bluuebunny/crossref_metadata_2025 huggingface dataset:
Symptoms and Comorbidities Differ Based on Race and Weight Status in Persons Living With HIV in the Northern United States: a Cross Sectional Study.
Authors: Butler Kierra R. , Harrell Faye R. , Rahim-Williams Bridgett , Robinson Jeffrey M. , Zhang Xuemin , Gyamfi Adwoa , Erlen Judith A. , Henderson Wendy A.
Published: August 2021

Background: Persons living with HIV (PLWHIV) on highly active antiretroviral treatments (HAART) may require specialized care based on health and demographic indicators. This study investigated the association of co-morbidities, race, weight status, gastrointestinal (GI), and cardiovascular symptoms (CV) and among PLWHIV. Methods: The Symptom Checklist, Co-Morbidity, and Sociodemographic Questionnaires were used to assessed weight status, GI, and CV symptoms among 283 PLWHIV. Data were analyzed using Latent Class Analysis on John's Macintosh Project 13 Platform. Results: Participants were majority Black (50%), 69% male, and 35% AIDS diagnosed. Ages were 25 to 66. Clusters included least symptomatic status, weight gain, and weight loss by Black and non-Black participants. The non-Black weight gain cluster reported a higher incidence of AIDS (70.6% vs 38.2%), nausea (70.6% vs 17.6%), diarrhea (70.6% vs 26.5%), and shortness of breath (58.8% vs 20.6%) compared to the Black weight gain cluster. The Black weight loss cluster reported a higher incidence of CV symptoms such as chest palpitations (42.2% vs 2.7%), chest pain (44.4% vs 8.1%), and shortness of breath (73.3% vs 35.1%), and a higher incidence of all GI symptoms with the most prominent being diarrhea (71.1% vs 48.6%) compared to the non-Black weight loss cluster. Conclusions: The existing racial disparities in health-related quality of life for PLWHIV may be improved through precision health and nutrition modifications. Continued research is needed investigating differential health outcomes among PLWHIV on HAART.Clinical Trial Registration Number: NCT00222716
Is a Non-Caloric Sweeteners-Free Diet Good To Treat Functional Gastrointestinal Disorder Symptoms? A Randomized Controlled Trial
Authors: Mendoza-Martínez Viridiana Montsserrat , Zavala-Solares Mónica Rocío , Espinosa-Flores Aranza Jhosadara , León-Barrera Karen Lorena , Alcántara-Suárez Raúl , Carrillo-Ruíz José Damian , Escobedo Galileo , Esquivel-Veláz Marcela , Melendez-Mier Guillermo , Bueno-Hernández Nallely
Published: August 2021

BackgroundA diet containing Non-Caloric Sweeteners (NCS) is used to reduce calorie intake and blood sugar peaks in overweight and obese subjects. Nevertheless, some animal studies suggest that NCS consumption may increase Functional Gastrointestinal Disorder symptoms (FGDs); however, there are scant clinical trials in humans. The aim of the study was to compare the effect of consuming a diet containing NCS (c-NCS) versus a Non-Caloric Sweetener-free diet (NCS-f) on FGDs in adult volunteers.MethodsThis was a randomized, controlled, parallel-group study using two different diets for five weeks: diet c-NCS contained 50-100 mg/day NCS (80% sucralose and 20% aspartame, acesulfame K, and saccharin); NCS-f diet contained less than 10 mg/day NCS. FGDs were recorded according to the Rome III criteria, gastrointestinal symptom questionnaire, Bristol scale, food frequency questionnaire, and consumption questionnaire at the beginning (PreTx) and at the end (PostTx) of the study by a gastroenterologist and a nutritionist. This study conducted according to the CONSORT guidelines and it was registered at clinicaltrials.gov (identifier code: NCT04129762).ResultsParticipants were more often women than men in both groups (59% and 62%), with a median age of 22 years. FGDs were similar in both groups at the beginning of the study (PreTx) but significantly increased in the diet c-NCS group after five weeks (PostTx). The percentage of participants with diarrhea (PreTx=19% versus PstTx=56%; p=0.02), post-prandial discomfort (PreTx=9% versus PstTx=39%; p=0.02), constipation (PreTx=30% versus PostTx=56%; p<0.01), and burning or retrosternal pain (PreTx=13% versus PostTx=33%; p<0.01) significantly increased in the diet c-NCS group. Conversely, abdominal pain (PreTx=15% versus PostTx=3%; p=0.04), post-prandial discomfort (PreTx=26% versus PostTx=6%; p=0.02), burning or retrosternal pain (PreTx=15% versus PostTx=0%; p=0.02), early satiety (PreTx=18% versus PostTx=3%; p<0.01), and epigastric pain (PreTx=38% versus PostTx=3%; p<0.01) significantly decreased in the NCS-f diet group.Conclusion This study shows that diet c-NCS associates with increased FGDs including diarrhea, post-prandial discomfort, constipation, and burning or retrosternal pain. Interestingly, NCS-f diet concurs with decreased FGDs such as abdominal pain, post-prandial discomfort, burning or retrosternal pain, early satiety, and epigastric pain. A NCS-f diet could be a complementary strategy to alleviate FGDs. Trial registration: The ethics committee of the hospital approved this study with the registration number DI/19/301/03/020. This trial was registered at clinicaltrials.gov (identifier code: NCT04129762).
Growth in Achondroplasia Including Stature, Weight, Weight-for-Height and Head Circumference from CLARITY: Achondroplasia Natural History Study— A Multi-Center Retrospective Cohort Study of Achondroplasia in the US
Authors: Hoover-Fong Julie , Schulze Kerry J , Alade Adekemi Y , Bober Michael B , Gough Ethan , Hashmi S Shahrukh , Hecht Jacqueline T , Legare Janet M , Little Mary Ellen , Modaff Peggy , Pauli Richard M , Rodriguez-Buritica David F , Serna Maria E , Smid Cory , Liu Chengxin , McGready John
Published: August 2021

