bluuebunny/crossref_metadata_2025 huggingface dataset:
Adoption of improved wheat production technology in Gorche district, Ethiopia
Authors: Atinafu Aklilu , Lejebo Messeret , Alemu Abera
Published: January 2022

Background

Ethiopia is a major producer of cereals and the largest wheat producer in sub-Saharan Africa. The wheat sub-sector is strategic for the Government of Ethiopia, where wheat has several food uses which can be prepared in modern or culturally processed techniques. Crop production and productivity including wheat is a function of all the recommended technology packages not only variety. Adoption of all recommended production technologies play a significant role in improving wheat production and productivity which in turn has clear implication on food security of Ethiopia and welfare of the farmers. Recent studies conducted focused on adoption of only single technology, primarily variety adoption, without considering its associated production technologies. Therefore, this study attempts to identify the major factors determining adoption of improved wheat (Shorma, Degelu, Danda and Kakawa) production technologies in Gorche district, Ethiopia.

Methodology

The finding of this study is based on primary data collected from 150 randomly selected households and secondary data collected from literature review. Primary data were collected from these respondents using structured and semi-structured interviews. Tobit model was applied to identify factors affecting the adoption and intensity of adoption of improved wheat production technology in the study area.

Result

The results of tobit model showed that land holding, annual income, level of education, membership in social organizations, access to credit, and positive attitude toward improved wheat production technology positively and significantly influence the adoption and intensity of adoption of the improved wheat production technology. On the other hand, age and market distance significantly and negatively impact adoption and intensity of adoption of the improved wheat production technology.

Conclusion

Adoption and intensity of adoption of improved wheat production technology is a function of socio-economic, demographic, farmer’s attitude and institutional factors. The policy relevance of our findings is that investment in education, strengthening social capital through available local social networks, provision of attitude-focused training and continuous technical support on improved wheat production technologies, improving income, expanding access to credit and market are important to facilitate adoption of improved wheat production technologies. Hence, addressing constraints associated with credit and market access, improvement in income, attitudes of farmers towards improved technology would improve the adoption and intensity of adoption of improved wheat production technologies.
Economic analysis and food security contribution of supplemental irrigation and farm ponds: evidence from northern Burkina Faso
Authors: Zongo Beteo , Barbier Bruno , Diarra Abdoulaye , Zorom Malicki , Atewamba Calvin , Combary Omer S. , Ouédraogo Souleymane , Toé Patrice , Hamma Yacouba , Dogot Thomas
Published: January 2022

Background

Dry spells are serious obstacles to rainfed agriculture in Sahelian countries. Various water harvesting techniques are used by farmers to reduce the impact of climate variability, but are not sufficient in the case of a prolonged drought lasting 2–3 weeks. The farmers believe supplemental irrigation is a good way to adapt rainfed agriculture to dry spells. In this study, we evaluated the food contribution and profitability of supplemental irrigation of rainfed crops comparing various farm ponds that collect runoff water from the surrounding landscape.

Methods

We analyzed the contribution of supplemental irrigation to food security and compared the profitability of different types of ponds constructed by farmers in northern Burkina Faso. Human cereal requirement was used as indicators to analyze the contribution of supplemental irrigation to food security. The criteria for analyzing the profitability of the selected ponds were gross margin (GM), net present value (NPV), internal rate of return (IRR) and payback period (PBP).

Results

Our results show that the additional yield of corn obtained with supplemental irrigation makes it possible to meet the monthly cereal needs of at least 17 people and generates an additional GM of FCFA 178,483 (US$ 309.26) compared to no irrigation. The estimate of the NPV, from IRR and PBP showed that the profitability of supplemental irrigation in 15 agricultural seasons varies between the type of ponds constructed.

Conclusions

Given the up-front cost and the farmers’ lack of resources, the ponds require a subsidy or a credit policy to facilitate the adoption of supplemental irrigation in Sahelian countries. However, the irrigation strategies to optimize agricultural income remain a field of research to be explored.
Metabolite-based dietary supplementation in human type 1 diabetes is associated with microbiota and immune modulation
Authors: Bell Kirstine J. , Saad Sonia , Tillett Bree J. , McGuire Helen M. , Bordbar Sara , Yap Yu Anne , Nguyen Long T. , Wilkins Marc R. , Corley Susan , Brodie Shannon , Duong Sussan , Wright Courtney J. , Twigg Stephen , de St Groth Barbara Fazekas , Harrison Leonard C. , Mackay Charles R. , Gurzov Esteban N. , Hamilton-Williams Emma E. , Mariño Eliana
Published: January 2022

Background

Short-chain fatty acids (SCFAs) produced by the gut microbiota have beneficial anti-inflammatory and gut homeostasis effects and prevent type 1 diabetes (T1D) in mice. Reduced SCFA production indicates a loss of beneficial bacteria, commonly associated with chronic autoimmune and inflammatory diseases, including T1D and type 2 diabetes. Here, we addressed whether a metabolite-based dietary supplement has an impact on humans with T1D. We conducted a single-arm pilot-and-feasibility trial with high-amylose maize-resistant starch modified with acetate and butyrate (HAMSAB) to assess safety, while monitoring changes in the gut microbiota in alignment with modulation of the immune system status.

