bluuebunny/crossref_metadata_2025 huggingface dataset:
Absence of Obesity Paradox in All-Cause Mortality Among Chinese Patients With an Implantable Cardioverter Defibrillator: A Multicenter Cohort Study
Authors: Zhou Bin , Sun Xuerong , Yu Na , Zhao Shuang , Chen Keping , Hua Wei , Su Yangang , Yang Jiefu , Liang Zhaoguang , Xu Wei , Tang Min , Zhang Shu
Published: December 2021

Background: The results of studies on the obesity paradox in all-cause mortality are inconsistent in patients equipped with an implantable cardioverter-defibrillator (ICD). There is a lack of relevant studies on Chinese populations with large sample size. This study aimed to investigate whether the obesity paradox in all-cause mortality is present among the Chinese population with an ICD.

Methods: We conducted a retrospective analysis of multicenter data from the Study of Home Monitoring System Safety and Efficacy in Cardiac Implantable Electronic Device–implanted Patients (SUMMIT) registry in China. The outcome was all-cause mortality. The Kaplan–Meier curves, Cox proportional hazards models, and smooth curve fitting were used to investigate the association between body mass index (BMI) and all-cause mortality.

Results: After inclusion and exclusion criteria, 970 patients with an ICD were enrolled. After a median follow-up of 5 years (interquartile, 4.1–6.0 years), in 213 (22.0%) patients occurred all-cause mortality. According to the Kaplan–Meier curves and multivariate Cox proportional hazards models, BMI had no significant impact on all-cause mortality, whether as a continuous variable or a categorical variable classified by various BMI categorization criteria. The fully adjusted smoothed curve fit showed a linear relationship between BMI and all-cause mortality (p-value of 0.14 for the non-linearity test), with the curve showing no statistically significant association between BMI and all-cause mortality [per 1 kg/m2 increase in BMI, hazard ratio (HR) 0.97, 95% CI 0.93–1.02, p = 0.2644].

Conclusions: The obesity paradox in all-cause mortality was absent in the Chinese patients with an ICD. Prospective studies are needed to further explore this phenomenon.
Effect of Shenfu Injection on Reperfusion Injury in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Segment Elevation Myocardial Infarction: A Pilot Randomized Clinical Trial
Authors: Wang Xiao , Miao Huangtai , Yan Yan , Guo Ruifeng , Gong Wei , He Yi , Wang Hui , Ma Xinliang , Nie Shaoping
Published: December 2021

Background: Shenfu injection is a traditional Chinese medicine formulation that alleviates ischemia-reperfusion injury through multiple pharmacologic effects. However, no data are available regarding its efficacy in patients with myocardial infarction. We aimed to examine the effects of Shenfu injection on infarct size in patients with ST segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Methods: From April 2016 to February 2018, 40 patients with first-time anterior STEMI undergoing primary PCI within 6 h of symptom onset were randomized 1:1 to intravenous Shenfu injection (80 ml Shenfu injection + 70 ml 5% glucose injection) or placebo (150 ml 5% glucose injection) before reperfusion. Treatment started before PCI and maintained for 5 days after PCI. The primary end point was infarct size assessed by CK-MB area under the curve (AUC) over 72 h and cardiac magnetic resonance (CMR) imaging 4 ± 1 days after PCI.

Results: Infarct size by area under the curve for CK-MB over 72 h did not differ between the Shenfu injection and placebo groups (5602.5 [3539.4–7526.4] vs. 6403.2 [2234.4–8340.6] ng·h/ml, P = 0.82). Among 32 patients who underwent CMR Imaging, a nominal reduction in infarct size was observed in the Shenfu injection group compared with the placebo group (23.9 [15.2–28.5] % vs. 27 [21.9–31.9] %, P = 0.42). After excluding patients with no or minimal infarct, there was a trend toward reduction in infarct size in the Shenfu injection group (24.1 [20.3–29.3] % vs. 29.1 [24.5–32] %, P = 0.18). Incidence of adverse events was similar between the groups.

Conclusions: This pilot study showed that the use of Shenfu injection was safe but did not reduce infarct size by CMR Imaging and CK-MB release kinetics in reperfused patients with STEMI. Larger studies (confining to patients with extensive infarct size) to evaluate the efficacy of Shenfu injection on reperfusion injury are warranted.

Clinical Trail Registration:clinicaltrials.gov, identifier: NCT02709798.
High Precision Mammography Lesion Identification From Imprecise Medical Annotations
Authors: An Ulzee , Bhardwaj Ankit , Shameer Khader , Subramanian Lakshminarayanan
Published: December 2021

Breast cancer screening using Mammography serves as the earliest defense against breast cancer, revealing anomalous tissue years before it can be detected through physical screening. Despite the use of high resolution radiography, the presence of densely overlapping patterns challenges the consistency of human-driven diagnosis and drives interest in leveraging state-of-art localization ability of deep convolutional neural networks (DCNN). The growing availability of digitized clinical archives enables the training of deep segmentation models, but training using the most widely available form of coarse hand-drawn annotations works against learning the precise boundary of cancerous tissue in evaluation, while producing results that are more aligned with the annotations rather than the underlying lesions. The expense of collecting high quality pixel-level data in the field of medical science makes this even more difficult. To surmount this fundamental challenge, we propose LatentCADx, a deep learning segmentation model capable of precisely annotating cancer lesions underlying hand-drawn annotations, which we procedurally obtain using joint classification training and a strict segmentation penalty. We demonstrate the capability of LatentCADx on a publicly available dataset of 2,620 Mammogram case files, where LatentCADx obtains classification ROC of 0.97, AP of 0.87, and segmentation AP of 0.75 (IOU = 0.5), giving comparable or better performance than other models. Qualitative and precision evaluation of LatentCADx annotations on validation samples reveals that LatentCADx increases the specificity of segmentations beyond that of existing models trained on hand-drawn annotations, with pixel level specificity reaching a staggering value of 0.90. It also obtains sharp boundary around lesions unlike other methods, reducing the confused pixels in the output by more than 60%.
Nature of the Interplay Between Periodontal Diseases and COVID-19
Authors: Cai Wenji , Marouf Nadya , Said Khalid N. , Tamimi Faleh
Published: December 2021