Background: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (Achondroplasia Natural History Study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at one month increments from birth through 18 years for clinical use and research for achondroplasia patients. Methods: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population. Results: Over 37,000 length/height, weight and head circumference measures from 1,374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves. Conclusion: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.
Severe Visual Loss Caused by Inhalational Methanol Poisoning in Fireworks Production: A Report on 3 Cases
Authors: Luo Lei , Zhu Xueqin , Li Jimeng , Yang Feng , Xiong YanYan , Xie Ying
Published: August 2021

BACKGROUND Explosion injury is a common occupational injury with fireworks production. There are few reports about the relationship of severe visual loss and acute methanol poisoning in fireworks laborers. CASE SUMMARY Here we report 3 patients of visual loss caused by inhalation exposure to high concentration of methanol, who were engaged in the granulation process of fireworks manufacturing industry. They presented with severe metabolic acidosis and visual impairments, accompanied with headache, chest tightness, shortness of breath, dizziness and vomiting. One patient developed bilateral blindness and two patients improved after timely hemodialysis treatment.CONCLUSION This case report emphasizes the risk of methanol poisoning in the fireworks industry or other factories using commercial alcohol. Early hemodialysis intervention and metabolic acidosis correction are crucial for rescuing visual impairment caused by methanol exposure. The awareness and supervision of commercial alcohol are indispensable for similar industrial manufactures.
Gene Expression Analysis Reveals Age and Ethnicity Signatures Between Young and Old Adults in Human PBMC
Authors: Hu Yang , Xu Yudai , Mao Lipeng , Lei Wen , Xiang Jan Jian , Zhu Guodong , Hu Yutian , Niu Haitao , Gao Feng , Gao Lijuan , Huang Li`an , Luo Oscar Junhong , Duan Jinhai , Chen Guobing
Published: August 2021

Background: Human immune system functions over an entire lifetime, yet how and why the immune system becomes less effective with age are not well understood. Therefore, the aim of this study is to exploit a large-scale population-based strategy to systematically identify genes and pathways differentially expressed as a function of chronological age. Despite the importance of age and race in shaping immune cell numbers and functions, it is unclear whether Asian and Caucasian immune systems go through similar gene expression changes throughout their lifespan, and to what extent these aging-associated variations are shared among ethnicities. Results: Here, we characterize peripheral blood mononuclear cells transcriptome from 19 healthy adults of RNA-seq data and 153 healthy subjects of micoarray data with 21~90 years of age using the weighted gene correlation network analyses (WGCNA). These data reveal a set of insightful gene expression modules and representative gene biomarkers for human immune system aging from Asian and Caucasian ancestry, respectively. Among them, the aging-specific modules may show an age-related gene expression variation spike around early-seventies. In addition, we find the top hub genes including NUDT7, CLPB, OXNAD1 and MLLT3 are shared between Asian and Caucasian aging related modules and further validated in human PBMCs from different age groups. Conclusion: Overall, our findings reveal how age and race differentially affect the immune systems between Asian and Caucasian, as well as discovered a common genetic variant that greatly impacts normal PBMC aging between Asian and Caucasian.
Parietal-Hippocampal rTMS Improves Cognitive Function in Alzheimer's Disease by Inducing Increased Dynamic Functional Connectivity of Default Mode Network
Authors: Wei Lili , Zhang Yingchun , Wang Jintao , Xu Luoyi , Yang Kehua , Lv Xinghui , Zhu Zhenwei , Gong Qian , Hu Weiming , Li Xia , Qian Mincai , Shen Yuedi , Chen Wei
Published: August 2021

