bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased METTL3-mediated m6A methylation inhibits embryo implantation by repressing HOXA10 expression in recurrent implantation failure
Authors: Xue Pingping , Zhou Wenbo , Fan Wenqiang , Jiang Jianya , Kong Chengcai , Zhou Wei , Zhou Jianmei , Huang Xiaoyang , Yang Haiyan , Han Qian , Zhang Bin , Xu Lingyun , Yu Bin , Chen Li
Published: December 2021

Background

Recurrent implantation failure (RIF) is a major limitation of assisted reproductive technology, which is associated with impaired endometrial receptivity. Although N6-methyladenosine (m6A) has been demonstrated to be involved in various biological processes, its potential role in the endometrium of women with RIF has been poorly studied.

Methods

Global m6A levels and major m6A methyltransferases/demethylases mRNA levels in mid-secretory endometrium from normal and RIF women were examined by colorimetric m6A quantification strategy and quantitative real-time PCR, respectively. The effects of METTL3-mediated m6A modification on embryo attachment were evaluated by an vitro model of a confluent monolayer of Ishikawa cells co-cultured with BeWo spheroids, and the expression levels of homeo box A10 (HOXA10, a well-characterized marker of endometrial receptivity) and its downstream targets were evaluated by quantitative real-time PCR and Western blotting in METTL3-overexpressing Ishikawa cells. The molecular mechanism for METTL3 regulating HOXA10 expression was determined by methylated RNA immunoprecipitation assay and transcription inhibition assay.

Results

Global m6A methylation and METTL3 expression were significantly increased in the endometrial tissues from women with RIF compared with the controls. Overexpression of METTL3 in Ishikawa cells significantly decreased the ration of BeWo spheroid attachment, and inhibited HOXA10 expression with downstream decreased β3-integrin and increased empty spiracles homeobox 2 expression. METTL3 catalyzed the m6A methylation of HOXA10 mRNA and contributed to its decay with shortened half-life. Enforced expression of HOXA10 in Ishikawa cells effectively rescued the impairment of METTL3 on the embryo attachment in vitro.

Conclusion

Increased METTL3-mediated m6A modification represents an adverse impact on embryo implantation by inhibiting HOXA10 expression, contributing to the pathogenesis of RIF.
TRIM38 triggers the ubiquitination and degradation of glucose transporter type 1 (GLUT1) to restrict tumor progression in bladder cancer
Authors: Wang Xiaojing , He Hongchao , Rui Wenbin , Zhang Ning , Zhu Yu , Xie Xin
Published: December 2021

Background

Loss-of-function mutations or abnormal expressions of E ubiquitin ligases contributes to tumorigenesis. TRIM38 was reported to regulate immunity, inflammatory responses or apoptosis, but its roles in tumor progression remain inconclusive. This study aimed to investigate the functional roles of TRIM38 in bladder cancer to identify effective targets.

Methods

Firstly, the expression data of ubiquitination-associated genes were derived from the TCGA-BLCA cohort. Univariate Cox regression method was utilized to screen prognostic genes. Colony formation assay, Transwell assay, sphere formation assays were used to assess functional roles of TRIM38. TAP/MS assay was used to identify downstream substrates of TRIM38. Fresh clinical BLCA tissues were collected to evaluate the clinicopathological features of patients with different TRIM38 expression. The subcutaneous tumor models were established to determine the drug efficacy of BAY-876.

Results

A list of ubiquitination-associated signature was identified based on the screening in TCGA-BLCA cohort. Subsequent validations revealed that TRIM38 was a significant suppressor in tumors, which was expressed lowly in BLCA. Kaplan–Meier analysis and correlation analysis suggested that patients with low TRIM38 expressions had shorter survival time and advanced clinical characteristics. Targeting TRIM38 reinforced BLCA cells proliferation, migration and stemness. Mechanistically, TRIM38 interacted with GLUT1, thereby promoting its ubiquitinoylation and degradation. Furthermore, TRIM38 deficiency relied on accumulated GLUT1 proteins to enhance BLCA malignant features and cellular glycolytic capacity. We accordingly investigated the efficacy of GLUT1 inhibitor (BAY-876) in BLCA and determined its IC50 values across cell lines. Tumor xenograft models further validated that BAY-876 could effectively suppress the in vivo growth of TRIM38low/− BLCA.

Conclusions

Our results suggested that TRIM38 plays a tumor suppressive role in BLCA pathogenesis and TRIM38/GLUT1 axis is a therapeutic vulnerability for clinical treatment, which possessing great translational significance.
Identifying and characterizing lincRNA genomic clusters reveals its cooperative functions in human cancer
Authors: Zhou Hanxiao , Gao Yue , Li Xin , Shang Shipeng , Wang Peng , Zhi Hui , Guo Shuang , Sun Dailin , Liu Hongjia , Li Xia , Zhang Yunpeng , Ning Shangwei
Published: December 2021

Background

Emerging evidence has revealed that some long intergenic non-coding RNAs (lincRNAs) are likely to form clusters on the same chromosome, and lincRNA genomic clusters might play critical roles in the pathophysiological mechanism. However, the comprehensive investigation of lincRNA clustering is rarely studied, particularly the characterization of their functional significance across different cancer types.

Methods

In this study, we firstly constructed a computational method basing a sliding window approach for systematically identifying lincRNA genomic clusters. We then dissected these lincRNA genomic clusters to identify common characteristics in cooperative expression, conservation among divergent species, targeted miRNAs, and CNV frequency. Next, we performed comprehensive analyses in differentially-expressed patterns and overall survival outcomes for patients from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) across multiple cancer types. Finally, we explored the underlying mechanisms of lincRNA genomic clusters by functional enrichment analysis, pathway analysis, and drug-target interaction.

