bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Chain Acylcarnitines Induce Senescence of Invariant Natural Killer T Cells in Hepatocellular Carcinoma
Authors: Cheng Xue , Tan Xiaosheng , Wang Wei , Zhang Ziyao , Zhu Rongfei , Wu Mi , Li Mingyu , Chen Yiqing , Liang Zhihui , Zhu Peng , Wu Xiongwen , Weng Xiufang
Published: December 2022

CD1d-restricted invariant natural killer T (iNKT) cells actively patrol the liver and possess valuable antitumor potential. However, clinical trials evaluating administration of iNKT cell–specific agonist α-galactosylceramide (α-GalCer) have failed to achieve obvious tumor regression. Improving the efficacy of iNKT cell–based immunotherapy requires a better understanding of the factors restraining the clinical benefits. In the context of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), we found circulating and hepatic iNKT cells were hyperactivated but demonstrated imbalances in ratio and defective α-GalCer responsiveness. Exogenous IL2 helped to expand residual α-GalCer–responsive clones with reduced T-cell receptor diversity. However, transcriptome-wide analysis revealed activation of the senescence-associated secretory phenotype and dampened cytotoxicity in iNKT cells, weakening their immune surveillance capacity. The senescent status of iNKT cells from the patients was further illustrated by cell-cycle arrest, impaired telomere maintenance, perturbed calcium transport-related biological processes, and altered metabolism. Lipidomic profiling revealed the accumulation of long-chain acylcarnitines (LCAC) and aberrant lipid metabolism in HCC tissue. Exogenous LCACs, especially palmitoyl-carnitine and stearoyl-carnitine, inhibited iNKT cell expansion and promoted senescence. Collectively, our results provide deeper insights into iNKT cell dysregulation and identify a cell senescence–associated challenge for iNKT cell–based immunotherapy in HBV-related HCC. The mechanistic links between iNKT cell senescence and accumulated LCACs suggest new targets for anti-HCC immunotherapies.

Significance:

Patients with HBV-related HCC exhibit a cell senescence–associated dysregulation of invariant natural killer cells that is related to altered lipid metabolism and accumulated LCACs in tumor tissue.
Deregulation of SPOP in Cancer
Authors: Zhang Hui , Jin Xiaofeng , Huang Haojie
Published: December 2022

Speckle-type POZ protein (SPOP) is a substrate-binding adaptor of the CULLIN3/RING-box1 E3 ubiquitin ligase complex. SPOP is frequently mutated in prostate and endometrial cancers, whereas it is overexpressed in renal cell carcinoma (RCC). SPOP can mediate both degradable and nondegradable polyubiquitination of a number of substrates with diverse biological functions such as androgen receptor (AR), SRC-3, TRIM24, BRD4, PD-L1, 53BP1, GLP/G9a, c-Myc, SENP7, among others. Cancer-associated SPOP mutants often impair SPOP binding and polyubiquitination of its substrates to influence various cancer-relevant pathways, which include androgen/AR signaling, DNA repair and methylation, cellular stress surveillance, cancer metabolism, and immunity. Although SPOP is recognized as a tumor suppressor in prostate and endometrial cancers, it acts like an oncoprotein in RCC. This review provides an overview of the recent progress in understanding of the upstream regulators of SPOP and its downstream targets, highlights the significant impact of SPOP mutations and overexpression on cancer pathogenesis, and discusses the potential of targeting SPOP for cancer treatment.
Aptima HR-HPV Testing of Cytology Specimens Is an Effective Supplement for p16 Staining to Improve Diagnostic Accuracy for HPV-Related Oropharyngeal Squamous Cell Carcinoma
Authors: Yang Xin , Hu Chunfang , Zhao Huan , Zhang Zhihui , Zhao Linlin , Yu Jing , Ni Xiaoguang , Guo Huiqin
Published: December 2022

Introduction: Regarding a small proportion of oropharyngeal squamous cell carcinoma (OPSCC) patients who tested p16-positive but human papillomavirus (HPV)-negative, we attempted to perform HPV testing to improve the accuracy of HPV detection in OPSCC patients. Methods: We simultaneously performed Aptima HPV testing of cytological specimens and p16 immunohistochemistry (IHC) staining of histologic biopsies from the same cohort of patients with head and neck SCC (HNSCC). The cytological specimens included fine-needle aspiration specimens from patients with enlarged nodes and endoscopic brushing specimens from the primary lesions of patients without enlarged nodes. Cases with discordant results for p16 IHC staining and Aptima HPV testing were reexamined by a third method, RNAscope testing. Results: Sixty patients with HNSCC (39 OPSCC and 21 non-OPSCC) were recruited for examination of HPV status. Among these patients, 28 were p16+/HPV+, 29 were p16−/HPV−, 2 were p16+/HPV−, and 1 was p16−/HPV+. The overall concordance rate between Aptima HPV testing and p16 IHC was 95.0%. Three cases with discordant results for these two methods were reexamined by RNAscope testing, and all were confirmed to be HPV negative. The prevalence of HPV in OPSCC and non-OPSCC patients was 61.5% (24/39) and 19.0% (4/21), respectively. The sensitivity and negative predictive values of Aptima HPV testing and p16 IHC were consistent at 100%, while the specificity and positive predictive values were 96.9% and 96.6% versus 93.8% and 93.3%, respectively. Additionally, 30 OPSCCs were simultaneously examined and diagnosed by both brush cytology and biopsy pathology; six of these SCCs were underdiagnosed by histopathology but accurately diagnosed by supplemental brush cytology. Conclusion: Aptima HPV testing of cytology specimens can be used as an adjuvant examination to identify false-positive OPSCC patients after p16 IHC of biopsies, while brush cytology may be a supplemental method for the histologic diagnosis of malignant oropharyngeal tumors.
Instrumento projetivo para estudos de representações sociais na saúde mental
Authors: Miranda Francisco Arnoldo Nunes de , Furegato Antonia Regina Ferreira
Published: December 2022