Results

HAMSAB supplement was administered for 6 weeks with follow-up at 12 weeks in adults with long-standing T1D. Increased concentrations of SCFA acetate, propionate, and butyrate in stools and plasma were in concert with a shift in the composition and function of the gut microbiota. While glucose control and insulin requirements did not change, subjects with the highest SCFA concentrations exhibited the best glycemic control. Bifidobacterium longum, Bifidobacterium adolescentis, and vitamin B7 production correlated with lower HbA1c and basal insulin requirements. Circulating B and T cells developed a more regulatory phenotype post-intervention.

Conclusion

Changes in gut microbiota composition, function, and immune profile following 6 weeks of HAMSAB supplementation were associated with increased SCFAs in stools and plasma. The persistence of these effects suggests that targeting dietary SCFAs may be a mechanism to alter immune profiles, promote immune tolerance, and improve glycemic control for the treatment of T1D.

Trial registration

ACTRN12618001391268. Registered 20 August 2018,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375792
Correction to: Human microbiota research in Africa: a systematic review reveals gaps and priorities for future research
Authors: Allali Imane , Abotsi Regina E. , Tow Lemese Ah. , Thabane Lehana , Zar Heather J. , Mulder Nicola M. , Nicol Mark P.
Published: January 2022

An amendment to this paper has been published and can be accessed via the original article.
General digital competences of beginning trainees in commercial vocational education and training
Authors: Findeisen Stefanie , Wild Steffen
Published: January 2022

Against the background of digital transformation processes that are currently changing the world of work, this paper examines general digital competences of beginning trainees in commercial vocational education and training (VET) programs. We are particularly interested in factors influencing digital competence profiles. From survey data including N = 480 trainees in one federal state in Germany, we were able to identify three different competence profiles (based on the trainees’ self-assessment of their general digital competence). Initial descriptive analysis reveals differences between competence profiles of different training professions (industrial clerks and retail salespersons reach higher competence levels than salespersons). However, regression results indicate that these differences can be explained by differences in school leaving certificates. Contrary to prior empirical evidence, we find no significant effect of trainees’ gender. Finally, the frequency of certain private digital activities (e.g. using office programs, conducting internet searches) affects digital competence profiles. Implications for both VET programs and further research are discussed.
Field evaluation of the entomopathogenic fungi enriched with organic amendments against Holotrichia consanguinea Blanchard (Coleoptera: Scarabaeidae) infesting groundnut crop
Authors: Patel Prakash S. , Deb Sushma , Rabari Prakash H. , Joshi Manishkumar J.
Published: January 2022

Background

White grubs are highly polyphagous and most destructive soil pests inflicting damage to a groundnut crop that causes economic yield losses in commercial groundnut production in India. In this study, potential of the two entomopathogenic fungi (EPF) viz., Metarhizium anisopliae (Metchnikoff) Sorokin and Beauveria bassiana (Balsamo) Vuillemin enriched with organic amendments like neem cake, castor cake, vermicompost and poultry manure was evaluated to manage buildup of white grub population in groundnut crop.

Results

Results showed that the plot treated with soil application of vermicompost @ 1 ton/ha + M. anisopliae 1.15 WP (1 × 108 cfu/g) @ 2 kg/ha showed the least amount of plant mortality due to white grub which was at par with castor cake @ 1 ton/ha + M. anisopliae 1.15 WP (1 × 108 cfu/g) @ 2 kg/ha and neem cake @ 1 ton/ha + M. anisopliae 1.15 WP (1 × 108 cfu/g) @ 2 kg/ha which showed only 1.74, 2.00 and 2.24% plant damage, respectively. Plots treated with vermicompost @ 1 ton/ha + M. anisopliae 1.15 WP (1 × 108 cfu/g) @ 2 kg/ha had the fewest (0.19) white grubs per one meter row length. Based on highest pod yield, net realization and net gain, the treatment with soil application of vermicompost @ 1 ton/ha + M. anisopliae 1.15 WP (1 × 108 cfu/g) @ 2 kg/ha was found most effective treatments for the management of white grub in groundnut.

Conclusions

Results indicated that M. anisopliae supplemented with various organic amendments, such as vermicompost, castor cake, and neem cake can be commercialized as a healthy alternative to minimize the use of synthetic pesticides in groundnut crops for white grub management.
Carbon-based nanomaterials engineered cement composites: a review
Authors: Lu Dong , Zhong Jing
Published: January 2022

Carbon-based nanomaterials (CNMs) have been extensively used to modify cement matrix thanks to their extraordinary specific surface area, high aspect ratio, and high strength and modulus. This review focuses on the current status of research on CNMs modified cement composites, especially the progress made in the past decade (from 2011 to 2021). At first, the primary properties of typical CNMs used for manufacturing cement composites, the treatments used to effectively disperse CNMs in water and cement matrix, and the corresponding characterization methods are reviewed. And then, the effects of introducing CNMs on the properties of cement composites (both fresh and hardened) are also discussed in this work. Finally, the knowledge gaps and remaining challenges for future work are discussed.
In-depth 3D magnetic inversion of basement relief
Authors: Santos Darcicléa F. , Silva Joao B. C. , Lopes Jozinei F.
Published: January 2022