Results

We identified lincRNA genomic clusters according to the algorithm. Clustering lincRNAs tended to be co-expressed, highly conserved, targeted by more miRNAs, and with similar deletion and duplication frequency, suggesting that lincRNA genomic clusters may exert their effects by acting in combination. We further systematically explored conserved and cancer-specific lincRNA genomic clusters, indicating they were involved in some important mechanisms of disease occurrence through diverse approaches. Furthermore, lincRNA genomic clusters can serve as biomarkers with potential clinical significance and involve in specific pathological processes in the development of cancer. Moreover, a lincRNA genomic cluster named Cluster127 in DLK1-DIO3 imprinted locus was discovered, which contained MEG3, MEG8, MEG9, MIR381HG, LINC02285, AL132709.5, and AL132709.1. Further analysis indicated that Cluster127 may have the potential for predicting prognosis in cancer and could play their roles by participating in the regulation of PI3K-AKT signaling pathway.

Conclusions

Clarification of the lincRNA genomic clusters specific roles in human cancers could be beneficial for understanding the molecular pathogenesis of different cancer types.
Gut microbiota modulation as a possible mediating mechanism for fasting-induced alleviation of metabolic complications: a systematic review
Authors: Angoorani Pooneh , Ejtahed Hanieh-Sadat , Hasani-Ranjbar Shirin , Siadat Seyed Davar , Soroush Ahmad Reza , Larijani Bagher
Published: December 2021

Background

Intermittent fasting has been reported to have positive effects on obesity, diabetes, cardiovascular diseases, hypertension, and several neurodegenerative diseases through different mechanisms such as alteration in the gut microbiota. This systematic review was conducted with the aim of providing an overview of the existing animal and human literature regarding the gut microbiota alterations in various fasting regimens.

Method

A systematic literature search was conducted on PubMed, Scopus and Web of Science databases up to May 2021 to find all relevant studies examining the gut microbiota alteration during the fasting. Original researches on animal models or human patients were included in this study.

Results

The search fulfilled 3072 documents from which 31 studies (20 animal and 11 human studies) were included. Upon fasting, abundance of several beneficial bacteria including Lactobacillus and Bifidobacterium shifted significantly. Moreover, some taxa, including Odoribacter which negatively associated with blood pressure bloomed during fasting. Ramadan fasting, as a kind of intermittent fasting, improves health parameters through positive changes in gut microbiota including upregulation of A. muciniphila, B. fragilis, Bacteroides and butyric acid–producing Lachnospiraceae.

Conclusion

The findings suggest that different fasting regimens including alternate-day fasting, calorie- and time-restricted fasting programs and Ramadan fasting could promote health maybe through the modulation of gut microbiome. However, further studies are needed to explore properly the connection between gut microbiota and meal frequency and timing.
Altered expressions of CXCR4 and CD26 on T-helper lymphocytes in hereditary hemorrhagic telangiectasia
Authors: Guilhem Alexandre , Portalès Pierre , Dupuis-Girod Sophie , Rivière Sophie , Vincent Thierry
Published: December 2021

Background

Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease characterized by a deregulated neo-angiogenesis. Besides a mainly vascular phenotype (muco-cutaneous telangiectases, arteriovenous malformations), a specific risk of infection is suggested by case series of severe and atypical infections as well as by reports of decreased T and natural killer (NK) lymphocyte counts. As some evidence supports a dysregulation of the CXCR4/CXCL12 chemotactic axis of HHT endothelial cells, we hypothesized that a similar phenomenon could occur on lymphocytes.

Methods

Eighteen HHT patients with history of severe infection (HSI) were matched in age and sex with 18 HHT without HSI and 18 healthy control subjects (HC). We assessed the cell count and the surface expression of CXCR4 and CD26 (CXCL12 inactivating peptidase) of circulating T-helper and T-cytotoxic lymphocytes (including naive, memory and activated subsets) and NK cells.

Results

The overall HHT group of 36 patients exhibited a reduction of circulating T-helper lymphocytes compared to HC (median: 517 vs. 1026 cells/mm3, p < 0.0001), correlated with age (r =  − 0.46, p = 0.005), requirement of intravenous iron or blood transfusions (median: 291 vs. 627 cells/mm3, p = 0.03) and CXCR4 surface expression (r = 0.353, p = 0.0345). CXCR4 and CD26 membrane expression were both decreased on HHT T-helper lymphocytes (median MFI ratio: 4.49 vs. 5.74 for CXCR4 and 3.21 vs. 4.33 for CD26, p = 0.03 and 0.0018 respectively) with an unchanged CXCR4/CD26 ratio. The HHT group with HSI had a higher CXCR4/CD26 ratio on the total T-lymphocyte population, as well as on the T-helper population and its naive subset (median on naive T-helper cells: 2.34 vs. 1.32, p = 0.0002).

Conclusions

Our findings support a dysregulation of the CXCL12/CXCR4 chemotaxis of T-helper lymphocytes in HHT patients, potentially linked to their T-helper lymphopenia and susceptibility to infection.
Blockade of glutamine-dependent cell survival augments antitumor efficacy of CPI-613 in head and neck cancer
Authors: Lang Liwei , Wang Fang , Ding Zhichun , Zhao Xiangdong , Loveless Reid , Xie Jin , Shay Chloe , Qiu Peng , Ke Yonggang , Saba Nabil F. , Teng Yong
Published: December 2021

Background

Alterations in metabolism are one of the emerging hallmarks of cancer cells and targeting dysregulated cancer metabolism provides a new approach to developing more selective therapeutics. However, insufficient blockade critical metabolic dependencies of cancer allows the development of metabolic bypasses, thus limiting therapeutic benefits.

