bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitreomacular Interface Abnormalities in Myopic Foveoschisis: Correlation With Morphological Features and Outcome of Vitrectomy
Authors: Fang Dong , Wang Li , Chen Lu , Liang Jia , Li Kunke , Mao Xingxing , Xie Ting , Zhang Shaochong
Published: January 2022

Purpose: To compare the morphologic characteristics and response to surgery of myopic foveoschisis (MF) with different patterns of vitreomacular interface abnormalities (VMIAs).

Methods: In this observational case series, 158 eyes of 121 MF patients with epiretinal membrane (ERM) or vitreomacular traction (VMT) based on optical coherence tomography (OCT) were enrolled. All the eyes were divided into two groups by the pattern of VMIAs: ERM and VMT group. Sixty-one eyes underwent pars plana vitrectomy (PPV) and were followed up for at least 6 months. The morphologic characteristics based on OCT and the surgical outcome were evaluated.

Outcome: ERM and VMT were found in 47.47 and 52.53% of the cases, respectively. A higher rate of foveal detachment (61.4 vs. 26.7%; p < 0.001) and a higher rate of outer lamellar macular hole (45.8 vs. 21.3%; p = 0.001) were detected in the eyes with VMT compared with those with ERM. In contrast, a lower rate of inner lamellar macular hole (28.9 vs. 60.0%; p = 0.001) was detected in the eyes with VMT compared with those with ERM. The disruption of the external limiting membrane (ELM) was more common in the eyes with VMT than in those with ERM (45.8 vs. 21.3%; p = 0.001). PPV was performed in 61 eyes with a mean follow-up time of 23.55 ± 19.92 months. After surgery, anatomical resolution was achieved in 51 eyes (83.6%). At the final visit, the mean central foveal thickness (CFT) decreased significantly from 547.83 to 118.74 μm, and the mean LogMAR BCVA improved significantly from 0.92 to 0.57. The VMT group was associated with a higher proportion of eyes with visual acuity improvement postoperatively (p = 0.02) and had more a decrease of CFT (P = 0.007) compared with the ERM group.

Conclusion: In the eyes with MF, outer retinal lesions occurred more frequently in the eyes with VMT, whereas inner retinal lesions occurred more frequently in the eyes with ERM. Tangential force generated by ERM may act as a causative factor for the inner retinal lesions in MF, and inward-directed force resulting from VMT may act as a causative factor for outer retinal lesions in MF.
Application of Bacteriophages to Limit Campylobacter in Poultry Production
Authors: Olson Elena G. , Micciche Andrew C. , Rothrock Michael J. , Yang Yichao , Ricke Steven C.
Published: January 2022

Campylobacteris a major foodborne pathogen with over a million United States cases a year and is typically acquired through the consumption of poultry products. The common occurrence ofCampylobacteras a member of the poultry gastrointestinal tract microbial community remains a challenge for optimizing intervention strategies. Simultaneously, increasing demand for antibiotic-free products has led to the development of several alternative control measures both at the farm and in processing operations. Bacteriophages administered to reduce foodborne pathogens are one of the alternatives that have received renewed interest.Campylobacterphages have been isolated from both conventionally and organically raised poultry. Isolated and cultivatedCampylobacterbacteriophages have been used as an intervention in live birds to target colonizedCampylobacterin the gastrointestinal tract. Application ofCampylobacterphages to poultry carcasses has also been explored as a strategy to reduceCampylobacterlevels during poultry processing. This review will focus on the biology and ecology ofCampylobacterbacteriophages in poultry production followed by discussion on current and potential applications as an intervention strategy to reduceCampylobacteroccurrence in poultry production.
Multiple Metabolic Phenotypes as Screening Criteria Are Correlated With the Plant Growth-Promoting Ability of Rhizobacterial Isolates
Authors: Shi Peng , Zhang Jianli , Li Xingyue , Zhou Liyun , Luo Hui , Wang Li , Zhang Yafan , Chou Minxia , Wei Gehong
Published: January 2022

Efficient screening method is the prerequisite for getting plant growth-promoting (PGP) rhizobacteria (PGPR) which may play an important role in sustainable agriculture from the natural environment. Many current traditional preliminary screening criteria based on knowledge of PGP mechanisms do not always work well due to complex plant–microbe interactions and may lead to the low screening efficiency. More new screening criteria should be evaluated to establish a more effective screening system. However, the studies focused on this issue were not enough, and few new screening criteria had been proposed. The aim of this study was to analyze the correlation between the metabolic phenotypes of rhizobacterial isolates and their PGP ability. The feasibility of using these phenotypes as preliminary screening criteria for PGPR was also evaluated. Twenty-one rhizobacterial isolates were screened for their PGP ability, traditional PGP traits, and multiple metabolic phenotypes that are not directly related to PGP mechanisms, but are possibly related to rhizosphere colonization. Correlations between the PGP traits or metabolic phenotypes and increases in plant agronomic parameters were analyzed to find the indicators that are most closely related to PGP ability. The utilization of 11 nutrient substrates commonly found in root exudates, such as D-salicin, β-methyl-D-glucoside, and D-cellobiose, was significantly positively correlated with the PGP ability of the rhizobacterial isolates. The utilization of one amino acid and two organic acids, namely L-aspartic acid, α-keto-glutaric acid, and formic acid, was negatively correlated with PGP ability. There were no significant correlations between four PGP traits tested in this study and the PGP ability. The ability of rhizobacterial isolates to metabolize nutrient substrates that are identical or similar to root exudate components may act as better criteria than PGP traits for the primary screening of PGPR, because rhizosphere colonization is a prerequisite for PGPR to affect plants.
Bacterial Gut Microbiota and Infections During Early Childhood
Authors: George Sergio , Aguilera Ximena , Gallardo Pablo , Farfán Mauricio , Lucero Yalda , Torres Juan Pablo , Vidal Roberto , O’Ryan Miguel
Published: January 2022

