bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from The Tumor Microbiome Reacts to Hypoxia and Can Influence Response to Radiation Treatment in Colorectal Cancer
Authors: Benej Martin , Hoyd Rebecca , Kreamer McKenzie , Wheeler Caroline E. , Grencewicz Dennis J. , Choueiry Fouad , Chan Carlos H.F. , Zakharia Yousef , Ma Qin , Dodd Rebecca D. , Ulrich Cornelia M. , Hardikar Sheetal , Churchman Michelle L. , Tarhini Ahmad A. , Robinson Lary A. , Singer Eric A. , Ikeguchi Alexandra P. , McCarter Martin D. , Tinoco Gabriel , Husain Marium , Jin Ning , Tan Aik C. , Osman Afaf E.G. , Eljilany Islam , Riedlinger Gregory , Schneider Bryan P. , Benejova Katarina , Kery Martin , Papandreou Ioanna , Zhu Jiangjiang , Denko Nicholas , Spakowicz Daniel
Published: July 2024

Abstract
Tumor hypoxia has been shown to predict poor patient outcomes in several cancer types, partially because it reduces radiation’s ability to kill cells. We hypothesized that some of the clinical effects of hypoxia could also be due to its impact on the tumor microbiome. Therefore, we examined the RNA sequencing data from the Oncology Research Information Exchange Network database of patients with colorectal cancer treated with radiotherapy. We identified microbial RNAs for each tumor and related them to the hypoxic gene expression scores calculated from host mRNA. Our analysis showed that the hypoxia expression score predicted poor patient outcomes and identified tumors enriched with certain microbes such as Fusobacterium nucleatum. The presence of other microbes, such as Fusobacterium canifelinum, predicted poor patient outcomes, suggesting a potential interaction between hypoxia, the microbiome, and radiation response. To experimentally investigate this concept, we implanted CT26 colorectal cancer cells into immune-competent BALB/c and immune-deficient athymic nude mice. After growth, in which tumors passively acquired microbes from the gastrointestinal tract, we harvested tumors, extracted nucleic acids, and sequenced host and microbial RNAs. We stratified tumors based on their hypoxia score and performed a metatranscriptomic analysis of microbial gene expression. In addition to hypoxia-tropic and -phobic microbial populations, analysis of microbial gene expression at the strain level showed expression differences based on the hypoxia score. Thus, hypoxia gene expression scores seem to associate with different microbial populations and elicit an adaptive transcriptional response in intratumoral microbes, potentially influencing clinical outcomes.
Significance:
Tumor hypoxia reduces radiotherapy efficacy. In this study, we explored whether some of the clinical effects of hypoxia could be due to interaction with the tumor microbiome. Hypoxic gene expression scores associated with certain microbes and elicited an adaptive transcriptional response in others that could contribute to poor clinical outcomes.
The future of data analysis is now: Integrating generative AI in neuroimaging methods development
Authors: DuPre Elizabeth , Poldrack Russell Alan
Published: July 2024

In this perspective, we highlight how emerging artificial intelligence tools are likely to impact the experiences of researchers conducting computational fMRI analyses. While calls for the automatization of statistical procedures date back at least to the inception of “data science” as a field, generative artificial intelligence offers new opportunities to advance field practice. We highlight how these tools are poised to impact both new neuroimaging methods development in areas such as image quality control and in day-to-day practice when generating analysis code. We argue that considering generative artificial intelligence as a catalyst for computational neuroscience—rather than as unique tools in their own right—can substantially improve its positioning in the research ecosystem. In particular, we argue that generative artificial intelligence will reinforce the importance of existing open science initiatives, rather than supplanting them. Overall, we call for clearer metrics by which neuroimaging results—whether generated by individual research teams or by generative artificial intelligence technologies—can be meaningfully compared.
Pharsalus repandus Melichar, 1906 (Hemiptera, Ricaniidae): first record of ant-attendance in the family, ethological notes, and new records from Brazil
Authors: DOMAHOVSKI ALEXANDRE CRUZ , PALADINI ANDRESSA
Published: July 2024

Ant attendance or trophobiosis is widely distributed in Auchenorrhyncha and can be deﬁned as a disjunctive association, an interspeciﬁc relationship between two symbiotic organisms. Aggregation behavior with or without ant mutualism has been documented for nymphs and adults in a few families of Fulgoromorpha whereas ant-attendance is reported for all planthopper families except for Ricaniidae. Based on field observations of Pharsalus repandus Melichar, 1906, the present work aims to record the first mutualistic interaction of ant-attendance in a species of the family Ricaniidae, report its aggregation behavior, its host plant, and expand its known distribution to the states of Paraná and Minas Gerais. Two ants were attending the planthoppers at the same time, identified as Camponotus (Myrmotrhix) rufipes (Fabricius, 1775) and Camponotus (Myrmobrachys) crassus Mayr, 1862. We noted direct contact and observed the ants employing antennal palpation behavior to stimulate the planthoppers to deliver honeydew.
Inside the Black Box: Detecting and Mitigating Algorithmic Bias Across Racialized Groups in College Student-Success Prediction
Authors: Gándara Denisa , Anahideh Hadis , Ison Matthew P. , Picchiarini Lorenzo
Published: July 2024