We have developed an iterative, efficient, and stable 3D magnetic inversion method to estimate the depth to the basement of a sedimentary basin, the volume of which is approximated by a grid of rectangular prisms with tops at an arbitrary surface and thicknesses estimated iteratively. To compute the thicknesses corrections at the kth iteration, we first compute an approximate sparse sensitivity matrix in which the nonnull elements of a given line are obtained by differentiating the fitting function at the observation position (which occupies the center of a small moving data window) relative to the thicknesses of the prisms situated inside the window. By moving the data window around, all nonnull elements of all lines are computed. This sparse matrix is used to calculate an approximate Gauss-Newton gradient and an approximate diagonal Gauss-Newton Hessian matrix. Finally, by dividing each element of the gradient vector by the corresponding diagonal element of the approximate Hessian matrix, we obtain the corrections of all parameters at a given iteration. The solution is stable because of (1) the small parameter corrections inherent to the method, combined with the initial estimate at the surface and (2) the application of a moving average operator to the solution. Any magnetization orientation, except horizontal (and parallel to any vertical side of the prisms), yields good results. In the case of magnetization inclinations of approximately 45°, the rectangular prisms may induce spurious ripples on the surface of the estimated relief, which can be eliminated by simultaneously reducing the horizontal dimensions of the prisms and applying an appropriate moving average to the solution. Application of our method to real data in a rift area discloses a confined basin with steep and asymmetric borders, confirming the practical utility of the method.
Overburden-borne internal demultiple formula
Authors: Dukalski Marcin , de Vos Koos
Published: January 2022

Imaging targets buried under highly reflective overburdens might require removal of a substantial amount of internal multiples. However, existing data-driven internal demultiple methods are either not accurate, not very user friendly, or both, as they (1) (only) kinematically predict only some of the multiples, (2) allow for false predictions (multiples leakage), (3) require primary-harming adaptive filtering, (4) can be computationally expensive or require user intervention, (5) require other than reflection data nontrivial inputs, and/or (6) the output cannot be readily quality controlled. We have developed a unifying surface-related multiple estimation/elimination (SRME)-like macrolayer internal demultiple algorithm, which addresses these issues and accurately eliminates all overburden-borne internal multiples. We find that the leading order terms of our formula correspond to some well-known approaches. This strongly suggests that the main benefit of using the Marchenko-equation-based methods comes from higher order terms, which provide transmission amplitude correction and suppress unphysical events predicted by lower order terms. We illustrate the efficacy of our formula with a numerical example, use it to identify outstanding limitations, and suggest some practical solutions to them. We also show that this approach is sufficiently general to be relatively easily extended to include, e.g., viscoelastic effects.
Are two too many when it comes to the treatment of anal canal cancer with concurrent radiation and mitomycin C?
Authors: Al Habsi Zainab , Abraham Aswin George , Al Balushi Mustafa , Tankel Gabriella , Mulder Karen E. , Warkentin Heather , Schiller Dan E. , Tankel Keith , Usmani Nawaid , Severin Diane , Paulson Kim , Karachiwala Hatim , Wong Clarence K. W. , Nijjar Tirath , Joseph Kurian
Published: January 2022

3

Background: Concurrent chemoradiation (CRT) with 2 doses of 5-fluorouracil (5-FU) and mitomycin C (MMC) is the standard of care for anal canal cancer (ACC) in North America while 1 dose of MMC is an acceptable practice. Given the lack of randomized data of 1 vs 2 doses of MMC on disease outcomes, we have conducted a population-based study to elucidate the impact of 1 vs. 2 doses of MMC on patterns of treatment failure (POF) and outcomes in ACC treatment. Zainab Al Habsi, Aswin Abraham, Mustafa Al Balushi, Gabriella Tankel, Karen Mulder, Heather Warkentin, Dan Schiller, Keith Tankel, Nawaid Usmani, Diane Severin, Kim Paulson, Hatim Karachiwala, Clarence Wong, Tirath Nijjar, Kurian Joseph. Methods: Data was collected from the provincial cancer registry of patients with stage I-III ACC who were treated with concurrent CRT from 2000 to 2018. Recurrence free survival (RFS), overall survival (OS), and ACC specific survival were calculated. Results: 428 patients with a median age of 58 years (29-88 years) were included in this analysis. 234 (54.7%) patients received 1 dose of MMC and 194 (45.3%) received 2 doses of MMC. At a median follow-up of 78.5 months (5-252 months), 89 (20.8%) patients developed disease recurrence: 44 (10.3%) loco-regionally, 39 (9.1%) distally and 6 (1.4%) had both local and distant recurrences. Cox Regression analysis showed that the dosage of MMC did not have an impact on overall recurrence (HR = 0.883, p = 0.561), whereas stage III was associated with increased risk for recurrence (HR = 5.238, p = 0.021). Subgroup analysis showed an association of stage IIIb and IIIc with recurrence (HR = 13.33, p = 0.008 and HR = 6.933, p = 0.011 respectively), but was not impacted by the use of 1 vs. 2 doses of MMC. The dosage of MMC did not show any association with local recurrence (HR = 1.136, p = 0.655) or distant recurrence (HR = 0.743, p = 0.267). However, in Stage IIIc patients, 2 doses of MMC showed a trend towards improved distant RFS (HR = 0.626,p = 0.084). Conclusions: Our analysis showed that the patterns of failure and the risk of loco-regional and distant failures were similar between patients who received 1 vs. 2 doses of MMC for stage groups I to IIIc. These finding support routine use of single dose of MMC along with 5FU and radiotherapy for definite chemoradiation. However, a trend towards better RFS was demonstrated with a second dose of MMC in patients with stage IIIc disease.
Circulating tumor DNA-based molecular residual disease detection and recurrence monitoring in patients with advanced or metastatic anal squamous cell carcinoma.
Authors: Azzi Georges , Tavallai Mehrad , Botta Gregory P. , Tejani Mohamedtaki Abdulaziz , Hanna Diana L. , Jurdi Adham Adel , Budde Griffin , Krinshpun Shifra , Maninder Minu , Aushev Vasily N. , Olshan Perry , Billings Paul R. , Aleshin Alexey , Kasi Pashtoon Murtaza
Published: January 2022

