bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pattern of mismatch repair proteins in colorectal cancer patients in tertiary cancer center.
Authors: Kale Ajinkya Shantaram , Saklani Avanish 
Published: August 2023

40 Background: Prevalence of MSI high in colorectal cancer patients in India has been debated in previous literature. Microsatellite instability pathway is one of the major pathways in carcinogenesis of colorectal carcinoma. MSI status has paramount significance in therapeutic and prognostic aspects of colorectal cancer management. MSI status can be evaluated by presence or absence of mismatch repair proteins. Aims & objectives: we aimed to determine the prevalence of MSI high in colorectal carcinoma and pattern of mismatch repair proteins. Methods: This was retrospective study which included consecutively operated colorectal carcinoma patients from 01 may 2022 to 31 December 2022 in our institute. Immunohistochemistry with four mismatch repair (MMR) proteins; MLH1, MSH2, MSH6, and PMS2 was performed. Correlation with various clinical and histopathological features was done. Results: total 296 colorectal carcinoma patients were included in our study. Fourty one (13.85%) patients were MSI high. Most common pattern of MMR protein expression loss was dual loss of MLH1 and PMS2 (n=18). Most common single protein loss was PMS2 (n=22). Most common location of tumor in MSI high patients was the right colon. (n=20). Out of 153 carcinoma rectum patients only five patients were MSI high. Conclusions: The study shows that prevalence of MSI high is more common in right colon cancer. Prevalence of MSI high is very low in carcinoma rectum. We discuss and compare our results with previous studies.
A novel non-invasive multi-target stool DNA methylation assay for early detection of gastrointestinal cancers.
Authors: Sun Li-Yue , Shen Ju , Zhong Yu-Yun , Yang Jiao-Jiao , Jiang Yu-Ying , Cheng Yan-Jun , Wang Xi-Ying , Wang Rui-Qi , Liu Fei , Liu Fang , Chen Meng-Jin , Ling Xiao-Mei , Wen Jie-Lun , Wang Fang , Zhang Xu-Hui 
Published: August 2023

41 Background: Gastrointestinal (GI) cancers accounts for one-third of the world’s cancer burden. Liquid biopsies such as SEPT9 methylation and Cologuard have been approved by the Food and Drug Administration for early detection of colorectal cancer (CRC), but not for other GI cancers. In addition, although CancerSEEK can be employed in the detecting of multiple GI cancers, it has low sensitivity and without localization. Stool is a promising sample for GI cancer detection because it contains the host’s exfoliated cells and circulating free DNA derived from GI cancer cells. Thus, we aimed to develop a sensitive and non-invasive multi-target stool DNA methylation test for early detection and localization of GI cancers. Methods: We prospectively enrolled 124 patients histologically diagnosed with GI cancer without treatment and 92 healthy controls who underwent GI cancer-related examinations every 3 years. Stool DNA was extracted from the supernatant of a mixture containing 5 g fresh stool and 25 ml preservative solution using the stool DNA extraction kit. The samples were subjected to bisulfite conversion using the EZ DNA Methylation Kit, and the treated with stool DNA multi-target methylation assay kit to detect the methylation levels of 3 target regions of stool DNA (PDX1, COL4A2-1, and FGF5) with qPCR. Based on the guidelines of the protocol, positive result was defined as ΔCt value (ΔCt = Ct (target gene) - Ct (GAPDH))＜10 for any three genes. Multiple logistic regression (MLR) models for single GI cancers were constructed including the ΔCt value of each gene to adjust for tissue of origin (TOO) of GI cancers. This study was approved by the Clinical Research Ethics Committee of Guangdong Second Provincial General Hospital (2021-KZ-138-03). Results: Overall, 98 of 124 patients (79%) tested positive, and 88 of 92 healthy controls (96%) tested negative. For each GI cancer type, the positivity rates were 71%, 83%, 75%, 81% and 91% for CRC (24/34), gastric cancer (GC, 19/23), esophageal cancer (EC, 18/24), pancreatic cancer (PC, 17/21) and ampullary cancer (AC, 20/22), respectively. Interestingly, among 4 positive healthy controls, 3 were diagnosed as advanced adenomas and one case was a pregnant woman. For the MLR model, the sensitivity of CRC was 88% (30/34), that of GC was 91% (21/23), EC was 88% (21/24), PC was 90% (19/21), and AC was 95% (21/22). Conclusions: The multi-target stool DNA methylation assay allowed early and accurate detection and identification of tissue of origin of GI cancers. [Table: see text]
Gut microbiome to predict durable response to immunotherapy in patients with hepatocellular carcinoma.
Authors: Zhao Caining , Liang Zhibing , Xu Wanli , Chen Wenqi , Li Shanshan , Kong Feng-Ming Spring 
Published: August 2023

