flexion tracking tasks at force levels ranging from 2.5 to 80% maximal voluntary contraction (MVC). The distal BB tendon CSA was recorded on ultrasound at rest and during the submaximal tracking tasks (instantaneous). Tendon stress was calculated as the ratio of tendon force during contraction to CSA using the resting and instantaneous measures of CSA, and statistically evaluated with multi-level modeling (MLM) and Johnson–Neyman regions of significance tests to determine the specific force levels above which the differences between calculation methods and groups became statistically significant. The tendon CSA was greatest at rest and decreased as the force level increased (p < 0.001), and was largest in young males (23.0 ± 2.90 mm2) followed by old males (20.87 ± 2.0 mm2) and young females (17.08 ± 1.54 mm2) (p < 0.001) at rest and across the submaximal force levels. Tendon stress was greater in the instantaneous compared with the resting CSA condition, and young males had the greatest difference in the values of tendon stress between the two conditions (20 ± 4%), followed by old males (19 ± 5%), and young females (17 ± 5%). The specific force at which the difference between the instantaneous and resting CSA stress values became statistically significant was 2.6, 6.6, and 10% MVC for old males, young females, and young males, respectively. The influence of using the instantaneous compared to resting CSA for tendon stress is sex-specific in young adults, and age-specific in the context of males. The instantaneous CSA should be used to provide a more accurate measure of in vivo tendon stress in humans.
The Protective Effect of a Novel Cross-Linked Hemoglobin-Based Oxygen Carrier on Hypoxia Injury of Acute Mountain Sickness in Rabbits and Goats
Authors: Zhang Jie , Wu Yue , Peng Xiao-Yong , Li Qing-Hui , Xiang Xin-Ming , Zhu Yu , Yan Qing-Guang , Lau Billy , Tzang Feichuen , Liu Liang-Ming , Li Tao
Published: September 2021

Hypoxia is the major cause of acute altitude hypoxia injury in acute mountain sickness (AMS). YQ23 is a kind of novel bovine-derived, cross-linked hemoglobin-based oxygen carrier (HBOC). It has an excellent capacity for carrying and releasing oxygen. Whether YQ23 has a protective effect on the acute altitude hypoxia injury in AMS is unclear. In investigating this mechanism, the hypobaric chamber rabbit model and plain-to-plateau goat model were used. Furthermore, this study measured the effects of YQ23 on the ability of general behavior, general vital signs, Electrocardiograph (ECG), hemodynamics, vital organ injury markers, and blood gases in hypobaric chamber rabbits and plain-to-plateau goats. Our results showed that the ability of general behavior (general behavioral scores, GBS) (GBS: 18 ± 0.0 vs. 14 ± 0.5, p < 0.01) and the general vital signs weakened [Heart rate (HR, beats/min): 253.5 ± 8.7 vs. 301.1 ± 19.8, p < 0.01; Respiratory rate (RR, breaths/min): 86.1 ± 5.2 vs. 101.2 ± 7.2, p < 0.01] after exposure to plateau environment. YQ23 treatment significantly improved the ability of general behavior (GBS: 15.8 ± 0.5 vs. 14.0 ± 0.5, p < 0.01) and general vital signs [HR (beats/min): 237.8 ± 24.6 vs. 301.1 ± 19.8, p < 0.01; RR (breaths/min): 86.9 ± 6.6 vs. 101.2 ± 7.2, p < 0.01]. The level of blood PaO2 (mmHg) (115.3 ± 4.7 vs. 64.2 ± 5.6, p < 0.01) and SaO2(%) (97.7 ± 0.7 vs. 65.8 ± 3.1, p < 0.01) sharply decreased after exposure to plateau, YQ23 treatment significantly improved the blood PaO2 (mmHg) (97.6 ± 3.7 vs. 64.2 ± 5.6, p < 0.01) and SaO2(%) (82.7 ± 5.2 vs. 65.8 ± 3.1, p < 0.01). The cardiac ischemia and injury marker was increased [troponin (TnT, μg/L):0.08 ± 0.01 vs. 0.12 ± 0.02, p < 0.01], as well as the renal [blood urea nitrogen (BUN, mmol/L): 6.0 ± 0.7 vs. 7.3 ± 0.5, p < 0.01] and liver injury marker [alanine aminotransferase (ALT, U/L): 45.8 ± 3.6 vs. 54.6 ± 4.2, p < 0.01] was increased after exposure to a plateau environment. YQ23 treatment markedly alleviated cardiac ischemia [TnT (μg/L):0.10 ± 0.01 vs 0.12 ± 0.02, p < 0.01] and mitigated the vital organ injury. Besides, YQ23 exhibited no adverse effects on hemodynamics, myocardial ischemia, and renal injury. In conclusion, YQ23 effectively alleviates acute altitude hypoxia injury of AMS without aside effects.
Paternal Resistance Exercise Modulates Skeletal Muscle Remodeling Pathways in Fathers and Male Offspring Submitted to a High-Fat Diet
Authors: Salomão Rebecca , Neto Ivo Vieira de Sousa , Ramos Gracielle Vieira , Tibana Ramires Alsamir , Durigan João Quaglioti , Pereira Guilherme Borges , Franco Octávio Luiz , Royer Carine , Neves Francisco de Assis Rocha , Carvalho Ana Carolina Andrade de , Nóbrega Otávio Toledo , Haddad Rodrigo , Prestes Jonato , Marqueti Rita de Cássia
Published: September 2021