Methods

A series of head and neck squamous cell carcinoma (HNSCC) cell lines and animal models were used to determine the efficacy of CPI-613 and CB-839 when given alone or in combination. Glutaminase 1 (GLS1) depletion was achieved by lentiviral shRNAs. Cell viability and apoptosis were determined in HNSCC cells cultured in 2D culture dish and SeedEZ™ 3D scaffold. Molecular alterations were examined by Western blotting and immunohistochemistry. Metabolic changes were assessed by glucose uptake, lactate production, glutathione levels, and oxygen consumption rate.

Results

We show here that HNSCC cells display strong addiction to glutamine. CPI-613, a novel lipoate analog, redirects cellular activity towards tumor-promoting glutaminolysis, leading to low anticancer efficacy in HNSCC cells. Mechanistically, CPI-613 inhibits the tricarboxylic acid cycle by blocking the enzyme activities of pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase, which upregulates GLS1 and eventually promotes the compensatory role of glutaminolysis in cancer cell survival. Most importantly, the addition of a GLS1 inhibitor CB-839 to CPI-613 treatment abrogates the metabolic dependency of HNSCC cells on glutamine, achieving a synergistic anticancer effect in glutamine-addicted HNSCC.

Conclusions

These findings uncover the critical role of GLS1-mediated glutaminolysis in CPI-613 treatment and suggest that the CB-839 and CPI-613 combination may potentiate synergistic anticancer activity for HNSCC therapeutic gain.
Pediatric focal segmental glomerulosclerosis: favorable transplantation outcome with plasma exchange
Authors: Fadel Fatina I. , Bazaraa Hafez M. , Abdel Mawla Mohamed A. , Salah Doaa M.
Published: December 2021

Background

Although kidney transplantation (KTX) is the treatment of choice for pediatric end stage kidney disease (ESKD); concerns for recurrence in cases of focal segmental glomerulosclerosis (FSGS) are still present. This study aimed to investigate the outcome of KTX in children with ESKD secondary to FSGS, with implementation of preemptive perioperative plasma exchange (PE) for non-genetically proven patients.

Methods

Forty FSGS pediatric kidney transplant recipients were studied. Of them: 12 patients (30%) had genetically proven NPHS2 mutations/familial and 28 (70%) were sporadic FSGS patients. All sporadic patients electively received 6 perioperative PE sessions. Patients with recurrence of proteinuria (n = 13; including 3 patients with genetic/familial and 10 patients with sporadic FSGS) were managed with PE and Rituximab (RTX). Kaplan-Meier curves were used to analyze graft and recurrence free survival data.

Results

The mean follow-up duration after KTX was 3.8 ± 2.86 years. Recurrence of proteinuria was encountered early postoperative in 11 patients (27.5%) and late (1.6 and 2.9 years after KTX) in 2 patients (5%). All patients with early recurrence achieved complete remission, while patients with late recurrence developed graft failure. Current serum creatinine and proteinuria levels were not different in patients received PE (n = 31) and patients did not PE (n = 9) (p = 0.308 and 0.287 respectively). Current serum creatinine and proteinuria levels in sporadic patients (n = 28) after prophylactic perioperative PE were not different from those of genetic/ familial patients (n = 12) (p = 0.303 and 0.144 respectively). Proteinuria was less in patients underwent native nephrectomy than others immediately postoperative and at assessment (p = 0.002 & 0.0031 respectively). One-year graft and patient survival was 93.8% with a mean 1-year serum creatinine of 0.67 ± 0.25 mg/dl. Three graft losses (7.5%) were due to chronic rejection 3.3, 3.75 and 4.17 years after KTX and 2 patients’ mortality (5%) occurred early postoperative (first 2 weeks).

Conclusion

FSGS transplanted children have favorable outcomes with perioperative PE for non-genetically proven cases. Early recurrence after KTX can be successfully managed with PE and RTX.
Effect of electro-acupuncture on ovarian function of women with diminished ovarian reserve: study protocol for a randomized controlled trial
Authors: Yang Le , Zhang Hanwang , Zhou Li , Gao Ying , Yang Lijuan , Hu Yajun , Xu Lu , Huang Dongmei
Published: December 2021

Background

Diminished ovarian reserve (DOR) is the precursor state of ovarian failure and can cause the decline of women’s reproductive function. DOR also leads to poor outcome of in vitro fertilization and embryo transfer (IVF-ET) by affecting the oocytes, high qualified embryo rate, pregnancy rate, etc. Some studies have demonstrated that acupuncture can improve ovarian function. But to date, there is limited evidence indicating that acupuncture or electro-acupuncture is efficient to DOR. This trial aims to evaluate the efficiency and safety of electro-acupuncture for the ovarian function and the following outcome of IVF-ET in DOR patients.

Methods

This will be a multicenter randomized controlled clinical trial. A total of more than 338 women with DOR will be randomly allocated to treatment and control groups in 1:1 ratio receiving acupuncture before undergoing IVF-ET. The primary outcome will be the clinical pregnancy rate per cycle of IVF-ET after acupuncture. The secondary outcomes will be ovarian reserve function, outcomes of IVT-ET, blood biochemical index, Massachusetts General Hospital Acupuncture Sensation Scale (MASS), scores from the self-rating anxiety and depression scale, quality of life, and pregnancy outcomes. The safety of acupuncture will also be assessed.