47 Background: Patients with hepatocellular carcinoma (HCC) can hardly benefit from immunotherapy (IO); however, few patients develop durable responses to IO (long-responder, LR). Gut microbiota implicate IO response in multiple cancers, while its characteristics in LRs of IO has not been well sketched. With these motivations, we applied metagenomics to comprehensively unveil intestinal flora profiles in LRs, and compare with less responders to investigate its potential in response prediction. Methods: Advanced HCC patients treated with anti-PD-1 with/without anti-CTLA-4 fall into 3 distinct subgroups: non-responders (NRs) presenting early disease progression within 6 months, long responders (LRs) who achieve durable disease control with a minimum of 12 months, and the remaining short responders (SRs). Fresh stool samples were collected for metagenomic sequencing at least 12 months after initiation of a variety of immunotherapy regimens in LRs, while samples were collected within 6 months of IO treatment for NRs and SRs. Metagenome profiles were annotated using Kraken, and significant differences were revealed by Lefse analysis. Results: A total of 66 patients with advanced HCC who received IO first time were enrolled, 38 patients were evaluated as LRs, 8 as SRs, and 20 as NRs. Metagenome profiling unveiled significant association in its diversity and composition with clinical response. The β-diversity increased gradually as the treatment response getting better (p < 0.001). The β-diversity was significantly lower in NRs in comparison with SRs (p < 0.05) and LR (p < 0.001), while there was no significance between SRs and LRs. Significant higher abundance of Clostridium_butyricum was observed in LRs compared with NRs. Moreover, anabolic pathways like fatty acid biogenesis were significantly enriched in LRs. Conclusions: Gut metagenomic diversities and profiles were related with IO response in advanced HCC patients, which could be potential prediction biomarkers of IO durable benefits. The enrichment of probiotics like Clostridium_butyricum and its derived fatty acid have a mechanistic impact on higher antitumor immunity, which need further verification study.
A comparative study of the effectiveness of multiagent platinum based concurrent plus adjuvant versus conventional single agent platinum based concurrent chemotherapy in carcinoma cervix.
Authors: Shah Salman Khurshid 
Published: August 2023

85 Background: Cervical cancer is the 4th most common cancer in females worldwide. Combination of external beam radiotherapy (EBRT) and intracavitary brachytherapy (BT) with concurrent chemotherapy is the current standard of care for locally advanced cervical cancer. Even though the trials used separate combinations, the common end point suggested that platinum is single most effective chemotherapy agent. Since the latest data on platinum based polychemotherapy globally indicates its overall benefit, further trials are required to determine what regimens would be ideal for treatment of cervical cancer with maximum benefits and least toxicities. Objectives: 1. To compare the response to doublet polychemotherapy with conventional chemotherapy in carcinoma cervix treated with chemoradiation. 2. To compare toxicity profile of doublet polychemotherapy with conventional chemotherapy. Methods: 66 patients of carcinoma cervix were enrolled in this study and were randomized to two arms. Arm A (n=34) was the experimental arm and the patients received concurrent weekly cycles of cisplatin(40mg/m2) plus gemcitabine (125mg/m2) along with EBRT followed by HDR brachytherapy, after 2-3 weeks of which they received 2 adjuvant cycles (21 days each) of gemcitabine (1000mg/m2 on Day1 and Day 8) and cisplatin (50mg/m2 on Day 1). Arm B(n=32) was the control arm and the patients received standard treatment which is concurrent weekly cycles single agent cisplatin(40mg/m2) with EBRT followed by HDR brachytherapy. EBRT doses ranged from 45Gy to 50.4 Gy at 1.8 to 2 Gy per fraction .BT application was either ICBT or ISBT depending on tumour response to EBRT, assessed by MRI. Patients were followed up for response assessment and late toxicities within 6 months of completion of treatment by clinical examination and MRI which was reported using RECIST 1.1 criteria. Results: On 6 month follow up MRI, number of patients achieving CR was 10% higher in the experimental arm (Arm A, n=33;97.06%) than the control arm (Arm B, n=28;87.5%).PR was seen in 2 patients, both from Arm B. Of the 3 patients presenting with PD at follow up 1 belonged to Arm A and 2 to Arm B (2.94% vs 6.25%). On pre-brachytherapy MRIs, the size reduction was better in Arm A and this reduction allowed a majority of patients in said arm to undergo ICBT instead of ISBT. The number of patients achieving >50% reduction post EBRT was 40% higher in Arm A. Acute GI and Hematological toxicities were seen in both arms but were higher in Arm A. as was Grade 3 neutropenia. Late toxicities were similar in both arms. Conclusions: The study concluded that the use of multiagent platinum-based chemotherapy in concurrent plus adjuvant setting can be advantageous. Improved tumour reduction can be achieved & disease can be made more amenable for ICBT. The accompanying toxicities were transient and clinically manageable.
Blood Lymphocyte Subsets and Proinflammatory Cytokine Profile in ROHHAD(NET) and non-ROHHAD(NET) Obese Individuals
Authors: Fava Daniela , Morandi Fabio , Prigione Ignazia , Angelelli Alessia , Bocca Paola , Pistorio Angela , Volpi Stefano , Patti Giuseppa , Pepino Carlotta , Casalini Emilio , Allegri Anna Elsa Maria , Di Iorgi Natascia , d’Annunzio Giuseppe , Napoli Flavia , Maghnie Mohamad 
Published: August 2023

AbstractContextRapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway.ObjectiveThe aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls.MethodsWe included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups.ResultsAnalysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P = .04) with a prevalence of CD4-T cells (P = .03) and a lower number of activated CD8-T cells (P = .02). With regard to regulatory subset, patients displayed increased regulatory B cells (P = .05) and type-1 regulatory T cells (P = .03). With regard to CD8-T cells, a lower number of T effector memory was observed (P = .02). In contrast, among CD4-T cells, we found a higher number of T naive (P = .04) and T effector (P = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P = .008 and P = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P = .03).ConclusionOur findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition.
Manduca sextacaterpillars parasitized by the waspCotesia congregatastop chewing despite an intact motor system
Authors: Miles Carol I. , Chen Wei Ping , Adamo Shelley A. , Kester Karen M. , Miller Dylan W. 
Published: August 2023

ABSTRACTThe parasitic wasp Cotesia congregata suppresses feeding in its host, the caterpillar Manduca sexta, during specific periods of wasp development. We examined both feeding behaviour and the neurophysiology of the mandibular closer muscle in parasitized and unparasitized control M. sexta to determine how the wasp may accomplish this. To test whether the wasps activated a pre-existing host mechanism for feeding cessation, we examined the microstructure of feeding behaviour in caterpillars that stopped feeding due to illness-induced anorexia or an impending moult. These microstructures were compared with that shown by parasitized caterpillars. While there were overall differences between parasitized and unparasitized caterpillars, the groups showed similar progression in feeding microstructure as feeding ended, suggesting a common pattern for terminating a meal. Parasitized caterpillars also consumed less leaf area in 100 bites than control caterpillars at around the same time their feeding microstructure changed. The decline in food consumption was accompanied by fewer spikes per burst and shorter burst durations in chewing muscle electromyograms. Similar extracellular results were obtained from the motorneuron of the mandibular closer muscle. However, chewing was dramatically re-activated in non-feeding parasitized caterpillars if the connectives posterior to the suboesophageal ganglion were severed. The same result was observed in unparasitized caterpillars given the same treatment. Our results suggest that the reduced feeding in parasitized caterpillars is not due to damage to the central pattern generator (CPG) for chewing, motor nerves or chewing muscles, but is more likely to be due to a suppression of chewing CPG activity by ascending or descending inputs.
Migratory songbirds exhibit seasonal modulation of the oxygen cascade
Authors: Ivy Catherine M. , Guglielmo Christopher G. 
Published: August 2023