The coronavirus disease 2019 (COVID-19) is mostly a mild condition, however, in some patients, it could progress into a severe and even fatal disease. Recent studies have shown that COVID-19 infection and severity could be associated with the presence of periodontitis, one of the most prevalent chronic diseases. This association could be explained by the fact that periodontitis and COVID-19 share some common risk factors that included chronic diseases, such as diabetes and hypertension as well as conditions such as age, sex, and genetic variants. Another possible explanation could be the systemic inflammation and the aspiration of periodontopathogens seen in patients with periodontitis, which could have a synergism with the virus or compromise the reaction of the body against COVID-19. This narrative review explores the nature of these associations, the evidence behind them, and their implications.
Growth Hormone Cotreatment for Low-Prognosis Patients According to the POSEIDON Criteria
Authors: Liu Xueying , Xu Jingxiao , Bi Lixin , Liu Peihao , Jiao Xue
Published: December 2021

Background

Poor ovarian response (POR) remains one of the most challenging conditions in assisted reproduction technology. Previous studies seemed to indicate that growth hormone (GH) was a potential solution for the dilemma of POR; however, the role GH played on the low-prognosis patients diagnosed and stratified by the POSEIDON criteria remains indistinct.

Methods

This retrospective study was performed among women with POR according to the POSEIDON criteria who failed a previous in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle, and the subsequent cycle was under GH cotreatment and conducted within 12 months. These participants were stratified into four groups according to the POSEIDON criteria. The comparison was implemented between the failed cycle and the cycle treated with GH. Generalized estimating equation (GEE) multivariate regression was applied for data analysis.

Results

A total of 428 low-prognosis women were included in this study. GH supplementation improved the live birth rates (47.66%, 28.33%, 45.45%, and 24.07%; in groups 1, 2, 3, and 4, respectively) and the clinical pregnancy rates (OR 19.16, 95% CI 7.87–46.63, p < 0.001; OR 7.44, 95% CI 1.65–33.55, p = 0.009; OR 10.19, 95% CI 2.39–43.52, p = 0.002; OR 27.63, 95% CI 4.46–171.11, p < 0.001; in groups 1, 2, 3, and 4, respectively) in all four POSEIDON groups. The number of oocytes retrieved was significantly elevated in the subgroups with normal ovarian reserve (IRR 1.47, 95% CI 1.36–1.59, p < 0.001; IRR 1.31, 95% CI 1.15–1.49, p < 0.001; in groups 1 and 2, respectively). The number of day-3 good-quality embryos was significantly elevated in the subgroups with either normal ovarian reserve or aged young (IRR 2.13, 95% CI 1.78–2.56, p < 0.001; IRR 1.54, 95% CI 1.26–1.89, p < 0.001; IRR 1.47, 95% CI 1.10–1.98, p = 0.010; in groups 1, 2, and 3, respectively).

Conclusion

Growth hormone cotreatment could ameliorate the pregnancy outcome for women with POR under the POSEIDON criteria who failed a previous IVF/ICSI cycle. The application of growth hormone for low-prognosis women who experienced a failed cycle might be considered and further studied.
The Study of Optimization of Flocculation and Destabilization Technology of Waste PEM Drilling Fluid in Bohai Oilfield
Authors: Liu Yang , Zhang Yuchen , Xie Tao , Yue Ming , Wang Dongsen , Li Bin
Published: December 2021

In light of the difficulty of solid-liquid separation of waste PEM drilling fluid in the Bohai oilfield, constructing an inorganic-organic flocculation system is proposed and the processing method of destabilization technology is optimized. The biggest influence factor on the flocculation process of PEM drilling fluid was determined by designing an orthogonal test. The flocculation mechanism was researched through single factor optimization, combined with zeta potential and particle size distribution test. The results showed that the most significant factors affecting the flocculation of waste PEM drilling fluid were the dosage of inorganic flocculant CaCl2 and flocculation pH value. When the dosage of inorganic flocculant CaCl2 was 1.2% (w/v), the dosage of organic flocculant SDYJ-2 was 0.05%, the flocculation pH value was 3, and the flocculation time was 5 min, the flocculation technology reached the optimization and then the liquid yield can reach 70.96%. The mechanism of flocculation and destabilization was as follows: the inorganic flocculant of CaCl2 mainly reduced the zeta potential of clay particles through electric neutralization. 1% CaCl2 could reduce the potential mean value of drilling fluid system from -38.1 mV to -32.5 mV, and then decrease the repulsion among suspensions. Through bridging curling and electric neutralization, the organic flocculant of SDYJ-2 can absorb and wrap the clay particles after flocculation destabilization to form a network spatial structure, which made clay particles aggregate into large flocs and particles. D50 can increase by 21.5 times, when the concentration of SDYJ-2 was 0.15%.
Tricking Parents: A Review of Mechanisms and Signals of Host Manipulation by Brood-Parasitic Young
Authors: Rojas Ripari Juan M. , Ursino Cynthia A. , Reboreda Juan C. , De Mársico María C.
Published: December 2021