Although some studies have shown that a high-fat diet (HFD) adversely affects muscle extracellular matrix remodeling, the mechanisms involved in muscle trophism, inflammation, and adipogenesis have not been fully investigated. Thus, we investigated the effects of 8 weeks of paternal resistance training (RT) on gene and protein expression/activity of critical factors involved in muscle inflammation and remodeling of fathers and offspring (offspring exposed to standard chow or HFD). Animals were randomly distributed to constitute sedentary fathers (SF; n = 7; did not perform RT) or trained fathers (TF n = 7; performed RT), with offspring from mating with sedentary females. After birth, 28 male pups were divided into four groups (n = 7 per group): offspring from sedentary father submitted either to control diet (SFO-C) or high-fat diet (SFO-HF) and offspring from trained father submitted to control diet (TFO-C) or high-fat diet (TFO-HF). Our results show that an HFD downregulated collagen mRNA levels and upregulated inflammatory and atrophy pathways and adipogenic transcription factor mRNA levels in offspring gastrocnemius muscle. In contrast, paternal RT increased MMP-2 activity and decreased IL-6 levels in offspring exposed to a control diet. Paternal RT upregulated P70s6k and Ppara mRNA levels and downregulated Atrogin1 mRNA levels, while decreasing NFκ-B, IL-1β, and IL-8 protein levels in offspring exposed to an HFD. Paternal physical training influences key skeletal muscle remodeling pathways and inflammatory profiles relevant for muscle homeostasis maintenance in offspring submitted to different diets.
Metabolic Influences of Gut Microbiota Dysbiosis on Inflammatory Bowel Disease
Authors: Sultan Salma , El-Mowafy Mohammed , Elgaml Abdelaziz , Ahmed Tamer A. E. , Hassan Hebatoallah , Mottawea Walid
Published: September 2021

Inflammatory bowel diseases (IBD) are chronic medical disorders characterized by recurrent gastrointestinal inflammation. While the etiology of IBD is still unknown, the pathogenesis of the disease results from perturbations in both gut microbiota and the host immune system. Gut microbiota dysbiosis in IBD is characterized by depleted diversity, reduced abundance of short chain fatty acids (SCFAs) producers and enriched proinflammatory microbes such as adherent/invasiveE. coliand H2S producers. This dysbiosis may contribute to the inflammation through affecting either the immune system or a metabolic pathway. The immune responses to gut microbiota in IBD are extensively discussed. In this review, we highlight the main metabolic pathways that regulate the host-microbiota interaction. We also discuss the reported findings indicating that the microbial dysbiosis during IBD has a potential metabolic impact on colonocytes and this may underlie the disease progression. Moreover, we present the host metabolic defectiveness that adds to the impact of symbiont dysbiosis on the disease progression. This will raise the possibility that gut microbiota dysbiosis associated with IBD results in functional perturbations of host-microbiota interactions, and consequently modulates the disease development. Finally, we shed light on the possible therapeutic approaches of IBD through targeting gut microbiome.
ImageTBAD: A 3D Computed Tomography Angiography Image Dataset for Automatic Segmentation of Type-B Aortic Dissection
Authors: Yao Zeyang , Xie Wen , Zhang Jiawei , Dong Yuhao , Qiu Hailong , Yuan Haiyun , Jia Qianjun , Wang Tianchen , Shi Yiyi , Zhuang Jian , Que Lifeng , Xu Xiaowei , Huang Meiping
Published: September 2021