6

Background: For patients with anal squamous cell carcinoma (ASCC), the current standard of care involves curative-intent definitive chemoradiation. For those that recur locally, salvage surgery maybe a consideration. ASCC, however, still lacks a non-invasive blood-based biomarker, which can be of value in this patient population for monitoring recurrence and/or response to immunotherapy later. Circulating tumor DNA (ctDNA) is a promising non-invasive tool to assess molecular residual disease (MRD) and recurrence in ASCC. Here, we evaluated real-world utility of ctDNA status to identify MRD and recurrence in ASCC patients across all stages. Methods: This is a retrospective analysis of patients with any stage ASCC receiving SOC or/and immunotherapy with immune checkpoint inhibitors. A personalized tumor-informed PCR/NGS-based assay (Signatera) was used for ctDNA detection, in the pre/on/post-treatment and surveillance setting. Results: In this study, plasma samples (n=105) were collected from 25 ASCC patients (13 females, 12 males; median age 66 years) at various timepoints for a median follow-up of 315 days (range: 59-1717), post-diagnosis; 12 patients were HPV-positive, 1 patient was HPV-negative, and 12 had unknown HPV status; 88% (22/25) of the patients had serial timepoints (≥2) available. ctDNA-positivity rates, test results, and ctDNA quantification by stage are summarized in Table. The quantitated ctDNA values (mean tumor molecules (MTM)/mL) increased in concordance with the stage of the disease, with values trending higher in stage III and IV. In addition, complete clinical outcome information was available for 22/25 patients at the time of releasing this data. Of the 96 plasma samples drawn from these patients, 68 (70%) were in the surveillance setting (post-definitive therapy). No recurrences were observed among 15 patients who cleared ctDNA on treatment and/or tested negative post-treatment, whereas, 6/7 ctDNA-positive patients were confirmed to have disease recurrence and 1 was pending confirmatory imaging. This often predated recurrence on scans. Conclusions: Measuring and monitoring MRD in patients with ASCC is feasible and has the potential to impact clinical decision making. Our study is the first to set the benchmark for the feasibility of using a tumor-informed assay in ASCC. Larger prospective studies are needed to explore the clinical utility of ctDNA status to guide disease surveillance and management of ASCC.[Table: see text]
Phase I/II trial of encorafenib, cetuximab, and nivolumab in patients with microsatellite stable, BRAFV600E metastatic colorectal cancer.
Authors: Morris Van K. , Parseghian Christine Megerdichian , Escano Michelle , Johnson Benny , Raghav Kanwal Pratap Singh , Dasari Arvind , Huey Ryan , Overman Michael J. , Willis Jason , Lee Michael Sangmin , Wolff Robert A. , Kee Bryan K. , Shen John Paul Y.C. , Morelli Maria Pia , Tam Alda , Foo Wai Chin , Xiao Lianchun , Kopetz Scott
Published: January 2022