Discussion

The results of this trial may provide high-quality evidence regarding the effectiveness of electro-acupuncture in the treatment of DOR and following outcomes of IVF-ET. This will also help patients with DOR and their physicians by offering a new treatment option.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900024626. Registered on 19 July 2019.
Comparison of plasma neurofilament light and total tau as neurodegeneration markers: associations with cognitive and neuroimaging outcomes
Authors: Marks Jordan D. , Syrjanen Jeremy A. , Graff-Radford Jonathan , Petersen Ronald C. , Machulda Mary M. , Campbell Michelle R. , Algeciras-Schimnich Alicia , Lowe Val , Knopman David S. , Jack Clifford R. , Vemuri Prashanthi , Mielke Michelle M. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2021

Background

Total tau protein (T-Tau) and neurofilament light chain (NfL) have emerged as candidate plasma biomarkers of neurodegeneration, but studies have not compared how these biomarkers cross-sectionally or longitudinally associate with cognitive and neuroimaging measures. We therefore compared plasma T-Tau and NfL as cross-sectional and longitudinal markers of (1) global and domain-specific cognitive decline and (2) neuroimaging markers of cortical thickness, hippocampal volume, white matter integrity, and white matter hyperintensity volume.

Methods

We included 995 participants without dementia who were enrolled in the Mayo Clinic Study of Aging cohort. All had concurrent plasma NfL and T-tau, cognitive status, and neuroimaging data. Follow-up was repeated approximately every 15 months for a median of 6.2 years. Plasma NfL and T-tau were measured on the Simoa-HD1 Platform. Linear mixed effects models adjusted for age, sex, and education examined associations between baseline z-scored plasma NfL or T-tau and cognitive or neuroimaging outcomes. Analyses were replicated in Alzheimer’s Disease Neuroimaging Initiative (ADNI) among 387 participants without dementia followed for a median of 3.0 years.

Results

At baseline, plasma NfL was more strongly associated with all cognitive and neuroimaging outcomes. The combination of having both elevated NfL and T-tau at baseline, compared to elevated levels of either alone, was more strongly associated at cross-section with worse global cognition and memory, and with neuroimaging measures including temporal cortex thickness and increased number of infarcts. In longitudinal analyses, baseline plasma T-tau did not add to the prognostic value of baseline plasma NfL. Results using ADNI data were similar.

Conclusions

Our results indicate plasma NfL had better utility as a prognostic marker of cognitive decline and neuroimaging changes. Plasma T-tau added cross-sectional value to NfL in specific contexts.

Trial registration

Not applicable
Design of telescopic nadir imager for geomorphology (TENGOO) and observation of surface reflectance by optical chromatic imager (OROCHI) for the Martian Moons Exploration (MMX)
Authors: Kameda Shingo , Ozaki Masanobu , Enya Keigo , Fuse Ryota , Kouyama Toru , Sakatani Naoya , Suzuki Hidehiko , Osada Naoya , Kato Hiroki , Miyamoto Hideaki , Yamazaki Atsushi , Nakamura Tomoki , Okamoto Takaya , Ishimaru Takahiro , Hong Peng , Ishibashi Ko , Takashima Takeshi , Ishigami Ryoya , Kuo Cheng-Ling , Abe Shinsuke , Goda Yuya , Murao Hajime , Fujishima Saori , Aoyama Tsubasa , Hagiwara Keiji , Mizumoto Satoko , Tanaka Noriko , Murakami Kousuke , Matsumoto Miho , Tanaka Kenji , Sakuta Hironobu
Published: December 2021

The JAXA’s Martian Moons Exploration (MMX) mission is planned to reveal the origin of Phobos and Deimos. It will remotely observe both moons and return a sample from Phobos. The nominal instruments include the TElescopic Nadir imager for GeOmOrphology (TENGOO) and Optical RadiOmeter composed of CHromatic Imagers (OROCHI). The scientific objective of TENGOO is to obtain the geomorphological features of Phobos and Deimos. The spatial resolution of TENGOO is 0.3 m at an altitude of 25 km in the quasi-satellite orbit. The scientific objective of OROCHI is to obtain material distribution using spectral mapping. OROCHI possesses seven wide-angle bandpass imagers without a filter wheel and one monochromatic imager dedicated to the observation during the landing phase. Using these two instruments, we plan to select landing sites and obtain information that supports the analysis of return samples.

Graphical Abstract
Detection of low-frequency earthquakes by the matched filter technique using the product of mutual information and correlation coefficient
Authors: Kurihara Ryo , Kato Aitaro , Kurata Sumito , Nagao Hiromichi
Published: December 2021

The matched filter technique is often used to detect microearthquakes such as deep low-frequency (DLF) earthquakes. It compares correlation coefficients (CC) between waveforms of template earthquakes and the observed data. Conventionally, the sum of CC at multiple seismic stations is used as an index to detect the DLF earthquakes. A major disadvantage of the conventional method is drastically reduced detection accuracy when there are too few seismic stations. The new matched filter method proposed in this study can accurately detect microearthquakes using only a single station. It adopts mutual information (MI) in addition to CC to measure the similarity between the template and target waveforms. The method uses the product of MI and CC (MICC) as an index to detect DLF earthquakes. This index shows a distinct peak corresponding to an earthquake signal in a synthetic data set consisting of artificial noise and the waveform of a DLF earthquake. Application of this single-station method to field observations of Kirishima volcano, one of the most active volcanoes in Japan, detected a total of 354 events from the data in December 2010, whereas the catalog of the Japan Meteorological Agency shows only two. Of the detected events, 314 (89%) are likely DLF earthquakes and other events may be false detections. Most of the false detections correspond to surface-wave arrivals from teleseismic events. The catalog of DLF earthquakes constructed here shows similar temporal behavior to that found by the conventional matched filter method using the sum of the CC of the six stations near the volcano. These results suggest that the proposed method can greatly contribute to the accurate cataloging of DLF earthquakes using only a single seismic station.