Colleges and universities are increasingly turning to algorithms that predict college-student success to inform various decisions, including those related to admissions, budgeting, and student-success interventions. Because predictive algorithms rely on historical data, they capture societal injustices, including racism. In this study, we examine how the accuracy of college student success predictions differs between racialized groups, signaling algorithmic bias. We also evaluate the utility of leading bias-mitigating techniques in addressing this bias. Using nationally representative data from the Education Longitudinal Study of 2002 and various machine learning modeling approaches, we demonstrate how models incorporating commonly used features to predict college-student success are less accurate when predicting success for racially minoritized students. Common approaches to mitigating algorithmic bias are generally ineffective at eliminating disparities in prediction outcomes and accuracy between racialized groups.
Enhanced procoagulant activity of select hemophilia B causing factor IX variants with emicizumab
Authors: Lee Kyumin , Chau Julia Q. , Suber Yani B. , Sternberg Anna R. , Pishko Allyson M. , George Lindsey A. , Bhoj Vijay G. , Doshi Bhavya S. , Samelson-Jones Benjamin J.
Published: July 2024

Emicizumab improves the procoagulant activity of select loss-of-function factor IX (FIX) variants with likely dysfunctional assembly of the intrinsic Xase complex, resulting in hemophilia B (HB). FVIII mimetics may represent an alternative nonfactor therapy for select patients with HB.
RBCs regulate platelet function and hemostasis under shear conditions through biophysical and biochemical means
Authors: Jiang Debbie , Houck Katie L. , Murdiyarso Lydia , Higgins Harrison , Rhoads Nicole , Romero Sophia K. , Kozar Rosemary , Nascimbene Angelo , Gernsheimer Terry B. , Sanchez Zyrina Alura C. , Ramasubramanian Anand K. , Adili Reheman , Dong Jing-fei
Published: July 2024

Red blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine 5′-diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here, we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood and vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50 × 103/μL) but not severe (10 × 103/μL) thrombocytopenia in vitro. Reduction in hematocrit by 45% increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote shear-induced platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood and vessel wall interface and in the fluidic phase of circulation.
High-sensitivity whole-mount in situ Hybridization of Mouse Oocytes and Embryos Visualizes the Super-resolution Structures and Distributions of mRNA Molecules
Authors: Sanada Takahiro , Kotani Tomoya
Published: July 2024

Mammalian oocytes accumulate more than ten thousand mRNAs, of which three to four thousand mRNAs are translationally repressed. The timings and sites of translational activation of these dormant mRNAs are crucial for promoting oocyte maturation and embryonic development. How these mRNAs are accumulated and distributed in oocytes is therefore a fundamental issue to be explored. A method that enables visualization of mRNA molecules with high resolution in a simple manner would be valuable for understanding how oocytes accumulate and regulate the dormant mRNAs. We have developed a highly sensitive whole-mount in situ hybridization method using in vitro-synthesized RNA probes and the tyramide signal amplification (TSA) system optimized for mouse oocytes and embryos. By using this method, Pou5f1/Oct4, Emi2, and cyclin B1 mRNAs were detected in immature oocytes and 2-cell stage embryos. Confocal microscopy showed that these mRNAs formed granular structures in the oocyte cytoplasm. The structures of Pou5f1/Oct4 and cyclin B1 mRNAs persisted in 2-cell stage embryos. Pou5f1/Oct4 RNA granules exhibited a solid-like property in immature oocytes and became liquid-like droplets in 2-cell stage embryos. Double-staining of cyclin B1 mRNA with Emi2 or Pou5f1/Oct4 mRNA revealed that these mRNAs were distributed as different RNA granules without overlapping each other and that the size of cyclin B1 RNA granules tended to be larger than that of Emi2 RNA granules. The structures and distribution patterns of these mRNAs were further analyzed by N-SIM super-resolution microscopy. This analysis revealed that the large-sized RNA granules consist of many small-sized granules, suggesting the accumulation and regulation of dormant mRNAs as basal-sized RNA granules. The method established in this study can easily visualize the structure and distribution of mRNAs accumulated in mammalian oocytes and embryos with high sensitivity and super-resolution. This method is useful for investigating the cellular and molecular mechanisms of translational control of mRNAs by which maturation and early developmental processes are promoted.
Enhancing growth and bioactive metabolites characteristics in Mentha pulegium L. via silicon nanoparticles during in vitro drought stress
Authors: El-Naggar Hany M. , Osman Amira R.
Published: July 2024

The development and production of secondary metabolites from priceless medicinal plants are restricted by drought stress. Mentha pulegium L. belongs to the Lamiaceae family and is a significant plant grown in the Mediterranean region for its medicinal and aesthetic properties. This study investigated the effects of three polyethylene glycol (PEG) (0, 5, and 10%) as a drought stress inducer and four silicon nanoparticle (SiNP) (0, 25, 50, and 100 ppm) concentrations as an elicitor to overcome the adverse effect of drought stress, on the growth parameters and bioactive chemical composition of M. pulegium L. plants grown in vitro. The experiment was performed as a factorial experiment using a completely randomized design (CRD) consisting of 12 treatments with two factors (3 PEG × 4 SiNPs concentrations), 6 replicates were used for each treatment for a total of 72 experimental units.