Background

Alzheimer’s disease, a neurodegenerative disease with significant social and economic impact, is mainly treated by focusing on decelerating cognition decline. Parietal-hippocampal repetitive transcranial magnetic stimulation (rTMS) improves memory and cognitive function in Alzheimer’s disease, however, the underlying therapeutic mechanism has not been elucidated.
Methods

A double-blind, randomized, sham-controlled parietal-hippocampal rTMS trial of mild-to-moderate Alzheimer's disease patients was conducted in the current study. High-frequency rTMS was applied to a subject-specific left lateral parietal region with the highest functional connectivity with the hippocampus based on resting-state fMRI. Patients were randomized to either rTMS or sham treatment (five sessions/week for a total of 10 sessions). A multimodal MRI scan and a complete neuropsychological battery of tests were conducted at baseline, immediately after the intervention and 12-week follow-up after the rTMS treatment. Primary outcomes were differences in the Mini Mental State Examination (MMSE) and Philadelphia Verbal Learning Test (PVLT) scores between the groups and between pre- and post-treatment. Moreover, flexible least squares (FLS) method was used to calculate the dynamic functional connectivity (dFC) of the default mode network (DMN), and dFC changes were compared between the groups and between pre- and post-treatment.
Results

Patients undergoing active rTMS treatment (n = 31) for two weeks showed higher MMSE, PVLT-Immediate recall, and PVLT-Short Delay recall scores, whereas those who underwent sham rTMS (n = 27) treatment did not show significant changes in these measures. Dynamic functional connectivity (dFC) magnitude of the default mode network (DMN) was significantly higher after two weeks of rTMS treatment in the patients who underwent active-rTMS treatment, however, no significant changes were observed in patients who received sham-rTMS treatment. dFC magnitude reduced to baseline level at 12-week follow-up, which resembled the trajectory of the cognitive measures. A significant positive correlation was observed between changes in MMSE and changes in the dFC magnitude of DMN in patients who underwent active-rTMS treatment, but not in those who received sham-rTMS treatment.
Conclusions

The findings of the current study indicate that fMRI-guided rTMS treatment improves memory and cognitive function of Alzheimer's disease patients. In addition, the findings indicate that the DMN functional connectivity contributes to therapeutic effectiveness of rTMS.
Trial registration:
China National Medical Research Platform (http://114.255.48.20/login, No:MR-33-20-004217), retrospectively registered 2020-12-23.
APOE Genetics Influence Murine Gut Microbiome
Authors: Zajac Diana J. , Green Stefan J. , Johnson Lance A. , Estus Steven
Published: August 2021

Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.
Increased Fasting Serum Level of Arsenic Caused by Intake of Fish Meat Promotes a Potential Risk of Hypertension
Authors: He Tingchao , Ohgami Nobutaka , Ohnuma Shoko , Naito Hisao , Yajima Ichiro , Tazaki Akira , Tamura Takashi , Kondo Takaaki , Wakai Kenji , Kato Masashi
Published: August 2021

Despite identification of arsenic intake from well drinking water in developing countries as a crucial hazard for health, the health effects of diet-mediated intake of arsenic on health in developed countries have remained unclear. The Japanese diet, which is regarded as a healthy diet, includes a high intake of seafoods that contain high levels of arsenic. The associations among intake of Japanese food including 54 food items classified into 6 categories, arsenic exposure and hypertension were investigated in 2,709 adults in Japan. Logistic regression analysis including serum sodium and potassium levels as confounders indicated a positive association between fasting serum level of arsenic (fsl-As) and prevalence of hypertension. Seaweed, bone-edible small fish and fish meat in seafoods were strong contributors to the increased fsl-As among the food items examined. Fish meat intake was identified as the greatest contributor to prevalence of hypertension. Since 94% of arsenic has been reported to be caused by dietary intake in Japan, our results suggest that increased fsl-As caused by intake of fish meat could be a potential risk for hypertension. Considering the worldwide trend of increased fish meat intake, arsenic in fish meat might be a new global hazardous material.
The Role of Indian Ocean Warming on Extreme Rainfall in Central China During Early Summer 2020: Without El Niño Influence
Authors: Cai Yinan , Chen Zesheng , Du Yan
Published: August 2021

