bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of intestinal microbiota in antithymocyte globulin–based myeloablative allogeneic hematopoietic cell transplantation
Authors: Gu Zhenyang , Xiong Qian , Wang Lu , Wang Lili , Li Fei , Hou Cheng , Dou Liping , Zhu Baoli , Liu Daihong
Published: January 2022

BACKGROUND

The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HCT) has been reported in platforms with T‐cell depletion or postcyclophosphamide‐based graft‐vs‐host disease (GVHD) prophylaxis regimens. It is still unclear whether it is the same in platforms of antithymocyte globulin (ATG)–based myeloablative allo‐HCT.

METHODS

A total of 603 fecal specimens from 100 consecutive patients receiving allo‐HCT were collected between December 2018 and July 2020. Fetal samples were profiled with next‐generation sequencing of bacterial 16S ribosomal RNA (rRNA) genes.

RESULTS

The diversity decreased to the lowest level at approximately day 12 after allo‐HCT and then increased over time. According to the diversity of 314 samples that were collected from 86 patients during the engraftment period, patients were grouped into the low‐ and high‐diversity groups. Two‐year overall survival in the high‐diversity group was significantly longer than that in the low‐diversity group (83.7% vs 60.6%, P = .026). Further analysis revealed that worse outcomes for patients with low diversity were associated with increased risk of worse outcomes for patients with low diversity (adjusted hazard ratio, 4.95; P = .046). Its association with relapse and GVHD was not found. Compositional analysis of fecal microbiota revealed that the abundance of bacteroides decreased greatly during allo‐HCT, whereas that of Enterococcus, Klebsiella, and Escherichia was found to be increased.

CONCLUSIONS

This study indicates that gut dysbiosis in platforms of ATG‐based myeloablative allo‐HCT featured loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period was an independent predictor of longer survival.

LAY SUMMARY

The correlation between intestinal microbiota and clinical outcomes after allogeneic hematopoietic stem cell transplantation (allo‐HCT) is reported in platforms with T‐cell depletion or postcyclophosphamide‐based graft‐vs‐host disease (GVHD) prophylaxis regimens.

It is still unclear whether it is the same pattern in platforms of antithymocyte globulin (ATG)–based T‐cell repletion myeloablative allo‐HCT.

Our study indicated that gut dysbiosis in platforms of ATG‐based myeloablative allo‐HCT also features loss of bacterial diversity. The diversity of the intestinal flora at the engraftment period is an independent predictor of longer survival.
Selective Growth of Single‐walled Carbon Nanotubes using Cobalt Disilicide
Authors: Liu Qidong , Yang Feng , Zhang Yan , Zhao Xue , Zhang Zeyao , Zhu Sheng , Li Yan
Published: January 2022

After chirality‐specified growth of single‐walled carbon nanotubes (SWCNTs) was realized by tungsten‐based intermetallic compound catalysts, here we developed a different kind of intermetallic compound, cobalt disilicide (CoSi2), as catalysts to selective grow carbon nanotubes by chemical vapor deposition (CVD). By using methane as carbon source, we obtained (11, 7) tubes with the selectivity of ∼24% and semiconducting SWCNTs (s‐SWCNTs) with the purity of ∼93% simultaneously. Because of the sensitivity of CoSi2 toward the oxygen‐containing environment at high temperatures, ethanol is not a good carbon feedstock. Our results not only expand the chirality library and catalyst database in the chirality‐selective synthesis of SWCNTs, but also further demonstrate the feasibility of intermetallic compound catalysts.
Real‐world data prognostic model of overall survival in patients with advanced NSCLC receiving anti‐PD‐1/PD‐L1 immune checkpoint inhibitors as second‐line monotherapy
Authors: Julian Cristina , Machado Robson J. M. , Girish Sandhya , Chanu Pascal , Heinzmann Dominik , Harbron Chris , Gershon Anda , Pfeiffer Shannon M. , Zou Wei , Quarmby Valerie , Zhang Qing , Chen Yachi
Published: January 2022

Background and aim

The objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non‐small cell lung cancer (aNSCLC) and to develop a novel prognostic model.

Methods

A total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second‐line monotherapy were selected from a real‐world deidentified database to build the cohort. Patients could not have received first‐line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti‐programmed cell death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1), and anti‐cytotoxic T‐lymphocyte‐associated protein 4 therapies.

Results

Patients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real‐world data cohort. The risk‐increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk‐decreasing prognostic factors were PD‐L1 positivity, longer time from advanced diagnosis to start of first‐line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c‐index for the OAK trial validation cohort was 0.65 and 0.67 for the real‐world data cohort.