12

Background: Encorafenib (E) and cetuximab (C) offers short-lived response and survival benefit for patients (pts) with MSS, BRAFV600E metastatic colorectal cancer (CRC). BRAF + EGFR inhibition induced a transient MSI-H phenotype in preclinical models of MSS, BRAFV600E CRC and may prime these tumors for response to immunotherapy with anti-PD-1 antibodies like nivolumab (N). Methods: In this single-arm, single-institution, phase I/II clinical trial, pts with treatment-refractory MSS, BRAFV600E metastatic CRC were eligible. No prior BRAF inhibitors, anti-EGFR antibody, or immunotherapy was permitted. Pts received E (300 mg PO daily), C (500 mg/m2 IV q14 days), and N (480 mg IV q28 days). The primary endpoints were best overall response (RECIST 1.1) and safety/tolerability (CTCAE v5). A Simon two-stage design (H0: p≤.22; Ha: p≥.45, where p= percentage of pts with radiographic response) was employed using a one-sided α=.05 and β=.20. In the first stage, ≥ 4/15 responses were needed in order for the trial to enroll 11 additional pts. Median progression-free survival (PFS) and overall survival (OS) were estimated via Kaplan-Meier. Results: All 26 pts have been enrolled - 23 patients treated, and 21 evaluable for response so far. Median age is 59 years (range, 32-85), and 14 (54%) are female. No dose-limiting toxicities occurred. Grade 3-4 treatment-related adverse events (AE) occurred in 4/22 (18%) patients. Grade 3 AEs included colitis, maculopapular rash, leukocytosis, and elevated amylase/lipase (all N=1). Grade 4 AEs in a single patient were myositis/myocarditis. Overall response rate is 45% (95% CI, 23-68), and disease control rate is 95% (95% CI, 75-100). Median PFS is 7.3 months (95% CI, 5.5-NA). Median OS is 11.4 months (95% CI, 7.6-NA). For the 9 pts thus far with responses, median duration of response is 8.1 months (95% CI, 7.3-NA). Updated results will be presented. Conclusions: E + C + N is effective and well-tolerated for pts with MSS, BRAFV600E metastatic CRC. The E+C+N regimen met its predefined efficacy endpoint and suggests a role for immunotherapy as a novel combination approach for this specific subpopulation of MSS metastatic CRC. A follow-up randomized phase II trial (SWOG 2107) to evaluate encorafenib/cetuximab with or without nivolumab in pts with MSS, BRAFV600E metastatic CRC will activate in early 2022. Clinical trial information: NCT04017650.
Colorectal cancer incidence in Texas border versus non-border counties.
Authors: LaPelusa Michael Brian , Machiorlatti Michael
Published: January 2022

21

Background: There are 32 counties and 2.8 million people in the Texas border region. The population is 88.4% Hispanic with estimates that 47% lack health insurance - not including non-US citizens, who are more likely to lack health insurance than US citizens. In 2014, 7 of the 20 US counties with the lowest CRC screening rates were in Texas, 6 of which were Texas border counties. It is unknown how the incidence of CRC in Texas border counties has changed over time compared to non-border counties. In this study, we investigate changes in the incidence of CRC in Texas border counties between 2000 and 2017. Methods: Data were obtained from the Texas Department of State Health Service’s Texas Cancer Registry. Cases of patients aged 18 or older between 2000 and 2017 were included in our analysis. Cases were excluded if they contained incomplete information regarding age, sex, year of diagnosis, site of diagnosis or poverty level. Simple descriptive statistics were calculated for all covariates. Chi-square tests of independence were created to examine the association between each categorical variable and border county status. Age-adjusted incidence rates (AAIR) were created for the state overall and by border status. SAS v9.4 was used for all data analysis. Results: In border counties from 2000 to 2017, the overall AAIR decreased from 65.9 (per 100,000) to 56.7. In those 50-64 years old and 65 years and older residing in border counties, the AAIR increased from 63.3 to 78.1 and decreased from 244 to 176.1, respectively. In non-border counties from 2000 to 2017, the overall AAIR decreased from 85.2 (per 100,000) to 57.3. In those 50-64 years old and 65 years and older residing in non-border counties, the AAIR decreased from 94.9 to 78.0 and from 303 to 168.5, respectively. Conclusions: The overall AAIR of CRC was lower in Texas border counties compared to non-border counties, which is likely a consequence of lower screening rates in border counties. The overall AAIR decreased at a slower rate in Texas border counties compared to non-border counties, which may represent lower rates of utilization of CRC screening over time in border counties. The increase in the AAIR among those 50-64 years old in Texas border counties warrants further investigation.
Detection of minimal residual disease (MRD) in colorectal cancer (CRC) patients UICC stage II/III by ultra-deep sequencing of cfDNA from post-surgery plasma.
Authors: McNamara Sylvie , Patel Rajesh D. , Adams Hans-Peter , Qu Xueping , Hinzmann Bernd , Wong Cheryl V , Heilek Gabrielle , Mantke Renè , Heise Michael , Steinmüller Thomas , Pross Matthias , Marusch Frank , Bais Carlos , Palma John F.
Published: January 2022