Type-B Aortic Dissection (TBAD) is one of the most serious cardiovascular events characterized by a growing yearly incidence, and the severity of disease prognosis. Currently, computed tomography angiography (CTA) has been widely adopted for the diagnosis and prognosis of TBAD. Accurate segmentation of true lumen (TL), false lumen (FL), and false lumen thrombus (FLT) in CTA are crucial for the precise quantification of anatomical features. However, existing works only focus on only TL and FL without considering FLT. In this paper, we propose ImageTBAD, the first 3D computed tomography angiography (CTA) image dataset of TBAD with annotation of TL, FL, and FLT. The proposed dataset contains 100 TBAD CTA images, which is of decent size compared with existing medical imaging datasets. As FLT can appear almost anywhere along the aorta with irregular shapes, segmentation of FLT presents a wide class of segmentation problems where targets exist in a variety of positions with irregular shapes. We further propose a baseline method for automatic segmentation of TBAD. Results show that the baseline method can achieve comparable results with existing works on aorta and TL segmentation. However, the segmentation accuracy of FLT is only 52%, which leaves large room for improvement and also shows the challenge of our dataset. To facilitate further research on this challenging problem, our dataset and codes are released to the public (Dataset, 2020).
Melatonin Alleviates Low-Temperature Stress via ABI5-Mediated Signals During Seed Germination in Rice (Oryza sativa L.)
Authors: Li Ruiqing , Jiang Meng , Song Yue , Zhang Huali
Published: September 2021

With increasing areas of direct sowing, low-temperature (LT) stress drastically affects global rice production. Exogenous applications of melatonin (MT) serve as one of the effective ways to improve seed germination under various stress conditions. In this study, we found that MT treatment greatly improved the LT stress-induced loss of germination percentage and the weak performance of seedlings under LT of constant 20°C (LT20). This was largely dependent on the activated antioxidant system and enhanced activities of storage substance utilization-associated enzymes. Moreover, we also detected that exogenous feeding of MT significantly increased the biosynthesis of gibberellin (GA) and endogenous MT but simultaneously inhibited the accumulation of abscisic acid (ABA) and hydrogen peroxide (H2O2) under LT20 stress. These results suggested that MT had antagonistic effects on ABA and H2O2. In addition, MT treatment also significantly enhanced the expression of CATALYSE 2 (OsCAT2), which was directly regulated by ABA-INSENSITIVE 5 (OsABI5), a core module of ABA-stressed signals, and thus promoting the H2O2 scavenging to reach reactive oxygen species (ROS) homeostasis, which consequently increased GA biosynthesis. However, in abi5 mutants, OsCAT2 failed in response to LT20 stress irrespective of MT treatment, indicating that OsABI5 is essential for MT-mediated seed germination under LT20 stress. Collectively, we now demonstrated that MT showed a synergistic interaction with an ABI5-mediated signal to mediate seed germination, partially through the direct regulation of OsCAT2.
Psychometric Properties of the Chinese Version of the Premonitory Urge for Tics Scale: A Preliminary Report
Authors: Li Ying , Woods Douglas W. , Gu Yi , Yu Liping , Yan Junjuan , Wen Fang , Wang Fang , Liu Jingran , Cui Yonghua
Published: September 2021

Premonitory urges (PUs) are sensory phenomena that immediately precede tics. The Premonitory Urge for Tics Scale (PUTS) is widely used to assess the severity of PUs, but the psychometric properties of PUTS and clinical features of PU in Chinese patients with tic disorders are still unclear. In this study, we examined the psychometric properties of the Chinese version of the PUTS in a large sample (including 367 Chinese pediatric patients with tic disorders). We found no difference in PU in different age groups. The exploratory factor analysis (EFA) of PUTS showed the emergence of four primary factors. The results of reliability and validity analyses indicated that the Chinese version showed good psychometric properties. It seemed that PU was associated with the severity of obsession symptoms in patients with tic disorders. Network analysis showed that Item 7 is a critical node for the PU, in addition to Items 1 and 4. Overall, the Chinese version of PUTS can be used in Chinese child and adolescent patients with tic disorders, particularly for patients with Tourette syndrome.
Effects of Depressed Mood on Syllogistic Reasoning: The Buffering Role of High Working Memory Span
Authors: Wasielewski Jaroslaw , Rydzewska Klara , Sedek Grzegorz
Published: September 2021