Os autores descrevem e discutem a utilização de um instrumento projetivo para coleta de dados de pesquisa. A coleta dos dados se dá através de desenhos em que se associam frases às imagens expressas. O recurso técnico-metodológico, denominado Técnica de Investigação Cotidiana - TSC, é composto por dezesseis desenhos focalizando a jornada de trabalho do enfermeiro e suas ocorrências numa unidade de atenção psiquiátrica. Com esse instrumento analisou-se a representação do enfermeiro sobre a sexualidade do doente mental bem como o cotidiano de trabalho do enfermeiro psiquiátrico e seu objeto de cuidados. O TSC é um recurso metodológico que possibilita captar representações sociais do cotidiano da enfermagem.
Association of Lp(a) (Lipoprotein[a]) and Hypertension in Primary Prevention of Cardiovascular Disease: The MESA
Authors: Rikhi Rishi , Bhatia Harpreet S. , Schaich Christopher L. , Ashburn Nicklaus , Tsai Michael Y. , Michos Erin D. , Chevli Parag A. , Herrington David M. , Tsimikas Sotirios , Shapiro Michael D.
Published: December 2022

Background:

This study explored the longitudinal relationship of Lp(a) (lipoprotein[a]) and hypertension to cardiovascular outcomes in a large multiethnic cohort free of baseline cardiovascular disease.

Methods:

Individuals from the MESA (Multi-Ethnic Study of Atherosclerosis; N=6674) were grouped as follows: group 1: Lp(a) <50 mg/dL and no hypertension; group 2: Lp(a) ≥50 mg/dL and no hypertension; group 3: Lp(a) <50 mg/dL and hypertension; and group 4: Lp(a) ≥50 mg/dL and hypertension. Kaplan-Meier curves and multivariable Cox proportional hazard models were used to assess the relationship of Lp(a) and hypertension with time to cardiovascular disease events.

Results:

Mean follow-up time was 13.9 (5.0) years and 809 participants experienced a cardiovascular disease event. A statistically significant interaction was found between Log[Lp(a)] and hypertension status (
P
=0.091). Compared with the reference group (Lp[a] <50 mg/dL and no hypertension), those with Lp[a] ≥50 mg/dL and no hypertension had no increased risk for cardiovascular disease events (hazard ratio, 1.09 [95% CI, 0.79–1.50]). However, those with Lp(a) <50 mg/dL and hypertension or Lp(a) ≥50 mg/dL and hypertension demonstrated a statistically significant increase in risk compared to the reference group (hazard ratio, 1.66 [95% CI, 1.39–1.98]) and (hazard ratio, 2.07 [95% CI, 1.63–2.62]), respectively. Among those with hypertension, Lp(a) was associated with a significant increase in cardiovascular disease risk (hazard ratio, 1.24 [95% CI, 1.01–1.53]).

Conclusions:

Although the major contribution to cardiovascular risk was hypertension, elevated Lp(a) significantly modified the association of hypertension with cardiovascular disease. More research is needed to understand mechanistic links among Lp(a), hypertension, and cardiovascular disease.
The impact of regional heterogeneity in whole-brain dynamics in the presence of oscillations
Authors: Perl Yonatan Sanz , Zamora-Lopez Gorka , Montbrió Ernest , Monge-Asensio Martí , Vohryzek Jakub , Fittipaldi Sol , Campo Cecilia González , Moguilner Sebastián , Ibañez Agustín , Tagliazucchi Enzo , Yeo B. T. Thomas , Kringelbach Morten L. , Deco Gustavo
Published: December 2022

Large variability exists across brain regions in health and disease, considering their cellular and molecular composition, connectivity, and function. Large-scale whole-brain models comprising coupled brain regions provide insights into the underlying dynamics that shape complex patterns of spontaneous brain activity. In particular, biophysically grounded mean-field whole-brain models in the asynchronous regime were used to demonstrate the dynamical consequences of including regional variability. Nevertheless, the role of heterogeneities when brain dynamics are supported by synchronous oscillating state, which is a ubiquitous phenomenon in brain, remains poorly understood. Here, we implemented two models capable of presenting oscillatory behavior with different levels of abstraction: a phenomenological Stuart–Landau model and an exact mean-field model. The fit of these models informed by structural- to functional-weighted MRI signal (T1w/T2w) allowed us to explore the implication of the inclusion of heterogeneities for modeling resting-state fMRI recordings from healthy participants. We found that disease-specific regional functional heterogeneity imposed dynamical consequences within the oscillatory regime in fMRI recordings from neurodegeneration with specific impacts on brain atrophy/structure (Alzheimer’s patients). Overall, we found that models with oscillations perform better when structural and functional regional heterogeneities are considered, showing that phenomenological and biophysical models behave similarly at the brink of the Hopf bifurcation.
Taxonomy and ecology of Achnanthidium (Bacillariophyta, Achnanthidiaceae) from southeastern Brazil with the description of six new species
Authors: COSTA LÍVIA F. , WETZEL CARLOS E. , MAQUARDT GISELE C. , ZANON JAQUES E. , ECTOR LUC , BICUDO DENISE C.
Published: December 2022