26

Background: Detection of primary tumor mutations in cell-free DNA (cfDNA) of post-surgery plasma of patients with R0-resected not-metastasized solid tumors is a strong indicator of recurrence of disease. We explored whether ultra-deep sequencing of cfDNA could improve sensitivity and specificity with respect to time-to-progression. Methods: 84 CRC patients UICC stage II/III were recruited into the prospective, observational study “Molecular Signatures in Colorectal Cancer”. Matched tumor tissue samples, plasma depleted blood cells (PDBC), and cfDNA (drawn 1 to 34 days after R0-resection, median 7 days) were processed with the Roche AVENIO Tumor Tissue and ctDNA Surveillance Kits*. Samples of 79 patients passed all quality controls, in particular cfDNA was sequenced ultra-deep with a median of 180 Mio. instead of 50 Mio. reads/sample. Somatic variants were identified with AVENIO Oncology Analysis software 2.0*. PDBC informed germline variants were removed. If a tissue baseline variant was detected in cfDNA with a significant adjusted p-value, the patient was defined ctDNA+, and ctDNA- otherwise. Results: 8 ctDNA+ patients (28 variants, median AF = 0.15%) were identified of which 4 had a progression of disease at two years. Sensitivity was 44% (95% CI [0.137, 0.788]), specificity was 94% (95% CI [0.86, 0.984]), positive predictive value was 50% (95% CI [0.157, 0.843]), and negative predictive value was 93% (95% CI [0.843, 0.977]). Comparison of time-to-progression of ctDNA+ and ctDNA- patients using the log-rank test resulted in a p-value of 0.0058. Comparison of survival times of ctDNA+ and ctDNA- patients resulted in a p-value of 0.0333. Multivariate analyses of times-to-progression resulted in ctDNA-status (p = 0.0022, hazard ratio (HR) = 7.098) and neoadjuvant therapy (p = 0.0010, HR = 6.618) as significant parameters. Conclusions: Even in this small cohort of CRC UICC stage II/III patients, MRD detection in post-surgery plasma is the strongest predictor of shorter time to progression. Ultra-deep sequencing of cfDNA samples did not influence MRD detection on a patient-level. *for Research Use Only; not for use in diagnostic procedures.
Colorectal cancer conversations on Twitter: A content analysis of global perceptions and outreach efforts.
Authors: Chu Alexander L. , Patel Vishal R. , Blanton Christopher J. , Gereta Sofia , Mackert Michael , Nortje Nico , Pignone Michael
Published: January 2022

35

Background: Screening is highly effective at reducing colorectal cancer (CRC) mortality. Social media is extensively used to communicate about cancer care, yet little is known about the role of these online platforms in promoting CRC screening and early diagnosis. This study tracked Twitter discussions about CRC and characterized participating users to better understand public communication and perceptions of CRC on social media. Methods: Tweets containing references to CRC were collected from January 2020 to April 2021 using Twitter’s Application Programming Interface. Account metadata was used to predict user demographic information and classify users as either organizations, individuals, or influencers. Influencers represent high-impact users, defined by sizeable follower counts or verified Twitter status. Latent Dirichlet Allocation, a natural language processing model, was used to identify observed topics of discussion in the collected tweets. Results: There were 72,229 unique CRC-related tweets by 31,170 users. Tweets reached a daily maximum after Chadwick Boseman, a well-known American actor, died from CRC. Individuals accounted for the majority of users (62.8%); organizations (35.2%); influencers (2%). Influencers made the most median impressions (35,853 impressions). Tweets contained the following topics: bereavement (27.9%), appeals for early detection (19.4%), research (14.0%), National Colorectal Cancer Awareness Month (NCCAM) (13.7%), screening access (12.5%), and risk factors (12.4%). Tweets referencing bereavement had the most user engagement. Links to clinical trial enrollment information were the least shared type of embedded content (0.3%). Conclusions: Discussions about CRC largely focused on bereavement and early detection. Online coverage of NCCAM, personal experiences, and celebrity deaths related to CRC effectively stimulated goal-oriented tweets about early detection. Our findings suggest that Twitter may be a suitable platform for promoting and communicating future public health recommendations about CRC.
Real-world persistence and adherence with oral trifluridine/tipiracil or regorafenib in patients with colorectal cancer.
Authors: Braiteh Fadi S. , Girman Cynthia J. , Young Jessica C. , Danese Mark D. , Irwin Debra E. , Kazerooni Reza , Salimi Tehseen , Morlock Robert , Epstein Robert S.
Published: January 2022

