bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone Deacetylase 2 Knockdown Ameliorates Morphological Abnormalities of Dendritic Branches and Spines to Improve Synaptic Plasticity in an APP/PS1 Transgenic Mouse Model
Authors: Nakatsuka Daiki , Izumi Takaya , Tsukamoto Tasuku , Oyama Miki , Nishitomi Kohei , Deguchi Yuichi , Niidome Kazuki , Yamakawa Hidekuni , Ito Hisanori , Ogawa Koichi
Published: November 2021

Disease-modifying therapies, such as neuroprotective and neurorestorative interventions, are strongly desired for Alzheimer’s disease (AD) treatment. Several studies have suggested that histone deacetylase 2 (HDAC2) inhibition can exhibit disease-modifying effects in AD patients. However, whether HDAC2 inhibition shows neuroprotective and neurorestorative effects under neuropathic conditions, such as amyloid β (Aβ)-elevated states, remains poorly understood. Here, we performed HDAC2-specific knockdown in CA1 pyramidal cells and showed that HDAC2 knockdown increased the length of dendrites and the number of mushroom-like spines of CA1 basal dendrites in APP/PS1 transgenic mouse model. Furthermore, HDAC2 knockdown also ameliorated the deficits in hippocampal CA1 long-term potentiation and memory impairment in contextual fear conditioning tests. Taken together, our results support the notion that specific inhibition of HDAC2 has the potential to slow the disease progression of AD through ameliorating Aβ-induced neuronal impairments.
Glucagon-Like Peptide-1 Agonist Exendin-4 Facilitates the Extinction of Cocaine-Induced Condition Place Preference
Authors: Zhu Changliang , Hong Tao , Li Hailiang , Jiang Shucai , Guo Baorui , Wang Lei , Ding Jiangwei , Gao Caibin , Sun Yu , Sun Tao , Wang Feng , Wang Yangyang , Wan Din
Published: November 2021

Accumulating studies suggest that the glucagon-like peptide-1 receptor agonist exendin-4 (Ex4) and toll-like receptor 4 (TLR4) play a pivotal role in the maladaptive behavior of cocaine. However, few studies have assessed whether Ex4 can facilitate the extinction of drug-associated behavior and attenuate the reinstatement of cocaine-induced condition place preference (CPP) in mice. The main objective of the present study was to evaluate Ex4’s ability to regulate the extinction and reinstatement of cocaine-induced CPP. C57BL/6 mice were conditioned to either cocaine (20 mg/kg) or an equivalent volume of saline to establish a cocaine-mediated CPP paradigm. To investigate the potential effects of Ex4 on extinction, animals received an intraperitoneal injection of Ex4 either immediately or 6 h after each extinction or only on the test day. The persistence of extinction was measured using the reinstatement paradigm evoked by 10 mg/kg of cocaine. To explore the possible impacts of Ex4 and neuroinflammation on cocaine, the expression levels of TLR4 within the hippocampus was detected using western blotting. As a result, we found that systemic administration of Ex4 immediately after each extinction training, instead of 6 h after each extinction and on the day of extinction test, was capable of facilitating extinction in the confined or non-confined CPP extinction paradigms and blocking the cocaine-primed reinstatement of cocaine-induced CPP. Additionally, we also observed that Ex4 was competent to alleviate TLR4 signaling that has been up-regulated by cocaine. Altogether, our findings indicated that the combination of Ex4 with daily extinction training was sufficient to facilitate extinction of the conditioned behavior, attenuate reinstatement of cocaine-induced CPP and inhibit TLR4 signaling. Thus, Ex4 deserves further investigation as a potential intervention for the treatment of cocaine use disorder.
A Model of Predictive Postural Control Against Floor Tilting in Rats
Authors: Konosu Akira , Funato Tetsuro , Matsuki Yuma , Fujita Akihiro , Sakai Ryutaro , Yanagihara Dai
Published: November 2021

Humans and animals learn the internal model of bodies and environments from their experience and stabilize posture against disturbances based on the predicted future states according to the internal model. We evaluated the mechanism of predictive control during standing, by using rats to construct a novel experimental system and comparing their behaviors with a mathematical model. In the experiments, rats (n = 6) that were standing upright using their hindlimbs were given a sensory input of light, after a certain period, the floor under them tilted backward. Initially, this disturbance induced a large postural response, including backward rotation of the center-of-mass angle and hindlimb segments. However, the rats gradually adjusted to the disturbance after experiencing 70 sequential trials, and a reduction in the amplitude of postural response was noted. We simulated the postural control of the rats under disturbance using an inverted pendulum model and model predictive control (MPC). MPC is a control method for predicting the future state using an internal model of the control target. It provides control inputs that optimize the predicted future states. Identification of the predictive and physiological parameters so that the simulation corresponds to the experiment, resulted in a value of predictive horizon (0.96 s) close to the interval time in the experiment (0.9–1.15 s). These results suggest that the rats predict posture dynamics under disturbance based on the timing of the sensory input and that the central nervous system provides plasticity mechanisms to acquire the internal model for MPC.
The Effect of Exogenous Bile Acids on Antioxidant Status and Gut Microbiota in Heat-Stressed Broiler Chickens
Authors: Yin Chang , Xia Bing , Tang Shanlong , Cao Aizhi , Liu Lei , Zhong Ruqing , Chen Liang , Zhang Hongfu
Published: November 2021