The present study aims to expand the knowledge on Achnanthidium species occurring in tropical areas of southern Brazil. For this purpose, 345 samples from 179 sampling sites distributed throughout the state of São Paulo were analyzed for ‘monoraphid’ diatom diversity. This paper focuses on samples with a high abundance of Achnanthidium species. The permanent slides and stubs were observed using light and scanning electron microscopy. Morphometric analysis was performed to discriminate between similar species through the Elliptical Fourier Descriptors analysis. For this, valve outlines from Brazilian species were compared to those from type material available from the literature. The ecological optimum and tolerance was calculated for taxa that presented more than 10 % of occurrence per habitat. In total, 12 Achnanthidium species were observed. Six are described as new: Achnanthidium acutum sp. nov., A. brasiliense sp. nov., A. parvicapitatum sp. nov., A. paulistanum sp. nov., A. ritae sp. nov. and A. vandevijveri sp. nov. The morphometric analysis supported the differentiation between some taxa. Nine species, with occurrences of at least 10 % per habitat, had their ecological optimum and tolerance calculated. In general, these species prefer slightly acidic to neutral pH, medium electrolyte cond. and mesotrophic water conditions.
Miconia amplipedunculata (Melastomataceae: Miconieae), a new species from the Caribbean lowlands of Panama
Authors: ALMEDA FRANK , ORTÍZ ORLANDO O.
Published: December 2022

Miconia  amplipedunculata is described as a new species that is known from a limited area in the Caribbean lowland rainforests of Panama. Line drawings, field photographs, a distribution map, and a comparative discussion of morphologically similar species are provided. This species is readily distinguished by its short-petiolate alternately 3-plinerved leaf blades, brown amorphous stellulate-lepidote indumentum on the primary and secondary veins of abaxial foliar surfaces and inflorescence, long-pedunculate (up to 12.5 cm) inflorescence, persistent bracts and bracteoles, unlobed truncate calyx, prominent subulate calyx teeth that exceed the calyx, 5-merous flowers, distally constricted anther filaments, and isometric and isomorphic stamens that lack appendages. The new species is compared with M. iteophylla, M. jefensis, M. ligulata, and M. peltata. All of these species, except M. ligulata, are also endemic to Panama.
An epithelial–mesenchymal transition-related prognostic model for colorectal cancer based on weighted gene co-expression network analysis
Authors: Zhang Lina , Qian Yucheng
Published: December 2022

Objective

To identify susceptibility modules and genes for colorectal cancer (CRC) using weighted gene co-expression network analysis (WGCNA).

Methods

Four microarray datasets were downloaded from the Gene Expression Omnibus database. We divided the tumor samples into three subgroups based on consensus clustering of gene expression, and analyzed the correlations between the subgroups and clinical features. The genetic features of the subgroups were investigated by gene set enrichment analysis (GSEA). A gene expression network was constructed using WGCNA, and a protein–protein interaction (PPI) network was used to identify the key genes. Gene modules were annotated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.

Results

We divided the cancer cases into three subgroups based on consensus clustering (subgroups I, II, III). The green module identified by WGCNA was correlated with clinical characteristics. Ten key genes were identified according to their degree of connectivity in the protein–protein interaction network: FYN, SEMA3A, AP2M1, L1CAM, NRP1, TLN1, VWF, ITGB3, ILK, and ACTN1.

Conclusion

We identified 10 hub genes as candidate biomarkers for CRC. These key genes may provide a theoretical basis for targeted therapy against CRC.
A support-based measure of adult attachment: Links between the Attachment Style Interview and an observational measure of parenting in a sample of at-risk mothers
Authors: Ostler Teresa , Zhan Min , Bronfman Elisa
Published: December 2022

The Attachment Style Interview (ASI) is increasingly being used to assess parenting suitability in adoption and fostering settings. More research is needed, however, to establish how the ASI relates to parenting behaviour. This study addressed this need by examining the relations between the ASI and an observational measure of parenting behaviour in 66 women with children between the ages of one and six years in the US. The Atypical Maternal Behavior Instrument for Assessment and Classification (AMBIANCE) provided an overall assessment of five disrupted parenting behavioural dimensions: (1) intrusive/negative; (2) role confused; (3) fearful/disoriented; (4) withdrawing; and (5) affective communication errors. A secure adult attachment style was associated with optimal parenting. Two insecure attachment styles, the insecure angry–dismissive and insecure enmeshed styles, were linked to disrupted parenting behaviours. Mothers with disrupted parenting struggled to make and maintain supportive relationships with close others. In addition, they were highly mistrustful of others and evidenced psychological constraints about closeness and attitudes of anger, and extreme self-reliance or contradictory attitudes about help and self-reliance. The findings were upheld in multivariate analyses which included maternal depression and other significant demographic variables. The study provides strong support for the utility of ASI as one useful assessment tool for fostering and adoption settings.
Thoughts on supporting healthcare ethics leadership, by the editors of Impact Ethics
Authors: Kaposy Chris , Petropanagos Angel
Published: December 2022