This study investigates the role of water vapor transport and sea surface temperature (SST) warming in the tropical Indian Ocean (TIO) on the heavy rainfall in central China during boreal early summer. In the past four decades, four significant rainfall events, in 1983, 1998, 2016, and 2020, occured in central China and caused severe floods, in which the year 2020 has the most extreme event. All four events are associated with significant TIO SST warming, associated with a strong and westward extending anomalous anticyclone on the western North Pacific (WNPAC). The anomalous winds in the northwestern flank of the WNPAC bring excess water vapor into central China. The water vapor, mainly carried from the central tropical Pacific, converges in central China and result in heavy rainfall. A theory of regional ocean-atmosphere interaction can well explain the processes, called the Indo-Western Pacific Ocean Capacitor (IPOC) effect. The WNPAC is usually associated with strong El Niño-Southern Oscillation (ENSO), except for the 2020 case. The 2020 event is extraordinary, without ensuring El Niño occurred in the previous winter. In 2020, the significant TIO warming sustained the anomalous WNPAC, inducing the most significant extreme rainfall event in central China. This study reveals that the IPOC effect can dramatically influence the East Asian climate even without involving the ENSO in the Pacific.
Variability of α/β Ratios for Prostate Cancer With the Fractionation Schedule: Caution Against Using the Linear-Quadratic Model for Hypofractionated Radiotherapy
Authors: Cui Ming , Gao Xianshu , Li Xiaoying , Ma Mingwei , Qi Xin , Shibamoto Yuta
Published: August 2021

Background: Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5-3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. Methods: The maximum likelihood principle in mathematical statistics was used to fit the parameters: k, α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification.Results: Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI: 1.59-1.98, P < 0.001), 3.46 Gy (95% CI: 3.08-3.83, P < 0.001), and 4.24 Gy (95% CI: 4.10-4.39, P < 0.001), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased.Conclusions: The LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.
Magnetic-resonance-guided Radiation Therapy With Simultaneous Integrated Boost at Mid-bladder Volume for Bladder Cancer
Authors: Petsuksiri Janjira , Sathitwatthanawirot Chanida , Puangragsa Utumporn , Phongprapun Wisawa , Dankulchai Pittaya , Apiwarodom Nantakan
Published: August 2021

Background and Purpose: To report the workflow and dose accumulation for bladder preservation for a bladder cancer patient, using magnetic-resonance-guided radiation therapy (MRgRT) and the simultaneous integrated boost (SIB) technique at mid-bladder volume.Materials and Methods: A muscle-invasive bladder cancer patient was treated with MRgRT. The patient was treated with the SIB technique at mid-bladder volume, with 45 Gy to the whole bladder (CTV WB) and 55 Gy to the tumor bed (CTV boost) in 20 fractions. Daily re-optimization with an adapt-to-position (ATP) strategy was utilized for dose adjustment to encompass the bladder within anisotropic planning target volume (PTV WB and PTV boost). Results: The mean daily treatment time was 55 minutes (range, 35–73). The actual whole-bladder and tumor-bed-boost doses were 45.74 ± 5.91 and 54.1 ± 4.62 Gy, respectively. PTV WB encompassing CTV WB was 95.69% ± 5.36%. PTV boost encompassing CTV boost was 97.52% ± 6.05%. The actual rectal and bowel doses were below the reference plan doses.Conclusions: The use of MRgRT with the SIB and ATP strategy proved feasible for bladder cancer treatment. Mid-bladder volume allowed treatment with the SIB technique under MR monitoring.
The Prognostic Value of Cardiac Biomarkers and Echocardiography in Critical COVID-19
Authors: Zwaenepoel Bert , Dhont Sebastiaan , Hoste Eric , Gevaert Sofie , Schaubroeck Hannah
Published: August 2021

Background Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores.Methods Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 hours of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index.Results A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value < 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value 0.011) were significantly associated with mortality, while other biomarkers (D-dimers, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7).Conclusion Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.
m⁶A Demethylase ALKBH5 Promotes Tumor Cell Proliferation by Destabilizing IGF2BPs Target Genes and Worsens the Prognosis of Patients with Non-Small Cell Lung Cancer
Authors: Tsuchiya Kazuo , Yoshimura Katsuhiro , Iwashita Yuji , Inoue Yusuke , Ohta Tsutomu , Watanabe Hirofumi , Yamada Hidetaka , Kawase Akikazu , Tanahashi Masayuki , Ogawa Hiroshi , Funai Kazuhito , Shinmura Kazuya , Suda Takafumi , Sugimura Haruhiko
Published: August 2021