49

Background: Trifluridine/tipiracil (FTD/TPI) and regorafenib are among the limited treatment options in later lines of therapy for patients with advanced colorectal cancer (CRC). While these treatments have demonstrated similar efficacy, differences have been observed in tolerability and data on the impact of such differences on real-world outcomes are limited. To better understand the real world use of FTD/TPI and regorafenib in the US, we report data for adherence/persistence among patients with CRC initiating these therapies. Methods: This was a retrospective cohort study among adults with CRC identified from the IBM MarketScan Commercial Claims and Medicare Supplemental Databases, who initiated FTD/TPI or regorafenib (index) from October 2015-September 2019 and had 6 months of continuous enrollment before the index date. Follow-up was until disenrollment or end of study period. Treatment cohorts were propensity score 1:1 matched, adjusting for differences in socio-demographics, comorbidities, and other baseline characteristics. Adherence and persistence outcomes included time to discontinuation (medication gap of >45 days), medication possession ratio (MPR; number of treated days/ duration of treatment), proportion of days covered (PDC; number of treated days/ days in specified time period), and number of prescriptions received. Results: A total of 1477 patients were included: 892 initiating FTD/TPI (60%) and 585 regorafenib (40%). Demographics were similar prior to matching: mean age was 58 and 59 years, and 57% and 59% were male, in the FTD/TPI and regorafenib groups, respectively. Mean Charlson Comorbidity Index score (excluding cancer) was 0.69 for FTD/TPI initiators and 0.62 for regorafenib initiators. For the matched cohorts (n=585 in each), measures of adherence and persistence (Table) showed longer time to discontinuation (2.5 vs. 2.0 months; p<0.01), and a higher MPR (0.90 vs. 0.87; p<0.01), PDC (at 3 months, 0.74 vs. 0.63; p<0.01), and proportion of patients receiving ≥2 prescriptions (76% vs. 63%; p<0.01) with FTD/TPI vs. regorafenib. Conclusions: Results of this real-world study suggest that patients with CRC initiating FTD/TPI have improved adherence and persistence with therapy compared with those initiating regorafenib. Reasons for this difference and potential impacts on health outcomes require further study. [Table: see text]
Long-term survival outcomes following resection of lung metastases (LM) from a colorectal primary.
Authors: Ramanujam Sangeetha , Dunn Catherine , Antippa Phillip , Kosmider Suzanne , To Yat Hang , Lee Margaret , Wong Vanessa , Caird Susan , Shapiro Jeremy David , McKendrick Joseph James , Wong Hui-Li , Ma Brigette , Lim Stephanie Hui-Su , Torres Javier , Zimet Allan Solomon , Lee Belinda , Gibbs Peter
Published: January 2022

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Background: Liver metastatectomy in oligometastatic colorectal cancer (CRC) can result in long-term disease control1. The benefit of resecting LM is unclear, with good survival outcomes from medical therapy (MT) alone and a recent randomised controlled trial failed to demonstrate an overall survival (OS) benefit2. Methods: We examined TRACC (Treatment of Recurrent and Advanced Colorectal Cancer), a multisite registry for metastatic colorectal cancer (mCRC) patients (pts) from September 2002 – July 2021, focusing on the longer-term outcomes for pts with lung only metastatic disease (LOM). Key clinicopathological, treatment and outcome variables were analysed. Survival outcomes were determined by Kaplan-Meier method. Results: Of 3928 pts, 341 (8.7%) had LOM. The median OS was significantly improved for LOM vs. all mCRC pts (44.5 months vs. 24.8 months, p = <0.0001). Of 341 LOM pts, 142 (42%) had lung resection (LRes),128 (38%) had MT, 71 (20%) best supportive care. Key clinicopathological characteristics are summarised in Table. OS was significantly longer for LRes vs. MT (3yrs-80.1% vs. 41.9%, p = <0.0001, 5 yrs-65.2% vs. 21.1%, p = 0.0001). 10 yr survival for LRes was 50%, with no survivors from MT. The median palliative chemotherapy free interval was 13 months (95% CI 3.1 – 18.7) with recurrence after LRes/death. 20/142 (14%) of the LRes pts had recurrent LRes (median time to repeat resection of 11.4 months, median survival of 66.9 months from repeat LRes). Conclusions: LM from mCRC have an indolent course, with good survival outcomes with MT alone. LRes provides a clinically meaningful palliative chemotherapy free interval and long term survival in selected pts. Significant differences in prognostic factors may have contributed to the observed survival differences between LRes and MT. Reference Dexiang Z, Li R, Ye W, Haifu W, Yunshi Z, Qinghai y, Shenyong Z, Bo X, Li L, Xiangou P, Haohao L, Lehi Y, Tianshu L, Jia f, Xinyu Q, Jianmin X. Outcome of patients with colorectal liver metastasis: analysis of 1,613 consecutive cases. Ann Surg Oncol. 2012 Sep;19(9):2860-8. doi:10.1245/s10434-012-2356-9.Epub 2012 Apr 12. PMID: 22526903. Treasure, T., Farewell, V., Macbeth, F. et al. Pulmonary Metastatectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial. Trials   20,718 (2019). https://doi.org/10.1186/s13063-019-3837-y [Table: see text]
Analysis of survival trends, clinical, and molecular characteristics of patients with early-onset colorectal cancer (EOCRC).
Authors: Soto Javier , Gutiérrez Alonso Natalia , Bringas Beranek Marianela , Catoya Villa Juan Luis , Gutierrez Ortiz de la Tabla Ana , López Jiménez Carlos , Alva Bianchi Manuel , Jiménez Rodríguez Roberto , Martín Lozano Rocío , Arregui Valles Marta , Aparicio Salcedo Inmaculada , Ortega Morán Laura , Torres Pérez-Solero Gabriela , Muñoz Martín Andrés J. , Calvo Ferrándiz Aitana , Blanco Codesido Montserrat , Martínez Delfrade Íñigo , Juliao Caamaño David Salomon , Martin Miguel , Garcia-Alfonso Pilar
Published: January 2022