Gut microbiota composition during the first years of life is variable, dynamic and influenced by both prenatal and postnatal factors, such as maternal antibiotics administered during labor, delivery mode, maternal diet, breastfeeding, and/or antibiotic consumption during infancy. Furthermore, the microbiota displays bidirectional interactions with infectious agents, either through direct microbiota-microorganism interactions or indirectly through various stimuli of the host immune system. Here we review these interactions during childhood until 5 years of life, focusing on bacterial microbiota, the most common gastrointestinal and respiratory infections and two well characterized gastrointestinal diseases related to dysbiosis (necrotizing enterocolitis and Clostridioides difficile infection). To date, most peer-reviewed studies on the bacterial microbiota in childhood have been cross-sectional and have reported patterns of gut dysbiosis during infections as compared to healthy controls; prospective studies suggest that most children progressively return to a “healthy microbiota status” following infection. Animal models and/or studies focusing on specific preventive and therapeutic interventions, such as probiotic administration and fecal transplantation, support the role of the bacterial gut microbiota in modulating both enteric and respiratory infections. A more in depth understanding of the mechanisms involved in the establishment and maintenance of the early bacterial microbiota, focusing on specific components of the microbiota-immunity-infectious agent axis is necessary in order to better define potential preventive or therapeutic tools against significant infections in children.
Mechanism and Structural Insights Into a Novel Esterase, E53, Isolated From Erythrobacter longus
Authors: Ding Yi , Nie Laiyin , Yang Xiao-Chen , Li Yang , Huo Ying-Yi , Li Zhengyang , Gao Yan , Cui Heng-Lin , Li Jixi , Xu Xue-Wei
Published: January 2022

Esterases are a class of enzymes that split esters into an acid and an alcohol in a chemical reaction with water, having high potential in pharmaceutical, food and biofuel industrial applications. To advance the understanding of esterases, we have identified and characterized E53, an alkalophilic esterase from a marine bacterium Erythrobacter longus. The crystal structures of wild type E53 and three variants were solved successfully using the X-ray diffraction method. Phylogenetic analysis classified E53 as a member of the family IV esterase. The enzyme showed highest activity against p-nitrophenyl butyrate substrate at pH 8.5–9.5 and 40°C. Based on the structural feature, the catalytic pocket was defined as R1 (catalytic center), R2 (pocket entrance), and R3 (end area of pocket) regions. Nine variants were generated spanning R1–R3 and thorough functional studies were performed. Detailed structural analysis and the results obtained from the mutagenesis study revealed that mutations in the R1 region could regulate the catalytic reaction in both positive and negative directions; expanding the bottleneck in R2 region has improved the enzymatic activity; and R3 region was associated with the determination of the pH pattern of E53. N166A in R3 region showed reduced activity only under alkaline conditions, and structural analysis indicated the role of N166 in stabilizing the loop by forming a hydrogen bond with L193 and G233. In summary, the systematic studies on E53 performed in this work provide structural and functional insights into alkaliphilic esterases and further our knowledge of these enzymes.
Characterization of a Type VI Secretion System vgrG2 Gene in the Pathogenicity of Burkholderia thailandensis BPM
Authors: Li Jin , Hu Wei-wei , Qu Guo-xin , Li Xiao-rong , Xiang Yi , Jiang Peng , Luo Jiang-qiao , He Wen-huan , Jin Yu-jia , Shi Qiong
Published: January 2022