Graphical Abstract
The economical lifestyle of CPR bacteria in groundwater allows little preference for environmental drivers
Authors: Chaudhari Narendrakumar M. , Overholt Will A. , Figueroa-Gonzalez Perla Abigail , Taubert Martin , Bornemann Till L. V. , Probst Alexander J. , Hölzer Martin , Marz Manja , Küsel Kirsten
Published: December 2021

Background

The highly diverseCand. Patescibacteria are predicted to have minimal biosynthetic and metabolic pathways, which hinders understanding of how their populations differentiate in response to environmental drivers or host organisms. Their mechanisms employed to cope with oxidative stress are largely unknown. Here, we utilized genome-resolved metagenomics to investigate the adaptive genome repertoire of Patescibacteria in oxic and anoxic groundwaters, and to infer putative host ranges.

Results

Within six groundwater wells,Cand. Patescibacteria was the most dominant (up to 79%) super-phylum across 32 metagenomes sequenced from DNA retained on 0.2 and 0.1 µm filters after sequential filtration. Of the reconstructed 1275 metagenome-assembled genomes (MAGs), 291 high-quality MAGs were classified asCand. Patescibacteria.Cand. Paceibacteria andCand. Microgenomates were enriched exclusively in the 0.1 µm fractions, whereas candidate division ABY1 andCand. Gracilibacteria were enriched in the 0.2 µm fractions. On average, Patescibacteria enriched in the smaller 0.1 µm filter fractions had 22% smaller genomes, 13.4% lower replication measures, higher proportion of rod-shape determining proteins, and of genomic features suggesting type IV pili mediated cell–cell attachments. Near-surface wells harbored Patescibacteria with higher replication rates than anoxic downstream wells characterized by longer water residence time. Except prevalence of superoxide dismutase genes in Patescibacteria MAGs enriched in oxic groundwaters (83%), no major metabolic or phylogenetic differences were observed. The most abundant Patescibacteria MAG in oxic groundwater encoded a nitrate transporter, nitrite reductase, and F-type ATPase, suggesting an alternative energy conservation mechanism. Patescibacteria consistently co-occurred with one another or with members of phyla Nanoarchaeota, Bacteroidota, Nitrospirota, and Omnitrophota. Among the MAGs enriched in 0.2 µm fractions,, only 8% Patescibacteria showed highly significant one-to-one correlation, mostly with Omnitrophota. Motility and transport related genes in certain Patescibacteria were highly similar to genes from other phyla (Omnitrophota, Proteobacteria and Nanoarchaeota).

Conclusion

Other than genes to cope with oxidative stress, we found little genomic evidence for niche adaptation of Patescibacteria to oxic or anoxic groundwaters. Given that we could detect specific host preference only for a few MAGs, we speculate that the majority of Patescibacteria is able to attach multiple hosts just long enough to loot or exchange supplies.
Treatment and outcome of COVID-19 patients in a specialized hospital during the third wave: advance of age and increased mortality compared with the first/second waves
Authors: Oda Yutaka , Shimada Motoko , Shiraishi Satoshi , Kurai Osamu
Published: December 2021

Purpose

To elucidate the clinical course of patients with coronavirus disease 2019 (COVID-19) treated at a specialized hospital mainly for those with mild and moderate severity during the third wave, and to compare that with the first and second (1st/2nd) waves.

Methods

We retrospectively reviewed the severity on admission, treatment, and outcome of a total of 581 patients from September, 2020, to March, 2021, and examined the risk factors for deterioration of respiratory condition, defined as requiring oxygen ≥ 7 L/min for 12 h.

Results

The median age was 78 (interquartile range 62−83) years, older than in the 1st/2nd waves (53 years), and 50% of the patients was male. The number of patients classified as mild (peripheral oxygen saturation (SpO2) ≥ 96%), moderate I, II, and severe (requiring admission to the ICU or mechanical ventilation) was 121, 324, 132, and 4, respectively. Favipiravir, ciclesonide, dexamethasone, and/or heparin were administered for treatment. Respiratory condition recovered in 496 (85%) patients. It worsened in 81 patients (14%); 51 (9%) of whom were transferred to tertiary hospitals and 30 (5%) died. Mortality rate increased by fivefold compared during the 1st/2nd waves. Age, male sex, increased body mass index, and C-reactive protein (CRP) on admission were responsible for worsening of the respiratory condition.

Conclusion

Patients were older in the third wave compared with the 1st/2nd waves. Respiratory condition recovered in 85%; whereas 5% of the patients died. Old age, male sex, increased body mass index, and CRP would be responsible for worsening of the respiratory condition.
Health care seeking behaviour for children with acute childhood illnesses and its relating factors in sub-Saharan Africa: evidence from 24 countries
Authors: Yaya Sanni , Odusina Emmanuel Kolawole , Adjei Nicholas Kofi
Published: December 2021

Background

Childhood illnesses and mortality rates have declined over the past years in sub-Saharan African countries; however, under-five mortality is still high in the region. This study investigated the magnitude and factors associated with health care seeking behaviour for children with childhood illnesses in 24 sub-Saharan African countries.