Background: The modification of N6-methyladenosine (m6A) in RNA and its eraser ALKBH5, an m6A demethylase, play important roles across various steps of human carcinogenesis. However, the involvement of ALKBH5 in non-smallcell lung cancer (NSCLC) development remains to be completely elucidated.Methods: The current study investigated the involvement of ALKBH5 in NSCLC development using immunostaining of clinical NSCLC specimens as well as cancer-related cellular functions (cell proliferation, migration ability, cell cycle, and apoptosis) in ALKBH5-knockdown lung cancer cell lines. Moreover, a microarray was utilized to comprehensively analyze mRNA and m6A in ALKBH5-knockdown cells. m6A target genes were identified using the methylated RNA immunoprecipitation (MeRIP) assay with m6A antibody. Furthermore, mRNA stability and protein expression owing to m6A modification (the target genes) were examined.Results: Clinicopathological analysis revealed that increased ALKBH5 expression was an independent prognostic factor associated with unfavorable overall survival in NSCLC (hazard ratios, 1.468; 95% confidence interval, 1.039–2.073). In vitro study revealed that ALKBH5 knockdown suppressed cell proliferation ability of PC9 and A549 cells as well as promoted G1 arrest and increased the number of apoptotic cells. Furthermore, ALKBH5 overexpression increased the cell proliferation ability of the immortalized cell lines BEAS2B and HEK293. Comprehensive analysis of microarray and MeRIP quantitative-polymerase chain reaction revealed that 3′ untranslated regions (3′ UTRs) of CDKN1A, TIMP3, E2F1, and CCNG2 mRNA were potential targets of ALKBH5. Depending on the lung cancer cell lines, increased expression of CDKN1A or TIMP3 and decreased cell proliferation were observed by ALKBH5 knockdown.These alterations were offset by a double knockdown of both ALKBH5 and one of the IGF2BPs. The decline of mRNAs was, at least partly, owing to the destabilization of these mRNAs by one of the IGF2BPs.Conclusions:Upregulation of ALKBH5 in NSCLC reduces m6A modifications on the 3′ UTR of specific genes. Loss of m6A causes a decrease in opportunity for recognition by IGF2BPs and destabilizes the target transcript, such as CDKN1A (p21) and TIMP3. Downregulation of CDKN1A (p21) and TIMP3 induces cell cycle alteration and inhibits apoptosis. The ALKBH5–IGF2BPs axis promotes cell proliferation and tumorigenicity, which in turn causes the unfavorable prognosis of NSCLC.
Effects of Acupuncture for Anorexia and Dietary Intake Loss in Cachexia Patients With Advanced Respiratory Illness (Pilot Study)
Authors: Maekura Tomonori , Maekura Ryoji , Miki Keisuke , Miki Mari , Kitada Seigo
Published: August 2021

Background: Weight loss and low body mass index with cachexia are serious and refractory clinical conditions in patients with advanced chronic respiratory disease. This pilot study aimed to determine whether acupuncture improves dietary intake through increased appetite stimulation, and nutritional biomarkers, in cachectic patients with advanced respiratory illness.Methods: This study used a single-arm, open experimental design, and was conducted among hospitalized patients whose dietary intake was extremely decreased due to poor appetite. Food intake, and biomarkers were evaluated before and after acupuncture (3 times a week for 3 weeks). Results: Ten patients (age: 70.5 years [interquartile range (IQR): 68.7–75.8 years], 50% females) completed the acupuncture treatment. Significant improvements in appetite loss (visual analog scale [VAS]: 58.6 mm [42–83 mm] to 37.2 mm [19.5–50.8 mm], p = 0.0039), amount of food intake (1461 Kcal/day [1204–1620 Kcal/day] to 1696 Kcal/day [1443–2047 Kcal/day], p = 0.0039), and serum nutritional biomarker (albumin: 3.3 g/dL [3–3.8 g/dL] to 3.5 [3.3–3.7 g/dL], p = 0.0293; pre-albumin: 14.4 mg/dL [10–19.5 mg/dL] to 16.7 mg/dL [11.1–21.6 mg/dL], p = 0.0137) were observed after acupuncture. Body weight loss (0 kg [-1.4 to 1.75 kg], p = 0.0078, 0% [-3.25% to 4.7%], p = 0.0078) 6 months after acupuncture was significantly improved versus 6 months before acupuncture (-3.8 kg [-6.4 to -0.3 kg], -5.2% [-11.8% to -0.83%]). Conclusions: Short-term acupuncture may be a novel and safe treatment for improving the appetite and nutritional status of cachectic patients with advanced chronic respiratory illness. Trial registration: UMIN000044859; Date of registration: July 14, 2021-Retrospectively registered; https://www.umin.ac.jp/
A gluten-free biscuit fortified with lemon IntegroPectin
Authors: Nuzzo Domenico , Scurria Antonino , Picone Pasquale , Guiducci Alessandro , Pagliaro Mario , Pantaleo Giuseppe , Albanese Lorenzo , Meneguzzo Francesco , Ciriminna Rosaria
Published: August 2021