Previous research provided consistent evidence for the existence of the unique cognitive limitation in depressed mood: the impairment of the construction of mental models. In the current research, we applied the classical paradigm using categorical syllogisms to examine the relationship between depressed mood and integrative reasoning, aiming at gathering research evidence on the moderating role of the operation span of working memory. Specifically, we examine the hypothesis that high working memory capacity is a buffering variable and acts as a protective factor preventing the negative impact of depressed mood on syllogistic reasoning. A categorical syllogism, in the simpler evaluative form, consists of two premises (that are assumed to be true) and a conclusion that is to be evaluated as valid (when it follows logically from the premises) or invalid (when it does not follow from the premises). In the cover story, we informed participants that they would read about some observations carried out in a normal garden (believable conclusions) versus in a garden with radical genetic transformations (unbelievable conclusions) in order to stimulate the emergence of belief bias. The participants were 115 high school students who filled out the BDI scale and completed the OSPAN task. In line with predictions, there were main effects of depressed mood and operation span on the accuracy of performance (worse performance in the group with a high in comparison to a low level of depressed mood and much worse performance in low compared to high OSPAN participants). The analyses yielded a strong interaction effect of Depressed mood × OSPAN × Conflict. For participants with high levels of working memory capacity, there were no limitations related to a high level of depressed mood in syllogistic reasoning. On the other hand, a different pattern emerged for participants with low working memory span. In this group, participants with a high level of depressed mood in comparison to those with a low level of depressed mood showed much higher limitations in syllogistic reasoning, especially in reasoning concerning conflict syllogisms. We discuss the implications of this research for recent therapeutic programs using computerized cognitive tasks aimed at individuals with a high level of depressed mood.
Multimodal Assemblies for Prefacing a Dispreferred Response: A Cross-Linguistic Analysis
Authors: Pekarek Doehler Simona , Polak-Yitzhaki Hilla , Li Xiaoting , Stoenica Ioana Maria , Havlík Martin , Keevallik Leelo
Published: September 2021

In this paper we examine how participants’ multimodal conduct maps onto one of the basic organizational principles of social interaction: preference organization – and how it does so in a similar manner across five different languages (Czech, French, Hebrew, Mandarin, and Romanian). Based on interactional data from these languages, we identify a recurrent multimodal practice that respondents deploy in turn-initial position in dispreferred responses to various first actions, such as information requests, assessments, proposals, and informing. The practice involves the verbal delivery of a turn-initial expression corresponding to English ‘I don’t know’ and its variants (‘dunno’) coupled with gaze aversion from the prior speaker. We show that through this ‘multimodal assembly’ respondents preface a dispreferred response within various sequence types, and we demonstrate the cross-linguistic robustness of this practice: Through the focal multimodal assembly, respondents retrospectively mark the prior action as problematic and prospectively alert co-participants to incipient resistance to the constraints set out or to the stance conveyed by that action. By evidencing how grammar and body interface in related ways across a diverse set of languages, the findings open a window onto cross-linguistic, cross-modal, and cross-cultural consistencies in human interactional conduct.
Current Status and Associated Factors of Depression and Anxiety Among the Chinese Residents During the Period of Low Transmission of COVID-19
Authors: Shen Xin , Yan Shijiao , Cao Hui , Feng Jing , Lei Zihui , Zhang Weixin , Lv Chuanzhu , Gan Yong
Published: September 2021

Background: The outbreak of coronavirus disease 2019 (COVID-19) has contributed to depression and anxiety among the general population in China. The purpose of this study is to investigate the prevalence and associated factors of these psychological problems among Chinese adults during the period of low transmission, which could reflect the long-term depression and anxiety of the COVID-19 outbreak.

Methods: A cross-sectional survey was conducted in China from 4 to 26 February 2021. Convenient sampling strategy was adopted to recruit participators. Participants were asked to filled out the questions that assessed questionnaire on the residents’ depression and anxiety.

Results: A total of 2,361 residents filled out the questionnaire. The mean age was 29.72 years (SD = 6.94) and majority of respondents were female (60.10%). Among the respondents, 421 (17.83%), 1470 (62.26%), and 470 (19.91%) were from eastern, central, and western China, respectively. 1704 (72.17%) consented COVID-19 information has been disclosed timely. 142 (6.01%) and 130 (5.51%) patients suffered from depression and anxiety symptoms. Furthermore, some influencing factors were found, including marital status, place of residence, employment status.