Methods

We used secondary data from Demographic and Health Surveys (DHSs) conducted between 2013 and 2018 across the 24 sub-Saharan African countries. Binary logistic regression models were applied to identify the factors associated with health care seeking behaviour for children with acute childhood illnesses. The results were presented using adjusted odds ratios (aOR) with 95% confidence intervals (CIs).

Results

Overall, 45% of children under-5 years with acute childhood illnesses utilized health care facilities. The factors associated with health care seeking behaviour for children with acute illnesses were sex of child, number of living children, education, work status, wealth index, exposure to media and distance to a health facility.

Conclusions

Over half of mothers did not seek appropriate health care for under-five childhood illnesses. Effective health policy interventions are needed to enhance health care seeking behaviour of mothers for childhood illnesses in sub-Saharan African countries.
Sleep in post-COVID-19 recovery period and its impact on different domains of quality of life
Authors: El Sayed Samir , Gomaa Sarah , Shokry Doaa , Kabil Ahmed , Eissa Ahmed
Published: December 2021

Background

COVID-19 pandemic became a global health problem affecting the life of millions of people all over the world. The effects of this pandemic were not only on the physical and medical aspects but also on the psychological issues including anxiety disorders, depressive manifestations, sleep problems and others. Sleep disorders were very commonly reported during the novel Coronavirus-19 pandemic either in the acute phase of COVID-19 infection or after recovery. These sleep problems might have a drastic burden on the recovered patients’ life. This study aimed to investigate the sleep in the post-Coronavirus-19 period and if has an impact on the different items of patients’ quality of life. This cross-sectional observational study investigated the sleep problems in 500 patients in the post recovery period using Insomnia Severity Index and Pittsburgh sleep quality index (PSQI), their relation to this critical period and their impact on different domains of Quality of Life which was assessed by the SF36 Health Survey.

Results

Socio-demographic characteristics of 500 post-Coronavirus-19 patients were collected; the insomnia severity index and Pittsburgh sleep quality index evaluated the sleep pattern. The quality of life was investigated using Short Form 36 scale. The study revealed high scores of insomnia severity index (13.01 ± 4.9), Pittsburgh sleep quality index (15.37 ± 4.43), also high scores of different items of scale of quality of life in the studied group.

Conclusion

Post-COVID-19 sleep disturbances were commonly reported in the recovery period, also these sleep deficits had an impact on the physical and mental aspects of quality of life, so these sleep problems must be managed properly especially in this critical pandemic era.
Effect of the use of dexmedetomidine as a local anesthetic adjuvant to bupivacaine 0.125% in epidural labor analgesia: randomized controlled study
Authors: Afandy Mohamed Elsayed , Abusabaa Motaz M. A. , Lotfy Hashem Adel , Mansour Radwa Fathy
Published: December 2021

Background

Multiple methods exist for the management of pain during normal labor. Epidural analgesia has been reported to be an effective method in that perspective. The current study was conducted to evaluate the efficacy of dexmedetomidine as an adjuvant to local anesthetics in epidural analgesia for pregnant females presented for normal delivery. Sixty pregnant females were included in this prospective randomized study, and they were divided into two equal groups: control group which received bupivacaine alone and dexmedetomidine group that received bupivacaine with dexmedetomidine. The primary outcome was the onset of analgesia, while the secondary outcomes included the duration of analgesia, hemodynamic changes, labor progress, neonatal outcomes, and maternal complications.

Results

Dexmedetomidine group was associated with earlier onset of analgesia (P ˂ 0.001), prolonged duration (P ˂ 0.001), and lower need for top-up doses (P ˂ 0.001) compared to control group. Also, sedation and maternal satisfaction were significantly better in the same group (P = 0.001, 0.025; respectively). Labor progress parameters and neonatal outcomes were comparable between the two groups. Dexmedetomidine group has lower heart rate and mean arterial blood pressure compared to the control group. Despite of dexmedetomidine group had higher incidence of hypotension and bradycardia, it was statistically insignificant when compared to control group.

Conclusions

Dexmedetomidine is a reliable and an effective adjuvant to the local anesthetics in epidural analgesia during normal delivery as it resulted in earlier onset and significant prolongation of the analgesic time with decrease in the top-up doses intake.

Trial registration

Pan African Clinical Trial Registry (PACTR201710002664704). Register on 3 October 2017.
Haemato-biochemical and ionic regulatory responses of the hybrid catfish, Heteroclarias, to sublethal concentrations of palm oil mill effluents
Authors: Owolabi Olufemi D. , Abdulkareem Saratu I. , Ajibare Adefemi O.
Published: December 2021

Background

Pollution arising from the noxiousness of palm oil mill effluent (POME) has become a serious threat to aquatic biotas. However, a paucity of information exists on fish response to POME-mediated oxidative stress, lipid peroxidation, haemato-biochemical, enzymatic and ionic changes. This study, therefore, evaluates the effects of 28-day exposure of Heteroclarias, a hybrid catfish, to POME. Juvenile Heteroclarias (n = 350, average weight: 11.90 ± 0.70 g and average length: 9.04 ± 0.71 cm) were exposed to sublethal concentrations (0-control, 4.00, 8.00 and 12.00 mg/l) of POME to determine its effects on red blood cells (RBC), haemoglobin (HB), packed cell volume (PCV), white blood cells (WBC), mean cell haemoglobin (MCH), mean cell haemoglobin concentration (MCHC) and mean cell volume (MCV). The activities of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), lactate dehydrogenase (LDH), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA), calcium (Ca+), potassium (K+), magnesium (Mg2+) and sodium (Na+) ions were also assayed in the gill and liver.