We report the first outcomes of producing a gluten-free biscuit by replacing 2.5 wt% of the rice flour used in the preparation of the cookie with lemon IntegroPectin, a new citrus pectin obtained from lemon processing waste via hydrodynamic cavitation showing exceptional antioxidant properties and (in vitro) high neuroprotective activity. The cookie’s friability, palate adhesion, flavor persistency and compactness remain virtually unchanged. Only the sweetness and the smell (flavor) of the functionalized cookie are lower than those of the commercial biscuit. Production of biscuits fortified with this new pectin might result not only in gluten-free and low-calorie cookies but also in a fortified cookie capable to aid in the prevention of chronic disease such as neuronal disorders.
Improving the Performance of Practical Quantum Key Distribution With Advantage Distillation Technology
Authors: Li Hong-Wei , Zhang Chun-Mei , Jiang Mu-Sheng , Cai Qing-Yu
Published: August 2021

To improve the maximal transmission distance and the maximal error rate tolerance, we apply the advantage distillation technology to analyze security of the practical decoy-sate quantum key distribution system. Based on the practical experimental parameters, the device-dependent quantum key distribution protocols and the measurement-device-independent quantum key distribution protocols have been respectively analyzed, and our analysis results demonstrate that the advantage distillation technology can significantly improve the performance of different quantum key distribution protocols. In the four-state and six-state device-dependent quantum key distribution protocols, we prove that the maximal transmission distance can be improved from 142 km to 180 km and from 146 km to 187 km respectively. In the four-state and six-state measurement-device-independent quantum key distribution protocols, we prove that the maximal transmission distance can be improved from 195 km to 273 km and from 200 km to 282 km respectively. More interestingly, the advantage distillation technology does not need to change the hardware devices about the quantum step, thus it can be conveniently to be applied in various practical quantum key distribution systems.
Course of long COVID symptoms over time in the ComPaRe long COVID prospective e-cohort
Authors: Tran Viet-Thi , Porcher Raphael , Pane Isabelle , Ravaud Philippe
Published: August 2021

About 10% of the people infected by the severe acute respiratory syndrome coronavirus 2 are reported to experience “long COVID,” that is, persistence of symptoms several weeks after infection. Day-by-day prevalence of long COVID symptoms was determined from responses to the Long COVID Symptom Tool by 837 patients (3075 person-months) with a confirmed infection and enrolled in the ComPaRe long COVID cohort, a prospective cohort of such patients in France. Nine months after disease onset, 88.7% patients reported persistent symptoms and 70% reported a high burden of disease. Over time, the prevalence progressively decreased for 19/53 symptoms (e.g., loss of taste/smell) and was stable for 29/53 symptoms (e.g., fatigue). For 5/53 symptoms (e.g., memory problems), prevalence increased rapidly over the first two months and then reached a plateau. These findings are important for understanding the underlying etiologies and mechanisms of long COVID.
Adolescent Breakfast Skipping Is Associated With Poorer Academic Performance: a School-based Study From Hidhabu Abote District, Ethiopia
Authors: Feye Dereje , Gobena Tesfaye , Brewis Alexandra , Roba Kedir Teji
Published: August 2021

Background: Breakfast is regarded as “the most important meal of the day”, suggested to positively affect learning in children and adolescent in terms of cognitive and school performance. Yet, studies in LMIC settings are few, and show very inconsistent results. Objective: To assess the prevalence and correlates of breakfast skipping and its association with school performance among randomly selected in-school adolescents in HidhabuAboteWereda North Shewa Zone, Central Ethiopia. Methods: A cross sectional study was conducted from November to December 2020. A total of 422 participants were selected randomly from high schools of Hidhabu Abote Wereda. Data were entered in to Epiata version 3.1 and exported to SPSS version 24 for analysis. Bivariate and multivariate binary logistic regression analysis identified factors that were significantly associated with the breakfast skipping. Odds ratio along with 95% Confidence interval was estimated to measure the strength of the association and level of statistical significance declared at p-value less than 0.05.Results: The magnitude of breakfast skipping was 41.3%, (95% CI: (36.6-46.0)].There was statistically significant association between breakfast skipping and overall academic performance [AOR: 5.18, 95%CI (1.54-7.46)], mathematics performance (3.88, 95%CI (1.34-11.22)], and English language performance scores [2.92, 95%CI (1.38-7.58)]. Being female [AOR = 1.857, 95% CI (1.05-3.27)], household food insecurity [AOR: 2.478, 95% CI (1.36-4.51)], and less maternal education [AOR: 1.89, 95%CL (3.38-7.77)] were independently associated with breakfast skipping. The primary reasons given for breakfast skipping were lack of time, lack of appetite in morning, and concerns around weight gain.Conclusion: Nearly half of in school adolescents were skipped breakfast meals, and reportedly in most cases for reasons unrelated to lack of food access. Students who skipped breakfast had lower levels of school performance.
Names Targeting p65 to Inhibit Cas3 Transcription by Onjisaponin B for Radiation Damage Therapy in p65+/- Mice
Authors: Wang Tao-yang , Hu Yong-jian , Wang Xia , Li Yu-feng , Zhang Fan , Yan Yi-di , Dou Wen-tao , Cheng Chen-yi , Xu Ping
Published: August 2021