ABSTRACT
Migratory flight requires birds to maintain intensive aerobic exercise for many hours or days. Maintaining O2 supply to flight muscles is therefore important during migration, especially since migratory songbirds have been documented flying at altitudes greater than 5000 m above sea level, where O2 is limited. Whether songbirds exhibit seasonal plasticity of the O2 cascade to maintain O2 uptake and transport during migratory flight is not well understood. We investigated changes in the hypoxic ventilatory response, haematology and pectoralis (flight) muscle phenotype of 6 songbird species from 3 families during migratory and non-migratory conditions. Songbirds were captured during southbound migration in southern Ontario, Canada. Half of the birds were assessed during migration, and the rest were transitioned onto a winter photoperiod to induce a non-migratory phenotype and measured. All species exhibited seasonal plasticity at various stages along the O2 cascade, but not all species exhibited the same responses. Songbirds tended to be more hypoxia tolerant during migration, withstanding 5 kPa O2 and breathed more effectively through slower, deeper breaths. Warblers had a stronger haemoglobin–O2 affinity during autumn migration (decrease of ∼4.7 Torr), while the opposite was observed in thrushes (increase of ∼2.6 Torr). In the flight muscle there was an ∼1.2-fold increase in the abundance of muscle fibres with smaller fibre transverse areas during autumn migration, but no changes in capillary:fibre ratio. These adjustments would enhance O2 uptake and transport to the flight muscle. Our findings demonstrate that in the O2 cascade there is no ideal migratory phenotype for all songbirds.
Extreme Ultraviolet Laser Photoelectron Spectroscopy of Flat Liquid Jet Generated Using Microfluidic Device
Authors: Yamamoto Yo-ichi , Yano Hiroto , Karashima Shutaro , Uenishi Ryuta , Orimo Natsumi , Nishitani Junichi , Suzuki Toshinori 
Published: August 2023

Abstract
We present photoelectron spectroscopy of liquid films generated in a vacuum with microfluidic devices based on liquid-liquid or gas-liquid collisions. The results are compared to those for a standard liquid microjet technique.
Quantifying the Association between Objectively Measured Physical Activity and Multiple Sclerosis in the UK Biobank
Authors: MENG QIER , CUI ERJIA , LEROUX ANDREW , MOWRY ELLEN M. , LINDQUIST MARTIN A. , CRAINICEANU CIPRIAN M. 
Published: August 2023

ABSTRACT

Introduction
Objectively measured physical activity (PA) data were collected in the accelerometry substudy of the UK Biobank. UK Biobank also contains information about multiple sclerosis (MS) diagnosis at the time of and after PA collection. This study aimed to 1) quantify the difference in PA between prevalent MS cases and matched healthy controls, and 2) evaluate the predictive performance of objective PA measures for incident MS cases.

Methods
The first analysis compared eight accelerometer-derived PA summaries between MS patients (N = 316) and matched controls (30 controls for each MS case). The second analysis focused on predicting time to MS diagnosis among participants who were not diagnosed with MS. A total of 19 predictors including eight measures of objective PA were compared using Cox proportional hazards models (number of events = 47; 585,900 person-years of follow-up).

Results
In the prevalent MS study, the difference between MS cases and matched controls was statistically significant for all PA summaries (P < 0.001). In the incident MS study, the most predictive variable of progression to MS in univariate Cox regression models was lower age (C = 0.604), and the most predictive PA variable was lower relative amplitude (RA, C = 0.594). A two-stage forward selection using Cox regression resulted in a model with concordance C = 0.693 and four predictors: age (P = 0.015), stroke (P = 0.009), Townsend deprivation index (P = 0.874), and RA (P = 0.004). A model including age, stroke, and RA had a concordance of C = 0.691.

Conclusions
Objective PA summaries were significantly different and consistent with lower activity among study participants who had MS at the time of the accelerometry study. Among individuals who did not have MS, younger age, stroke history, and lower RA were significantly associated with a higher risk of a future MS diagnosis.
Carbohydrate Ingestion during Prolonged Cycling Improves Next-Day Time Trial Performance and Alters Amino Acid Concentrations
Authors: CLAUSS MATTHIEU , SKATTEBO ØYVIND , RASEN DÆHLI MALIN , DITTA VALSDOTTIR THORHILDUR , EZZATKHAH BASTANI NASSER , IVAR JOHANSEN EGIL , JENSEN KOLNES KRISTOFFER , STEEN SKÅLHEGG BJØRN , JENSEN JØRGEN 
Published: August 2023

ABSTRACT

Introduction
Exercise with low carbohydrate availability increases protein degradation, which may reduce subsequent performance considerably. The present study aimed to investigate the effect of carbohydrate ingestion during standardized exercise with and without exhaustion on protein degradation and next-day performance.