The percentage of shoot formation was inversely proportional to the PEG concentration; for the highest PEG concentration, the lowest percentage of shoot formation (70.26%) was achieved at 10% PEG. SiNPs at 50 ppm enhanced shoot formation, the number of shoots, shoot height, fresh and dry weight, rosmarinic acid, total phenols, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. The methanol extract from M. pulegium revealed the presence of significant secondary metabolites using gas chromatography‒mass spectrometry (GC–MS). The principal constituents of the extract were limonene (2.51, 2.99%), linalool (3.84, 4.64%), geraniol (6.49, 8.77%), menthol (59.73, 65.43%), pulegone (3.76, 2.76%) and hexadecanoic acid methyl ester or methyl palmitate (3.2, 4.71%) for the 0 ppm SiNPs, PEG 0% and 50 ppm SiNPs, and PEG 10%, respectively. Most of the chemical components identified by GC‒MS in the methanol extract were greater in the 50 ppm SiNP and 10% PEG treatment groups than in the control group. SiNP improves drought tolerance by regulating biosynthesis and accumulating some osmolytes and lessens the negative effects of polyethylene glycol-induced drought stress.

Based on the results, the best treatment for most of the parameters was 50 ppm SiNPs combined with 10% PEG, the morphological and chemical characteristics were inversely proportional to the PEG concentration, as the highest PEG concentration (10%) had the lowest results. Most parameters decreased at the highest SiNP concentration (100 ppm), except for the DPPH scavenging percentage, as there was no significant difference between the 50 and 100 ppm SiNPs.
Complete plastome genomes of three medicinal heliotropiaceae species: comparative analyses and phylogenetic relationships
Authors: Alawfi Mohammad S. , Alzahrani Dhafer A. , Albokhari Enas J.
Published: July 2024

Background

Heliotropiaceae is a family of the order Boraginales and has over 450 species. The members of the family Heliotropiaceae have been widely reported to be used in traditional medicine Over time, the classification of Heliotropiaceae has remained uncertain and has moved from family to subfamily, or conversely.

Results

In the present study, we sequenced, analyzed, and compared the complete plastomes of Euploca strigosa, Heliotropium arbainense, and Heliotropium longiflorum with the genomes of related taxa. The lengths of the plastomes of E. strigosa, H. arbainense, and H. longiflorum were 155,174 bp, 154,709 bp, and 154,496 bp, respectively. Each plastome consisted of 114 genes: 80 protein-coding genes, 4 ribosomal RNA genes, and 30 transfer RNA genes. The long repeats analysis indicated that reverse, palindromic, complement and forward repeats were all found in the three plastomes. The simple repeats analysis showed that the plastomes of E. strigosa, H. arbainense, and H. longiflorum contained 158, 165, and 151 microsatellites, respectively. The phylogenetic analysis confirmed two major clades in the Boraginales: clade I comprised Boraginaceae, while clade II included Heliotropiaceae, Ehretiaceae, Lennoaceae, and Cordiaceae. Inside the family Heliotropiaceae, E. strigosa is nested within the Heliotropium genus.

Conclusions

This study expands our knowledge of the evolutionary relationships within Heliotropiaceae and offers useful genetic resources.
Apolipoprotein E E3/E4 genotype is associated with an increased risk of premature coronary artery disease
Authors: Li Youqian , Zhong Wei , Huang Changjing , Peng Junyin , Li Hanlin
Published: July 2024

Objective

Dyslipidemia is one of the causes of coronary heart disease (CAD), and apolipoprotein E (APOE) gene polymorphism affects lipid levels. However, the relationship between APOE gene polymorphisms and premature CAD (PCAD, male CAD patients with ≤ 55 years old and female with ≤ 65 years old) risk had different results in different studies. The aim of this study was to assess this relationship and to further evaluate the relationship between APOE gene polymorphisms and PCAD risk in the Hakka population.

Methods

This study retrospectively analyzed 301 PCAD patients and 402 age matched controls without CAD. The APOE rs429358 and rs7412 polymorphisms were genotyped by polymerase chain reaction (PCR) -chip technique. The distribution of APOE genotypes and alleles between the case group and the control group was compared. The relationship between APOE genotypes and PCAD risk was obtained by logistic regression analysis.

Results

The frequency of the APOE ɛ3/ɛ4 genotype (18.9% vs. 10.2%, p = 0.001) and ε4 allele (11.1% vs. 7.0%, p = 0.007) was higher in the PCAD patients than that in controls, respectively. PCAD patients with ɛ2 allele had higher TG level than those with ɛ3 allele, and controls carried ɛ2 allele had higher HDL-C level and lower LDL-C level than those carried ɛ3 allele. Regression logistic analysis showed that BMI ≥ 24.0 kg/m2 (BMI ≥ 24.0 kg/m2 vs. BMI 18.5–23.9 kg/m2, OR: 1.763, 95% CI: 1.235–2.516, p = 0.002), history of smoking (Yes vs. No, OR: 5.098, 95% CI: 2.910–8.930, p < 0.001), ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 2.203, 95% CI: 1.363–3.559, p = 0.001), ε4 allele (ε4 vs. ε3, OR: 2.125, 95% CI: 1.333–3.389, p = 0.002), and TC level (OR: 1.397, 95% CI: 1.023–1.910, p = 0.036) were associated with PCAD.