Results

Exposure to POME caused significant (p < 0.05) concentration-dependent decrease in RBC, HB, PCV, MCV, MCH and MCHC values, whereas a significant (p < 0.05) concentration-dependent increase in WBC was observed in POME-exposed fish compared to the control. ALT, AST, LDH, GPx, SOD and CAT activities in the gill and liver significantly (p < 0.05) increased in a concentration-dependent manner. MDA level significantly (p < 0.05) increased in the gill relative to control, while in the liver it was insignificantly different. Both tissues exhibited an increase in Ca+, K+, Mg2+ and Na+ levels at the highest toxicant concentration with a rise of 77.93, 38.46, 109.54 and 41.99% recorded for the electrolytes in the gill and 79.17, 26.92, 55.48 and 38.78% in the liver above the control value, respectively. The levels of all the electrolytes except K+ were higher in the gill than the liver and were in the order: Na+ > K+ > Mg+ > Ca2+ in both tissues.

Conclusions

These results may be used as a suitable tool for pollution assessment and policy formulation to mitigate the discharge of untreated POME into aquatic ecosystems and their impacts on resident organisms.
You are more than what you eat: potentially adaptive enrichment of microbiome functions across bat dietary niches
Authors: Ingala Melissa R. , Simmons Nancy B. , Dunbar Miranda , Wultsch Claudia , Krampis Konstantinos , Perkins Susan L.
Published: December 2021

Background

Animals evolved in a microbial world, and their gut microbial symbionts have played a role in their ecological diversification. While many recent studies report patterns of phylosymbiosis between hosts and their gut bacteria, fewer studies examine the potentially adaptive functional contributions of these microbes to the dietary habits of their hosts. In this study, we examined predicted metabolic pathways in the gut bacteria of more than 500 individual bats belonging to 60 species and compare the enrichment of these functions across hosts with distinct dietary ecologies.

Results

We found that predicted microbiome functions were differentially enriched across hosts with different diets. Using a machine-learning approach, we also found that inferred microbiome functions could be used to predict specialized host diets with reasonable accuracy. We detected a relationship between both host phylogeny and diet with respect to microbiome functional repertoires. Because many predicted functions could potentially fill nutritional gaps for bats with specialized diets, we considered pathways discriminating dietary niches as traits of the host and fit them to comparative phylogenetic models of evolution. Our results suggest that some, but not all, predicted microbiome functions may evolve toward adaptive optima and thus be visible to the forces of natural selection operating on hosts over evolutionary time.

Conclusions

Our results suggest that bats with specialized diets may partially rely on their gut microbes to fulfill or augment critical nutritional pathways, including essential amino acid synthesis, fatty acid biosynthesis, and the generation of cofactors and vitamins essential for proper nutrition. Our work adds to a growing body of literature suggesting that animal microbiomes are structured by a combination of ecological and evolutionary processes and sets the stage for future metagenomic and metabolic characterization of the bat microbiome to explore links between bacterial metabolism and host nutrition.
Correction to: The role of diaphragmatic ultrasound as a predictor of successful extubation from mechanical ventilation in respiratory intensive care unit
Authors: Mohamed Randa Salah Eldin , Mohamed Abeer Salah Eldin , Fathalah Waleed Fouad , Mohamed Mohamed Farouk , Ahmed Ahmed Aelgharib
Published: December 2021

An amendment to this paper has been published and can be accessed via the original article.
Suicide and other causes of death among working-age and older adults in the year after discharge from in-patient mental healthcare in England: matched cohort study
Authors: Musgrove Rebecca , Carr Matthew J. , Kapur Nav , Chew-Graham Carolyn A. , Mughal Faraz , Ashcroft Darren M. , Webb Roger T.
Published: December 2021

Background

Evidence for risk of dying by suicide and other causes following discharge from in-patient psychiatric care throughout adulthood is sparse.

Aims

To estimate risks of all-cause mortality, natural and external-cause deaths, suicide and accidental, alcohol-specific and drug-related deaths in working-age and older adults within a year post-discharge.

Method

Using interlinked general practice, hospital, and mortality records in the Clinical Practice Research Datalink we delineated a cohort of discharged adults in England, 2001–2018. Each patient was matched to up to 20 general population comparator patients. Cumulative incidence (absolute risks) and hazard ratios (relative risks) were estimated separately for ages 18–64 and ≥65 years with additional stratification by gender and practice-level deprivation.

Results

The 1-year cumulative incidence of dying post-discharge was 2.1% among working-age adults (95% CI 2.0–2.3) and 14.1% (95% CI 13.6–14.5) among older adults. Suicide risk was particularly elevated in the first 3 months, with hazard ratios of 191.1 (95% CI 125.0–292.0) among working-age adults and 125.4 (95% CI 52.6–298.9) in older adults. Older patients were vulnerable to dying by natural causes within 3 months post-discharge. Risk of dying by external causes was greater among discharged working-age adults in the least deprived areas. Relative risk of suicide in discharged working-age women relative to their general population peers was double the equivalent male risk elevation.

Conclusions

Recently discharged adults at any age are at increased risk of dying from external and natural causes, indicating the importance of close monitoring and provision of optimal support to all such patients, particularly during the first 3 months post-discharge.
Prevalence and Risk Factors of Sarcopenia in Patients With Diabetes: A Meta-analysis
Authors: Feng Liyuan , Gao Qianqian , Hu Kaiyan , Wu Mei , Wang Zhe , Chen Fei , Mei Fan , Zhao Li , Ma Bin
Published: December 2021

Context

The prevalence of sarcopenia in patients with diabetes is 3 times higher than that in patients without diabetes and is associated with a poor prognosis.