Conclusion: This study revealed that anxiety and depression still are potential depression and anxiety for some residents, which suggested early recognition and initiation of interventions during the period of low transmission is still indispensable.
“Like I’m Talking to a Real Person”: Exploring the Meaning of Transference for the Use and Design of AI-Based Applications in Psychotherapy
Authors: Holohan Michael , Fiske Amelia
Published: September 2021

AI-enabled virtual and robot therapy is increasingly being integrated into psychotherapeutic practice, supporting a host of emotional, cognitive, and social processes in the therapeutic encounter. Given the speed of research and development trajectories of AI-enabled applications in psychotherapy and the practice of mental healthcare, it is likely that therapeutic chatbots, avatars, and socially assistive devices will soon translate into clinical applications much more broadly. While AI applications offer many potential opportunities for psychotherapy, they also raise important ethical, social, and clinical questions that have not yet been adequately considered for clinical practice. In this article, we begin to address one of these considerations: the role of transference in the psychotherapeutic relationship. Drawing on Karen Barad’s conceptual approach to theorizing human–non-human relations, we show that the concept of transference is necessarily reconfigured within AI-human psychotherapeutic encounters. This has implications for understanding how AI-driven technologies introduce changes in the field of traditional psychotherapy and other forms of mental healthcare and how this may change clinical psychotherapeutic practice and AI development alike. As more AI-enabled apps and platforms for psychotherapy are developed, it becomes necessary to re-think AI-human interaction as more nuanced and richer than a simple exchange of information between human and nonhuman actors alone.
How Knowledge-Hiding Behavior Among Manufacturing Professionals Influences Functional Interdependence and Turnover Intention
Authors: Jena Lalatendu Kesari , Swain Deepika
Published: September 2021

Objectives: Knowledge hiding is inappropriate behavior of employees at the workplace that makes the entire organization suffer a subtle yet significant loss. Lack of sharing makes the journey of learning an arduous process. This, in turn, gives rise to a series of uncivil behaviors, hence resulting in a decrease of functional interdependence (FI). The cascading result toll is a turnover intention (TI), resting only after turnover—an actual separation from the employer. Statistical analysis of the empirical data collected depicts the intensity of influence of FI and TI as a result of the knowledge-hiding behavior.

Methods: Three hundred sixty-three executives employed in three public and two private manufacturing organizations in eastern India were the respondents in our study. To analyze the difference in variables of the study, a t-test was carried out. The statistical findings suggest no significant difference among study variables. This specifies that, despite a considerable difference in levels of management, there was no significant difference in perceiving workplace incivility, knowledge-hiding behavior, FI, and TI items of our instruments.

Results: Correlation findings show a negative association between workplace incivility and functional interdependence (r = −0.37 when the value of p is <0.01) and a positive association among workplace incivility and turnover intention (r = 0.32 when the value of p is <0.01). The condensed effect of workplace incivility (β = −0.59 when the value of p is <0.001) along with an important presence of knowledge-hiding behavior (β = −0.68 when the value of p is <0.01) when the dependent variable is FI indicates that knowledge-hiding behavior is mediating a partial association among workplace incivility and FI. Similarly, the effect of workplace incivility (β = 0.43 when the value of p is <0.01) is decreased when the impact of knowledge-hiding behavior (β = 0.66 when the value of p is <0.001) was sizeable with TI being the dependent variable.

Conclusion: The effect of knowledge hiding is inversely proportional to FI, whereas sharing has a direct relation with TI. An exhaustive data sample and a rigorous statistical analysis may give a clear picture of the amount of impact of TI and FI due to the lack of knowledge sharing and/or knowledge hiding.
Electrophysiological Signatures of Perceiving Alternated Tone in Mandarin Chinese: Mismatch Negativity to Underlying Tone Conflict
Authors: Zeng Yuyu , Fiorentino Robert , Zhang Jie
Published: September 2021

Although phonological alternation is prevalent in languages, the process of perceiving phonologically alternated sounds is poorly understood, especially at the neurolinguistic level. We examined the process of perceiving Mandarin 3rd tone sandhi (T3 + T3 → T2 + T3) with a mismatch negativity (MMN) experiment. Our design has two independent variables (whether the deviant undergoes tone sandhi; whether the standard and the deviant have matched underlying tone). These two independent variables modulated ERP responses in both the first and the second syllables. Notably, despite the apparent segmental conflict between the standard and the deviant in all conditions, MMN is only observed when neither the standard nor the deviant undergoes tone sandhi, suggesting that discovering the underlying representation of an alternated sound could interfere with the generation of MMN. A tentative model with three hypothesized underlying processing mechanisms is proposed to explain the observed latency and amplitude differences across conditions. The results are also discussed in light of the potential electrophysiological signatures involved in the process of perceiving alternated sounds.
Polyphenols Extraction From Vegetable Wastes Using a Green and Sustainable Method
Authors: Doria Enrico , Boncompagni Eleonora , Marra Antonio , Dossena Maurizia , Verri Manuela , Buonocore Daniela
Published: September 2021