Conclusions

Based on baseline demographic and clinical factors from a real‐world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second‐line monotherapy, and it performed well in the real‐world data and clinical trial cohorts.
Parallel CPU–GPU computing technique for discrete element method
Authors: Skorych Vasyl , Dosta Maksym
Published: January 2022

The efficiency of the simulations with the discrete element method (DEM) is significantly improved using a novel computational strategy. The new method is developed with a focus on platforms equipped with multi‐core central processing units (CPU) and general‐purpose graphics processing units (GPU). The DEM calculations are performed in parallel on the CPU and on the GPU using pre‐calculated Verlet lists with a posteriori analysis of their consistency. The operations related to the search for possible contacts are performed on the CPU, whereas the processing of interactions, and integration of motion, are executed on the GPU. Performance analysis done for various types of tasks has shown that the new method allows to significantly decrease the average computational time and to utilize available computational resources more efficiently compared to the sequential CPU–GPU execution mode. Furthermore, due to more efficient calculations, the overall energy requirement for the proposed strategy does not exceed the demand for conventional sequential CPU–GPU computations.
Circular CPM promotes chemoresistance of gastric cancer via activating PRKAA2‐mediated autophagy
Authors: Fang Lang , Lv Jialun , Xuan Zhe , Li Bowen , Li Zheng , He Zhongyuan , Li Fengyuan , Xu Jianghao , Wang Sen , Xia Yiwen , Jiang Tianlu , Zhang Lu , Wang Linjun , Zhang Diancai , Xu Hao , Yang Li , Xu Zekuan , Wang Weizhi
Published: January 2022

Background

Chemotherapy can significantly improve the disease‐free survival and overall survival of patients with advanced gastric cancer (GC). 5‐fluorouracil (5‐FU) is frequently applied in the clinic, acting as a first‐line chemotherapy drug of advanced GC, which could be used alone or combining platinum drugs. However, its efficacy is significantly attenuated by chemoresistance, which is associated with patients’ poor survival. Recently, there is evidence suggesting that dysregulation of autophagy may contribute to drug resistance in cancer, and circular RNAs (circRNAs) also take part in chemoresistance. However, whether circRNAs participate in 5‐FU chemoresistance through autophagy remains largely unknown.

Methods

RNA sequencing technologies and bioinformatics analysis were performed in GC. Sanger sequencing, Actinomycin D assay and RNase R assay confirmed the circular structure of circular CPM (circCPM). Various cell line models and animal models were used to explore related functions in vitro and in vivo. Quantitative Real‐time PCR (qRT‐PCR), fluorescence in situ hybridization, ribonucleic acid; (RNA) pulldown assays, RNA binding protein immunoprecipitation assays and Luciferase reporter assays were applied to explore involved pathways.

Results

circCPM was up‐regulated in 5‐FU resistant GC cell lines and tissue. Moreover, high circCPM expression is positively associated with poor survival. Silencing circCPM greatly improved chemosensitivity in vitro and in vivo. Mechanistically, it directly binds to miR‐21‐3p in the cytoplasm and therefore increases the expression of PRKAA2, contributing to the activation of autophagy and chemoresistance.

Conclusion

Our results reveal that circCPM has a crucial role in regulating GC autophagy and 5‐FU resistance by targeting PRKAA2. It may function as a new theory basis for assessing the curative effect of GC and reversing 5‐FU chemoresistance.
Ameloblastoma with adenoid features: Case report with cyto‐histopathologic correlation and molecular findings
Authors: Jofre Sebastian A. , Roth Maxwell , Lahouti Arash H. , Gersten Adam , Azad Abul Kalam , Kelsch Robert D. , Asiry Saeed , Goldstein Yitzchak , Naeem Rizwan , Rao Rema
Published: January 2022

Ameloblastomas are benign but locally aggressive odontogenic tumors that commonly present as expansile lesions in the tooth‐bearing areas. Fine‐needle aspiration (FNA) biopsies of ameloblastomas are rare in clinical practice, and only a handful of case reports and series have described their cytologic features. We present the case of a 70‐year‐old woman with a large and disfiguring maxillary sinus soft tissue mass sampled via transcutaneous FNA. Aspirate smears were composed of small clusters of cohesive and monotonous basaloid cells. The accompanying cellblock showed similar clusters of basaloid cells in gland‐like, or “adenoid,” configurations, eliciting a differential diagnosis that included sinonasal and salivary gland neoplasms. Excisional surgery material was consistent with ameloblastoma with adenoid morphology. Next‐generation sequencing (NGS) analysis demonstrated FGFR2 and SMO pathogenic variants. This case exemplifies several uncommonly described features of ameloblastomas in cytology, including cyto‐histologic correlation, adenoid morphology, and NGS findings. Awareness of the cytologic features of this neoplasm are important for cytopathologists confronted with maxillary sinus lesions.
Assessing severity, treatment response, and phenotype in HS
Authors: Buechler Connor R. , Daveluy Steven
Published: January 2022

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, tunnels, and scarring in intertriginous areas. However, disease presentation and phenotype can vary widely, leading to unique challenges in determining disease burden and response to therapy. Over three dozen severity measures have been used at various times to provide static staging and track response to clinical interventions, and there are at least five proposed classification systems for clinical phenotypes, derived by either statistical methods or expert opinion. As yet, no single staging, outcome‐measurement, or phenotyping schema has proven to be far superior to the others in clinical practice, and very few studies have attempted to map proposed phenotypes to either outcome or clinical response to therapy. In this review, we discuss proposed phenotype schemas as well as provider‐scored, patient‐scored, and composite scoring systems that have been proposed for grading HS severity. We include relevant benefits and drawbacks to their routine use, with a focus on the most popular and recently developed systems, in the hope of providing a framework upon which future studies can be built to ensure the best possible care for those suffering from this debilitating disease.
Total Synthesis of (−)‐Magnoshinin and (+)‐Merrilliaquinone: Application of a Late‐Stage Oxidative Functionalization Protocol
Authors: Salam Abdus , Kumar Dileep , Sahu Tonish Kumar , Khan Rahimuddin , Khan Tabrez
Published: January 2022