Conclusions

In summary, BMI ≥ 24.0 kg/m2, history of smoking, APOE ɛ3/ɛ4 genotype, and TC level were independent risk factors for PCAD. It means that young individuals who are overweight, have a history of smoking, and carried APOE ɛ3/ɛ4 genotype had increased risk of PCAD.
Conditional survival and the prognostic value of serum carcinoembryonic antigen level in oldest old with colorectal cancer
Authors: He Weijing , Yang Yufei , Liu Qi , Luo Dakui , Li Qingguo , Li Xinxiang
Published: July 2024

Background

To evaluate the clinical value of serum CEA levels and their implications on the diagnostic value of the conventional TNM staging system in the oldest-old patients with colorectal cancer (CRC).

Methods

The recruited subjects were colorectal cancer patients aged 85 and older. The cutoff value for normal CEA level is 5 ng/mL. Patients with elevated CEA levels were categorized as stage C1, and those with normal CEA levels as stage C0. A number of Cox proportional hazard regression models were established to evaluate the prognosis of different prognostic factors with hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan–Meier method was utilized to display the disparate prognostic impact of multiple clinicopathological factors with the log-rank test.

Results

A total of 17,359 oldest-old patients diagnosed with CRC were recruited from the SEER database. The conditional survival of oldest-old patients with CRC was dismal with a 1-year conditional survival of only 11%, 18%, and 30% for patients surviving 1, 3, and 5 years, respectively. Patients with stage C1 exhibited a 48.5% increased risk of CRC-specific mortality compared with stage C0 (HR = 1.485, 95%CI = 1.393–1.583, using stage C0 patients as the reference, P < 0.001). All the stage C0 patients indicated lower HRs relative to the corresponding stage C1 patients.

Conclusions

Dismal conditional survival of oldest-old patients with CRC should be given additional consideration. C stage influences the prognosis of oldest-old patients with CRC.
“Multidisciplinary fast-track” care can significantly reduce risk of mortality among hip fracture patients at least 80 years old: a single-center retrospective study
Authors: Zhong Yinbo , Liu Mingxia , Cheng Zhenzhen , Yao Yuanyuan , Yu Yang , Luo Ge , Zheng Bin , Yan Min
Published: July 2024

Background

“Multidisciplinary fast-track” (MFT) care can accelerate recovery and improve prognosis after surgery, but whether it is effective in older people after hip fracture surgery is unclear.

Methods

We retrospectively compared one-year all-cause mortality between hip fracture patients at least 80 years old at our institution who underwent hip fracture surgery between January 2014 and December 2018 and who then received MFT or conventional care. Multivariable regression was used to assess the association between MFT care and mortality after adjustment for confounders.

Results

The final analysis included 247 patients who received MFT care and 438 who received conventional orthopedic care. The MFT group showed significantly lower one-year mortality (8.9% vs. 14.4%, P = 0.037). Log-rank testing of Kaplan-Meier survival curves confirmed the survival advantage. However, the two groups did not differ significantly in rates of mortality during hospitalization or at 30 or 90 days after surgery. Regression analysis confirmed that MFT care was associated with lower risk of one-year mortality (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.281–0.788, P = 0.04), and the survival benefit was confirmed in subgroups of patients with anemia (HR 0.453, 95% CI 0.268–0.767, P = 0.003) and patients with American Society of Anesthesiologists grade III (HR 0.202, 95% CI 0.08–0.51, P = 0.001).

Conclusions

MFT care can reduce one-year mortality among hip fracture patients at least 80 years old. This finding should be verified and extended in multi-center randomized controlled trials.
Fecal microbiota composition is a better predictor of recurrent Clostridioides difficile infection than clinical factors in a prospective, multicentre cohort study
Authors: van Rossen Tessel M. , van Beurden Yvette H. , Bogaards Johannes A. , Budding Andries E. , Mulder Chris J.J. , Vandenbroucke-Grauls Christina M.J.E.
Published: July 2024

Introduction

Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea. Fidaxomicin and fecal microbiota transplantation (FMT) are effective, but expensive therapies to treat recurrent CDI (reCDI). Our objective was to develop a prediction model for reCDI based on the gut microbiota composition and clinical characteristics, to identify patients who could benefit from early treatment with fidaxomicin or FMT.

Methods

Multicentre, prospective, observational study in adult patients diagnosed with a primary episode of CDI. Fecal samples and clinical data were collected prior to, and after 5 days of CDI treatment. Follow-up duration was 8 weeks. Microbiota composition was analysed by IS-pro, a bacterial profiling technique based on phylum- and species-specific differences in the 16–23 S interspace regions of ribosomal DNA. Bayesian additive regression trees (BART) and adaptive group-regularized logistic ridge regression (AGRR) were used to construct prediction models for reCDI.