Obligate avian brood parasites depend entirely on heterospecific hosts for rearing their offspring. From hatching until independence, the young parasites must deal with the challenge of obtaining sufficient parental care from foster parents that are attuned to provisioning their own offspring. Parent-offspring communication is mediated by complex begging displays in which nestlings and fledglings exhibit visual (e.g., gaping and postures) and vocal (e.g., begging calls) traits that serve as signals to parents to adjust and allocate parental effort. Parasites can manipulate host parental behavior by exploiting these stable parent-offspring communication systems in their favor. During the past 30 years, the study of host exploitation by parasitic chicks has yielded important insights into the function and evolution of manipulative signals in brood parasites. However, despite these major advances, there are still important gaps in our knowledge about how parasitic nestling and fledglings tune into the host’s communication channels and the adaptive value of the visual and acoustic signals they exhibit. Here we review the literature pertaining to host manipulation by parasitic young, focusing on four non-mutually exclusive mechanisms (i.e., host chick mimicry, begging exaggeration, host-attuned begging calls, and sensory exploitation) and the function and evolution of the signals involved, with the aim to summarize and discuss putative adaptations for stimulating parental feeding and escaping host discrimination. Finally, we bring some concluding remarks and suggest directions for future research on the ways in which brood parasites adapt to the communication systems of other birds to exploit the necessary parental care.
The Chemosensory Transcriptome of a Diving Beetle
Authors: Montagné Nicolas , Jager Muriel , Chertemps Thomas , Persyn Emma , Jaszczyszyn Yan , Meslin Camille , Jacquin-Joly Emmanuelle , Manuel Michaël
Published: December 2021

Insects astoundingly dominate Earth’s land ecosystems and have a huge impact on human life. Almost every aspect of their life relies upon their highly efficient and adaptable chemosensory system. In the air, most chemical signals that are detected at long range are hydrophobic molecules, which insects detect using proteins encoded by multigenic families that emerged following land colonization by insect ancestors, namely the odorant-binding proteins (OBPs) and the odorant receptors (ORs). However, land-to-freshwater transitions occurred in many lineages within the insect tree of life. Whether chemosensory gene repertoires of aquatic insects remained essentially unchanged or underwent more or less drastic modifications to cope with physico-chemical constraints associated with life underwater remains virtually unknown. To address this issue, we sequenced and analyzed the transcriptome of chemosensory organs of the diving beetle Rhantus suturalis (Coleoptera, Dytiscidae). A reference transcriptome was assembled de novo using reads from five RNA-seq libraries (male and female antennae, male and female palps, and wing muscle). It contained 47,570 non-redundant unigenes encoding proteins of more than 50 amino acids. Within this reference transcriptome, we annotated sequences coding 53 OBPs, 48 ORs, 73 gustatory receptors (GRs), and 53 ionotropic receptors (IRs). Phylogenetic analyses notably revealed a large OBP gene expansion (35 paralogs in R. suturalis) as well as a more modest OR gene expansion (9 paralogs in R. suturalis) that may be specific to diving beetles. Interestingly, these duplicated genes tend to be expressed in palps rather than in antennae, suggesting a possible adaptation with respect to the land-to-water transition. This work provides a strong basis for further evolutionary and functional studies that will elucidate how insect chemosensory systems adapted to life underwater.
Spondyloocular Syndrome: A Novel XYLT2 Variant with Description of the Neonatal Phenotype
Authors: Doddato Gabriella , Fabbiani Alessandra , Fallerini Chiara , Bruttini Mirella , Hadjistilianou Theodora , Landi Martino , Coradeschi Caterina , Grosso Salvatore , Tomasini Barbara , Mencarelli Maria Antonietta , Renieri Alessandra , Ariani Francesca
Published: December 2021

Spondyloocular syndrome (SOS) is a skeletal disorder caused by pathogenic variants in XYLT2 gene encoding a xylotransferase involved in the biosynthesis of proteoglycans. This condition, with autosomal recessive inheritance, has a high phenotypic variability. It is characterized by bone abnormalities (osteoporosis, fractures), eye and cardiac defects, hearing impairment, and varying degrees of developmental delay. Until now only 20 mutated individuals have been reported worldwide. Here, we describe two siblings from consanguineous healthy parents in which a novel homozygous frameshift variant c.1586dup p(Thr530Hisfs*) in the XYLT2 gene was detected by exome sequencing (ES). The first patient (9 years) presented short stature with skeletal defects, long face, hearing loss and cataract. The second patient, evaluated at a few days of life, showed macrosomia, diffuse hypertrichosis on the back, overabundant skin in the retronucal area, flattened facial profile with drooping cheeks, elongated eyelid rims, wide and flattened nasal bridge and turned down corners of the mouth. During the prenatal period, high nuchal translucency and intestinal hyperechogenicity were observed at ultrasound. In conclusion, these two siblings with a novel pathogenic variant in XYLT2 further expand the clinical and mutational spectrum of SOS.
AC093797.1 as a Potential Biomarker to Indicate the Prognosis of Hepatocellular Carcinoma and Inhibits Cell Proliferation, Invasion, and Migration by Reprogramming Cell Metabolism and Extracellular Matrix Dynamics
Authors: Liu Xiaoling , Wang Chenyu , Yang Qing , Yuan Yue , Sheng Yunjian , Li Decheng , Ojha Suvash Chandra , Sun Changfeng , Deng Cunliang
Published: December 2021

Purpose: The risk signature composed of four lncRNA (AC093797.1, POLR2J4, AL121748.1, and AL162231.4.) can be used to predict the overall survival (OS) of patients with hepatocellular carcinoma (HCC). However, the clinical significance and biological function of AC093797.1 are still unexplored in HCC or other malignant tumors. In this study, we aimed to investigate the biological function of AC093797.1 in HCC and screen the candidate hub genes and pathways related to hepatocarcinogenesis.