A unified approach for the first enantioselective total synthesis of magnoshinin and merrilliaquinone is reported. The key feature of the synthesis is the DDQ assisted chemoselective late‐stage oxidative functionalization of the polyoxygenated chiral tetralin core accessed by utilizing the relayed asymmetric induction strategy. Then, the follow‐up of chemoselective redox chemistry facilitates the synthesis of (−)‐magnoshinin (28.2 % overall yield) and (+)‐merrilliaquinone (20.6 % overall yield) along the shortest route, starting from the known 3‐(2,4,5‐trimethoxyphenyl)propanoic acid.
Gold micro‐particles for knee osteoarthritis
Authors: Rasmussen Sten , Kjær Petersen Kristian , Kristiansen Martin Kaae , Skallerup Jakob , Aboo Christopher , Thomsen Mikkel Eggert , Skjoldemose Emilie , Jørgensen Nia Kristine , Stensballe Allan , Arendt‐Nielsen Lars
Published: January 2022

Background

This exploratory study investigates if intra‐articular injected gold microparticles in knee osteoarthritis (KOA) reduce immunomodulatory‐based pain via proteomic changes in the synovial fluid (SF) and serum.

Methods

Thirty patients with moderate KOA were included. Intraarticular injections with 20 mg gold microparticles (72.000 particles, 20–40 µm in diameter) using the patient's synovial fluid (SF) as carrier were performed. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscores for pain, stiffness, and function were assessed at inclusion, 8 weeks and 2 years The PainDetect questionnaire, pain pressure threshold (PPT), temporal summation (TS), and conditioned pain modulation (CPM), and pain diary were assessed at inclusion and 8 weeks. Proteome analysis was performed on SF and blood samples before and after 8 weeks of treatment.

Results

A decrease in WOMAC scores (pain (p = 0.0001), stiffness (p = 0.0088), activity (p = 0.0001)), PainDetect (p = 0.0002) and increase in PPT (p = 0.001) and CPM (p = 0.021) and a decrease in TS (p = 0.03) were found after 8 weeks compared to inclusion assessments. At 2 years follow‐up compared to baseline there was a decrease in WOMAC scores (pain (p = 0.0001), stiffness (p = 0.007), activity (p = 0.0001)) and PainDetect (p = 0.0001). In SF, 28 different proteins were downregulated and 11 upregulated (p < 0.05) mainly associated immune response. Similarly, 31 proteins were downregulated and 1 upregulated in serum (p < 0.05) reflecting key immune response and anatomical structure development processes. No adverse effects related to the treatment were recorded.

Conclusions

Gold microparticles injected intra‐articular in KOA joints may provide pain relief and an inflammatory modulatory effect based on proteome changes found in SF and serum. A randomized, controlled, double‐blind study is needed to infer a conclusion.

Significance

This study indicates that intra‐articular gold may provide advantages in clinical practice for managing knee osteoarthritic pain. The use of intraarticular gold can add new knowledge to the treatment of inflammation and pain.
Serotonin receptors in epilepsy: Novel treatment targets?
Authors: Sourbron Jo , Lagae Lieven
Published: January 2022

Despite the availability of over 30 antiseizure medications (ASMs), there is no “one size fits it all,” so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5‐hydroxytryptamine, 5‐HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5‐HT. There are 14 different 5‐HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5‐HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each “5‐HT subtype” separately and its relation to “epilepsy or seizures.” Most research underlines the antiseizure activity of 5‐HT1A,1D,2A,2C,3 agonism and 5‐HT6 antagonism. Consistently, FA, which has recently been approved for the treatment of seizures in Dravet syndrome, is an agonist of 5‐HT1D,2A,2C receptors. Even though each study focused on a distinct seizure/epilepsy type and generalization of different findings could lead to false interpretations, we believe that the available preclinical and clinical studies emphasize the role of serotonergic modulation, especially stimulation, as a promising avenue in epilepsy treatment.
Immunomodulatory effects of the polysaccharide from Sinonovacula constricta on RAW264.7 macrophage cells
Authors: Liu Zhidong , Liu Zhifang , Li Laihao , Zhang Junjie , Zhao Qiancheng , Lin Na , Zhong Wenzhu , Jiang Mei
Published: January 2022

This study aimed to evaluate the immunomodulatory effect of the polysaccharide from Sinonovacula constricta (SCP‐1‐1) in RAW264.7 cells. SCP‐1‐1 with a molecular weight of 440.0 kDa consisted of glucose and mannose. The immunomodulatory assay results showed that SCP‐1‐1 could significantly enhance phagocytic ability, NO production, and some cytokines (TNF‐α, IL‐6, and IL‐1β) secretion of RAW264.7 cell in a dose‐dependent manner. Western blot analysis results demonstrated that SCP‐1‐1 could regulate the expression levels of the key proteins in the signaling pathways of RAW264.7 cell and might associated with NF‐κβ and PI3K signaling pathway. These findings could contribute to elucidate the immunomodulatory activities of the polysaccharide from Sinonovacula constricta.
Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B
Authors: Erken Robin , Loukachov Vladimir , van Dort Karel , van den Hurk Anne , Takkenberg R. Bart , de Niet Anniki , Jansen Louis , Willemse Sophie , Reesink Henk , Kootstra Neeltje
Published: January 2022

Background and Aims

HBV can integrate in the host genome of the hepatocyte and recent findings suggest that integrated HBV contributes to the persistent production of viral proteins. Here, we quantified the levels of integrated HBV in patients with chronic hepatitis B (CHB) and analyzed the relation between HBV integration, virological activity (plasma HBV DNA and HBsAg levels), and clinical outcomes.