Burkholderia thailandensis is a clinically underestimated conditional pathogen in the genus Burkholderia, the pathogenicity of the infection caused by B. thailandensis remains poorly understood. According to previous studies, Type-VI secretion system (T6SS) is a protein secreting device widely existing in Gram-negative bacilli. Valine-glycine repeat protein G (VgrG) is not only an important component of T6SS, but also a virulence factor of many Gram-negative bacilli. In one of our previous studies, a unique T6SS vgrG gene (vgrG2 gene) was present in a virulent B. thailandensis strain BPM (BPM), but not in the relatively avirulent B. thailandensis strain E264 (E264). Meanwhile, transcriptome analysis of BPM and E264 showed that the vgrG2 gene was strongly expressed in BPM, but not in E264. Therefore, we identified the function of the vgrG2 gene by constructing the mutant and complemented strains in this study. In vitro, the vgrG2 gene was observed to be involved in the interactions with host cells. The animal model experiment showed that the deletion of vgrG2 gene significantly led to the decrease in the lethality of BPM and impaired its ability to trigger host immune response. In conclusion, our study provides a new perspective for studying the pathogenicity of B. thailandensis and lays the foundation for discovering the potential T6SS effectors.
Recombinant Bivalent Live Vectored Vaccine Against Classical Swine Fever and HP-PRRS Revealed Adequate Heterogeneous Protection Against NADC30-Like Strain
Authors: Li Liwei , Chen Jinxia , Cao Zhengda , Cao Yunlei , Guo Ziqiang , Tong Wu , Zhou Yanjun , Li Guoxin , Jiang Yifeng , Liu Changlong , Yu Lingxue , Qiao Sina , Liu Jiachen , Tong Guangzhi , Gao Fei
Published: January 2022

The recombinant bivalent live vectored vaccine rPRRSV-E2 has been proved to be a favorable genetic engineering vaccine against classical swine fever (CSF) and highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS). NADC30-like strains have recently emerged in China and caused severe disease, and it is necessary to evaluate the vaccine candidate for the currently circulating viruses. This study established a good challenge model to evaluate the candidate rPRRSV-E2 vaccine in preventing infection with a representative NADC30-like strain (ZJqz21). It was shown that the challenge control piglets displayed clinical signs typical of PRRSV, including a persistent fever, dyspnea, moderate interstitial pneumonia, lymph node congestion, and viremia. In contrast, the rPRRSV-E2 vaccination significantly alleviated the clinical signs, yielded a high level of antibodies, provided adequate protection against challenge with ZJqz21, and inhibited viral shedding and the viral load in target tissues. Our results demonstrated that the recombinant bivalent live vectored vaccine strain rPRRSV-E2 can provide efficient protection against the challenge of heterologous circulating NADC30-like strain and could be a promising vaccine candidate for the swine industry.
New Horizons for Phenotyping Behavior in Rodents: The Example of Depressive-Like Behavior
Authors: Leite-Almeida Hugo , Castelhano-Carlos Magda J. , Sousa Nuno
Published: January 2022

The evolution of the field of behavioral neuroscience is significantly dependent on innovative disruption triggered by our ability to model and phenotype animal models of neuropsychiatric disorders. The ability to adequately elicit and measure behavioral parameters are the fundaments on which the behavioral neuroscience community establishes the pathophysiological mechanisms of neuropsychiatric disorders as well as contributes to the development of treatment strategies for those conditions. Herein, we review how mood disorders, in particular depression, are currently modeled in rodents, focusing on the limitations of these models and particularly on the analyses of the data obtained with different behavioral tests. Finally, we propose the use of new paradigms to study behavior using multidimensional strategies that better encompasses the complexity of psychiatric conditions, namely depression; these paradigms provide holistic phenotyping that is applicable to other conditions, thus promoting the emergence of novel findings that will leverage this field.
Clinical Characteristics and Follow-Up of Seizures in Children With Anti-NMDAR Encephalitis
Authors: Zhang Jianzhao , Sun Jing , Zheng Ping , Feng Shuo , Yi Xiaoli , Ren Haitao , Chen Qian
Published: January 2022

Objective: To analyze the seizure characteristics of children with anti-NMDAR encephalitis.

Methods: This was a retrospective analysis of 50 children with anti-NMDAR encephalitis between July 1, 2013, and July 1, 2019.

Results: Fifty children with anti-NMDAR encephalitis were included in this study, of which 34 (68.0%) had seizures. During the follow-up, three patients with anti-NMDAR encephalitis secondary to herpes simplex virus encephalitis had persistent seizures. The average duration of seizures in the remaining patients was 14.6 days (range 1–47 days). Compared to patients without seizures, those with seizures were more likely to experience consciousness disturbances (p = 0.008) and epileptic form discharge on electroencephalograms (p = 0.002). The Glasgow coma scale scores (p = 0.014), and Rankin scale scores (p = 0.019) were also different. The cranial MRI findings of children were reviewed, and clinical characteristics were compared between children without cranial lesions and those with lesions in the limbic system and neocortex. Compared to children in the non-lesion group, children with lesions in the limbic system and neocortex had a higher incidence of status epilepticus. Further, children in the limbic system and neocortical lesions groups were more likely to be taking anti-seizure medications (ASMs) and receive second-line drugs.

Conclusion: Long-term oral ASMs are not recommended for most children with anti-NMDAR encephalitis. Children with involvement of the limbic system and neocortex are prone to status epilepticus, and sequelae of epilepsy may remain when the neocortex is involved.
Vertebrobasilar Junction Angle Over 90°: A Potential Imaging Marker Associated With Vertebrobasilar Atherosclerosis
Authors: Li Jia , Yang Wen-Jie , Zheng Lu , Du Heng , Chu Winnie Chiu-Wing , Leung Thomas Wai-Hong , Chen Xiang-Yan
Published: January 2022

Objective: Whether the cerebral vascular variations play an important role in the progression of intracranial atherosclerosis is yet largely unclear. We aimed to investigate the relationship between the magnitude of the vertebrobasilar junction (VBJ) angle and the imaging features of vertebrobasilar artery atherosclerosis.