Food systems have the potential to support human health, respecting the environmental sustainability principles. Food sustainability, enclosed in the concept of environmental sustainability, involves different aspects, including the recycling of food waste derived from the agri-food production chain, the use of biotechnologies ensuring the sustainability of the recovery processes of bioactive compounds from food waste and, last but not least, the awareness of having to consume and waste less food. Food loss and waste is generated during the whole supply chain, from production to household utilization. The utilization of agricultural wastes as an abundant, renewable and low-cost source for the production of high value-added products is currently explored. The bioactive compounds present in these sources have been proved to possess a wide range of biological activities; therefore, research is needed into the application of environmentally friendly traditional and advanced techniques with low production costs in the extraction, isolation and purification of phytochemical compounds from agricultural wastes in high yields and at maximal quality. Authors of this manuscript propose and discuss an innovative and sustainable extraction system of polyphenols from vegetable waste, based on an enzymatic pre-treatment coupled with a solid-liquid extraction by using a particular extractor (Naviglio Estrattore®). This extraction system, organic solvent free, allowed to extract relevant amount of polyphenols (flavonoids in particular) from several vegetable waste products.
Comparison of the Efficacy of ShuoTong Ureteroscopy and Simple Flexible Ureteroscopy in the Treatment of Unilateral Upper Ureteral Calculi
Authors: Lai Longhui , Zhang Wenzhao , Zheng Fangjian , Wang Tao , Bai Peide , Liu Zhengsheng , Zheng Jiaxin , Shao Zhiqiang , Duan Bo , Wang Huiqiang , Xing Jinchun , Chen Huixin , Huang Yushan , Chen Bin
Published: September 2021

Background: ShuoTong ureteroscopy (Sotn-ureteroscopy, ST-URS), a new lithotripsy operation method developed on the basis of ureteroscopy, is widely used to treat ureteral stones in China. Its composition includes rigid ureteral access sheath, standard mirror, lithotripsy mirror, and ShuoTong perfusion aspirator (ST-APM). Here, we compared the efficacy and safety of the ST-URS and the flexible ureteroscope (F-URS) holmium laser lithotripsy in the treatment of unilateral upper ureteral calculi.

Methods: Retrospective analysis was conducted on the clinical data of 280 patients who met the inclusion 1) urinary tract CT was diagnosed with unilateral single upper ureteral calculi above the L4 lumbar spine; 2) patient age was from 18 to 80 years old; 3) patients were informed and consented to this study; and 4) patients were approved by the hospital ethics committee (proof number: KY-2019-020) and the exclusion criteria for unilateral upper ureteral calculi in the First Affiliated Hospital of Xiamen University from January 2018 to November 2020, and they were divided into the ST-URS group and the flexible ureteroscopy (F-URS) group.

Results: The stone-free rate of 1 day after operation of the ST-URS group was significantly higher than the F-URS group (63.71 vs. 34.62%, P < 0.0001). The operative time (38.45 vs. 46.18 min, P = 0.005) and hospitalization cost (27,203 vs. 33,220 Yuan, P < 0.0001) of the ST-URS group were significantly lower than the F-URS group. There were no significant differences in the success rate of ureteral access sheath placement, operative blood loss, stone-free rate of 1 month after operation, postoperative complications, postoperative hospital stay, and postoperative visual analog scale (VAS) pain score between the two groups (P > 0.05). In subgroups of a diameter of calculi ≥ 1.5 cm, calculi CT numerical value ≥ 1,000 Hounsfield unit and the preoperative hydronephrosis range ≥ 3.0 cm, ST-URS shows more advantages in the operative time, stone-free rate of 1 day after the operation, the hospitalization cost, and the incidence of postoperative complications.

Conclusion: In unilateral upper ureteral stones treated with a holmium laser, compared with the simple F-URS, the ST-URS has a shorter operative time, lower hospitalization cost, and a higher stone-free rate of 1 day after the operation, suggesting that the ST-URS could be more widely applied in clinics.