Background: p65 is activated following radiation injury. The formation of p65 is regulated by Onjisaponin B (OB) in Alzheimer's disease models. In addition, there is a binding site for p65 in the promoter region of CAS3. In the present study, the use of OB as an intervention to modulate p65/Cas3 following radiation injury was studied.Methods: Cellular and animal experiments, immunofluorescence, HE staining, Western blotting, qRT-PCR, comet and DNA ladder assays, and flow cytometry were used to confirm the expression of p65 and Cas3.Results: The results demonstrated that if the expression of p65 was silenced in V79 and TC cells, OB did not significantly inhibit the activation of p65 or Cas3 following irradiation, or significantly inhibit the phosphorylation of p65 and its transfer into the nucleus. Overexpression of p65 in V79 and MTEC-1 cells resulted in OB significantly inhibiting the activation of p65 and Cas3, and the phosphorylation and translocation of p65 into the nucleus. In p65+/- mice, expression of the p65 gene was knocked down, leading to increased tissue apoptosis and inflammation, and serious tissue pathological changes. The inhibition of p65 activation by OB after exposure to radiation was not apparent in the thymus, but it was in the lung, indicating that OB has a regulatory effect on endogenous p65.Conclusions:In summary, OB interfered with radiation injury by targeting and regulating p65/Cas3. Therefore, it was confirmed that p65 is an important target molecule for the treatment of radiation injury.
Neuronal Induction and Bioenergetics Characterization of Human Forearm Adipose Stem Cells from Parkinson’s Disease Patients and Healthy Controls
Authors: González-Casacuberta Ingrid , Vilas Dolores , Pont-Sunyer Claustre , Tobías Ester , Cantó Judith , Valls-Roca Laura , García-García Francesc Josep , Garrabou Glòria , Grau-Junyent Josep Maria , Martí Maria Josep , Cardellach Francesc , Morén Constanza
Published: August 2021

Background: Neurodegenerative diseases, such as Parkinson’s disease, are heterogeneous disorders with multifactorial nature involving impaired bioenergetics; that are on the rise with the increasing global population and average lifespan. Without definite therapeutic options, both stem regenerative medicine and bioenergetics have been proposed as promising therapeutic targets in the neurologic field. The rationale of the present study was to assess human derived adipose stem cells (hASC) potential to transdifferentiate into neuronal-like cells (NhASC and neurospheres), as well as to explore hASC bioenergetic profile. Methods: To this purpose, hASC derived from the forearm of both healthy controls and clinical diagnosed Parkinson’s disease patients (PD) were included in this study and transdifferentiated through neuronal induction. Results: Morphological, growth features and neuronal protein expression markers of differentiated neuron-like NhASC and neurospheres were achieved. Increased MAP-2 neuronal marker protein expression upon neuronal induction (p<0.05 from undifferentiated hASC vs. 28 and 36 days of differentiation) and increased bIII tubulin neuronal marker protein expression upon neuronal induction (p<0.05 from undifferentiated hASC vs. 6, 28 and 36 days of differentiation) were found. Bioenergetic profile was detectable through high resolution respirometry approaches in hASC but did not lead to differential oxidative capacity rates in healthy or clinical diagnosed PD hASC. Conclusions: We have confirmed the capability of transdifferentiation to neuronal-like profile of hASC derived from the forearem of human subjects and characterized the bioenergetic oxidative profile of hASC. Despite the latter did not lead to significant differential respiration profiles, trends to suboptimal maximal respiratory capacity in PD were found. The neuronal induction leading to positive neuronal protein expression markers is a relevant issue that encourages the suitability of the NhASC models in neurodegeneration.
Tree - Open Grassland Mosaics Drive the Herbaceous Structure and Diversity in Mediterranean Holm Oak Meadows
Authors: Ibañez Mercedes , Chocarro Cristina , Leiva María José , Sebastià Maria Teresa
Published: August 2021