Bile acids are critical for lipid absorption, however, their new roles in maintaining or regulating systemic metabolism are irreplaceable. The negative impacts of heat stress (HS) on growth performance, lipid metabolism, and antioxidant status have been reported, but it remains unknown whether the bile acids (BA) composition of broiler chickens can be affected by HS. Therefore, this study aimed to investigate the modulating effects of the environment (HS) and whether dietary BA supplementation can benefit heat-stressed broiler chickens. A total of 216 Arbor Acres broilers were selected with a bodyweight approach average and treated with thermal neutral (TN), HS (32°C), or HS-BA (200 mg/kg BA supplementation) from 21 to 42 days. The results showed that an increase in average daily gain (P < 0.05) while GSH-Px activities (P < 0.05) in both serum and liver were restored to the normal range were observed in the HS-BA group. HS caused a drop in the primary BA (P = 0.084, 38.46%) and Tauro-conjugated BA (33.49%) in the ileum, meanwhile, the secondary BA in the liver and cecum were lower by 36.88 and 39.45% respectively. Notably, results were consistent that SBA levels were significantly increased in the serum (3-fold, P = 0.0003) and the ileum (24.89-fold, P < 0.0001). Among them, TUDCA levels (P < 0.01) were included. Besides, BA supplementation indeed increased significantly TUDCA (P = 0.0154) and THDCA (P = 0.0003) levels in the liver, while ileal TDCA (P = 0.0307), TLCA (P = 0.0453), HDCA (P = 0.0018), and THDCA (P = 0.0002) levels were also increased. Intestinal morphology of ileum was observed by hematoxylin and eosin (H&E) staining, birds fed with BA supplementation reduced (P = 0.0431) crypt depth, and the ratio of villous height to crypt depth trended higher (P = 0.0539) under the heat exposure. Quantitative RT-PCR showed that dietary supplementation with BA resulted in upregulation of FXR (P = 0.0369), ASBT (P = 0.0154), and Keap-1 (P = 0.0104) while downregulation of iNOS (P = 0.0399) expression in ileum. Moreover, 16S rRNA gene sequencing analysis and relevance networks revealed that HS-derived changes in gut microbiota and BA metabolites of broilers may affect their resistance to HS. Thus, BA supplementation can benefit broiler chickens during high ambient temperatures, serving as a new nutritional strategy against heat stress.
Visceral Adiposity Associates With Malnutrition Risk Determined by Royal Free Hospital-Nutritional Prioritizing Tool in Cirrhosis
Authors: Wang Xiaoyu , Li Yifan , Sun Mingyu , Guo Gaoyue , Yang Wanting , Hui Yangyang , Yu Zihan , Li Chaoqun , Fan Xiaofei , Wang Bangmao , Zhang Jie , Zhao Xingliang , Jiang Kui , Sun Chao
Published: November 2021

Mounting evidence has suggested the clinical significance of body composition abnormalities in the context of cirrhosis. Herein, we aimed to investigate the association between visceral adiposity and malnutrition risk in 176 hospitalized patients with cirrhosis. The adiposity parameters were obtained by computed tomography (CT) as follows: total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR). Malnutrition risk was screened using Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Visceral adiposity was determined given a higher VSR based on our previously established cutoffs. Multivariate analysis implicated that male gender (OR = 2.884, 95% CI: 1.360–6.115, p = 0.006), BMI (OR = 0.879, 95% CI: 0.812–0.951, P = 0.001), albumin (OR = 0.934, 95% CI: 0.882–0.989, P = 0.019), and visceral adiposity (OR = 3.413, 95% CI: 1.344–8.670, P = 0.010) were independent risk factors of malnutrition risk. No significant difference was observed regarding TATI, SATI, and VATI among patients with low or moderate and high risk of malnutrition. In contrast, the proportion of male patients embracing visceral adiposity was higher in high malnutrition risk group compared with that in low or moderate group (47.27 vs. 17.86%, p = 0.009). Moreover, this disparity was of borderline statistical significance in women (19.05 vs. 5.88%, p = 0.061). Assessing adipose tissue distribution might potentiate the estimation of malnutrition risk in cirrhotics. It is pivotal to recognize visceral adiposity and develop targeted therapeutic strategies.
Navigating Multi-Scale Cancer Systems Biology Towards Model-Driven Clinical Oncology and Its Applications in Personalized Therapeutics
Authors: Gondal Mahnoor Naseer , Chaudhary Safee Ullah
Published: November 2021