Methods: Adult patients with acute ischemic stroke or transient ischemic attack undergoing a 3.0-tesla vessel wall magnetic resonance imaging (VW-MRI) scanning were consecutively included. Imaging features of vertebrobasilar artery atherosclerosis were assessed on the reconstructed short axis of VW-MRI at the most stenotic site. The VBJ angle degree was measured on magnetic resonance angiography and classified into the angle ≥90° or <90°.

Results: Among 68 patients (mean age = 63.5 ± 9.4 years old; 63.2% were male) with vertebrobasilar atherosclerosis, 33 had a VBJ angle ≥90° and 35 had a VBJ angle <90°. Compared to the vertebrobasilar plaques with VBJ angle <90°, those with VBJ angle ≥90° had a heavier plaque burden (84.35 vs. 70.58%, p < 0.001) and higher prevalence of intraplaque hemorrhage (17.1 vs. 3.3%, p = 0.01). In the regression analyses, the VBJ angle ≥90° was also robustly associated with plaque burden (odds ratio, 1.11; 95% confidential interval, 1.043–1.18; p = 0.001) and intraplaque hemorrhage (odds ratio, 5.776; 95% confidential interval, 1.095–30.46; p = 0.039) of vertebrobasilar atherosclerosis.

Conclusion: The VBJ angle over 90° might aggravate the vessel wall condition of the atherosclerotic vertebrobasilar arteries, which might serve as a potential risk factor for vertebrobasilar atherosclerosis.
Validation of a Classroom Version of the Eating in the Absence of Hunger Paradigm in Preschoolers
Authors: Hohman Emily E. , McNitt Katherine M. , Eagleton Sally G. , Francis Lori A. , Keller Kathleen L. , Savage Jennifer S.
Published: January 2022

Eating in the absence of hunger (EAH), a measure of children's propensity to eat beyond satiety in the presence of highly palatable food, has been associated with childhood obesity and later binge eating behavior. The EAH task is typically conducted in a research laboratory setting, which is resource intensive and lacks ecological validity. Assessing EAH in a group classroom setting is feasible and may be a more efficient alternative, but the validity of the classroom assessment against the traditional individually-administered paradigm has not been tested. The objective of this study was to compare EAH measured in a classroom setting to the one-on-one version of the paradigm in a sample of Head Start preschoolers. Children (n = 35) from three classrooms completed both classroom and individual EAH tasks in a random, counterbalanced order. In the group condition, children sat with peers at their classroom lunch tables; in the individual condition, children met individually with a researcher in a separate area near their classroom. In both conditions, following a meal, children were provided free access to generous portions of six snack foods (~750 kcal) and a selection of toys for 7 min. Snacks were pre- and post-weighed to calculate intake. Parents completed a survey of their child's eating behaviors, and child height and weight were measured. Paired t-tests and intraclass correlation coefficients were used to compare energy intake between conditions, and correlations between EAH intake and child BMI, eating behaviors, and parent feeding practices were examined to evaluate concurrent validity. Average intake was 63.0 ± 50.4 kcal in the classroom setting and 53.7 ± 44.6 in the individual setting, with no significant difference between settings. The intraclass correlation coefficient was 0.57, indicating moderate agreement between conditions. Overall, the EAH protocol appears to perform similarly in classroom and individual settings, suggesting the classroom protocol is a valid alternative. Future studies should further examine the role of age, sex, and weight status on eating behavior measurement paradigms.
A Comparative Study on a Novel Fibula Malleolus Cap to Increase the Accuracy of Oncologic Jaw Reconstruction
Authors: Pu Jingya Jane , Choi Wing Shan , Yeung Wai Kan , Yang Wei-Fa , Zhu Wang-Yong , Su Yu-Xiong
Published: January 2022

Objectives

Although computer-assisted surgery using fibula flap has been widely applied for oncologic jaw reconstruction in recent years, the inaccurate positioning of the fibula harvest guide brings sliding and rotational errors, which leads to compromised accuracy in simultaneous implant placement and dental rehabilitation. This study aimed to develop a novel three-dimensional (3D)-printed patient-specific fibula malleolus cap to increase oncologic reconstruction accuracy.

Methods

In this prospective comparative study with a recent historical control cohort, patients in need of oncologic jaw reconstruction with fibula free flaps were recruited. In the study group, the fibula was harvested with the guide of the malleolus cap, whereas in the control group, without the malleolus cap. Deviations of location and angulation of distal fibula osteotomies, jaw reconstruction segments, and simultaneous dental implants were compared.

Results

Twenty patients were recruited, with 10 in each arm. The application of the malleolus cap significantly reduced the deviations in locations and angles of distal fibula osteotomies, from 9.5 to 4.1 mm and 25.3° to 8.7°. For the simultaneous dental implants placed in the fibula flaps, there was a significant increase in the accuracy of implant platform locations (the average deviation from 3.2 to 1.3 mm), apex locations (from 3.8 to 1.5 mm), and angles (from 11.3° to 4.6°). No significant difference was detected in the accuracy of fibula reconstruction segments.