Approach and Results

We developed and validated a multistep Arthrobacter luteus (Alu)‐PCR that specifically amplifies integrated HBV and RT‐Alu‐PCR detecting mRNA transcripts derived from integrated HBV. Pretreatment liver biopsy samples and baseline characteristics of 124 patients with CHB either treated for 48 weeks with pegylated interferon plus adefovir or tenofovir or receiving no treatment were available for analysis. Integrated HBV sequences containing open reading frame S and X (but not C) and S and X mRNA transcripts derived from integrated HBV could be detected and quantified in liver biopsies. Integrated HBV levels correlated with HBV DNA, HBsAg, alanine aminotransferase plasma levels, and the liver histology activity index but not to levels of intrahepatic covalently closed circular DNA (cccDNA), plasma pregenomic RNA, or hepatitis B core‐related antigen. Multivariable logistic regression analysis showed that lower baseline HBV integration levels were independently associated with HBsAg loss (functional cure) within 5 years follow‐up.

Conclusions

Integrated HBV levels are strongly correlated with surrogate markers for virological activity but not to cccDNA levels and are predictive for HBsAg loss. Our data suggest that integrated HBV is closely related to HBV replication and may therefore be an important tool in the evaluation and development of treatment modalities aiming to cure CHB.
Metastatic tumor antigen 1 contributes to hepatocarcinogenesis posttranscriptionally through RNA‐binding function
Authors: Li Yung‐Tsung , Liu Chun‐Jen , Kao Jia‐Horng , Lin Li‐Feng , Tu Hui‐Chu , Wang Chih‐Chiang , Huang Po‐Hsi , Cheng Huei‐Ru , Chen Pei‐Jer , Chen Ding‐Shinn , Wu Hui‐Lin
Published: January 2022

Background and Aims:

Both nuclear and cytoplasmic overexpression of metastatic tumor antigen 1 (MTA1) contributes to tumorigenesis of HCC. Most studies have focused on nuclear MTA1 whose function is mainly a chromatin modifier regulating the expression of various cancer‐promoting genes. By contrast, the molecular mechanisms of cytoplasmic MTA1 in carcinogenesis remain elusive. Here, we reveal a role of MTA1 in posttranscriptional gene regulation.

Approach and Results:

We conducted the in vitro and in vivo RNA‐protein interaction assays indicating that MTA1 could bind directly to the 3′‐untranslated region of MYC RNA. Mutation at the first glycine of the conserved GXXG loop within a K‐homology II domain‐like structure in MTA1 (G78D) resulted in the loss of RNA‐binding activity. We used gain‐ and loss‐of‐function strategy showing that MTA1, but not the G78D mutant, extended the half‐life of MYC and protected it from the lethal‐7–mediated degradation. The G78D mutant exhibited lower activity in promoting tumorigenesis than wild‐type in vitro and in vivo. Furthermore, RNA‐immunoprecipitation sequencing analysis demonstrated that MTA1 binds various oncogenesis‐related mRNAs besides MYC. The clinical relevance of cytoplasmic MTA1 and its interaction with MYC were investigated using HBV‐HCC cohorts with or without early recurrence. The results showed that higher cytoplasmic MTA1 level and MTA1‐MYC interaction were associated with early recurrence.

Conclusions:

MTA1 is a generic RNA‐binding protein. Cytoplasmic MTA1 and its binding to MYC is associated with early recurrence in patients with HBV‐HCC. This function enables it to regulate gene expression posttranscriptionally and contributes to hepatocarcinogenesis.
Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery
Authors: Pais Raluca , Aron‐Wisnewsky Judith , Bedossa Pierre , Ponnaiah Maharajah , Oppert Jean‐Michel , Siksik Jean‐Michel , Genser Laurent , Charlotte Frederic , Thabut Dominique , Clement Karine , Ratziu Vlad
Published: January 2022

Background and Aims

It remains unclear to what extent and which components of advanced liver disease improve after bariatric surgery. We herein describe the histological outcome in patients with advanced NASH and its relationship with weight loss and metabolic improvement.

Approach and Results

One hundred ninety‐six patients with advanced NASH underwent bariatric surgery, 66 of whom agreed to a follow‐up liver biopsy at 6 ± 3 years (36 with advanced fibrosis [AF] and 30 with high activity [HA] grade without AF). Liver biopsies LBs were centrally read and histological response was defined as the disappearance of AF or HA. Bariatric surgery induced major histological improvement: 29% of patients had normal histology at follow‐up biopsy; 74% had NASH resolution without fibrosis progression; and 70% had ≥1 stage fibrosis regression. However, AF persisted in 47% of patients despite NASH resolution and some degree of fibrosis reversal, only evidenced by the EPoS seven‐tier staging classification. These patients had lower weight loss and reduced hypertension or diabetes remission rates. Older age and sleeve gastrectomy were the only independent predictors for persistent AF after adjustment for duration of follow‐up. All HA patients had major histological improvement: 50% normal histology, 80% NASH resolution, and 86% a ≥1 grade steatosis reduction. Patients with normal liver at follow‐up had the largest weight loss and metabolic improvement. Independent predictors of normal liver were amount of weight loss, high histological activity, and the absence of AF before surgery.