Rapid advancements in high-throughput omics technologies and experimental protocols have led to the generation of vast amounts of scale-specific biomolecular data on cancer that now populates several online databases and resources. Cancer systems biology models built using this data have the potential to provide specific insights into complex multifactorial aberrations underpinning tumor initiation, development, and metastasis. Furthermore, the annotation of these single- and multi-scale models with patient data can additionally assist in designing personalized therapeutic interventions as well as aid in clinical decision-making. Here, we have systematically reviewed the emergence and evolution of (i) repositories with scale-specific and multi-scale biomolecular cancer data, (ii) systems biology models developed using this data, (iii) associated simulation software for the development of personalized cancer therapeutics, and (iv) translational attempts to pipeline multi-scale panomics data for data-drivenin silicoclinical oncology. The review concludes that the absence of a generic, zero-code, panomics-based multi-scale modeling pipeline and associated software framework, impedes the development and seamless deployment of personalizedin silicomulti-scale models in clinical settings.
Predicting Pathological Complete Response After Neoadjuvant Chemotherapy in Advanced Breast Cancer by Ultrasound and Clinicopathological Features Using a Nomogram
Authors: Cui Hao , Zhao Dantong , Han Peng , Zhang Xudong , Fan Wei , Zuo Xiaoxuan , Wang Panting , Hu Nana , Kong Hanqing , Peng Fuhui , Wang Ying , Tian Jiawei , Zhang Lei
Published: November 2021

Background and Aims

Prediction of pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for breast cancer is critical for surgical planning and evaluation of NAC efficacy. The purpose of this project was to assess the efficiency of a novel nomogram based on ultrasound and clinicopathological features for predicting pCR after NAC.

Methods

This retrospective study included 282 patients with advanced breast cancer treated with NAC from two centers. Patients received breast ultrasound before NAC and after two cycles of NAC; and the ultrasound, clinicopathological features and feature changes after two cycles of NAC were recorded. A multivariate logistic regression model was combined with bootstrapping screened for informative features associated with pCR. Then, we constructed two nomograms: an initial-baseline nomogram and a two-cycle response nomogram. Sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) were analyzed. The C-index was used to evaluate predictive accuracy.

Results

Sixty (60/282, 21.28%) patients achieved pCR. Triple-negative breast cancer (TNBC) and HER2-amplified types were more likely to obtain pCR. Size shrinkage, posterior acoustic pattern, and elasticity score were identified as independent factors by multivariate logistic regression. In the validation cohort, the two-cycle response nomogram showed better discrimination than the initial-baseline nomogram, with the C-index reaching 0.79. The sensitivity, specificity, and NPV of the two-cycle response nomogram were 0.77, 0.77, and 0.92, respectively.

Conclusion

The two-cycle response nomogram exhibited satisfactory efficiency, which means that the nomogram was a reliable method to predict pCR after NAC. Size shrinkage after two cycles of NAC was an important in dependent factor in predicting pCR.
Repeat Breast-Conserving Surgery Versus Salvage Mastectomy for Ipsilateral Breast Tumour Recurrence After Breast-Conserving Surgery in Breast Cancer Patients: A Meta-Analysis
Authors: Mo Caiqin , Ruan Weihong , Lin Junyu , Chen Huaying , Chen Xiangjin
Published: November 2021

Background

Salvage mastectomy (SM) is the standard surgery for ipsilateral breast tumour recurrence (IBTR). However, whether repeat breast-conserving surgery (RBCS) is an alternative method remains unclear. We performed a meta-analysis to compare the effects of RBCS and SM after IBTR for breast-conserving surgery (BCS).

Methods

We searched PubMed, Cochrane, Wiley Online and Embase for controlled studies comparing RBCS and SM after IBTR for BCS (published between 1993 and 2019, published in English). Our main endpoints were the secondary local recurrence rate (SLRR), distant metastasis rate (DMR) and overall survival (OS). We used a random-effects model or fixed-effects model for data pooling.

Results

Fifteen of the 424 eligible studies were ultimately included, and all studies were retrospective cohort studies (n=2532 participants). 1) SLRR: The SLRR of RBCS was higher than SM (pooled relative rate (pRR) = 1.87, 95% CI 1.22 - 2.86, P=0.004). Stratified analysis was performed according to whether radiotherapy was performed after salvage surgery (radiotherapy group: 2ndRT, no radiotherapy group: no-2ndRT), and the following results were revealed: pRR=0.43 (95% CI 0.20-0.95, P=0.04) for group 2ndRT; and pRR=2.30 (95% CI 1.72-3.06, P<0.00001) for group no-2ndRT. These results showed that the main cause of heterogeneity was salvage radiotherapy. 2) DMR: No significant difference in the DMR was observed between RBCS and SM (pRR = 0.61, 95% CI 0.37 - 1.01, P=0.05). 3) OS: No significant difference in OS was observed between RBCS and SM (pRR=0.65, 95% CI 0.39 - 1.08, P=0.10).

Conclusions

The SLRR of RBCS was higher than SM for ITBR after BCS, but survival was not affected. RBCS may be used as an alternative for IBTR patients after BCS with strict control for several indications, such as tumor size, recurrence interval and biological behavior, and attaching importance to subsequent salvage radiotherapy and systematic therapy.
An Early-Onset Advanced Rectal Cancer Patient With Increased KRAS Gene Copy Number Showed A Primary Resistance to Cetuximab in Combination With Chemotherapy: A Case Report
Authors: Fang Tian , Liang Tingting , Wang Yizhuo , Wu Haitao , Liu Shuhan , Xie Linying , Zhang Zhihao , Liang Jiaying , Yao Cheng , Tan Yehui , Wang Chang
Published: November 2021