Conclusions

We developed a novel fibula malleolus cap to overcome the sliding and rotational errors during fibula flap harvesting for oncologic jaw reconstruction, with increased accuracy in simultaneous dental implants. This is a step forward to achieve a satisfactory functional outcome of jaw reconstruction with dental rehabilitation.
Radiomics for Diagnosis and Radiotherapy of Nasopharyngeal Carcinoma
Authors: Zhang Yu-mei , Gong Guan-zhong , Qiu Qing-tao , Han Yun-wei , Lu He-ming , Yin Yong
Published: January 2022

Nasopharyngeal carcinoma (NPC) is a malignant tumor of the head and neck. The primary clinical manifestations are nasal congestion, blood-stained nasal discharge, headache, and hearing loss. It occurs frequently in Southeast Asia, North Africa, and especially in southern China. Radiotherapy is the main treatment, and currently, imaging examinations used for the diagnosis, treatment, and prognosis of NPC include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET)-CT, and PET-MRI. These methods play an important role in target delineation, radiotherapy planning design, dose evaluation, and outcome prediction. However, the anatomical and metabolic information obtained at the macro level of images may not meet the increasing accuracy required for radiotherapy. As a technology used for mining deep image information, radiomics can provide further information for the diagnosis and treatment of NPC and promote individualized precision radiotherapy in the future. This paper reviews the application of radiomics in the diagnosis and treatment of nasopharyngeal carcinoma.
Inositol Polyphosphate 4-Phosphatase Type II Is a Tumor Suppressor in Multiple Myeloma
Authors: Wang Yafei , Chen Lin , Li Qian , Gao Shuang , Liu Su , Ma Jing , Xie Ying , Wang Jingya , Cao Zeng , Liu Zhiqiang
Published: January 2022

Inositol polyphosphate-4-phosphatase type II (INPP4B) has been identified as a tumor suppressor, while little is known about its expression and function in multiple myeloma (MM). In this study, we evaluated the expression of INPP4B in 28 cases of newly diagnosed MM patients and 42 cases of extramedullary plasmacytoma (EMP) patients compared with normal plasma cells and found that low INPP4B expression was correlated with poor outcomes in MM patients. Moreover, expression of INPP4B in seven MM cell lines was all lower than that in normal plasma cells. In addition, loss of function of INPP4B promoted cell proliferation in MM cells; however, gain of function suppressed MM cells proliferation and arrested the cell cycle at G0/G1 phage. Meanwhile, knockdown of INPP4B enhanced resistance, but overexpression promoted sensitivity to bortezomib treatment in MM cells. Mechanistically, we found that INPP4B exerted its role via inhibiting the phosphorylation of Akt at lysine 473 but not threonine 308, which attenuated the activation of the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Therefore, we identified an inhibitory effect of INPP4B in MM, and our findings suggested that loss of INPP4B expression is a risk factor of aggressive MM.
Pathogenic Variant Profile of Hereditary Cancer Syndromes in a Vietnamese Cohort
Authors: Tran Van Thuan , Nguyen Sao Trung , Pham Xuan Dung , Phan Thanh Hai , Nguyen Van Chu , Nguyen Huu Thinh , Nguyen Huu Phuc , Doan Phuong Thao Thi , Le Tuan Anh , Nguyen Bao Toan , Jasmine Thanh Xuan , Nguyen Duy Sinh , Nguyen Hong-Dang Luu , Nguyen Ngoc Mai , Do Duy Xuan , Tran Vu Uyen , Nguyen Hue Hanh Thi , Le Minh Phong , Nguyen Yen Nhi , Do Thanh Thuy Thi , Truong Dinh Kiet , Tang Hung Sang , Phan Minh-Duy , Nguyen Hoai-Nghia , Giang Hoa , Tu Lan N.
Published: January 2022

Background

Hereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.

Methods

1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.

Results

A total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.

Conclusion

This is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.
Correlation Analyses of Clinical Manifestations and Variant Effects in KCNB1-Related Neurodevelopmental Disorder
Authors: Xiong Juan , Liu Zhonghua , Chen Shimeng , Kessi Miriam , Chen Baiyu , Duan Haolin , Deng Xiaolu , Yang Lifen , Peng Jing , Yin Fei
Published: January 2022

Objective:Vitro functional analyses of KCNB1 variants have been done to disclose possible pathogenic mechanisms in KCNB1-related neurodevelopmental disorder. “Complete or partial loss of function (LoF),” “dominant-negative (DN) effect” are applied to describe KCNB1 variant's molecular phenotypes. The study here aimed to investigate clinical presentations and variant effects associations in the disorder.

Methods: We reported 10 Chinese pediatric patients with KCNB1-related neurodevelopmental disorder here. Functional experiments on newly reported variants, including electrophysiology and protein expression, were performed in vitro. Phenotypic, functional, and genetic data in the cohort and published literature were collected. According to their variants' molecular phenotypes, patients were grouped into complete or partial LoF, and DN effect or non-dominant-negative (non-DN) effect to compare their clinical features.