Methods: RT-qPCR was employed to detect AC093797.1 in HCC tissues and cell lines. The role of AC093797.1 in HCC was evaluated via the cell-counting kit-8, transwell, and wound healing assays. The effects of AC093797.1 on tumor growth in vivo were clarified by nude mice tumor formation experiments. Then, RNA-sequencing and bioinformatics analysis based on subcutaneous tumor tissue was performed to identify the hub genes and pathways associated with HCC.

Results: The expression of AC093797.1 decreased in HCC tissues and cell lines, and patients with low expressed AC093797.1 had poor overall survival (OS). AC093797.1 overexpression impeded HCC cell proliferation, invasion, and migration in vitro and suppressed tumor growth in vivo. Compared with the control group, 710 differentially expressed genes (243 upregulated genes and 467 downregulated genes) were filtered via RNA-sequencing, which mainly enriched in amino acid metabolism, extracellular matrix structure constituents, cell adhesion molecules cams, signaling to Ras, and signaling to ERKs.

Conclusion: AC093797.1 may inhibit cell proliferation, invasion, and migration in HCC by reprograming cell metabolism or regulating several pathways, suggesting that AC093797.1 might be a potential therapeutic and prognostic marker for HCC patients.
Identification of a Pyroptosis-Related Gene Signature for Predicting Overall Survival and Response to Immunotherapy in Hepatocellular Carcinoma
Authors: Zheng Susu , Xie Xiaoying , Guo Xinkun , Wu Yanfang , Chen Guobin , Chen Xiaochun , Wang Meixia , Xue Tongchun , Zhang Boheng
Published: December 2021

Pyroptosis is a novel kind of cellular necrosis and shown to be involved in cancer progression. However, the diverse expression, prognosis and associations with immune status of pyroptosis-related genes in Hepatocellular carcinoma (HCC) have yet to be analyzed. Herein, the expression profiles and corresponding clinical characteristics of HCC samples were collected from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Then a pyroptosis-related gene signature was built by applying the least absolute shrinkage and selection operator (LASSO) Cox regression model from the TCGA cohort, while the GEO datasets were applied for verification. Twenty-four pyroptosis-related genes were found to be differentially expressed between HCC and normal samples. A five pyroptosis-related gene signature (GSDME, CASP8, SCAF11, NOD2, CASP6) was constructed according to LASSO Cox regression model. Patients in the low-risk group had better survival rates than those in the high-risk group. The risk score was proved to be an independent prognostic factor for overall survival (OS). The risk score correlated with immune infiltrations and immunotherapy responses. GSEA indicated that endocytosis, ubiquitin mediated proteolysis and regulation of autophagy were enriched in the high-risk group, while drug metabolism cytochrome P450 and tryptophan metabolism were enriched in the low-risk group. In conclusion, our pyroptosis-related gene signature can be used for survival prediction and may also predict the response of immunotherapy.
Prevalence and Correlates of Zinc Deficiency Among Vietnamese Women of Reproductive Age in Ho Chi Minh City: A Single Hospital-Based Survey
Authors: Nguyen Vinh Quang , Lam Phong Van , Goto Aya , Nguyen Tu Van T. , Vuong Thanh Nhan T. , Nguyen Tien Minh , Nguyen Minh Ha , Truong Anh Tuyet T. , Tran Truc Phuong T. , Vo Chien Duc
Published: December 2021

Background and Objectives: Zinc is a micronutrient that plays an important role in metabolism, cell growth regulation, and differentiation. Vietnam has many population groups living in poverty. The daily food of Vietnamese people is mainly rice, which contains very little zinc. This cross-sectional study was conducted to determine the prevalence of, and factors related to, zinc deficiency in women of reproductive age.

Methods and Study Design: The sample population was non-pregnant women of reproductive age (18–49 years old) who visited Nguyen Tri Phuong Hospital Gynecological Outpatient Clinic. The subjects were interviewed and data on background characteristics, anthropometric measurements, and blood tests (serum zinc concentration, complete blood count, albumin, and ferritin) were collected.

Results: The prevalence of zinc deficiency, as defined by the International Zinc Nutrition Consultative Group (IZiNCG), was 85% [61/72; 95% confidence interval (CI) = 74–91%], and the prevalence of severe zinc deficiency was 37% (27/72; 95% CI = 26–50%). There were significant associations of albumin concentration, marital status, and past pregnancy history with severe zinc deficiency.

Conclusions: More than three-fourths of Vietnamese women of reproductive age had zinc deficiency at our study site in Ho Chi Minh City. This health issue requires greater attention in order to swiftly promote preventive actions, and further surveillance to confirm our study findings.
EASINESS: E. coli Assisted Speedy affINity-maturation Evolution SyStem
Authors: Zhang Hai-nan , Xue Jun-biao , Wang Aru Ze-ling , Jiang He-wei , Merugu Siva Bhararth , Li Da-wei , Tao Sheng-ce
Published: December 2021