Mutations in KRAS (codon 12/13), NRAS, BRAFV600E, and amplification of ERBB2 and MET account for 70–80% of anti-epidermal growth factor receptor (EGFR) monoclonal antibody primary resistance. However, the list of anti-EGFR monoclonal antibody primary resistance biomarkers is still incomplete. Herein, we report a case of wild-type RAS/BRAF metastatic colorectal cancer (CRC) with resistance to anti-EGFR monoclonal antibody and chemotherapy. Initially, mutation detection in postoperative tumor tissue by using amplification-refractory mutation system polymerase chain reaction indicated wild-type RAS/BRAF without point mutations, insertion deletions, or fusion mutations. Therefore, we recommended combined therapy of cetuximab and FOLFIRI after failure of platinum-based adjuvant chemotherapy, but the disease continued to progress. Next generation sequencing analysis of the postoperative tumor tissue revealed that KRAS copy number was increased and detected SMAD4, RNF43, and PREX2 mutations. This is the first case of advanced CRC with increased copy numbers of KRAS resistant to cetuximab and chemotherapy, which results in poor patient survival, and other mutated genes may be associated with the outcomes. Our findings indicate KRAS copy number alterations should also be examined, especially with anti-EGFR monoclonal antibody therapy in CRC, since it may be related with the primary resistance to these drugs.
Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives
Authors: Barchiesi Giacomo , Roberto Michela , Verrico Monica , Vici Patrizia , Tomao Silverio , Tomao Federica
Published: November 2021

Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metastatic breast cancer—olaparib and talazoparib—based on two phase III trials, which showed a progression-free survival benefit when compared to chemotherapy. Safety profile was manageable with supportive therapies and dose reductions/interruptions. In addition, other PARP inhibitors are currently under investigation, such as talazoparib, rucaparib, and veliparib. Subsequently, we will discuss the potential role of PARP inhibitors in the future. Clinical research areas are investigating PARP inhibitors in combination with other agents and are including patients without germline BRCA mutations: ongoing phase II/III studies are combining PARP inhibitors with immunotherapy, while phases I and II trials are combining PARP inhibitors with other targeted agents such as ATM and PIK3CA inhibitors. Moreover, several clinical trials are enrolling patients with somatic BRCA mutation or patients carrying mutations in genes, other than BRCA1/2, involved in the homologous recombination repair pathway (e.g., CHECK2, PALB2, RAD51, etc.).
Patient and Provider Experience With Cystic Fibrosis Telemedicine Clinic
Authors: Hendra Kalen , Neemuchwala Fatima , Chan Marilynn , Ly Ngoc P. , Gibb Elizabeth R.
Published: November 2021

In response to the novel coronavirus (COVID-19) pandemic, all in-person cystic fibrosis (CF) appointments were converted to telemedicine visits at UCSF Benioff Children's Hospital. The purpose of our study was to learn about the experiences that patients, families, and providers had with telemedicine visits and to assess their interest in using telemedicine in the future. Our hypothesis was that most patients, families, and providers want to continue telemedicine visits in the future. An anonymous 11-question survey was distributed to patients, families, and providers in November and December 2020. The survey was completed by 46 of 72 families (64% response rate) and 24 of 25 providers (96% response rate). Thirty-seven families (80%) and 21 providers (88%) were satisfied with their telemedicine experience. Thirty-three families (72%) want to have telemedicine visits in the future. Thirty-five families (76%) and 22 providers (92%) were satisfied with their experience using Zoom. Forty families (87%) and 19 providers (90%) want 2 or more visits each year to be via telemedicine. Our study showed that most families and providers were satisfied with telemedicine, would like to continue using telemedicine, and prefer to have at least 2 of the 4 recommended annual CF visits via telemedicine. Our survey identified the following benefits to telemedicine: decreased travel time, decreased cost, and avoiding exposure to COVID. However, we need to ensure that we do not exacerbate existing health disparities for families that do not speak English and/or do not have the internet capabilities to support telemedicine technology.
Transition From Full Mu Opioid Agonists to Buprenorphine in Opioid Dependent Patients—A Critical Review
Authors: Soyka Michael
Published: November 2021

Methadone, a full opioid agonist at the mu-, kappa-, and delta-receptor, and buprenorphine, a partial agonist at the mu receptor, are first-line medications in opioid maintenance treatment. Transition from methadone to buprenorphine may precipitate withdrawal, and no accepted algorithm for this procedure has been developed. Current treatment strategies recommend transfer from methadone to buprenorphine predominantly in patients at low doses of methadone (30–40 mg/day). There are some reports indicating that transition from higher doses of methadone may be possible. A number of dosing strategies have been proposed to soften withdrawal symptoms and facilitate transfer including use of other opioids or medications and especially microdosing techniques for buprenorphine. The case series and studies available thus far are reviewed.
Comparative Evaluation of Forsythiae Fructus From Different Harvest Seasons and Regions by HPLC/NIR Analysis and Anti-inflammatory and Antioxidant Assays
Authors: Qu Qian , Li Yuefei , Dong Qi , Li Shupeng , Du Hongliang , Wang Zhihua , Gong Xiaopei , Zhang Wenchang , Lv Weijie , Chao Limin , Liu Mengjie , Tang Xinggang , Guo Shining
Published: November 2021