Results

209 patients were included, of which 25% developed reCDI. Variables related to microbiota composition provided better prediction of reCDI and were preferentially selected over clinical factors in joint prediction models. Bacteroidetes abundance and diversity after start of CDI treatment, and the increase in Proteobacteria diversity relative to baseline, were the most robust predictors of reCDI. The sensitivity and specificity of a BART model including these factors were 95% and 78%, but these dropped to 67% and 62% in out-of-sample prediction.

Conclusion

Early microbiota response to CDI treatment is a better predictor of reCDI than clinical prognostic factors, but not yet sufficient enough to predict reCDI in daily practice.
PET-CT-guided, symptom-based, patient-initiated surveillance versus clinical follow-up in head neck cancer patients (PETNECK2): study protocol for a multicentre feasibility study and non-inferiority, randomised, phase III trial
Authors: Nankivell Paul , Gaunt Piers , Gaunt Claire , Sissons Julia , Liaskou Evaggelia , Jefferson Yolande , Fulton-Lieuw Tessa , Mittal Saloni , Mehanna Hisham ,   PETNECK2 Research Team, Abou-Foul Ahmad , Karwath Andreas , Lorenc Ava , Main Barry , Greaves Colin , Moore David , Secher Denis , Watson Eila , Gkoutos Georgios , Ozakinci Gozde , Wolstenholme Jane , Dretzke Janine , Brett Jo , Duda Joan , Matheson Lauren , Jepson Marcus , Wells Mary , Calvert Melanie , Rhodes Pat , Kiely Philip , Thomas Steve , Winter Stuart , Wong Wai-lup
Published: July 2024

Background

Approximately 40% of treated head and neck cancer (HNC) patients develop recurrence. The risk of recurrence declines with time from treatment. Current guidelines recommend clinical follow-up every two months for the first two years after treatment, with reducing intensity over the next three years. However, evidence for the effectiveness of these regimes in detecting recurrence is lacking, with calls for more flexible, patient-centred follow-up strategies.

Methods

PETNECK2 is a UK-based multi-centre programme examining a new paradigm of follow-up, using positron emission tomography-computed tomography (PET-CT)-guided, symptom-based, patient-initiated surveillance. This paradigm is being tested in a unblinded, non-inferiority, phase III, randomised controlled trial (RCT). Patients with HNC, one year after completing curative intent treatment, with no clinical symptoms or signs of loco-regional or distant metastasis will be randomised using a 1:1 allocation ratio to either regular scheduled follow-up, or to PET-CT guided, patient-initiated follow-up. Patients at a low risk of recurrence (negative PET-CT) will receive a face-to-face education session along with an Information and Support (I&S) resource package to monitor symptoms and be in control of initiating an urgent appointment when required. The primary outcome of the RCT is overall survival. The RCT also has an in-built pilot, a nested QuinteT Recruitment Intervention (QRI), and a nested mixed-methods study on patient experience and fear of cancer recurrence (FCR). An initial, single-arm feasibility study has been completed which determined the acceptability of the patient-initiated surveillance intervention, the completion rates of baseline questionnaires, and optimised the I&S resource prior to implementation in the RCT.

Discussion

We hypothesise that combining an additional 12-month post-treatment PET-CT scan and I&S resource will both identify patients with asymptomatic recurrence and identify those at low risk of future recurrence who will be empowered to monitor their symptoms and seek early clinical follow-up when recurrence is suspected. This change to a patient-centred model of care may have effects on both quality of life and fear of cancer recurrence.

Trial registration

ISRCTN: 13,709,798; 15-Oct-2021.
Associations between modifiable risk factors and hepatocellular carcinoma: a trans-ancestry Mendelian randomization study
Authors: Wei Xiaoxia , Yang Chenglei , Lin Qiuling , Qiu Moqin , Wen Qiuping , Zhou Zihan , Jiang Yanji , Chen Peiqin , Liang Xiumei , Cao Ji , Tang Juan , Wei Yuying , Yu Hongping , Liu Yingchun
Published: July 2024

Background

Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear.

Methods

We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations.

Results

In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results.

Conclusions

Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC.
Study Protocol: Pegasus: psychotherapy incorporating horses for ‘therapy-resistant’ adolescents with autism spectrum disorders, a study with series of randomised, baseline controlled n-of-1 trials
Authors: den Boer Jenny C. , Klip Helen , Blonk Anita , Lenselink Monique , Kaijdoe Shireen P.T. , Tielkes Melanie , van Zandbeek Amber , Bres Gerdine , Herinx Mandy , Staal Wouter G. , Rommelse Nanda
Published: July 2024

Background

For people with autism spectrum disorder (ASD), daily life can be highly stressful with many unpredictable events that can evoke emotion dysregulation (ED): a strong difficulty with appropriately negative affect regulation. For some of the patients with ASD, treatment as usual does not prove to be effective for ED. They may be at risk of life-long impairment, development of other disorders and loss of motivation for most regular forms of therapy. A highly promising method that may prove effective for therapy-resistant individuals with ASD is Psychotherapy incorporating horses (PIH). PIH uses the interactions of the horse and the patients on the ground and does not include horseriding. While often met with prejudgment and scepticism, reports from parents and therapists as well as a recent systematic review suggest that PIH may have beneficial effects on youths with ASD. Therefore, we examine clinical outcomes both in the short and in the long terms of PIH offered to adolescents with ASD and severe ED despite regular therapy.