Conclusions

Although bariatric surgery successfully reverses active steatohepatitis, AF can persist for many years and is associated with lesser weight loss and metabolic improvement. Weight loss alone may not be sufficient to reverse AF.
Nonalcoholic Fatty Liver Disease and Associated Risk Factors in a Community‐Based Sample of Mexican‐Origin Adults
Authors: Garcia David O. , Morrill Kristin E. , Lopez‐Pentecost Melissa , Villavicencio Edgar A. , Vogel Rosa M. , Bell Melanie L. , Klimentidis Yann C. , Marrero David G. , Thomson Cynthia A.
Published: January 2022

The incidence of nonalcoholic fatty liver disease (NAFLD) is highest among Mexican‐origin (MO) adults. Few studies have estimated the prevalence of NAFLD in this subpopulation, particularly by sex and age. We assessed the prevalence of NAFLD in a community sample of MO adults residing in a border region of southern Arizona and determined risk factors associated with NAFLD. A total of 307 MO adults (n = 194 women; n = 113 men) with overweight or obesity completed an in‐person study visit, including vibration‐controlled transient elastography (FibroScan) for the assessment of NAFLD status. A continuous attenuation parameter score of ≥288 dB/m (≥5% hepatic steatosis) indicated NAFLD status. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for NAFLD. We identified 155 participants (50%) with NAFLD, including 52% of women and 48% of men; there were no sex differences in steatosis (men, 287.8 dB/m; women, 288.4 dB/m). Sex, age, patatin‐like phospholipase domain containing 3 (PNPLA3) risk allele carrier status, comorbidities, and cultural and behavioral variables were not associated with NAFLD status. There was some evidence for effect modification of body mass index (BMI) by sex (P
interaction = 0.08). The estimated OR for an increase in BMI of 5 kg/m2 was 3.36 (95% CI, 1.90, 5.91) for men and 1.92 (95% CI, 1.40, 2.64) for women. In post hoc analyses treating steatosis as a continuous variable in a linear regression, significant effect modification was found for BMI by sex (P
interaction = 0.03), age (P = 0.05), and PNPLA3 risk allele carrier status (P = 0.02). Conclusion: Lifestyle interventions to reduce body weight, with consideration of age and genetic risk status, are needed to stem the higher rates of NAFLD observed for MO populations.
The accuracy improvement of sap flow prediction in Picea crassifolia Kom. based on the back‐propagation neural network model
Authors: Li Yuanhang , Chen Qi , He Kangning , Wang Zuoxiao
Published: January 2022

Tree transpiration is an important water movement process in forest ecosystems, and it plays a decisive role in the coupling feedback of hydrological and ecological processes. Therefore, identifying the impact of different factors on sap flow can promote efficient water management and improve assessment of the climate change impacts. However, the interaction between sap flow and control factors is not clear, and there is no accurate model to predict sap flow change of Picea crassifolia Kom. This study explored the correlation between sap flow and environmental factors and compared the performances of the back‐propagation neural network (BPANN) and multiple regression (MLR) models, and the importance of the time‐lag effect and different soil moisture conditions in the response mechanism of sap flow was also explained. A higher fitting performance was found in the BPANN model (R2 > 0.90) based on the relationships between air temperature (Ta), air relative humidity (RH), solar radiation (Rn) and vapour pressure deficit (VPD) and sap flux density (Q) than that MLR (R2 = 0.8915). The correlation was improved due to the consideration of time‐lag effect. Other variables, such as maximum temperature (Tmax), wind speed (WS) and precipitation (P), explained smaller portions of the variance in sap flow, while minimum temperature (Tmin) and leaf area index (LAI) had almost no effect. Moreover, the R2 of the water stress condition (REW <0.38) was lower than that of the non‐water stress condition (REW ≥0.38), and even lower than the R2 of the whole experimental period. Therefore, the sap flow prediction model based on BPANN could more reasonably explain the nonlinear relationship between transpiration and control factors, which provided a basis for the estimation of plant water‐use and the construction and management of ecological vegetation in alpine arid and semi‐arid areas, especially in response to the continuous enhancement of aridification and climate warming.
A randomized trial of risk‐adapted screening for prostate cancer in young men—Results of the first screening round of the PROBASE trial
Authors: Arsov Christian , Albers Peter , Herkommer Kathleen , Gschwend Jürgen , Imkamp Florian , Peters Inga , Kuczyk Markus , Hadaschik Boris , Kristiansen Glen , Schimmöller Lars , Antoch Gerald , Rummeny Ernst , Wacker Frank , Schlemmer Heinz , Benner Axel , Siener Roswitha , Kaaks Rudolf , Becker Nikolaus
Published: January 2022