Forsythiae Fructus (FF), the dry fruit of Forsythia suspensa (Thunb.) Vahl, has a long history of use in traditional Chinese Medicine for its heat-clearing and detoxifying properties. It possesses clinical therapeutic effects and biological functions showing efficacy in handling different diseases. To investigate the FF differences in Henan, Shanxi, and Shaanxi in August and October, the surface morphology, mid-infrared and near-infrared spectrums, and HPLC were analyzed. Concurrently, the anti-inflammatory and antioxidant effects on LPS-induced J774A.1 cells were evaluated by western blot and RT-qPCR. The results showed that FF from different Harvest Seasons and Regions are provided with different microstructures and mid-infrared and near-infrared spectrums, and the levels of forsythiaside A and phillyrin of FF from Shanxi in August and phillygenin of FF from Shaanxi in August were the highest. Meanwhile, FF from Shanxi and Shaanxi in August markedly reduced the levels of inflammatory cytokines and mediators (TNF-α, IL-1β, NF-κB, and iNOS) and the protein expression levels of phosphorylated total IKKα/β and nuclear NF-κB. In August, SXFF and SAXFF also promoted the mRNA expression levels of HO-1 and NQO1 and the protein expression levels of HO-1 and nuclear Nrf2 and suppressed the protein expression levels of KEAP1. Spearman correlation analysis showed that phillygenin had a strong correlation with the protein expression on LPS-induced J774A.1 cells. In summary, our results showed that FF from harvest seasons and regions contributed to the distinct differences in microstructure, the mid-infrared and near-infrared spectrums, and compound content. More importantly, FF from Shanxi and Shaanxi in August showed marked anti-inflammatory and antioxidant activities, but with some differences, which may be because of different contents of phillygenin and phillyrin of lignans in FF.
The Disulfiram/Copper Complex Induces Autophagic Cell Death in Colorectal Cancer by Targeting ULK1
Authors: Hu Yeting , Qian Yucheng , Wei Jingsun , Jin Tian , Kong Xiangxing , Cao Hongfeng , Ding Kefeng
Published: November 2021

Colorectal cancer (CRC) is highly prevalent worldwide, but there has been limited development of efficient and affordable treatment. Induced autophagy has recently been recognized as a novel therapeutic strategy in cancer treatment, and disulfiram (DSF), a well-known antialcohol drug, is also found to inhibit tumor growth in various malignancies. Recently, DSF has been reported to induce excessive autophagy in oral squamous cells; however, little is known about whether it can induce autophagy and suppress proliferation in CRC. In this study, we investigate the effect of DSF with copper (DSF/Cu) on CRC both in vitro and in vivo and find that the combination significantly inhibits CRC cell viability and mainly induces autophagy instead of apoptosis. Furthermore, we use whole genome CRISPR library screening and identify a new mechanism by which DSF triggers autophagy by ULK1. Overall, these findings provide a potential CRC treatment.
Ginsenoside Rb1 ameliorates Glycemic Disorder in Mice With High Fat Diet-Induced Obesity via Regulating Gut Microbiota and Amino Acid Metabolism
Authors: Yang Xueyuan , Dong Bangjian , An Lijun , Zhang Qi , Chen Yao , Wang Honglin , Song Ziteng
Published: November 2021

Accumulating evidences suggested an association between gut microbiome dysbiosis and impaired glycemic control. Ginsenoside Rb1 (Rb1) is a biologically active substance of ginseng, which serves anti-diabetic effects. However, its working mechanism especially interaction with gut microbes remains elusive in detail. In this study, we investigated the impact of Rb1 oral supplementation on high fat diet (HFD) induced obesity mice, and explored its mechanism in regulating blood glucose. The results showed that higher liver weight and lower cecum weight were observed in HFD fed mice, which was maintained by Rb1 administration. In addition, Rb1 ameliorated HFD induced blood lipid abnormality and improved insulin sensitivity. Several mRNA expressions in the liver were measured by quantitative real-time PCR, of which UCP2, Nr1H4, and Fiaf were reversed by Rb1 treatment. 16S rRNA sequencing analysis indicated that Rb1 significantly altered gut microbiota composition and increased the abundance of mucin-degrading bacterium Akkermansia spp. compared to HFD mice. As suggested via functional prediction, amino acid metabolism was modulated by Rb1 supplementation. Subsequent serum amino acids investigation indicated that several diabetes associated amino acids, like branched-chain amino acids, tryptophan and alanine, were altered in company with Rb1 supplementation. Moreover, correlation analysis firstly implied that the circulation level of alanine was related to Akkermansia spp.. In summary, Rb1 supplementation improved HFD induced insulin resistance in mice, and was associated with profound changes in microbial composition and amino acid metabolism.
Antioxidant Activity, Molecular Docking, Quantum Studies and In Vivo Antinociceptive Activity of Sulfonamides Derived From Carvacrol
Authors: de Oliveira Aldo S. , Llanes Luana C. , Nunes Ricardo J. , Nucci-Martins Catharina , de Souza Anacleto S. , Palomino-Salcedo David L. , Dávila-Rodríguez María J. , Ferreira Leonardo L. G. , Santos Adair R. S. , Andricopulo Adriano D.
Published: November 2021