Results: Nine causative KCNB1 variants in 10 patients were identified in the cohort, including eight novel and one reported. Epilepsy (9/10), global developmental delay (10/10), and behavior issues (7/10) were common clinical features in our patients. Functional analyses of 8 novel variants indicated three partial and five complete LoF variants, five DN and three non-DN effect variants. Patient 1 in our series with truncated variants, whose functional results supported haploinsufficiency, had the best prognosis. Cases in complete LoF group had earlier seizure onset age (64.3 vs. 16.7%, p = 0.01) and worse seizure outcomes (18.8 vs. 66.7%, p = 0.03), and patients in DN effect subgroup had multiple seizure types compared to those in non-DN effect subgroup (65.5 vs. 30.8%, p = 0.039).

Conclusion: Patients with KCNB1 variants in the Asian cohort have similar clinical manifestations to those of other races. Truncated KCNB1 variants exhibiting with haploinsufficiency molecular phenotype are linked to milder phenotypes. Individuals with complete LoF and DN effect KCNB1 variants have more severe seizure attacks than the other two subgroups.
Targeting TIGIT Inhibits Bladder Cancer Metastasis Through Suppressing IL-32
Authors: Wu Kang , Zeng Jun , Shi Xulian , Xie Jiajia , Li Yuqing , Zheng Haoxiang , Peng Guoyu , Zhu Guanghui , Tang Dongdong , Wu Song
Published: January 2022

Bladder cancer is a highly metastatic tumor and one of the most common malignancies originating in the urinary tract. Despite the efficacy of immune checkpoints, including programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), the effect of immunotherapy for bladder cancer remains unsatisfactory. Therefore, it is urgent to develop new targets to expand immunotherapeutic options. In this study, we utilized single-cell sequencing to explore the cell composition of tumors and detected a subset of Treg cells with high expression of T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and interleukin (IL)-32. The antitumor immune response was suppressed by this subset of Treg cells, while IL-32 promoted bladder cancer metastasis. Nevertheless, targeting TIGIT not only reversed immunosuppression by restoring the antitumor immune response mediated by T cells but also suppressed the secretion of IL-32 and inhibited the metastasis of bladder cancer cells. Thus, our study provided novel insights into immunosuppression in bladder cancer and highlighted TIGIT as a novel target for immunotherapy of bladder cancer. We also illustrated the mechanism of the dual effect of targeting TIGIT and revealed the metastasis-promoting effect of IL-32 in bladder cancer. Collectively, these findings raise the possibility of utilizing TIGIT as a target against bladder cancer from the bench to the bedside.
Dynamics of Individual Red Blood Cells Under Shear Flow: A Way to Discriminate Deformability Alterations
Authors: Atwell Scott , Badens Catherine , Charrier Anne , Helfer Emmanuèle , Viallat Annie
Published: January 2022

In this work, we compared the dynamics of motion in a linear shear flow of individual red blood cells (RBCs) from healthy and pathological donors (Sickle Cell Disease (SCD) or Sickle Cell-β-thalassemia) and of low and high densities, in a suspending medium of higher viscosity. In these conditions, at lower shear rates, biconcave discocyte-shaped RBCs present an unsteady flip-flopping motion, where the cell axis of symmetry rotates in the shear plane, rocking to and fro between an orbital angle ±ϕ observed when the cell is on its edge. We show that the evolution of ϕ depends solely on RBC density for healthy RBCs, with denser RBCs displaying lower ϕ values than the lighter ones. Typically, at a shear stress of 0.08 Pa, ϕ has values of 82 and 72° for RBCs with average densities of 1.097 and 1.115, respectively. Surprisingly, we show that SCD RBCs display the same ϕ-evolution as healthy RBCs of same density, showing that the flip-flopping behavior is unaffected by the SCD pathology. When the shear stress is increased further (above 0.1 Pa), healthy RBCs start going through a transition to a fluid-like motion, called tank-treading, where the RBC has a quasi-constant orientation relatively to the flow and the membrane rotates around the center of mass of the cell. This transition occurs at higher shear stresses (above 0.2 Pa) for denser cells. This shift toward higher stresses is even more remarkable in the case of SCD RBCs, showing that the transition to the tank-treading regime is highly dependent on the SCD pathology. Indeed, at a shear stress of 0.2 Pa, for RBCs with a density of 1.097, 100% of healthy RBCs have transited to the tank-treading regime vs. less than 50% SCD RBCs. We correlate the observed differences in dynamics to the alterations of RBC mechanical properties with regard to density and SCD pathology reported in the literature. Our results suggest that it might be possible to develop simple non-invasive assays for diagnosis purpose based on the RBC motion in shear flow and relying on this millifluidic approach.
Salivary Exosomes: From Waste to Promising Periodontitis Treatment
Authors: Nik Mohamed Kamal Nik Nur Syazana , Shahidan Wan Nazatul Shima
Published: January 2022

Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.
The CRISPR/Cas9-Mediated Modulation of SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 8 in Alfalfa Leads to Distinct Phenotypic Outcomes
Authors: Singer Stacy D. , Burton Hughes Kimberley , Subedi Udaya , Dhariwal Gaganpreet Kaur , Kader Kazi , Acharya Surya , Chen Guanqun , Hannoufa Abdelali
Published: January 2022

Alfalfa (Medicago sativa L.) is the most widely grown perennial leguminous forage and is an essential component of the livestock industry. Previously, the RNAi-mediated down-regulation of alfalfa SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE 8 (MsSPL8) was found to lead to increased branching, regrowth and biomass, as well as enhanced drought tolerance. In this study, we aimed to further characterize the function of MsSPL8 in alfalfa using CRISPR/Cas9-induced mutations in this gene. We successfully generated alfalfa genotypes with small insertions/deletions (indels) at the target site in up to three of four MsSPL8 alleles in the first generation. The efficiency of editing appeared to be tightly linked to the particular gRNA used. The resulting genotypes displayed consistent morphological alterations, even with the presence of up to two wild-type MsSPL8 alleles, including reduced leaf size and early flowering. Other phenotypic effects appeared to be dependent upon mutational dosage, with those plants with the highest number of mutated MsSPL8 alleles also exhibiting significant decreases in internode length, plant height, shoot and root biomass, and root length. Furthermore, MsSPL8 mutants displayed improvements in their ability to withstand water-deficit compared to empty vector control genotypes. Taken together, our findings suggest that allelic mutational dosage can elicit phenotypic gradients in alfalfa, and discrepancies may exist in terms of MsSPL8 function between alfalfa genotypes, growth conditions, or specific alleles. In addition, our results provide the foundation for further research exploring drought tolerance mechanisms in a forage crop.
Agro-Fruit-Forest Systems Based on Argan Tree in Morocco: A Review of Recent Results
Authors: Chakhchar Abdelghani , Ben Salah Imane , El Kharrassi Youssef , Filali-Maltouf Abdelkarim , El Modafar Cherkaoui , Lamaoui Mouna
Published: January 2022

The argan tree, Argania spinosa (L.) Skeels, is a horticultural forestry species characterized by its endemicity and adaptation to arid and semi-arid zones in the southwest of Morocco. Despite its limited geographical distribution, argan tree presents large genetic diversity, suggesting that improvement of argan is possible. This species plays important ecological, and socioeconomic roles in the sustainable development of the country. The integration of arganiculture into Moroccan agricultural policy has been implemented through a sector strategy, which is fully aligned with the conservation and regeneration of argan forest. A. spinosa is suitable for incorporation into different agroforestry productive systems under agro-fruit-forest model and its domestication will provide a powerful means of socio-economic and environmental management. Here, we provide an overview of the argan tree literature and highlight the specific aspects of argan stands, as agro-forest systems, with the aim of developing an adequate strategy of conservation and domestication of this species. We introduce promising programs and projects for argan plantations and arganiculture, which have been adopted to relieve anthropogenic pressure on the natural argan forest.
Genetic Diversity and Population Structure of Sorghum [Sorghum Bicolor (L.) Moench] Accessions as Revealed by Single Nucleotide Polymorphism Markers
Authors: Enyew Muluken , Feyissa Tileye , Carlsson Anders S. , Tesfaye Kassahun , Hammenhag Cecilia , Geleta Mulatu
Published: January 2022

Ethiopia is the center of origin for sorghum [Sorghum bicolor (L.) Moench], where the distinct agro-ecological zones significantly contributed to the genetic diversity of the crops. A large number of sorghum landrace accessions have been conserved ex situ. Molecular characterization of this diverse germplasm can contribute to its efficient conservation and utilization in the breeding programs. This study aimed to investigate the genetic diversity of Ethiopian sorghum using gene-based single nucleotide polymorphism (SNP) markers. In total, 359 individuals representing 24 landrace accessions were genotyped using 3,001 SNP markers. The SNP markers had moderately high polymorphism information content (PIC = 0.24) and gene diversity (H = 0.29), on average. This study revealed 48 SNP loci that were significantly deviated from Hardy–Weinberg equilibrium with excess heterozygosity and 13 loci presumed to be under selection (P < 0.01). The analysis of molecular variance (AMOVA) determined that 35.5% of the total variation occurred within and 64.5% among the accessions. Similarly, significant differentiations were observed among geographic regions and peduncle shape-based groups. In the latter case, accessions with bent peduncles had higher genetic variation than those with erect peduncles. More alleles that are private were found in the eastern region than in the other regions of the country, suggesting a good in situ conservation status in the east. Cluster, principal coordinates (PCoA), and STRUCTURE analyses revealed distinct accession clusters. Hence, crossbreeding genotypes from different clusters and evaluating their progenies for desirable traits is advantageous. The exceptionally high heterozygosity observed in accession SB4 and SB21 from the western geographic region is an intriguing finding of this study, which merits further investigation.
Systemic Acquired Resistance-Mediated Control of Pine Wilt Disease by Foliar Application With Methyl Salicylate
Authors: Jeon Hee Won , Park Ae Ran , Sung Minjeong , Kim Namgyu , Mannaa Mohamed , Han Gil , Kim Junheon , Koo Yeonjong , Seo Young-Su , Kim Jin-Cheol
Published: January 2022