There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk‐adapted prostate‐specific antigen‐based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5 ng/mL), intermediate (1.5‐2.99 ng/mL) or high (≥3 ng/mL) risk group. In cases of confirmed PSA values ≥3 ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N = 23 341) were offered PSA screening immediately at age 45; the other half (N = 23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N = 344) into the high risk group. Repeat PSA measurement confirmed high‐risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen‐detected aggressive (ISUP ≥3) PCa in 45‐year‐old men is very low. DRE did not turn out effective for early detection of PCa.
A serum lipidomics study for the identification of specific biomarkers for endometrial polyps to distinguish them from endometrial cancer or hyperplasia
Authors: Yan Xingxu , Zhao Wen , Wei Jinxia , Yao Yaqi , Sun Guijiang , Wang Lei , Zhang Wenqing , Chen Siyu , Zhou Wenjie , Zhao Huan , Li Xiaomeng , Xiao Yu , Li Yubo
Published: January 2022

Endometrial diseases, including endometrial polyps (EP), endometrial cancer (EC) and endometrial hyperplasia (EH), are common gynecological diseases that affect women of childbearing and perimenopausal age. Clinically, biopsy or imaging methods are usually used to screen and diagnose these diseases; however, due to the invasiveness and heterogeneity of these tests, a noninvasive, convenient, objective and accurate biomarker is needed for the differential diagnosis of EP, EC or EH. In the present study, serum samples from 326 patients with endometrial diseases and 225 healthy volunteers were analyzed using nontargeted lipidomics. A combination of multivariate and univariate analyses was used to identify and qualify six, eight and seven potential biomarkers in the sera from patients with EP, EC and EH, respectively. Using a logistic regression algorithm and receiver operating characteristic (ROC) curve analysis, a biomarker panel including four specific EP biomarkers, 6‐keto‐PGF1α, PA(37:4), LysoPC(20:1) and PS(36:0), showed good classification and diagnostic ability in distinguishing EP from EC or EH. The biomarker panel for distinguishing EP from EC yielded an area under the curve (AUC) of 0.915, sensitivity of 100% and specificity of 72.41%, while that for distinguishing EP from EH yielded an AUC of 1.000, sensitivity of 100% and specificity of 100%. The two diagnostic models also showed good diagnostic abilities in the validation set. Therefore, this biomarker panel can be used as a rapid diagnostic method to assist in imaging examinations and provide a reference for clinicians in the identification and diagnosis of endometrial diseases.
Alcohol consumption, DNA methylation and colorectal cancer risk: Results from pooled cohort studies and Mendelian randomization analysis
Authors: Zhou Xuan , Wang Lijuan , Xiao Jiarui , Sun Jing , Yu Lili , Zhang Han , Meng Xiangrui , Yuan Shuai , Timofeeva Maria , Law Philip J. , Houlston Richard S. , Ding Kefeng , Dunlop Malcolm G. , Theodoratou Evropi , Li Xue
Published: January 2022

Alcohol consumption is thought to be one of the modifiable risk factors for colorectal cancer (CRC). However, the causality and mechanisms by which alcohol exerts its carcinogenic effect are unclear. We evaluated the association between alcohol consumption and CRC risk by analyzing data from 32 cohort studies and conducted two‐sample Mendelian randomization (MR) analysis to examine for casual relationship. To explore the effect of alcohol related DNA methylation on CRC risk, we performed an epigenetic MR analysis with data from an epigenome‐wide association study (EWAS). We additionally performed gene‐alcohol interaction analysis nested in the UK Biobank to assess effect modification between alcohol consumption and susceptibility genes. We discovered distinct effects of alcohol on CRC incidence and mortality from the meta‐analyses, and genetic predisposition to alcohol drinking was causally associated with an increased CRC risk (OR = 1.79, 95% CI: 1.23‐2.61) using two‐sample MR approaches. In epigenetic MR analysis, two alcohol‐related CpG sites (cg05593667 and cg10045354 mapped to COLCA1/COLCA2 gene) were identified causally associated with an increased CRC risk (P < 8.20 × 10−4). Gene‐alcohol interaction analysis revealed that carriage of the risk allele of the eQTL (rs3087967) and mQTL (rs11213823) polymorphism of COLCA1/COLCA2 would interact with alcohol consumption to increase CRC risk (PInteraction = .027 and PInteraction = .016). Our study provides comprehensive evidence to elucidate the role of alcohol in CRC and highlights that the pathogenic effect of alcohol on CRC could be partly attributed to DNA methylation by regulating the expression of COLCA1/COLCA2 gene.
Risk compounds, potential mechanisms and biomarkers of traditional Chinese medicine‐induced reproductive toxicity
Authors: Li Qiuju , Yan Xiaoyu , Zhang Ying , Zhou Jie , Yang Liang , Wu Shuangyue , Peng Cheng , Pan Xiaoqi
Published: January 2022