Methods
Seven trained male cyclists (V̇O2max 66.8 ± 1.9 mL·kg−1·min−1; mean ± SEM) cycled to exhaustion (~2.5 h) at a power output eliciting 68% of V̇O2max (W68%). This was followed by repeating 1-min work/1-min recovery intervals at 90% of V̇O2max (W90%) until exhaustion. During W68%, cyclists consumed a placebo water drink (PLA) the first time and a carbohydrate drink (CHO), 1 g carbohydrate·kg−1·h−1, the second time. The participants performed the same amount of work under the two conditions, separated by at least 1 wk. A standardized diet was provided to the participants so that the two conditions were isoenergetic. To test the impact of carbohydrates on recovery, participants completed a time trial (TT) the next day.

Results
Carbohydrate ingestion maintained carbohydrate availability during W68% and W90%: total carbohydrate oxidation was significantly higher in CHO (P = 0.022), and plasma glucose concentration was maintained compared with PLA (P = 0.025). Next-day performance during TT was better after CHO ingestion (CHO, 41:49 ± 1:38 min; PLA, 42:50 ± 1:46 min; P = 0.020; effect size d = 0.23, small), as was gross efficiency (CHO, 18.6% ± 0.3%; PLA, 17.9% ± 0.3%; P = 0.019). Urinary nitrogen excretion (P = 0.897) and urinary 3-methylhistidine excretion (P = 0.673) did not significantly differ during the study period. Finally, tyrosine and phenylalanine plasma concentrations increased in PLA but not in CHO (P = 0.018).

Conclusions
Carbohydrate ingestion during exhaustive exercise reduced deterioration in next-day performance through reduced metabolic stress and development of fatigue. In addition, some parameters point toward less protein degradation, which would preserve muscle function.
The Impact of Exercise Training and Supplemental Oxygen on Peripheral Muscles in Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial
Authors: NEUNHÄUSERER DANIEL , HUDELMAIER MARTIN , NIEDERSEER DAVID , VECCHIATO MARCO , WIRTH WOLFGANG , STEIDLE-KLOC EVA , KAISER BERNHARD , LAMPRECHT BERND , ERMOLAO ANDREA , STUDNICKA MICHAEL , NIEBAUER JOSEF 
Published: August 2023

ABSTRACT

Objective
Exercise training is a cornerstone of the treatment of chronic obstructive pulmonary disease, whereas the related interindividual heterogeneity in skeletal muscle dysfunction and adaptations are not yet fully understood. We set out to investigate the effects of exercise training and supplemental oxygen on functional and structural peripheral muscle adaptation.

Methods
In this prospective, randomized, controlled, double-blind study, 28 patients with nonhypoxemic chronic obstructive pulmonary disease (forced expiratory volume in 1 second, 45.92% ± 9.06%) performed 6 wk of combined endurance and strength training, three times a week while breathing either supplemental oxygen or medical air. The impact on exercise capacity, muscle strength, and quadriceps femoris muscle cross-sectional area (CSA) was assessed by maximal cardiopulmonary exercise testing, 10-repetition maximum strength test of knee extension, and magnetic resonance imaging, respectively.

Results
After exercise training, patients demonstrated a significant increase in functional capacity, aerobic capacity, exercise tolerance, quadriceps muscle strength, and bilateral CSA. Supplemental oxygen affected significantly the training impact on peak work rate when compared with medical air (+0.20 ± 0.03 vs +0.12 ± 0.03 W·kg−1, P = 0.047); a significant increase in CSA (+3.9 ± 1.3 cm2, P = 0.013) was only observed in the training group using oxygen. Supplemental oxygen and exercise-induced peripheral desaturation were identified as significant opposing determinants of muscle gain during this exercise training intervention, which led to different adaptations of CSA between the respective subgroups.

Conclusions
The heterogenous functional and structural muscle adaptations seem determined by supplemental oxygen and exercise-induced hypoxia. Indeed, supplemental oxygen may facilitate muscular training adaptations, particularly in limb muscle dysfunction, thereby contributing to the enhanced training responses on maximal aerobic and functional capacity.