Impact Ethics ( www.impactethics.ca ) is a Canadian bioethics blog with a diversity of contributors who come from a range of backgrounds – from academics and clinicians to activists and concerned citizens. Our authors are also diverse with respect ethnicity, race, culture, and gender. We publish commentaries about ethical issues in healthcare that affect Canadians. As editors of the blog and as practicing healthcare ethicists, we make note of three crucial determinants of leadership in healthcare ethics. First, leadership in healthcare ethics requires building relationships with other leaders, including those who do not hold formal leadership roles. Second, it is essential for leaders to be open to learning new knowledge and to learning about new practices in healthcare ethics. Third, leaders must have an orientation towards the future, which means building capacity for healthcare ethics within their organizations. The Impact Ethics blog can be used to support each of these determinants of ethics leadership.
The Antecedents of Instagram Store Purchase Intention: Exploring the Role of Trust in Social Commerce
Authors: Asma  , Afreen Afsha
Published: December 2022

Social media platforms are now serving the dual purpose of social interaction as well as commercial transactions. It is an extension of e-commerce on social media, leveraging social support for shopping purposes. This study has taken selected community-related factors and vendors-related factors to investigate their impact on purchase intention from Instagram store. Acknowledging that social commerce possesses a different environment than that of e-commerce, we have also tested the mediating role of trust in determining consumer purchase intention from an Instagram store. The present study used the Stimulus–Organism–Response model along with trust transference theory and psychological reactance theory to propose a theoretical framework to understand purchase intention with regard to the Instagram store. This study has tested the impact of physical shopping constraint on purchase intention which had previously not been tested empirically with regard to social commerce. Taking empirical data from 304 Instagram users, the study revealed community factors to have a more significant impact than vendors attributes. The findings of the study advance our understanding of how purchase intention is formed on Instagram store and highlight the importance of trust in this mechanism.
Gaps in Evidence-based Treatment of Concurrent Attention Deficit Hyperactivity Disorder and Opioid Use Disorder: A Scoping Review
Authors: Ramey Olivia L. , Bonny Andrea E. , Silva Almodóvar Armando , Nahata Milap C.
Published: December 2022

Objectives:

To describe the effectiveness of medications for the treatment of opioid use disorder (OUD) and attention deficit/hyperactivity disorder (ADHD).

Data Sources:

Literature search of PubMed, Embase, Web of Science, CINAHL, Medline, PsycINFO, and Google Scholar was performed for studies published from inception to October 25, 2022.

Study Selection and Data Extraction:

Studies were included if patients were diagnosed with OUD and ADHD and had pharmacotherapy for either condition. Abstracts, commentaries, reviews, case reports, case series, non-English articles, and animal studies were omitted.

Data Synthesis:

This review found 18 studies. Treatment of ADHD was evaluated for impact on ADHD and OUD outcomes, while treatment of OUD was evaluated for OUD-related outcomes. Outcomes assessed included markers for symptom intensity, adherence, and treatment failure. While results were mixed, treatment of ADHD was largely associated with improvements in ADHD severity and retention in OUD treatment programs. ADHD severity was associated with higher rates of illicit substance abuse and worse OUD-related outcomes. It could not be determined which medications for treatment of OUD should be prioritized.

Relevance to Patient Care and Clinical Practice:

This review summarized key findings from studies that treated ADHD or OUD among dually diagnosed patients and highlighted methodological considerations for future research.

Conclusions:

Treatment of ADHD is warranted among patients with OUD and ADHD to improve retention in OUD treatment programs and reduce illicit substance abuse. Pharmacotherapy for the treatment of ADHD or OUD should continue to be determined based on patients' characteristics and the capabilities of the treatment program.
Implementation of pharmaceutical care service to elderly cancer patients in a tertiary care hospital in South India
Authors: Fariya Shaik , Mary Martin Daniel Priya Jovita , Raj John Stephen , Sureshkumar Kaoshik , Suthakar Monisha , Muhasaparur Ganesan Rajanandh
Published: December 2022

Purpose

The goal of this study is to identify drug-related problems (DRPs) for elderly cancer patients receiving chemotherapy by implementing pharmaceutical care services.

Methods

In this interventional study, patients were followed after each cycle till 12 weeks. The MOATT-MASCC teaching tool was used to educate patients about their therapy. The outcome measures included the occurrences of any DRPs such as inappropriate medication dose, dosage form, route of administration, therapeutic duplication, failure of the patient to adhere to the medication regimen, adverse drug reactions (ADRs), and drug–drug interactions (DDIs) and to resolve it.