With the increasing application of traditional Chinese medicine (TCM), TCM‐induced reproductive toxicity has gradually aroused people's concern. Various TCM, such as Tripterygium wilfordii Hook. f., Radix Aconiti lateralis Preparata and Rhizoma Pinelliae, are currently reported to cause reproductive toxicity in humans and animals. However, a summary of the material bases, mechanisms and biological markers of TCM‐induced reproductive toxicity is still lacking. This review filled the gap by searching and summarising relevant studies and articles published on PubMed, CNKI and Web of Science databases from January 2000 to November 2021. The risk ingredients involved in TCM‐induced reproductive toxicity were divided into glycosides, alkaloids, phenols, terpenoids, anthraquinones, lactones, plant toxin proteins, animal toxins and so forth. Potential mechanisms underlying TCM‐induced reproductive toxicity, including steroidogenic toxicity, lipids metabolism abnormity, energy insufficiency, oxidative stress and apoptosis, were illustrated. We also outlined possible biomarkers, especially biomarkers of effect involved in TCM‐induced reproductive toxicity, including anti‐oxidant enzymes, signalling pathways, genes and growth factors.
Three‐dimensional‐printed polycaprolactone/polypyrrole conducting scaffolds for differentiation of human olfactory ecto‐mesenchymal stem cells into Schwann cell‐like phenotypes and promotion of neurite outgrowth
Authors: Entezari Maedeh , Mozafari Masoud , Bakhtiyari Mehrdad , Moradi Fatemeh , Bagher Zohreh , Soleimani Mansoureh
Published: January 2022

Implantation of a suitable nerve guide conduit (NGC) seeded with sufficient Schwann cells (SCs) is required to improve peripheral nerve regeneration efficiently. Given the limitations of isolating and culturing SCs, using various sources of stem cells, including mesenchymal stem cells (MSCs) obtained from nasal olfactory mucosa, can be desirable. Olfactory ecto‐MSCs (OE‐MSCs) are a new population of neural crest‐derived stem cells that can proliferate and differentiate into SCs and can be considered a promising autologous alternative to produce SCs. Regardless, a biomimetic physicochemical microenvironment in NGC such as electroconductive substrate can affect the fate of transplanted stem cells, including differentiation toward SCs and nerve regeneration. Therefore, in this study, the effect of 3D printed polycaprolactone (PCL)/polypyrrole (PPy) conductive scaffolds on differentiation of human OE‐MSCS into functional SC‐like phenotypes was investigated. Biological evaluation of 3D printed scaffolds was examined by in vitro culturing the OE‐MSCs on samples surfaces, and conductivity showed no effect on increased cell attachment, proliferation rate, viability, and distribution. In contrast, immunocytochemical staining and real‐time polymerase chain reaction analysis indicated that 3D structures coated with PPy could provide a favorable microenvironment for OE‐MSCs differentiation. In addition, it was found that differentiated OE‐MSCs within PCL/PPy could secrete the highest amounts of nerve growth factor and brain‐derived neurotrophic factor neurotrophic factors compared to pure PCL and 2D culture. After co‐culturing with PC12 cells, a significant increase in neurite outgrowth on PCL/PPy conductive scaffold seeded with differentiated OE‐MSCs. These findings indicated that 3D printed PCL/PPy conductive scaffold could support differentiation of OE‐MSCs into SC‐like phenotypes to promote neurite outgrowth, suggesting their potential for neural tissue engineering applications.
Asian Ethnicity and Femoral Geometry in Atypical Femur Fractures: Independent or Interdependent Risk Factors?
Authors: Dhanekula Nitesh D , Crouch Gareth , Byth Karen , Lau Sue Lynn , Kim Albert , Graham Edward , Ellis Andrew , Clifton‐Bligh Roderick J , Girgis Christian M
Published: January 2022

The earliest reports of atypical femur fractures (AFF) emerged from Asia. In the West, epidemiologic studies report a greater incidence of AFFs among subjects of Asian background. Asian ethnicity is an established risk factor for AFF, but clear mechanisms to explain this risk and implications for the general development of AFF are open questions. Ethno‐specific differences in bisphosphonate action and femoral geometry have been proposed as hypotheses. In a retrospective cohort of 163 female patients presenting with AFFs or typical femur fractures (TFF), relative contributions of Asian ethnicity, proximal femoral geometry, and bisphosphonate use in AFF status were examined. There was a fourfold higher proportion of Asian subjects in the AFF compared with TFF groups (31.6%, 30/95 versus 7.4%, 5/68). Asian subjects had smaller femurs in femoral head, neck, and axial dimensions. A multiple logistic regression model for AFF status was fitted adding Asian ethnicity to three previously reported independent predictors of AFF including femoral geometry, which together comprise the Sydney AFF Score (age ≤80 years, femoral neck width <37 mm than non‐Asian, lateral cortical width at lesser trochanter ≥5 mm). Asian ethnicity was a robust independent predictor of AFF, imparting sevenfold increase in the odds of AFF after adjusting for all three variables (95% confidence interval [CI] 2.2–23.2, p = 0.001) or for overall AFF score (95% CI 2.2–22.3 p = 0.001). Overall Asian subjects had higher rates of bisphosphonate use than non‐Asian subjects (67.6% versus 47.2%, p = 0.034). Among AFF bisphosphonate users, Asian subjects had lower AFF scores than non‐Asians (Sydney AFF Score ≤1, 45.5% Asian subjects versus 22.2% non‐Asian subjects, p = 0.05). Asian ethnicity is a strong independent risk factor for AFF, unaccounted for by ethno‐specific differences in proximal femoral geometry. Bisphosphonate use may be associated with a greater predisposition for AFF in Asian subjects compared with non‐Asian subjects. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Prognostic factors for predicting severity and mortality in hospitalized COVID‐19 patients
Authors: Aljohani Fahad Dakilallah , Khattab Amin , Elbadawy Hossein M. , Alhaddad Aisha , Alahmadey Ziab , Alahmadi Yaser , Eltahir Heba M. , Matar Heba M. H. , Wanas Hanaa
Published: January 2022

Background

Coronavirus disease 2019, COVID‐19, has reached all the corners of the world and was declared by the WHO as a global pandemic and public health emergency of international concern on the January 31, 2020. Allocating quick and specific biomarkers to predict the disease severity upon admission to hospital became a crucial need. This study, therefore, aimed at exploring the relationship between laboratory results in COVID‐19 patients admitted to hospital and the final outcome in these patients.