The synthesis and antioxidant, antinociceptive and antiedematogenic activities of sulfonamides derived from carvacrol—a druglike natural product—are reported. The compounds showed promising antioxidant activity, and sulfonamide derived from morpholine (S1) demonstrated excellent antinociceptive and antiedematogenic activities, with no sedation or motor impairment. The mechanism that underlies the carvacrol and derived sulfonamides’ relieving effects on pain has not yet been fully elucidated, however, this study shows that the antinociceptive activity can be partially mediated by the antagonism of glutamatergic signaling. Compound S1 presented promising efficacy and was predicted to have an appropriate medicinal chemistry profile. Thus, derivative S1 is an interesting starting point for the design of new leads for the treatment of pain and associated inflammation and prooxidative conditions.
Pan-Cancer Analysis Reveals Alternative Splicing Characteristics Associated With Immune-Related Adverse Events Elicited by Checkpoint Immunotherapy
Authors: He Xiujing , Yu Jing , Shi Hubing
Published: November 2021

Immune-related adverse events (irAEs) can impair the effectiveness and safety of immune checkpoint inhibitors (ICIs) and restrict the clinical applications of ICIs in oncology. The predictive biomarkers of irAE are urgently required for early diagnosis and subsequent management. The exact mechanism underlying irAEs remains to be fully elucidated, and the availability of predictive biomarkers is limited. Herein, we performed data mining by combining pharmacovigilance data and pan-cancer transcriptomic information to illustrate the relationships between alternative splicing characteristics and irAE risk of ICIs. Four distinct classes of splicing characteristics considered were associated with splicing factors, neoantigens, splicing isoforms, and splicing levels. Correlation analysis confirmed that expression levels of splicing factors were predictive of irAE risk. AddingDHX16expression to the bivariate PD-L1 protein expression-fPD1 model markedly enhanced the prediction for irAE. Furthermore, we identified 668 and 1,131 potential predictors based on the correlation of the incidence of irAEs with splicing frequency and isoform expression, respectively. The functional analysis revealed that alternative splicing might contribute to irAE pathogenesis via coordinating innate and adaptive immunity. Remarkably, autoimmune-related genes and autoantigens were preferentially over-represented in these predictors for irAE, suggesting a close link between autoimmunity and irAE occurrence. In addition, we established a trivariate model composed of CDC42EP3-206, TMEM138-211, and IRX3-202, that could better predict the risk of irAE across various cancer types, indicating a potential application as promising biomarkers for irAE. Our study not only highlights the clinical relevance of alternative splicing for irAE development during checkpoint immunotherapy but also sheds new light on the mechanisms underlying irAEs.
Centromere-Specific Retrotransposons and Very-Long-Chain Fatty Acid Biosynthesis in the Genome of Yellowhorn (Xanthoceras sorbifolium, Sapindaceae), an Oil-Producing Tree With Significant Drought Resistance
Authors: Liu Hui , Yan Xue-Mei , Wang Xin-rui , Zhang Dong-Xu , Zhou Qingyuan , Shi Tian-Le , Jia Kai-Hua , Tian Xue-Chan , Zhou Shan-Shan , Zhang Ren-Gang , Yun Quan-Zheng , Wang Qing , Xiang Qiuhong , Mannapperuma Chanaka , Van Zalen Elena , Street Nathaniel R. , Porth Ilga , El-Kassaby Yousry A. , Zhao Wei , Wang Xiao-Ru , Guan Wenbin , Mao Jian-Feng
Published: November 2021

In-depth genome characterization is still lacking for most of biofuel crops, especially for centromeres, which play a fundamental role during nuclear division and in the maintenance of genome stability. This study applied long-read sequencing technologies to assemble a highly contiguous genome for yellowhorn (Xanthoceras sorbifolium), an oil-producing tree, and conducted extensive comparative analyses to understand centromere structure and evolution, and fatty acid biosynthesis. We produced a reference-level genome of yellowhorn, ∼470 Mb in length with ∼95% of contigs anchored onto 15 chromosomes. Genome annotation identified 22,049 protein-coding genes and 65.7% of the genome sequence as repetitive elements. Long terminal repeat retrotransposons (LTR-RTs) account for ∼30% of the yellowhorn genome, which is maintained by a moderate birth rate and a low removal rate. We identified the centromeric regions on each chromosome and found enrichment of centromere-specific retrotransposons of LINE1 andGypsyin these regions, which have evolved recently (∼0.7 MYA). We compared the genomes of three cultivars and found frequent inversions. We analyzed the transcriptomes from different tissues and identified the candidate genes involved in very-long-chain fatty acid biosynthesis and their expression profiles. Collinear block analysis showed that yellowhorn shared the gamma (γ) hexaploidy event withVitis viniferabut did not undergo any further whole-genome duplication. This study provides excellent genomic resources for understanding centromere structure and evolution and for functional studies in this important oil-producing plant.
Revisiting Women Empowerment Through a Cultural Lens a In-Depth Analysis of Empowerment Methodologies in Horticulture in Rural Ethiopia
Authors: De Smet Sarah , Boroş Smaranda
Published: November 2021