Results

On 186 patients, there were 38% ADRs, 16% DDIs, 6% non-adherence to therapy, 4% medical conditions for which no medication was prescribed, and 1% therapeutic duplication and transcribing error was identified. A total of 226 ADRs were documented. Nausea and vomiting were the most frequently occurring ADRs (24%) and platinum compounds caused the highest number of ADRs. Assessments of causality showed that the majority of cases are ‘probable’ (50%). In evaluating the severity of ADRs, 53% of ADRs were ‘moderate’ and 51% of ADRs were ‘probably’ preventable. Upon assessing the DDIs, 35% of the prescriptions had ‘monitor therapy’. All of the DRPs, that were identified were notified to the treating oncologists and resolved without any disagreement.

Conclusions

Pharmaceutical care is essential for elderly cancer patients. Oncologists and pharmacists should work together to identify and manage DRPs as well as educate patients about their disease. This will help in improved patient care and a better therapeutic outcome.
How Self-Identity and Social Identity Grow Environmentally Sustainable Restaurants’ Brand Communities Via Social Rewards
Authors: Jang Yoon Jung , Kim Eojina
Published: December 2022

This study proposes a model that can be used to understand customers’ attitudes to restaurants’ sustainability initiatives on brand communities. The study incorporates identity theories and suggests a theoretical model for customer engagement that represents associations among self-identity and social identity constructs, customer engagement, and customers’ sustainable behavioral changes. Members of restaurants’ brand communities participated in the survey. Structural equation modeling and multigroup analysis were used to test hypothesized relationships. The findings confirm the positive and strong effects of self-identity and social identity on customer engagement, which appear to significantly influence customers’ commitment to brands and their sustainable behavioral changes. Interestingly, the effects of self-identity on customer engagement and of customer engagement on sustainable behavioral changes are significantly greater in the high social reward group than in the low social reward group, indicating the moderating role of social rewards. Finally, several meaningful implications arise from the study.
Fat tissue is a poor predictor of 1 year outcomes after total knee arthroplasty: A secondary analysis of a randomized clinical trial
Authors: Palanne Riku , Rantasalo Mikko , Vakkuri Anne , Olkkola Klaus T. , Vahlberg Tero , Skants Noora
Published: December 2022

Background and objective:

Obesity may increase the risk of adverse events after total knee arthroplasty (TKA). Although body mass index (BMI) is commonly used in categorizing obesity, its accuracy is limited. Body fat percentage (BFP) might indicate adiposity status and predict arthroplasty-related outcomes better than BMI. We investigated whether BFP is predictive of TKA-related outcomes.

Methods:

In this secondary analysis, BFP was measured preoperatively from 294 participants of a randomized trial that investigated the effects of tourniquet and anesthesia methods on TKA. Data concerning in-hospital assessments and events were collected. Knee range of motion (ROM) was measured, the Brief Pain Inventory–short form and Oxford Knee Score questionnaires were used to collect data on patient-reported pain and function, and the 15-dimensional health-related questionnaire was used to assess quality of life preoperatively and 3 and 12 months postoperatively. The patients reported satisfaction to TKA 3 and 12 months postoperatively. Data concerning infectious and thromboembolic events within 90 postoperative days and revision surgery, manipulation under anesthesia, and mortality within 1 year were collected. A separate post hoc analysis was performed for 399 participants to assess the effects of BMI on the respective outcomes.

Results:

A 1-unit increase in BFP affected the ROM by −0.37° (95% confidence interval (CI) = −0.60 to −0.13) 12 months after surgery. BFP was not significantly associated with the operation time or adverse events. However, the number of most adverse events remained too low for adjusted analysis. A 1-unit increase in BMI increased the operation time by 0.57 min (95% CI = 0.10 to 1.04) and affected the ROM by −0.47° (95% CI = −0.74 to −0.20) 12 months postoperatively. Neither BFP nor BMI was significantly associated with acute pain, pain management, length of stay, or with pain, function, quality of life, or satisfaction to TKA at 12 months after surgery.

Conclusions:

BFP seems to be a poor predictor of in-hospital results and of patient-reported outcomes 1 year after TKA.

Twitter handle

In this secondary analysis of a randomized trial, body fat percentage was poorly predictive of clinical outcomes during hospital stay and of patient-reported outcomes 1 year after TKA.
Monocyte or white blood cell counts and β2 microglobulin predict the durable efficacy of daratumumab with lenalidomide
Authors: Shimazu Yutaka , Kanda Junya , Kaneko Hitomi , Imada Kazunori , Yamamura Ryosuke , Kosugi Satoru , Shimura Yuji , Ito Tomoki , Fuchida Shin-ichi , Uchiyama Hitoji , Fukushima Kentaro , Yoshihara Satoshi , Hanamoto Hitoshi , Tanaka Hirokazu , Uoshima Nobuhiko , Ohta Kensuke , Yagi Hideo , Shibayama Hirohiko , Onda Yoshiyuki , Tanaka Yasuhiro , Adachi Yoko , Matsuda Mitsuhiro , Iida Masato , Miyoshi Takashi , Matsui Toshimitsu , Takahashi Ryoichi , Takakuwa Teruhito , Hino Masayuki , Hosen Naoki , Nomura Shosaku , Shimazaki Chihiro , Matsumura Itaru , Takaori-Kondo Akifumi , Kuroda Junya ,   The Kansai Myeloma Forum
Published: December 2022

Background:

Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab.