Antibodies are one of the most important groups of biomolecules for both clinical and basic research and have been developed as potential therapeutics. Affinity is the key feature for biological activity and clinical efficacy of an antibody, especially of therapeutic antibodies, and thus antibody affinity improvement is indispensable and still remains challenging. To address this issue, we developed the E. coliAssisted Speed affINity-maturation Evolution SyStem (EASINESS) for continuous directed evolution of Ag–Ab interactions. Two key components of EASINESS include a mutation system modified from error-prone DNA polymerase I (Pol I) that selectively mutates ColE1 plasmids in E. coli and a protein–protein interaction selection system from mDHFR split fragments. We designed a GCN4 variant which barely forms a homodimer, and during a single round of evolution, we reversed the homodimer formation activity from the GCN4 variant to verify the feasibility of EASINESS. We then selected a potential therapeutic antibody 18A4Hu and improved the affinity of the antibody (18A4Hu) to its target (ARG2) 12-fold in 7 days while requiring very limited hands-on time. Remarkably, these variants of 18A4Hu revealed a significant improved ability to inhibit melanoma pulmonary metastasis in a mouse model. These results indicate EASINESS could be as an attractive choice for antibody affinity maturation.
Nitric Oxide Synthase Regulates Gut Microbiota Homeostasis by ERK-NF-κB Pathway in Shrimp
Authors: Hong Pan-Pan , Zhu Xiao-Xu , Yuan Wen-Jie , Niu Guo-Juan , Wang Jin-Xing
Published: December 2021

The gut microbiota is a complex group of microorganisms that is not only closely related to intestinal immunity but also affects the whole immune system of the body. Antimicrobial peptides and reactive oxygen species participate in the regulation of gut microbiota homeostasis in invertebrates. However, it is unclear whether nitric oxide, as a key mediator of immunity that plays important roles in antipathogen activity and immune regulation, participates in the regulation of gut microbiota homeostasis. In this study, we identified a nitric oxide synthase responsible for NO production in the shrimpMarsupenaeus japonicus. The expression ofNosand the NO concentration in the gastrointestinal tract were increased significantly in shrimp orally infected withVibrio anguillarum. After RNA interference ofNosor treatment with an inhibitor of NOS, L-NMMA, NO production decreased and the gut bacterial load increased significantly in shrimp. Treatment with the NO donor, sodium nitroprusside, increased the NO level and reduced the bacterial load significantly in the shrimp gastrointestinal tract. Mechanistically,V. anguillaruminfection increased NO levelviaupregulation of NOS and induced phosphorylation of ERK. The activated ERK phosphorylated the NF-κB-like transcription factor, dorsal, and caused nuclear translocation of dorsal to increase expression of antimicrobial peptides (AMPs) responsible for bacterial clearance. In summary, as a signaling molecule, NOS-produced NO regulates intestinal microbiota homeostasis by promoting AMP expression against infected pathogensviathe ERK-dorsal pathway in shrimp.
Sirtuin 7 Regulates Nitric Oxide Production and Apoptosis to Promote Mycobacterial Clearance in Macrophages
Authors: Zhang Su , Liu Yaya , Zhou Xuefeng , Ou Min , Xiao Guohui , Li Fang , Wang Zhongyuan , Wang Zhaoqin , Liu Lei , Zhang Guoliang
Published: December 2021

The host immune system plays a pivotal role in the containment of Mycobacterium tuberculosis (Mtb) infection, and host-directed therapy (HDT) is emerging as an effective strategy to treat tuberculosis (TB), especially drug-resistant TB. Previous studies revealed that expression of sirtuin 7 (SIRT7), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, was downregulated in macrophages after Mycobacterial infection. Inhibition of SIRT7 with the pan-sirtuin family inhibitor nicotinamide (NAM), or by silencing SIRT7 expression, promoted intracellular growth of Mtb and restricted the generation of nitric oxide (NO). Addition of the exogenous NO donor SNAP abrogated the increased bacterial burden in NAM-treated or SIRT7-silenced macrophages. Furthermore, SIRT7-silenced macrophages displayed a lower frequency of early apoptotic cells after Mycobacterial infection, and this could be reversed by providing exogenous NO. Overall, this study clarified a SIRT7-mediated protective mechanism against Mycobacterial infection through regulation of NO production and apoptosis. SIRT7 therefore has potential to be exploited as a novel effective target for HDT of TB.
Gut Microbiota–Medication Interaction in Rheumatic Diseases
Authors: Zhang Lingshu , Chu Cong-Qiu
Published: December 2021

Besides its contribution to the development of rheumatic diseases, the gut microbiota interact with anti-rheumatic drugs. The intestinal microbiota can directly metabolize many drugs and indirectly change drug metabolism through a complex multi-dimensional interaction with the host, thus affecting individual response to drug therapy and adverse effects. The focus of the current review is to address recent advances and important progress in our understanding of how the gut microbiota interact with anti-rheumatic drugs and provide perspectives on promoting precision treatment, drug discovery, and better therapy for rheumatic diseases.
Social Behaviour of Humpback Whales (Megaptera novaeangliae) in Hervey Bay, Eastern Australia, a Preferential Female Stopover During the Southern Migration
Authors: Franklin Trish , Franklin Wally , Brooks Lyndon , Harrison Peter , Pack Adam A. , Clapham Phillip J.
Published: December 2021