As previous research in international development has clearly demonstrated (see Banerjee and Prasad, 2008 for an overview), cultural values have an impact on the conceptualization of empowerment. In this paper we explore the implications of Power Distance as a cultural dimension for the use of participatory methodologies toward achieving women empowerment in rural areas in the Global South. Our critical analysis of cultural differences between the intervention facilitator (a Western-based NGO) and a rural community in SNNPR (Southern Nations, Nationalities and People’s Regions) in Ethiopia reveals how discrepancies in the perception of cultural values impacted the different stages of the intervention. These discrepancies ranged from the principles of facilitation (facilitation from the back and its paradoxical effects in such hierarchical contexts) to the focus on tools (on equality between individuals rather than focus on the family as the smallest unit). Discrepancies also surfaced from the selection criteria of participants (highly vulnerable groups; one spouse per family; number of participants from one community all of which prevented the impact of the intervention to be more powerful in the long run) and from how the participants are organized during trainings (the ratio of mixed vs. segregated groups and the criteria of group segregation – this can play a large role in regard to the potential openness of conversations and the creation of safe spaces to explore new identities which are the key to empowerment). Through all the stages of the intervention, we make suggestions on how to better implement such methodologies in the future, in a context-sensitive manner, by considering the cultural differences in assumptions and practices.
The Influence of Chinese College Students’ Physical Exercise on Life Satisfaction: The Chain Mediation Effect of Core Self-evaluation and Positive Emotion
Authors: Liu Feiyang , Zhu Zhengguang , Jiang Bo
Published: November 2021

Physical exercise is an important way for college students to maintain their physical health, and life satisfaction is one of the important indicators of college students’ mental health. Therefore, this study aims to explore the relationship between physical exercise and life satisfaction of college students. Additionally, we also seek to demonstrate the chain mediating effects of core self-evaluation and positive emotion on this relationship. A total of 794 Chinese college students, 324 men and 470 women, participated in the study. The participants were 17–25years old (M=19.96±1.54). They completed the Exercise Adherence Questionnaire, Core Self-evaluation Scale, Positive Affect and Negative Affect Scale, and Satisfaction with Life Scale. Results showed a strong positive relationship between physical exercise and life satisfaction and verified the mediating effect of core self-evaluation and positive emotion on this relationship. The results also confirmed the chain mediating model between physical exercise, core self-evaluation, positive emotion, and life satisfaction. It enlightens us that we should pay more attention to the organic combination of students’ physical activities and mental health education.
Meteorological Factors and the COVID-19 Pandemic: The Backdrop of Pakistan
Authors: Riaz Muhammad , Akhtar Muhammad Nadeem , Jinghong Shu , Gul Habib
Published: November 2021

Coronavirus victims have been confirmed all around the world and millions of people are being put into self-isolation. In this backdrop, a superior appreciation of the effective parameters in epidemic spreading can cause a cogent assessment toward COVID-19. In this vein, the consequences of weather indicators on the spread of COVID-19 can play an instrumental role in the current coronavirus situation enveloping the world. These elements entail time, maximum and minimum temperature, humidity, wind speed, and rainfall. By such an incorporation, their consequent effects on coronavirus in Pakistan are explored. In the current study, principal elements are considered including the number of infected patients with coronavirus in Pakistan. The autoregressive distribution lag (ARDL) approach is used to analyze the effects and relationships of variables with the COVID-19 expansion rate extracting data from April 1, 2020 to April 30, 2021. The results revealed that maximum and minimum temperature, humidity, wind speed, and rainfall had a significant positive correlation with total and confirmed cases of COVID-19. Lastly, this brief communication attempts to clarify the outbreak of coronavirus in the region.
Individual and Environmental Correlates of Adolescents’ Moral Decision-Making in Moral Dilemmas
Authors: Bacchini Dario , De Angelis Grazia , Dragone Mirella , Esposito Concetta , Affuso Gaetana
Published: November 2021

While extensive research has been conducted on adults’ judgments in moral sacrificial dilemmas, there is little research on adolescents. The present study aimed at: (1) adding further empirical evidence about adolescents’ moral decisions (deontological vs. utilitarian) in sacrificial moral dilemmas and (2) investigating how these moral decisions relate with gender, school grade, emotional traits (callous-unemotional traits), context-related experiences (perceived parental rejection and community violence exposure), and moral-related factors (moral disengagement and universalism value). A sample of 755 Italian adolescents (54.7% females; Mean age=16.45,SD=1.61) attending the second and the fifth year of secondary school took part in the study. Two sacrificial trolley-type dilemmas (where harmful actions promote the greater good) were presented. In the “switch” scenario (impersonal sacrificial dilemma), the choice is whether to hit a switch to save five people killing only one person. In the “footbridge” scenario (personal sacrificial dilemma), the choice is whether to push a large man off a footbridge saving five persons. For each scenario, participants had to indicate whether the proposed action was “morally acceptable” or not. Data were analyzed performing generalized linear mixed models. Our results showed that: (1) Adolescents were more likely to indicate as admissible to hit the switch rather than to push the large man; (2) male adolescents, compared to females, were more likely to say it was morally acceptable to intervene in the footbridge dilemma, whereas younger adolescents said it was morally acceptable both in the switch and the footbridge situations; and (3) higher levels of callous-unemotional traits, perceived parental rejection, and moral disengagement, on the one hand, and lower levels of universalism, on the other hand, were associated to higher admissibility to intervene in the footbridge scenario. Higher community violence exposure was associated with a lower propensity to intervene in the switch scenario. Overall, the present study expands the research on sacrificial dilemmas involving a sample of adolescents. The findings support previous studies concerning the role of emotions in making moral decisions but, at the same, open new perspectives regarding the role of contextual experiences and moral-related factors.
Treatment of Symptom Clusters in Schizophrenia, Bipolar Disorder and Major Depressive Disorder With the Dopamine D3/D2 Preferring Partial Agonist Cariprazine
Authors: Batinic Borjanka , Ristic Ivan , Zugic Milica , Baldwin David S.
Published: November 2021