Objectives:

We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status.

Design:

We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database.

Methods:

We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database.

Results:

In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen.

Conclusion:

We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts.
A missed case of hereditary hemorrhagic telangiectasia: A case report
Authors: Zhang Jia , Pan Gaoyun , Zou Yingying , Chen Xiaoshu , Pan Jingye , Wang Yi , Quan Shichao , Zou He
Published: December 2022

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant disorder characterized by abnormal blood vessel formation. When an abnormal vascular architecture affects the lungs and central nervous system, serious complications can occur. We report a missed case of hereditary hemorrhagic telangiectasia with pulmonary arteriovenous malformations and cerebral arteriovenous malformations. A 22-year-old Chinese female was taken to the emergency room because of unconsciousness. Emergency head contrast-enhanced computed tomography and transthoracic contrast echocardiography showed that she had cerebral arteriovenous malformations and pulmonary arteriovenous malformations. The patient experienced multiple spontaneous epistaxis since childhood, for which she was treated at a local hospital for a brief period. Her mother also had pulmonary arteriovenous malformations. The patient was diagnosed with hereditary hemorrhagic telangiectasia according to the consensus Curaçao diagnostic criteria and eventually died of hereditary hemorrhagic telangiectasia. The case report highlights the importance of early diagnosis and intervention for hereditary hemorrhagic telangiectasia. Given that hereditary hemorrhagic telangiectasia is frequently undiagnosed, increasing the physician’s awareness of hereditary hemorrhagic telangiectasia can play an important role in the timely diagnosis and treatment of these patients.
An Assessment of the Safety of Surgery and Hardware Placement in de-novo Spinal Infections. A Systematic Review and Meta-Analysis of the Literature
Authors: Pluemer Jonathan , Freyvert Yevgeniy , Pratt Nathan , Robinson Jerry E , Cooke Jared A , Tataryn Zachary L , Godolias Periklis , Daher Zeyad A , Oskouian Rod J. , Chapman Jens R.
Published: December 2022

Objectives

Primary objectives were outcomes comparison of instrumented surgery used for de-novo spinal infections in terms of infection recurrence, reoperations, primary failure, mortality, and length of stay relative to non-instrumented surgery. Secondary objectives were outcomes for surgical and non-surgical treatment of de-novo spinal infections regarding recurrence of infection, mortality, quality of life, and length-of-stay.

Methods

A systematic literature review was performed using the PubMed database. Studies comparing outcome variables of patients with de-novo spinal infections (DNSI) treated with and without instrumentation and surgical versus non-surgical treatment were included. Studies primarily focusing on epidural abscesses or non-de-novo infections were excluded. A meta-analysis was performed for infection recurrence, reoperation, primary treatment failure, mortality, and quality-of-life parameters.

Results

A total of 17 retrospective studies with 2.069 patients met the inclusion criteria. 1.378 patients received surgical treatment with or without instrumentation; 676 patients were treated non-surgically. For the comparison of instrumented to non-instrumented surgery Odds-Ratios were .98 (P = .95) for infection recurrence, .83 (P = .92) for primary failure, .53 (P = .02) for mortality and .32 (P = .05) for reoperation. For the comparison of non-surgical to surgical treatment, Odds-Ratios were .98 (P = .95) for infection recurrence, and 1.05 (P = .89) for mortality.

Conclusion

Available data support that instrumented surgery can be performed safely without higher rates of infection recurrence or primary failure and lower reoperation and mortality rates compared to nonsurgical treatment for DNSI. Furthermore, spine surgical treatment may generally be performed without higher risk of infection recurrence and mortality and better quality-of-life outcomes compared to generic non-surgical treatment.
Claiming Land Rights: Politics of Space and Identity—A Study of the Tea Garden Community of Assam
Authors: Das Phulmoni , Hazarika Robin
Published: December 2022

Land and identity issues are interlinked and landlessness becomes a cause of ethnic unrest in the Northeast region of India. Colonial land and forest policy not only impacted the lives of indigenous people but also affected the land relation of indigenous and other immigrant communities of Assam. Even the post-colonial state has also been continuing the legacy of colonial state, which resulted in the land deprivation of tribals and Adivasis of Assam. It is in this context the present study discusses the landlessness of the tea garden community of Assam. Despite living in Assam for more than a hundred years, they are constantly facing the issue of landlessness and land alienation, which subsequently created a threat to their identity, culture and livelihood. The article is based on the arguments and narratives drawn from the tea garden community of Assam and the role of state is also highlighted in this context.
The premonitory phase of migraine is due to hypothalamic dysfunction: revisiting the evidence
Authors: Gollion Cedric , De Icco Roberto , Dodick David W. , Ashina Hakan
Published: December 2022

Objective

To critically appraise the evidence for and against premonitory symptoms in migraine being due to hypothalamic dysfunction.

Discussion

Some premonitory symptoms (e.g. fatigue, mood changes, yawning, and food craving) are associated with the physiologic effects of neurotransmitters such as orexins, neuropeptide Y, and dopamine; all of which are expressed in hypothalamic neurons. In rodents, electrophysiologic recordings have shown that these neurotransmitters modulate nociceptive transmission at the level of second-order neurons in the trigeminocervical complex (TCC). Additional insights have been gained from neuroimaging studies that report hypothalamic activation during the premonitory phase of migraine. However, the available evidence is limited by methodologic issues, inconsistent reporting, and a lack of adherence to ICHD definitions of premonitory symptoms (or prodromes) in human experimental studies.