Agonistic competitive social behaviour in humpback whales [Megaptera novaeangliae(Borowski, 1781)] has been extensively studied and reported in previous research. However, non-agonistic social behaviour in humpback whale pods has not been systematically studied. We investigated the social behaviour of 3,949 humpback whale pods over a period of 14 years during August, September, and October in Hervey Bay (Queensland, eastern Australia), a preferential female stopover early in the southern migration. Modelling and analyses of the data examined the factors influencing the occurrence and timing of non-agonistic social behaviour pods, agonistic competitive pods and newly associated pods. Non-agonistic social behaviour was observed more frequently during August when mature females, including early pregnant and resting females, co-occur and socially interact with immature males and females. Overall, relatively few mature males visit Hervey Bay. Agonistic competitive behaviour was observed with increasing frequency during September and October when mother-calf pods, with few escorts predominated. Mother-calf pods in Hervey Bay spent most of their time alone involved in maternal care. Agonistic competitive behaviour is related to the decreasing numbers of potentially oestrous females toward the end of the season. Non-agonistic social behaviour and agonistic competitive behaviour were more frequently observed in larger and newly associated pods. Overall, non-agonistic social behaviour pods were more prevalent than agonistic competitive social behaviour pods. The results of this study substantiate that non-agonistic social behaviour may be more prevalent than aggressive agonistic social behaviour in site-specific locations and habitats, depending upon the classes and timings of humpback whales using such habitats.
The Concept of Oceanian Sovereignty in the Context of Deep Sea Mining in the Pacific Region
Authors: Tilot Virginie C. , Guilloux Bleuenn , Willaert Klaas , Mulalap Clement Y. , Bambridge Tamatoa , D’Arcy Paul , Mawyer Alexander , Gaulme François , Kacenelenbogen Edwige , Jeudy de Grissac Alain , Moreno Navas Juan , Dahl Arthur
Published: December 2021

Based on an interdisciplinary experience addressing traditional dimensions in marine resource management in the Pacific, the socio-ecological interconnectivity between island communities, the ocean realm and the legal context concerning the management of seabed resources (Tilot, 2006, 2010; Tilot et al., 2018, 2021a,b; Mulalap et al., 2020; Willaert, 2020a,b, c; 2021; DOSI, 2021), this paper proposes to discuss the relevance and efficacy of the concept of “Oceanian Sovereignty” (Bambridge et al., 2021) in the context of Deep Sea Mining, from the different legal, environmental, anthropological, social, political, and economic science perspectives. The policies and practices developed in the Pacific in this context could well serve as a suitable model elsewhere to reconcile competing perspectives in addition to sustaining the Human Well-being and Sustainable Livelihoods (HWSL) and the health of the Global Ocean.
Stable Extent of Recurrently Active Cardiac and Cutaneous Sarcoidosis
Authors: Patterson Karen C. , Rosenbach Misha , Bravo Paco E. , Dubroff Jacob G.
Published: December 2021

Background: Recurrent or persistently active sarcoidosis is a risk factor for permanent organ damage. Whether this damage is due to accumulated focal injuries or progressive disease extent is not known, as the natural history of chronic inflammation in sarcoidosis is poorly characterized. The objective of this study is to determine the pattern of disease in recurrently active sarcoidosis.

Methods: We identified patients with recurrent cardiac sarcoidosis (N = 21) retrospectively from an imaging database, and with recurrent cutaneous sarcoidosis (N = 17) from a prospective registry. The longitudinal patterns of cardiac sarcoidosis were established by findings on cardiac positron emission tomography scans, and of cutaneous sarcoidosis by the validated Cutaneous Sarcoidosis Activity and Morphology Instrument clinical scoring system. Patterns of recurrent disease were compared to baseline findings.

Results: Recurrent sarcoidosis occurred in a nearly identical pattern and distribution as baseline disease, and spread of disease was rarely observed for both cardiac and cutaneous sarcoidosis: 97% of heart segments positive on recurrence scans were positive on baseline scans, and only one new region of facial disease was observed. In some cases, recurrence followed years of apparent remission.

Discussion: Across phenotypes, and across a long period of follow-up, the extent of sarcoidosis was stable in spite of fluctuations in disease activity. For patients with a demonstrated history of recurrent disease affecting critical organs, our findings support the need for long-term follow-up.
Alterations in Gastric Mucosal Microbiota in Gastric Carcinogenesis: A Systematic Review and Meta-Analysis
Authors: Yang Yingyun , Ji Ruoyu , Zhao Xinyu , Cao Xinyuan , Wang Qiang , Jiang Qingwei , Zhang Yizhen , Zheng Weiyang , Wu Xi , Yang Aiming
Published: December 2021

Background: The gastric microbiota profile alters during gastric carcinogenesis. We aimed to identify the alterations in the alpha diversity and relative abundance of bacterial phyla and genera of gastric microbiota in the development of gastric cancer (GC).

Methods: The systematic review was performed based on a published protocol with the registration number CRD42020206973. We searched through PubMed, EMBASE and Cochrane databases, as well as conference proceedings and references of review articles (May 2021) for observational studies reporting either the relative abundance of bacterial phyla or genera, or alpha diversity indexes in both GC and non-cancer groups. Selection of studies and data extraction were performed independently by two researchers, with disagreements resolved through discussion. Risk of bias was assessed using the self-modified Newcastle-Ottawa Scale. Results of random-effects meta-analyses were presented as mean differences (MD).

Results: Our systematic review included 751 GC patients and 792 non-cancer patients from 14 case-control studies. Gastric cancer group had fewer operational taxonomic units (OTUs) (MD = −68.52, 95%CI: −126.65 to −10.39) and a lower Simpson index (MD = −0.13, 95%CI: −0.20 to −0.07) compared with non-cancer group. At the phylum level, gastric cancer group had a higher abundance of Firmicutes (MD = 7.11, 95%CI: 1.76 to 12.46). At the genus level, Streptococcus (MD = 3.03, 95%CI: 0.07 to 6.00) and Lactobacillus (MD = 5.15, 95%CI: 1.27 to 9.04) were found to be enriched in GCgroup. The relative abundance of the rest bacterial phyla or genera analyzed in our study did not significantly differ between two groups. Subgroup analyses indicated that the source of samples was the major source of interstudy heterogeneity.