Methods

A total of 35 adolescents aged 11–18 years with ASD will receive PIH during 15 sessions once a week with randomization to five different groups differentiating in baseline phase from 2 to 6 weeks. PIH uses horses to promote social awareness and self-awareness as well as relationship management and self-management. The primary outcome is the response to treatment on the Emotion Dysregulation Index (EDI). The secondary outcome measures include ASD symptom severity, quality of life, self-esteem, global and family functioning, and goal attainment. Assessments take place at the baseline (T0), at the end of baseline phase A (T1), after completion of intervention phase B (T2), after the end of post-measurement phase C (T3) and after one year (T4). Qualitative interviews of participants, parents and therapists will be held to reveal facilitators and barriers of PIH and a cost-effectiveness study will be performed.

Discussion

This study aims at contributing to clinical practice for adolescents with ASD and persistent emotion regulation problems despite 1.5 year of treatment by offering Psychotherapy incorporating horses in a study with series of randomised, baseline controlled n-of-1 trials.

Trial registration

www.ClinicalTrials.gov NCT05200351, December 10th 2021.
The impact of exercise on growth factors in postmenopausal women: a systematic review and meta-analysis
Authors: Nasir Yasaman , Hoseinipouya Mohammad Reza , Eshaghi Hesam , Rahimi Mohammad Hossein
Published: July 2024

Background

Aging results in many changes in health status, body composition, muscle strength, and, ultimately, functional capacity. These changes coincide with significant alterations in the endocrine system, such as insulin-like growth factor-1 (IGF-1) and IGF-binding proteins (IGFBPs), and may be associated with many symptoms of aging. The objectives of this study is to investigate the potential influence of different types of exercise, such as resistance training and aerobic training, on IGF-1 and IGFBP-3 levels in postmenopausal women.

Methods

Medline, Scopus, and Google Scholar databases were systematically searched up to November 2023. The Cochrane Collaboration tool was used to assess the risk of bias and the quality of the studies. The random-effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were used to estimate the overall effect. Between-study heterogeneity was assessed using the chi-squared and I2 tests.

Results

Seventeen studies were included in the present systematic review and 16 studies were included in the meta-analysis. The pooled results from 16 studies (21 trials) with 1170 participants examining the impact of exercise on IGF-1 concentration showed a significant increase in IGF-1, and the pooled results among six studies (trials) showed a significant decrease in IGFBP-3 concentration (730 participants). In addition, resistance training and aerobic training had a significant effect on increasing IGF-1 concentration post-exercise compared with placebo.

Conclusion

Based on this meta-analysis, Women who have completed menopause and followed an exercise routine showed changes in IGF-1 and IGFBP-3 levels that can indirectly be associated with risk of chronic age-related conditions.
Ready to leave? – Adolescents’ and parents’ perceptions of transition from paediatric to adult rheumatology care
Authors: Vermé A. , Wenemark Marika , Jungner J. Granhagen , Broström E. , Bartholdson C.
Published: July 2024

Background

In Sweden, approximately 2000 children live with Juvenile Idiopathic Arthritis (JIA). About half of them continue to have an active disease and need to transfer to adult rheumatology care. This study aimed to investigate Swedish adolescents’ and parents´ perceptions of readiness for transition from pediatric to adult rheumatology care.

Methods

The study was a cross-sectional quantitative study. Patients at the pediatric rheumatology clinic at a university hospital in Sweden and members of The Swedish National Organization for Young Rheumatics aged 14–18 and their parents were invited to participate in the study. Data was collected with the Readiness for Transition Questionnaire (RTQ) focusing on adolescents' transition readiness, adolescents' healthcare behaviors and responsibility, and parental involvement. Data were analyzed with descriptive statistics. Comparative analyses were made using non-parametric tests with significance levels of 0.05 as well as factor analyses and logistic regression.

Results

There were 106 adolescents (85 girls, 20 boys) and 96 parents answering the RTQ. The analysis revealed that many adolescents and parents experienced that the adolescents were ill-prepared to take over responsibility for several healthcare behaviors, such as booking specialty care appointments, calling to renew prescriptions and communicating with medical staff on phone and to transfer to adult care. Parents and adolescents alike stated that it was especially difficult for the adolescents to take responsibility for healthcare behaviors meaning that the adolescents had to have direct interaction with the healthcare professionals (HCPs) at the paediatric rheumatology clinic, for example to renew prescriptions. It was evident that the adolescents who perceived they were ready to take responsibility for the aspects related to direct interaction with HCPs were more overall ready to be transferred to adult care.