Conclusions

The current trend to accept that premonitory symptoms are due to hypothalamic dysfunction might be premature. More rigorously designed studies are needed to ascertain whether the neurobiologic basis of premonitory symptoms is due to hypothalamic dysfunction or rather reflects modulatory input to the trigeminovascular system from several cortical and subcortical areas. On a final note, the available epidemiologic data raises questions as to whether the existence of premonitory symptoms and even more so a distinct premonitory phase is a true migraine phenomenon.

Graphical Abstract

Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at:https://www.youtube.com/watch?v=d4Y2x0Hr4Q8.
Measurements of Antibacterial Activity of Seed Crude Extracts in Cultivated Rice and Wild Oryza Species
Authors: Yoshida Yuri , Nosaka-T Misuzu , Yoshikawa Takanori , Sato Yutaka
Published: December 2022

Seeds are continuously exposed to a wide variety of microorganisms in the soil. In addition, seeds contain large amounts of carbon and nitrogen sources that support initial growth after germination. Thus, seeds in the soil can easily promote microbial growth, and seeds are susceptible to decay. Therefore, seed defense against microorganisms is important for plant survival. Seed-microbe interactions are also important issues from the perspective of food production, in seed quality and shelf life. However, seed-microbe interactions remain largely unexplored. In this study, we established a simple and rapid assay system for the antibacterial activity of rice seed crude extracts by colorimetric quantification methods by the reduction of tetrazolium compound. Using this experimental system, the diversity of effects of rice seed extracts on microbial growth was analyzed usingEscherichia colias a bacterial model. We used collections of cultivated rice, comprising 50 accessions of Japanese landraces, 52 accessions of world rice core collections, and of 30 wildOryzaaccessions. Furthermore, we attempted to find genetic factors responsible for the diversity by genome-wide association analysis. Our results demonstrate that this experimental system can easily analyze the effects of seed extracts on bacterial growth. It also suggests that there are various compounds in rice seeds that affect microbial growth. Overall, this experimental system can be used to clarify the chemical entities and genetic control of seed-microbe interactions and will open the door for understanding the diverse seed-microbe interactions through metabolites.
Changes in microbial community structure and co-metabolism during the domestication of ofloxacin-degrading bacteria
Authors: Li Yanhong , Zhang Jing , Sha Naiqing , Tang Shen , Peng Yuqing , Zhao Yao
Published: December 2022

Background

Ofloxacin (OFL) is stable and difficult to degrade. It has been detected in water, soil, and plants throughout the world. This study domesticated OFL-contaminated livestock manure soil with simplified carbon sources to identify flora capable of effectively degrading OFL. The changes in the structural composition and diversity of the microbial community and the functional abundance of the soil flora were analyzed by metagenome sequencing technology. The Biolog-ECO microplate method was used to study the utilization of 31 different carbon sources by selected bacteria and to identify the best co-metabolized carbon source for degradation.

Results

Amino acid carbon sources were more likely to cause significant changes in community structures with increasing OFL concentrations during the acclimation stage. The abundance of Sphingobacterium decreased from 69.23% to 9.84%, while Alcaligenes increased from 0.27% to 62.79%, and Stenotrophomonas increased from 11.63% to 33.33%, becoming the dominant genus. The results suggested that Stenotrophomonas and Alcaligenes were potential candidate bacteria for the degradation of quinolone antibiotics, such as OFL. Compared with the first stage of acclimation, there was an 87% increase (the concentration was 30 mg·L−1) in the OFL degradation rate by functional flora obtained by gradient acclimation, and the functional abundance of the microbial community also increased and stabilized with the depth of the domestication process. The most significant changes in membrane transport were observed in the functional abundance of the microbial community, and it was found that itaconic acid, Tween 80, and L-aspartic acid could increase the biomass of the microbial community under OFL stress.

Conclusion

Significant changes in the bacterial composition and functional abundance of the microbial community resulted from the addition of amino acid carbon sources, together with the OFL concentration. Functional flora resulting from domestication were better able to degrade OFL. The addition of a co-metabolic carbon source significantly enhanced the biomass of the functional flora. In this study, co-metabolism was performed by adding specific carbon sources, thus achieving metabolic diversity of functional flora and ultimately efficient biodegradation of OFL. This was an important discovery in the field of microbial remediation of environmental contamination.
The human immune cell simulated anti-breast cancer nanorobot: the efficient, traceable, and dirigible anticancer bio-bot
Authors: Seyedi Seyed Mohammad Reza , Asoodeh Ahmad , Darroudi Majid
Published: December 2022

Background

Various types of cancer therapy strategies have been investigated and successfully applied so far. There are a few modern strategies for improving drug selectivity and biocompatibility, such as nanoparticle-based drug delivery systems. Herein, we designed the traceable enzyme-conjugated magnetic nanoparticles to target human breast cancer cells by simulating the innate immune cell’s respiratory explosion response.