Conclusion: This systematic review suggested that gastric microbiota dysbiosis occurred in gastric carcinogenesis, with alpha diversity declined and microbiota composition altered.
Extracorporeal Membrane Oxygenation in Immunocompromised Patients With Acute Respiratory Distress Syndrome—A Retrospective Cohort Study
Authors: Cheng Chiao-Feng , Chen You-Yi , Shih Ming-Chieh , Huang Yi-Min , Tseng Li-Jung , Lai Chien-Heng , Lan Ting-Yuan , Lu Cheng-Hsun , Hsieh Song-Chou , Li Ko-Jen , Chi Nai-Hsin , Yu Hsi-Yu , Chen Yih-Sharng , Wang Chih-Hsien
Published: December 2021

Objective: Although the negative impact of immunosuppression on survival in patients with acute respiratory distress syndrome (ARDS) treated by extracorporeal membrane oxygenation (ECMO) is well known, short-term outcomes such as successful weaning rate from ECMO and subgroups benefit most from ECMO remain to be determined. The aims of this study were (1) to identify the association between immunocompromised status and weaning from ECMO in patients of ARDS, and (2) to identify subgroups of immunocompromised patients who may benefit from ECMO.

Methods: This retrospective cohort study enrolled patients who received ECMO for ARDS from 2010 to 2020. Immunocompromised status was defined as having a hematological malignancy, active solid tumor, solid organ transplant, or autoimmune disease.

Results: This study enrolled 256 ARDS patients who received ECMO, of whom 68 were immunocompromised. The multivariable analysis showed that immunocompromised status was not independently associated with failure to wean from ECMO. In addition, the patients with an autoimmune disease (14/24, 58.3%) and organ transplantation (3/3, 100%) had a numerically higher weaning rate from ECMO than other immunocompromised patients. For causes of ARDS, most patients with pulmonary hemorrhage (6/8, 75%) and aspiration (5/9, 55.6%) could be weaned from ECMO, compared to only a few of the patients with interstitial lung disease (2/9, 22.2%) and sepsis (1/4, 25%).

Conclusions: Immunocompromised status was not an independent risk factor of failure to wean from ECMO in patients with ARDS. For patients with pulmonary hemorrhage and aspiration-related ARDS, ECMO may be beneficial as bridge therapy.
The Viral Founder Effect and Economic-Driven Human Mobility Shaped the Distinct Epidemic Pattern of HIV-1 CRF01_AE in Northeast China
Authors: An Minghui , Zhao Bin , Wang Lin , Chu Zhenxing , Xu Junjie , Ding Haibo , Han Xiaoxu , Shang Hong
Published: December 2021

Background: In China, two distinct lineages shaped the epidemic of HIV-1 CRF01_AE among men who have sex with men (MSM), of which the uneven distributions were observed geographically. One lineage spread across China, while another dominated in Northeast China. Understanding the drivers of viral diffusion would provide guidelines for identifying the source and hotspots of HIV transmission among MSM to target interventions in China.

Methods: We collected the pol sequences between 2002–2017 to reconstruct the spatiotemporal history of CRF01_AE lineages in Shenyang, one economic center of Northeast China, using the Bayesian phylogeographic and phylodynamic approaches. Importantly, for the datasets with the high sample density, we did the down-sampling to avoid the sampling bias.

Results: Two lineages accounted for 97%, including 426 and 1516 sequences, and homosexuals and bisexuals were above 80%. One lineage appeared earlier 7 years than another (1993 vs. 2002) among homosexuals and bisexuals, whereas among heterosexuals, both lineages were observed firstly in 2002. 96% viral migrations within one lineage were from homosexuals toward bisexuals (49%) and male-heterosexuals (46%). Within another, except for homosexuals (72%), bisexuals (23%) served as the top second source, and female-heterosexuals (11%) were the third recipients following bisexuals (44%) and male-heterosexuals (39%). Although the basic reproduction number (R0) of two lineages were similar and both of the effective production number (Re) fell below 1 at the most recent sampling time, the starts of the Re declining varied.

Conclusions: Our findings revealed that throughout the viral national spread chain, Shenyang is the source for the initial expanding of one lineage, where is only a sink of another, proving that the viral founder effect and regional human mobility contributed to the uneven distribution of two lineages, and emphasizing the important roles of the area where the virus originated and economy-driven migrants in HIV transmission.
Developing and Validating Novel Nomograms for Predicting the Overall Survival and Cancer-Specific Survival of Patients With Primary Vulvar Squamous Cell Cancer
Authors: Zhou Weili , Yue Yangyang
Published: December 2021

Background: To develop and validate novel nomograms for better predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with vulvar squamous cell cancer (VSCC).

Methods: A retrospective analysis using a population-based database between 2004 and 2016 was carried. A 10-fold cross-validation with 200 repetitions was used to choose the best fit multivariate Cox model based on the net-benefit of decision curve analysis. Net-benefit, Harrell's C concordance statistic (C-statistic) of calibration plot, and area under the receiver operating characteristic curve (AUC) were used to evaluate the model prediction accuracy. Nomograms of the OS and CSS were generated based on the best fit model.