Cariprazine is currently approved for the treatment of patients with schizophrenia (USA and EU), and for manic, depressive, and episodes with mixed features in bipolar I disorder (USA): several randomized controlled studies have also explored its efficacy in patients with major depressive disorder. This review summarizes its current therapeutic uses and potential advantages for treating the main symptoms of schizophrenia, bipolar I and major depressive disorder, considering its pharmacodynamic properties, efficacy, and tolerability. Its predominantly D3 receptor preferring affinity, with functional selectivity according to the prevailing neuronal environment, contributes to its efficacy across a wide array of psychopathological symptoms (including reality distortion, disorganized thought, negative symptoms, mood disturbance, anhedonia, and cognitive impairment), and to a favorable side effect profile. Cariprazine may be a “drug of choice” in patients with predominant negative and cognitive symptoms of schizophrenia, as well as those with metabolic syndrome. Further investigation of its relative efficacy when compared to aripiprazole or other active comparators is warranted. Its effectiveness in the treatment of bipolar mania, bipolar I depression and bipolar I episodes with mixed features, with minimal accompanying metabolic changes is well-established. The longer half-life and delayed time to relapse in patients diagnosed with schizophrenia when compared to other second-generation antipsychotics represent other advantages, given the high rates of non-adherence and frequent relapses seen in clinical practice. Its efficacy in overlapping symptom domains in other major psychiatric disorders appears promising.
Understanding the Barriers and Facilitators to Sharing Patient-Generated Health Data Using Digital Technology for People Living With Long-Term Health Conditions: A Narrative Review
Authors: Simpson Emma , Brown Richard , Sillence Elizabeth , Coventry Lynne , Lloyd Karen , Gibbs Jo , Tariq Shema , Durrant Abigail C.
Published: November 2021

Using digital technology to share patient-generated health data has the potential to improve the self-management of multiple long-term health conditions. Sharing these data can allow patients to receive additional support from healthcare professionals and peer communities, as well as enhance their understanding of their own health. A deeper understanding of the concerns raised by those living with long-term health conditions when considering whether to share health data via digital technology may help to facilitate effective data sharing practices in the future. The aim of this review is to identify whether trust, identity, privacy and security concerns present barriers to the successful sharing of patient-generated data using digital technology by those living with long-term health conditions. We also address the impact of stigma on concerns surrounding sharing health data with others. Searches of CINAHL, PsychInfo and Web of Knowledge were conducted in December 2019 and again in October 2020 producing 2,581 results. An iterative review process resulted in a final dataset of 23 peer-reviewed articles. A thorough analysis of the selected articles found that issues surrounding trust, identity, privacy and security clearly present barriers to the sharing of patient-generated data across multiple sharing contexts. The presence of enacted stigma also acts as a barrier to sharing across multiple settings. We found that the majority of literature focuses on clinical settings with relatively little attention being given to sharing with third parties. Finally, we suggest the need for more solution-based research to overcome the discussed barriers to sharing.
Mental Health Problems Due to Social Isolation During the COVID-19 Pandemic in a Mexican Population
Authors: Genis-Mendoza Alma Delia , Martínez-Magaña José Jaime , López-Narváez María Lilia , González-Castro Thelma Beatriz , Juárez-Rojop Isela Esther , Nicolini Humberto , Tovilla-Zárate Carlos Alfonso , Castillo-Avila Rosa Giannina
Published: November 2021

Introduction: Social isolation due to the COVID-19 pandemic has been identified as a risk factor of several mental disorders. Therefore, the present work aimed to evaluate the effect of social isolation experienced during the COVID-19 pandemic on the mental health of a Mexican population.

Materials and Methods: A cross-sectional online survey was conducted in individuals of 18 years of age and over. The questioner was structured to identify onset or worsening of psychiatric symptoms due to social isolation by COVID-19. The survey included changes in eating habits, changes in personal hygiene habits, the starting the use or increased the use of psychoactive substances, symptoms of depression or post-traumatic stress.

Results: A total of 1,011 individuals were included in the analysis. The majority were women (68.84%). Changes in eating habits were reported in 38.51% of the participants, 67.80% reported having their physical self-perception distorted or having started a low-calorie diet. Regarding symptoms of depression, 46.10% participants indicated to have at least one depressive symptom, and 4.46% reported suicidal ideation during social isolation. Interestingly, 6.09% of individuals reported that they used to have depressive symptoms prior the COVID-19 pandemic and those symptoms decreased due to social isolation. Additionally, 2.27% of individuals presented symptoms of post-traumatic stress due to the possibility of getting COVID-19.

Conclusions: In this work we identified how social isolation has impacted the mental health of the Mexican population. We observed that practically all the symptoms evaluated were affected during isolation, such as personal hygiene and eating habits. Depression and suicidal ideation were the ones that increased the most in the general population, while in individuals who had symptoms of depression before isolation, these symptoms decreased during social isolation.