Methods

Retrospective analysis was performed on the medical records of 310 COVID‐19‐positive patients admitted to Uhod Hospital, the referral hospital in the area of Madinah, Kingdom of Saudi Arabia, between the April 13 and the July 29, 2020. The association of laboratory results with the survival/mortality outcomes was studied.

Results

It was demonstrated that lymphopenia, prolonged aPTT, high INR, high D. dimer and high CK are valuable prognostic predictors of the severity of the disease at early stages that can determine the outcome. Based on the results of the multiple logistic regression, the variables that are associated with death outcome are aPTT, HR, RR, ALT and CK level

Conclusion

It is proposed to perform these tests on admission to hospital for moderate to severe COVID‐19 patients to improve the management of those cases and reduce mortality.
An agronomic‐economic approach to connect manure nutrients back to grain‐producing regions
Authors: Duke Joshua M. , McGrath Joshua M.
Published: January 2022

Stakeholders for nutrient‐impaired watersheds have long discussed the causes and consequences of nutrient surpluses associated with intensive livestock production. Nonetheless, nutrient surpluses relative to crop requirement, particularly with phosphorus (P), persist and continue to contribute to water quality impairment. Nutrient life‐cycle analysis shows that mineral P, from soil minerals or mined fertilizer P, flows to livestock regions from grain‐producing regions. Although creating a return flow of these nutrients to grain fields seems like an easy solution, significant economic obstacles exist to creating a connected manureshed over large geographic distances. To limit the impact of manure use on local surface water, state, federal, and nongovernmental actors have largely targeted their interventions in manure source areas. Even manure transport programs tend to focus on obstacles at the point of production in manure source areas. However, if we are to realize connected manuresheds that cost‐effectively distribute manure nutrients beyond the current publicly funded incentive programs, we must address obstacles to manure utilization in potential sink areas that supply grain to livestock regions. Further, we can harness the power of computer‐mediated market design and scientific research to build even more‐effective markets that generate manure nutrient transfers of an order of magnitude that will substantively improve water quality in source areas. This manuscript offers economic insights into potential improvements to current manure nutrient relocation programs. Under the right conditions, these improvements will relocate more manure, generate more environmental benefits, and improve the profitability of most participating farmers.
Attrition from HIV care among youth initiating ART in youth‐only clinics compared with general primary healthcare clinics in Khayelitsha, South Africa: a matched propensity score analysis
Authors: Cassidy Tali , Cornell Morna , Runeyi Pumeza , Dutyulwa Thembie , Kilani Charllen , Duran Laura Trivino , Zokufa Nompumelelo , de Azevedo Virginia , Boulle Andrew , Horsburgh C. Robert , Fox Matthew P.
Published: January 2022

Introduction

Youth living with HIV (YLWH) are less likely to initiate antiretroviral therapy (ART) and remain in care than older adults. It is important to identify effective strategies to address the needs of this growing population and prevent attrition from HIV care. Since 2008, two clinics have offered youth‐targeted services exclusively to youth aged 12–25 in Khayelitsha, a high HIV‐prevalence, low‐income area in South Africa. We compared ART attrition among youth in these two clinics to youth in regular clinics in the same area.

Methods

We conducted a propensity score matched cohort study of individuals aged 12–25 years initiating ART at eight primary care clinics in Khayelitsha between 1 January 2008 and 1 April 2018. We compared attrition, defined as death or loss to follow‐up, between those attending two youth clinics and those attending general primary healthcare clinics, using Cox proportional hazards regression. Follow‐up time began at ART initiation and ended at attrition, clinic transfer or dataset closure. We conducted sub‐analyses of patients attending adherence clubs.

Results

The distribution of age, sex and CD4 count at ART initiation was similar across Youth Clinic A (N = 1383), Youth Clinic B (N = 1299) and general clinics (N = 3056). Youth at youth clinics were more likely than those at general clinics to have initiated ART before August 2011 (Youth Clinic A: 16%, Youth Clinic B: 23% and general clinics: 11%). Youth clinics were protective against attrition: HR 0.81 (95% CI: 0.71–0.92) for Youth Clinic A and 0.85 (0.74–0.98) for Youth Clinic B, compared to general clinics. Youth Clinic A club patients had lower attrition after joining an adherence club than general clinic patients in adherence clubs (crude HR: 0.56, 95% CI: 0.32–0.96; adjusted HR: 0.48, 95% CI: 0.28–0.85), while Youth Clinic B showed no effect (crude HR: 0.83, 95% CI: 0.48–1.45; adjusted HR: 1.07, 95% CI: 0.60–1.90).

Conclusions

YLWH were more likely to be retained in ART care in two different youth‐targeted clinics compared to general clinics in the same area. Our findings suggest that multiple approaches to making clinics more youth‐friendly can contribute to improving retention in this important group.