Conclusion

Adolescents need more support to feel prepared to transfer to adult care. With the results from this study, we can develop, customize, and optimize transitional care programs in Sweden for adolescents.
Supplementation of vitamin E as an addition to a commercial renal diet does not prolong survival of cats with chronic kidney disease
Authors: Krofič Žel Martina , Tavčar Kalcher Gabrijela , Vovk Tomaž , Žegura Bojana , Lusa Lara , Tozon Nataša , Nemec Svete Alenka
Published: July 2024

Background

The aim of this double-blind, placebo-controlled study was to investigate the effect of vitamin E supplementation as an addition to a commercial renal diet on survival time of cats with different stages of chronic kidney disease (CKD). In addition, we were interested whether vitamin E supplementation affects selected oxidative stress and clinical parameters. Thirty-four cats with CKD and 38 healthy cats were included in the study. Cats with CKD were classified according to the IRIS Guidelines; seven in IRIS stage 1, 15 in IRIS stage 2, five in IRIS stage 3 and seven in IRIS stage 4. Cats with CKD were treated according to IRIS Guidelines. Cats with CKD were randomly assigned to receive vitamin E (100 IU/cat/day) or placebo (mineral oil) for 24 weeks in addition to standard therapy. Plasma malondialdehyde (MDA) and protein carbonyl (PC) concentrations, DNA damage of peripheral lymphocytes and plasma vitamin E concentrations were measured at baseline and four, eight, 16 and 24 weeks thereafter. Routine laboratory analyses and assessment of clinical signs were performed at each visit.

Results

Vitamin E supplementation had no effect on the survival time and did not reduce the severity of clinical signs. Before vitamin E supplementation, no significant differences in vitamin E, MDA and PC concentrations were found between healthy and CKD cats. However, plasma MDA concentration was statistically significantly higher (p = 0.043) in cats with early CKD (IRIS stages 1 and 2) than in cats with advanced CKD (IRIS stages 3 and 4). Additionally, DNA damage was statistically significantly higher in healthy cats (p ≤ 0.001) than in CKD cats. Plasma vitamin E concentrations increased statistically significantly in the vitamin E group compared to the placebo group four (p = 0.013) and eight (p = 0.017) weeks after the start of vitamin E supplementation. During the study and after 24 weeks of vitamin E supplementation, plasma MDA and PC concentrations and DNA damage remained similar to pre-supplementation levels in both the placebo and vitamin E groups.

Conclusions

Vitamin E supplementation as an addition to standard therapy does not prolong survival in feline CKD.
An end-to-end approach for single-cell infrared absorption spectroscopy of bacterial inclusion bodies: from AFM-IR measurement to data interpretation of large sample sets
Authors: Duverger Wouter , Tsaka Grigoria , Khodaparast Ladan , Khodaparast Laleh , Louros Nikolaos , Rousseau Frederic , Schymkowitz Joost
Published: July 2024

Background

Inclusion bodies (IBs) are well-known subcellular structures in bacteria where protein aggregates are collected. Various methods have probed their structure, but single-cell spectroscopy remains challenging. Atomic Force Microscopy-based Infrared Spectroscopy (AFM-IR) is a novel technology with high potential for the characterisation of biomaterials such as IBs.

Results

We present a detailed investigation using AFM-IR, revealing the substructure of IBs and their variation at the single-cell level, including a rigorous optimisation of data collection parameters and addressing issues such as laser power, pulse frequency, and sample drift. An analysis pipeline was developed tailored to AFM-IR image data, allowing high-throughput, label-free imaging of more than 3500 IBs in 12,000 bacterial cells. We examined IBs generated in Escherichia coli under different stress conditions. Dimensionality reduction analysis of the resulting spectra suggested distinct clustering of stress conditions, aligning with the nature and severity of the applied stresses. Correlation analyses revealed intricate relationships between the physical and morphological properties of IBs.

Conclusions

Our study highlights the power and limitations of AFM-IR, revealing structural heterogeneity within and between IBs. We show that it is possible to perform quantitative analyses of AFM-IR maps over a large collection of different samples and determine how to control for various technical artefacts.
An approach designed to fail deaf children and their parents and how to change it
Authors: Humphries Tom , Mathur Gaurav , Napoli Donna Jo , Rathmann Christian
Published: July 2024

The matter of raising and educating deaf children has been caught up in percepts of development that are persistently inaccurate and at odds with scientific research. These percepts have negatively impacted the health and quality of life of deaf children and deaf people in general. The all too prevalent advice is to raise the child strictly orally and wait to see what happens. Only when the child is seriously behind is a completely accessible language – a sign language – introduced, and that is far too late for protecting cognitive health. The medical profession, along with others, needs to offer parents better advice and better supports so that neither the children nor their parents wait and watch as the oral-only method fails. All must take responsible action to assure an approach that succeeds.
Integrated proteomic and metabolomic profiling of lymph after trauma-induced hypercoagulopathy and antithrombotic therapy
Authors: Zheng Yangkang , Wang Pengyu , Cong Lin , Shi Qi , Zhao Yongjian , Wang YongJun
Published: July 2024

Background

Routine coagulation tests are not widely accepted diagnostic criteria of trauma-induced hypercoagulopathy (TIH) due to insensitivity. Lymphatic vessels drain approximately 10% of the interstitial fluid into the lymphatic system and form lymph.