Objective

To investigate the global pooled prevalence and risk factors of sarcopenia in patients with diabetes.

Data Sources

Relevant studies published until November 30, 2020, were identified from the PubMed, Embase, Web of Science, WanFang, CNKI, VIP, and CBM databases.

Study Selection

Participants with age ≥ 18 years with clinically diagnosed diabetes. Sex and diabetes type were not restricted.

Data Extraction

The data were extracted by 2 reviewers independently using a standard data collection form.

Data Synthesis

The pooled prevalence of sarcopenia in patients with diabetes was 18% (95% CI, 16-20); subgroup analysis showed that sarcopenia was more prevalent in males than in females, as well as being more prevalent in Asia than in South America and Oceania. Age (odds ratio [OR], 1.10), glycated hemoglobin (HbA1c) (OR = 1.16), visceral fat area (VFA) (OR = 1.03), diabetic nephropathy (OR = 2.54), duration of diabetes (OR = 1.06), and high-sensitivity C-reactive protein (hs-CRP) (OR = 1.33) were risk factors for sarcopenia in patients with diabetes.

Conclusions

Sarcopenia was more prevalent in patients with diabetes. Age, HbA1c, VFA, diabetic nephropathy, duration of diabetes, and hs-CRP were the probable risk factors. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide information on its prevention.
Targeting 11-Beta Hydroxylase With [131I]IMAZA: A Novel Approach for the Treatment of Advanced Adrenocortical Carcinoma
Authors: Hahner Stefanie , Hartrampf Philipp E , Mihatsch Patrick W , Nauerz Marc , Heinze Britta , Hänscheid Heribert , Teresa Fuß Carmina , Werner Rudolf A , Pamporaki Christina , Kroiss Matthias , Fassnacht Martin , Buck Andreas K , Schirbel Andreas
Published: December 2021

Context

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. Theranostic approaches with adrenal specific radiotracers hold promise for improved diagnostics and treatment.

Objective

Here, we report a new theranostic approach to advanced ACC applying (R)-1-[1-(4-[123I]iodophenyl)ethyl]-1H-imidazole-5-carboxylic acid azetidinyl amide ([123I]IMAZA) for diagnostic imaging and [131I]IMAZA for radionuclide therapy.

Methods

Sixty-nine patients with nonresectable, metastatic ACCs were screened using a diagnostic [123I]IMAZA scan. Patients with significant uptake in all tumoral lesions were offered treatment with [131I]IMAZA. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1), and adverse effects were assessed by Common Toxicity Criteria (version 5.0).

Results

After screening, 13 patients were treated with a median of 25.7 GBq [131I]IMAZA (range 18.1-30.7 GBq). Five individuals received a second treatment course. Best response was a decrease in the RECIST target lesions of –26% in 2 patients. Five patients with disease stabilization experienced a median progression-free survival of 14.3 months (range 8.3-21.9). Median overall survival in all patients was 14.1 months (4.0-56.5) after therapy. Treatment was well tolerated, in other words no severe toxicities (CTCAE grade ≥3) were observed.

Conclusion

In patients with advanced ACC refractory to standard therapeutic regimens, [131I]IMAZA treatment was associated with disease stabilization and nonsignificant tumor size reduction in a significant patient fraction and only limited toxicities. High [131I]IMAZA-uptake in tumor lesions was observed in 38.5% of patients with advanced ACC, rendering [131I] IMAZA a potential treatment option in a limited, well-defined patient fraction. Further clinical trials will be necessary to evaluate the full potential of this novel theranostic approach.
The Hippo Pathway Effectors YAP and TAZ Regulate LH Release by Pituitary Gonadotrope Cells in Mice
Authors: Lalonde-Larue Ariane , Boyer Alexandre , Dos Santos Esdras Corrêa , Boerboom Derek , Bernard Daniel J , Zamberlam Gustavo
Published: December 2021

The Hippo transcriptional coactivators YAP and TAZ exert critical roles in morphogenesis, organ size determination and tumorigenesis in many tissues. Although Hippo kinase cascade activity was recently reported in the anterior pituitary gland in mice, the role of the Hippo effectors in regulating gonadotropin production remains unknown. The objective of this study was therefore to characterize the roles of YAP and TAZ in gonadotropin synthesis and secretion. Using a conditional gene targeting approach (cKO), we found that gonadotrope-specific inactivation of Yap and Taz resulted in increased circulating levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in adult male mice, along with increased testosterone levels and testis weight. Female cKO mice had increased circulating LH (but not FSH) levels, which were associated with a hyperfertility phenotype characterized by higher ovulation rates and larger litter sizes. Unexpectedly, the loss of YAP/TAZ did not appear to affect the expression of gonadotropin subunit genes, yet both basal and GnRH-induced LH secretion were increased in cultured pituitary cells from cKO mice. Likewise, pharmacologic inhibition of YAP binding to the TEAD family of transcription factors increased both basal and GnRH-induced LH secretion in LβT2 gonadotrope-like cells in vitro without affecting Lhb expression. Conversely, mRNA levels of ChgA and SgII, which encode key secretory granule cargo proteins, were decreased following pharmacologic inhibition of YAP/TAZ, suggesting a mechanism whereby YAP/TAZ regulate the LH secretion machinery in gonadotrope cells. Together, these findings represent the first evidence that Hippo signaling may play a role in regulating pituitary LH secretion.