Background: Mediterranean holm oak meadows are semi‑natural savannah‑like agroecosystems that result from traditional silvo‑pastoral practices, which shaped these systems into a mosaic of trees and open grassland. However, traditional silvo-pastoral uses are declining with the implications that this may have on the herbaceous layer, a very biodiverse and valuable resource of these systems. Here, we aim at assessing the influence of the tree – open grassland mosaic on the structure, diversity, and composition of the herbaceous layer. Specifically, assessing the canopy effect (a) under representative Iberian canopy types, considering traditional Quercus species stands and Pinus pinea plantations at different locations; and (b) along seasonality. Results: The different components of the herbaceous layer performed differential responses to the presence/absence of tree canopies, as for instance shows the dominance of grasses under the canopy, while legumes and forbs were favoured in the open grassland. Also, there was a certain a reduction in the species richness in P. pinea dominated plots compared to plots dominated by Quercus species. There was a reduction of the aboveground biomass under the canopy at the more environmentally constrained location. Such canopy effects were generally more pronounced in spring that in autumn.Conclusion: It is highly advisable preserve the tree – open grassland mosaic and traditional Quercus species stands to maximize and preserve plant specific and functional diversity. The the optimum tree coverage might be dependent, not only on the primary ecosystem service (i. e. forage provision), but also on local conditions.
Factors Influencing Decision-Making of Terminally Ill Cancer Patients and Their Families Regarding Where to Stay and Receive Final-Month Care: A Preliminary Study
Authors: Eriko Hayashi , Fumiyasu Fukano , Hideki Onishi
Published: August 2021

Background:Advance care planning is essential for a better terminal phase, although many patients do not make a choice regarding the place of receiving terminal care even one month before the expected end of life. This study explores the factors that influence patients with a life-expectancy of less than one month when they are admitted to the palliative care ward or other terminal care institutions.Methods: Self-administered questionnaire surveys were completed by patients and caregiver questionnaire surveys were completed by patients and caregivers. We assessed patient symptoms using Support Team Assessment Schedule-Japan (STAS-J), and all patients’ families answered the self-reported questionnaire, Caregiver Reaction Assessment-Japan (CRA-J).Results: The family care burden score for “Impact on schedule” was significantly higher for the palliative care ward inpatient group than for the non-inpatient group (21.0±1.5 vs. 17.6±1.8; ρ <0.01).Conclusions: Family burden might influence the choice of facility when patients with a survival prognosis of less than one month are admitted to the palliative care ward for reducing the burden of long-term care. Nurses should take care of family caregiver’s physical and psychosocial health, especially before the patient’s admission to the palliative care ward. The results of this study show that caregiver support is needed to reduce the feeling of family burden related to impact on schedule, enabling them to choose the best place for terminal care.
The rumen microbiome of yak co-evolves with its host probably adding the adaptation to its harsh environments
Authors: Zhao Congcong , Wang Lamei , Ke Shanlin , Chen Xinhua , Kenéz Ákos , Xu Wei , Wang Dangdang , Zhang Fan , Li Yong , Cui Zhanhong , Qiao Yu , Wang Jing , Sun Wenjuan , Zhao Jianhua , Yao Junhu , Yu Zhongtang , Cao Yangchun
Published: August 2021

Background

Rumen microbes play an important role in ruminant energy supply and animal performance. Previous studies showed that yak (Bos grunniens) rumen microbiome and fermentation differ from other ruminants. However, little is understood on the features of the rumen microbiome that make yak adapted to its unique environmental and dietary conditions. Here we investigated the rumen microbiome and metabolome to understand how yak adapts to the coarse forage and harsh environment in the high Qinghai-Tibetan plateau.
Result

Metataxonomic analysis of the rumen microbiota revealed that yak (Bos grunniens), domesticated cattle (Bos taurus), and dzo (a hybrid between the yak and domestic cattle) have distinct rumen microbiota. Metagenomic analysis displayed a larger gene pool encoding a richer repertoire of carbohydrate-active enzymes (CAZymes) in the rumen microbiome of yak and dzo than cattle. Some of the genes encoding glycoside hydrolases (GH) that mediate the digestion of cellulose and hemicellulose were significantly enriched in the rumen of yak than cattle, but the cattle rumen microbiome had more genes assigned to GH57 that primarily includes amylases. The rumen fermentation profile differed also, with cattle having a higher molar proportion of acetate but a lower molar proportion of propionate than dzo and yak. Metabolomic analysis showed differences in both rumen microbial metabolic pathways and metabolites, mainly amino acids, carboxylic acids, sugars, and bile acids. Notably, styrene degradation, primary bile acid biosynthesis, glyoxylate, and dicarboxylate metabolism significantly differed between cattle and dzo; streptomycin biosynthesis was significantly different between cattle and yak; and the pathways for biotin metabolism and styrene degradation significantly differed between dzo and yak. Correlation analysis revealed certain microbial species correlated with differential rumen metabolites. Nine differential metabolites showed a positive correlation with seven species belonging to Bacteroides and Alistipes but a negative correlation with ten species belonging to Prevotella and Ruminococcus.
Conclusion

The present study showed that the rumen microbiome of yak and its host had probably co-evolved aiding in the adaptation of yak to the harsh dietary environment of the Qinghai-Tibetan plateau. In particular, the yak rumen microbiome has more enzymes involved in the degradation of rough forage than that of cattle, providing sufficient energy for its host.