Pine wilt disease (PWD), caused by the pinewood nematode, is the most destructive disease in pine forest ecosystems worldwide. Extensive research has been done on PWD, but effective disease management is yet to be devised. Generally, plants can resist pathogen attack via a combination of constitutive and inducible defenses. Systemic acquired resistance (SAR) is an inducible defense that occurs by the localized infection of pathogens or treatment with elicitors. To manage PWD by SAR in pine trees, we tested previously known 12 SAR elicitors. Among them, methyl salicylate (MeSA) was found to induce resistance against PWD in Pinus densiflora seedlings. In addition, the foliar applications of the dispersible concentrate-type formulation of MeSA (MeSA 20 DC) and the emulsifiable concentrate-type formulation of MeSA (MeSA 20 EC) resulted in significantly reduced PWD in pine seedlings. In the field test using 10-year-old P. densiflora trees, MeSA 20 DC showed a 60% decrease in the development of PWD. Also, MeSA 20 EC gave the best results when applied at 0.1 mM concentration 2 and 1 weeks before pinewood nematode (PWN) inoculation in pine seedlings. qRT-PCR analysis confirmed that MeSA induced the expression of defense-related genes, indicating that MeSA can inhibit and delay the migration and reproduction of PWN in pine seedlings by modulating gene expression. These results suggest that foliar application of MeSA could reduce PWD incidence by inducing resistance and provide an economically feasible alternative to trunk-injection agents for PWD management.
Lexical Input in the Grammatical Expression of Stance: A Collexeme Analysis of the INTRODUCTORY IT PATTERN
Authors: Wang Zhong , Fan Weiwei , Fang Alex Chengyu
Published: January 2022

Previous research on the INTRODUCTORYITPATTERN unveiled various lexical and grammatical aspects of its use as a grammatical stance device, including the range of the most frequently used adjectival and verbal stance lexemes, associated stance meanings, the most frequent sub-patterns, and the distinct uses in various contextual settings of the pattern. However, the stance meanings of the pattern, which are deeply rooted in the associated lexical resources, are still understudied. This study explores the meanings of the INTRODUCTORYITPATTERN by referring to the stance meanings of the pattern associated with the adjectival and verbal lexemes that are statistically attracted to the pattern. The research samples were extracted from the British component of the InternationalCorpusof English (ICE-GB). The samples were manually annotated for different stance types and a collexeme analysis was performed to identify the full range of stance lexemes statistically associated with the INTRODUCTORYITPATTERN (collexemes). The results show that both adjectival and verbal collexemes are statistically and functionally significant for the delivery of discrete stance types/subtypes. Adjectival collexemes are frequently deployed for all four stance types:Epistemicstance,Evaluationstance,Dynamicstance, andDeonticstance, while verbal collexemes are valuable lexical resources for theEpistemicstance, as their use entails modalized evidentiality, pointing to epistemic judgment of the writer-speaker toward events/propositions. Close examination of the use of adjectival and verbal collexemes identified three fundamental meanings of the INTRODUCTORYITPATTERN. First, the pattern is inherently evaluative as it tends to attract more lexemes with evaluative meanings and associates evaluative meanings with superficially non-evaluative lexemes. Second, it features a scalarized expression of diversified stance types/subtypes, thus, especially reflective of the scalarized semantic feature of stance expression. Third, it connotates an overwhelmingly positive likelihood judgment. The article concludes by discussing the limitations of this study.
Listening Effort Informed Quality of Experience Evaluation
Authors: Sun Pheobe Wenyi , Hines Andrew
Published: January 2022

Perceived quality of experience for speech listening is influenced by cognitive processing and can affect a listener's comprehension, engagement and responsiveness. Quality of Experience (QoE) is a paradigm used within the media technology community to assess media quality by linking quantifiable media parameters to perceived quality. The established QoE framework provides a general definition of QoE, categories of possible quality influencing factors, and an identified QoE formation pathway. These assist researchers to implement experiments and to evaluate perceived quality for any applications. The QoE formation pathways in the current framework do not attempt to capture cognitive effort effects and the standard experimental assessments of QoE minimize the influence from cognitive processes. The impact of cognitive processes and how they can be captured within the QoE framework have not been systematically studied by the QoE research community. This article reviews research from the fields of audiology and cognitive science regarding how cognitive processes influence the quality of listening experience. The cognitive listening mechanism theories are compared with the QoE formation mechanism in terms of the quality contributing factors, experience formation pathways, and measures for experience. The review prompts a proposal to integrate mechanisms from audiology and cognitive science into the existing QoE framework in order to properly account for cognitive load in speech listening. The article concludes with a discussion regarding how an extended framework could facilitate measurement of QoE in broader and more realistic application scenarios where cognitive effort is a material consideration.