Subjective

The purpose of this study was to identify the potential lymph biomarkers for TIH.

Methods

Eighteen male Sprague-Dawley rats were randomly assigned to the sham (non-fractured rats with sham surgery and vehicle treatment), the VEH (fractured rats with vehicle treatment) and the CLO (fractured rats with clopidogrel treatment) group. Thoracic duct lymph was obtained to perform proteomics and untargeted metabolomics.

Results

A total of 1207 proteins and 16,695 metabolites were identified. The top 5 GO terms of lymph proteomics indicated that oxidative stress and innate immunity were closely associated with TIH and antithrombotic therapy. The top 5 GO terms of lymph metabolomics showed that homocystine and lysophosphatidylcholine were the differential expressed metabolites (DEMs) between the sham and VEH groups, while cholic acid, docosahexaenoic acid, N1-Methyl-2-pyridone-5-carboxamide, isoleucine and testosterone are the DEMs between the VEH and CLO group.

Conclusions

This study presents the first proteomic and metabolomic profiling of lymph after TIH and antithrombotic therapy, and predicts the possible lymph biomarkers for TIH.
Role of O-linked N-acetylglucosamine protein modification in oxidative stress-induced autophagy: a novel target for bone remodeling
Authors: Li Shengqian , Ren Wenhao , Zheng Jingjing , Li Shaoming , Zhi Keqian , Gao Ling
Published: July 2024

O-linked N-acetylglucosamine protein modification (O-GlcNAcylation) is a dynamic post-translational modification (PTM) involving the covalent binding of serine and/or threonine residues, which regulates bone cell homeostasis. Reactive oxygen species (ROS) are increased due to oxidative stress in various pathological contexts related to bone remodeling, such as osteoporosis, arthritis, and bone fracture. Autophagy serves as a scavenger for ROS within bone marrow-derived mesenchymal stem cells, osteoclasts, and osteoblasts. However, oxidative stress-induced autophagy is affected by the metabolic status, leading to unfavorable clinical outcomes. O-GlcNAcylation can regulate the autophagy process both directly and indirectly through oxidative stress-related signaling pathways, ultimately improving bone remodeling. The present interventions for the bone remodeling process often focus on promoting osteogenesis or inhibiting osteoclast absorption, ignoring the effect of PTM on the overall process of bone remodeling. This review explores how O-GlcNAcylation synergizes with autophagy to exert multiple regulatory effects on bone remodeling under oxidative stress stimulation, indicating the application of O-GlcNAcylation as a new molecular target in the field of bone remodeling.

Graphical Abstract
Leveraging continuous glucose monitoring as a catalyst for behaviour change: a scoping review
Authors: Jospe Michelle R. , Richardson Kelli M. , Saleh Ahlam A. , Bohlen Lauren C. , Crawshaw Jacob , Liao Yue , Konnyu Kristin , Schembre Susan M.
Published: July 2024

Background

Amidst the escalating prevalence of glucose-related chronic diseases, the advancements, potential uses, and growing accessibility of continuous glucose monitors (CGM) have piqued the interest of healthcare providers, consumers, and health behaviour researchers. Yet, there is a paucity of literature characterising the use of CGM in behavioural intervention research. This scoping review aims to describe targeted populations, health behaviours, health-related outcomes, and CGM protocols in randomised controlled trials (RCTs) that employed CGM to support health behaviour change.

Methods

We searched Ovid MEDLINE, Elsevier Embase, Cochrane Central Register of Controlled Trials, EBSCOhost PsycINFO, and ProQuest Dissertations & Theses Global from inception to January 2024 for RCTs of behavioural interventions conducted in adults that incorporated CGM-based biological feedback. Citation searching was also performed. The review protocol was registered (https://doi.org/10.17605/OSF.IO/SJREA).

Findings

Collectively, 5389 citations were obtained from databases and citation searching, 3995 articles were screened, and 31 were deemed eligible and included in the review. Most studies (n = 20/31, 65%) included adults with type 2 diabetes and reported HbA1c as an outcome (n = 29/31, 94%). CGM was most commonly used in interventions to target changes in diet (n = 27/31, 87%) and/or physical activity (n = 16/31, 52%). 42% (n = 13/31) of studies provided prospective CGM-based guidance on diet or activity, while 61% (n = 19/31) included retrospective CGM-based guidance. CGM data was typically unblinded (n = 24/31, 77%) and CGM-based biological feedback was most often provided through the CGM and two-way communication (n = 12/31, 39%). Communication typically occurred in-person (n = 13/31, 42%) once per CGM wear (n = 13/31; 42%).

Conclusions

This scoping review reveals a predominant focus on diabetes in CGM-based interventions, pointing out a research gap in its wider application for behaviour change. Future research should expand the evidence base to support the use of CGM as a behaviour change tool and establish best practices for its implementation.

Trial registration

doi.org/10.17605/OSF.IO/SJREA.