Results: Of the 6,792 patients with VSCC, 5,094 (75%) and 1,698 (25%) were allocated to the training and validation cohort, respectively. All the variables were balanced between the training and validation cohorts. Age, insurance, tumor size, pathological grade, radiotherapy, chemotherapy, invasion depth, lymphadenectomy, sentinel lymph nodes biopsy, surgery, N stage, and M stage were in the best fit model for generating nomograms. The decision curve analysis, calibration plot, and receiver operating characteristic (ROC) curve show the better prediction performance of the model compared to previous studies. The C-statistics of our model for OS prediction are 0.80, 0.83, and 0.81 in the training, validation, and overall cohorts, respectively, while for CSS prediction are 0.83, 0.85, and 0.84. The AUCs for 3- and 5-year OS are the same and are 0.81, 0.83, and 0.81 in the training, validation, and overall cohorts, respectively. The AUCs for 3- and 5-year CSS are 0.78 and 0.80, 0.79 and 0.80, and 0.79 and 0.80 in those three cohorts.

Conclusions: Our model shows the best prediction accuracy of the OS and CSS for patients with vulvar cancer (VC), which is of significant clinical practice value.
Evaluation of Choroidal Thickness Using Optical Coherent Tomography: A Review
Authors: Xie Rui , Qiu Bingjie , Chhablani Jay , Zhang Xinyuan
Published: December 2021

The choroid is the main source of blood and nourishment supply to the eye. The dysfunction of the choroid has been implicated in various retinal and choroidal diseases. The identification and in-depth understanding of pachychoroid spectrum disorders are based on the tremendous progress of optical coherence tomography (OCT) technology in recent years, although visibility of choroid is challenging in the era of the time or spectral domain OCT. The recent rapid revolution of OCTs, such as the enhanced depth imaging OCT and the swept-source OCT, has greatly contributed to the significant improvement in the analysis of the morphology and physiology of the choroid precisely, especially to the choroid–scleral boundary and vasculature. The present review highlights the recently available evidence on the measurement methodology and the clinical significance of choroidal thickness in retinal or choroidal disorders.
Multi-Enzyme Supplementation Modifies the Gut Microbiome and Metabolome in Breeding Hens
Authors: Liu Yuchen , Zeng Dan , Qu Lujiang , Wang Zhong , Ning Zhonghua
Published: December 2021

Laying and reproductive performance, egg quality, and disease resistance of hens decrease during the late laying period. Exogenous enzymes promote nutrient digestibility and utilization and improve the intestinal environment. However, the specific regulation of the gut microbiome and metabolome by exogenous enzymes remains unelucidated. This study was conducted to evaluate effects of dietary multi-enzyme supplementation on egg and reproductive performance, egg quality, ileum microbiome, and metabolome of breeders. Here, 224 Hy-Line Brown breeding hens (55 weeks old) were randomly allocated to two groups: dietary controls fed basal diet (DC), and test hens fed 0.2 g/kg corn enzyme diet (CE). Serum levels of total protein, globulin, immunoglobulin Y, and antibodies against the Newcastle disease virus and avian influenza H9 strain were significantly increased (p < 0.05). Egg albumen height, Haugh unit, and fertilization and hatching rates were also significantly increased (p < 0.05) in the CE-fed group. 16S rRNA sequence analysis showed that CE strongly affected both α- and β-diversity of the ileal microbiota. LEfSe analysis revealed that the potentially beneficial genera Lactobacillus, Enterococcus, Faecalicoccus, and Streptococcus were enriched as biomarkers in the CE-fed group. Microbial functional analysis revealed that the functional genes associated with harmful-substance biodegradation was significantly increased in the CE-fed group. Additionally, Spearman correlation analysis indicated that changes in microbial genera were correlated with differential metabolites. In summary, dietary multi-enzyme addition can improve egg quality, humoral immunity, and reproductive performance and regulate the intestinal microbiome and metabolome in breeders. Therefore, multi-enzymes could be used as feed additive to extend breeder service life.
Citrulline Accumulation Mechanism of Pediococcus acidilactici and Weissella confusa in Soy Sauce and the Effects of Phenolic Compound on Citrulline Accumulation
Authors: Zhou Kai , Zhang Xiao , Li Bingyong , Shen Chaoqun , Sun Yuan-Ming , Yang Jianyuan , Xu Zhen-Lin
Published: December 2021

Citrulline is one of the major precursors of ethyl carbamate in soy sauce, and the accumulation of citrulline is attributed to the metabolism of arginine by bacteria with the arginine deiminase (ADI) pathway. However, key strains and factors affecting citrulline accumulation are not yet clear. In this study, two key strains of Pediococcus acidilactici and Weissella confusa were isolated from soy sauce moromi, and the regularity of citrulline formation was studied. Results showed that the conversion rates from arginine to citrulline (A/C rate) and the citrulline accumulation ability of W. confusa and P. acidilactici significantly increased in the presence of different concentrations of NaCl, indicating that salt stress was the main factor for citrulline accumulation. The inconsistent expression of arc genes by salt stress was the reason for citrulline accumulation for P. acidilactici, but for W. confusa, it may be due to the influence of arginine/citrulline on the transportation system: the intracellular citrulline could neither transport to extracellular space nor convert into ornithine. Environmental factors greatly influenced citrulline accumulation of the two key bacteria; A/C rate and citrulline formation in both strains decreased at low temperature (15°C) under high salt stress, but opposite effects were observed for the two key strains under anaerobic light condition. Moreover, quercetin and gallic acid significantly decreased the A/C rate and citrulline accumulation ability of the two key strains. The optimal quercetin and gallic acid as suggested by simulation experiment were 100 and 10 mg/l, respectively, and the lowest A/C rate of 28.4% and citrulline level of 1326.7 mg/l were achieved in the simulation system. This study explored the main factors for citrulline formation by the two key strains and proposed a targeted way to control citrulline in soy sauce.