Methods

The human immune cell simulated anti-breast cancer-nanorobot (hisABC-NB) was produced by conjugating the mouse-derived iNOS and human-originated MPO enzymes on the folate-linked chitosan-coated Fe3O4 nanoparticles. The synthesized nanoparticles were functionalized with folic acid as the breast cancer cell detector. Then, the hisABC-NB’s stability and structural properties were characterized by studying Zeta-potential, XRD, FTIR, VSM, FESEM, and DLS analysis. Next, the selectivity and anti-tumor activity of the hisABC-NB were comparatively analyzed on both normal (MCF-10) and cancerous (MCF-7) human breast cells by analyzing the cells’ survival, apoptotic gene expression profile (P53, BAX, BCL2), and flow cytometry data. Finally, the hisABC-NB’s traceability was detected by T2-weighted MRI imaging on the balb-c breast tumor models.

Results

The hisABC-NB significantly reduced the MCF-7 human breast cancer cells by inducing apoptosis response and arresting the cell cycle at the G2/M phase compared with the normal cell type (MCF-10). Moreover, the hisABC-NB exhibited a proper MRI contrast at the tumor region of treated mice compared with the non-treated type, which approved their appropriate MRI-mediated traceability.

Conclusion

The hisABC-NB’s traceability, dirigibility, and selective cytotoxicity were approved, which are the three main required factors for an efficient anticancer compound. Therefore, it has the potential to be used as an intelligent safe anticancer agent for human breast cancer treatment. However, several in vitro and in vivo studies are required to clarify its selectivity, stability, and safety.
Association between gut microbiota and longevity: a genetic correlation and mendelian randomization study
Authors: He Dan , Liu Li , Zhang Zhen , Yang Xuena , Jia Yumeng , Wen Yan , Cheng Shiqiang , Meng Peilin , Li Chun’e , Zhang Huijie , Pan Chuyu , Zhang Feng
Published: December 2022

Background

Longevity is one of the most complex phenotypes, and its genetic basis remains unclear. This study aimed to explore the genetic correlation and potential causal association between gut microbiota and longevity.

Results

Linkage disequilibrium score (LDSC) regression analysis and a bi-directional two-sample Mendelian Randomization (MR) analysis were performed to analyze gut microbiota and longevity-related traits. LDSC analysis detected four candidate genetic correlations, including Veillonella (genetic correlation = 0.5578, P = 4.67 × 10− 2) and Roseburia (genetic correlation = 0.4491, P = 2.67 × 10− 2) for longevity, Collinsella (genetic correlation = 0.3144, P = 4.07 × 10− 2) for parental lifespan and Sporobacter (genetic correlation = 0.2092, P = 3.53 × 10− 2) for healthspan. Further MR analysis observed suggestive causation between Collinsella and parental longevity (father’s age at death) (weighted median: b = 1.79 × 10− 3, P = 3.52 × 10− 2). Reverse MR analysis also detected several causal effects of longevity-related traits on gut microbiota, such as longevity and Sporobacter (IVW: b = 7.02 × 10− 1, P = 4.21 × 10− 25). Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study.

Conclusion

Our study found evidence that gut microbiota is causally associated with longevity, or vice versa, providing novel clues for understanding the roles of gut microbiota in aging development.
An uncharacterized protein NY1 targets EAT1 to regulate anther tapetum development in polyploid rice
Authors: Kamara Nabieu , Lu Zijun , Jiao Yamin , Zhu Lianjun , Wu Jinwen , Chen Zhixiong , Wang Lan , Liu Xiangdong , Shahid Muhammad Qasim
Published: December 2022

Background

Autotetraploid rice is a useful germplasm for the breeding of polyploid rice; however, low fertility is a major hindrance for its utilization. Neo-tetraploid rice with high fertility was developed from the crossing of different autotetraploid rice lines. Our previous research showed that the mutant (ny1) of LOC_Os07g32406 (NY1), which was generated by CRISPR/Cas9 knock-out in neo-tetraploid rice, showed low pollen fertility, low seed set, and defective chromosome behavior during meiosis. However, the molecular genetic mechanism underlying the fertility remains largely unknown.

Results

Here, cytological observations of the NY1 mutant (ny1) indicated that ny1 exhibited abnormal tapetum and middle layer development. RNA-seq analysis displayed a total of 5606 differentially expressed genes (DEGs) in ny1 compared to wild type (H1) during meiosis, of which 2977 were up-regulated and 2629 were down-regulated. Among the down-regulated genes, 16 important genes associated with tapetal development were detected, including EAT1, CYP703A3, CYP704B2, DPW, PTC1, OsABCG26, OsAGO2, SAW1, OsPKS1, OsPKS2, and OsTKPR1. The mutant of EAT1 was generated by CRISPR/Cas9 that showed abnormal tapetum and pollen wall formation, which was similar to ny1. Moreover, 478 meiosis-related genes displayed down-regulation at same stage, including 9 important meiosis-related genes, such as OsREC8, OsSHOC1, SMC1, SMC6a and DCM1, and their expression levels were validated by qRT-PCR.

Conclusions

Taken together, these results will aid in identifying the key genes associated with pollen fertility, which offered insights into the molecular mechanism underlying pollen development in tetraploid rice.