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Background: Over the last decades the incidence of EOCRC (age 50 or less) has dramatically increased, and so has the scientific interest in this field, given that clinical and molecular characteristics in these patients are not well understood, and may be critical to identify prognostic factors. Methods: We conducted a retrospective analysis of 554 patients with metastatic colorectal cancer (mCRC), analyzing the PFS and OS of 68 (12.25%) patients with EOCRC, as well as their clinical and molecular characteristics. We used a log-rank test to compare PFS and OS, and the estimate of hazard ratio (HR) between the studied groups was calculated by means of Cox proportional hazard model. We also used the exact test of Fisher to identify significant association between categoric variants, while Mann-Whitney test was applied to identify significant differences between numeric values. Results: We performed a survival analysis: those patients with EOCRC had significantly higher median PFS in first line of treatment (16.2 vs. 11.3 months, p = 0.042) and significantly higher median OS (121.5 vs. 58.1 months, p = 0.011). Several characteristics were significantly more frequent in patients with EOCRC (n=68): BMI < 18.5 (n = 16, OR = 1.9, p = 0.046), primary tumor site at transverse colon (n = 9, OR = 2.61, p = 0.03) and ECOG 0 (n = 32, OR = 2.21, p = 0.003). Having peritoneal metastases almost reached statistical signification (n = 17, OR = 1.82, p = 0.055). Some other characteristics were less frequent: BMI 25-30 (n = 13, OR = 0.51, p = 0.046), primary tumor site at sigmoid colon (n = 14, OR = 0.49, p = 0.038) and former-smoker status (n = 7, OR = 0.44, p = 0.048). Moreover, mean values of LDH at diagnosis were significantly higher in EOCRC patients (359 U/L vs. 280 U/L, p = 0.015). EOCRC patients received a significantly higher number of lines of chemotherapy (2.94 vs. 2.38, p = 0.027) and underwent more surgeries (2,42 vs. 1.24, p < 0,001) than patients with > 50 years. Significant differences in tumor mutational status (BRAF, KRAS, NRAS, MSI, PI3K and HER2), sex, primary tumor resection or number of metastatic sites between groups were not found. Conclusions: This retrospective analysis showed that EOCRC patients had significant higher rates of PFS in first-line treatment and OS. Moreover, EOCRC patients had more frequently BMI < 18.5, primary tumor located at transverse colon and ECOG 0.
Patterns of colorectal cancer (CRC) screening rates among the average risk U.S. population.
Authors: Fisher Deborah A , Engel-Nitz Nicole , Miller-Wilson Lesley-Ann , Le Lisa , Limburg Paul J.
Published: January 2022

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Background: There is consensus that the proportion of the average-risk US population up-to-date with CRC screening (58-65%) is insufficient. However, estimates of average risk CRC screening rates are inconsistent and impacted by inclusion of higher-risk individuals, and differing study designs. Accurate measurement of population screening rates is key to addressing gaps in care and assessing the impact of newer CRC screening tests. Methods: The study included individuals aged 50-75 years in a large de-identified claims database, with continuous enrollment during year of analysis, and a variable length baseline enrollment of 1-10 years. Average-risk designation excluded higher risk diagnoses (CRC familial syndromes, colorectal polyp or history of colorectal polyp, history of/current CRC, family history of gastrointestinal cancer, and inflammatory bowel disease). Up-to-date status was assessed within guideline-based time periods: colonoscopy (10 years); FIT or FOBT (annually); mt-sDNA (3 years); flexible sigmoidoscopy/CT colonography (5 years). Analyses assessed the proportion estimated as up-to-date and examined the sensitivity to: a) patient population (average-risk only vs. including higher-risk); b) study design (yearly cross-sectional vs. cohort of 50-year-old patients; c) methods (percent in patients with 10 years of enrollment vs. Kaplan Meier (KM) of censored variable pre-screening period). Results: The cross-sectional analysis average-risk population included 5.3 million individuals. Estimates of the proportion of those up-to-date with screening guidelines for average-risk patients varied by study design, population, and estimation method. KM estimates among the average-risk population (50-75) showed 49-50% were up-to-date in each calendar year. Including higher-risk patients in the KM analysis resulted in 70% up-to-date among the mixed average+higher-risk population. Using a cohort study design (average-risk patients aged 60 with 10 years of baseline data), 65% were up-to-date by age 60. Conclusions: In the base case analysis only half of average risk individuals were up-to-date with CRC screening, a rate lower than typically cited. Sensitivity analyses resulted in substantially different estimates and demonstrate the importance of clearly communicating the methodology used to define the study population. Higher rates quoted in the lay press and medical publications may be based on mixed populations of average+higher-risk individuals or on study designs that do not represent the full population at risk.
Pathogenic variants among Mexican patients with colorectal cancer referred for genetic cancer risk assessment.
Authors: Rodriguez Olivares Jose Luis , Chavarri Guerra Yanin , Arteaga Jazmin , De la Mora Molina Hector , Soto Perez De Celis Enrique , Candanedo Gonzalez Fernando , Rivero García Pamela , Castillo Danielle , Weitzel Jeffrey N.
Published: January 2022

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Background: Lynch syndrome (LS) is the most frequent hereditary cancer syndrome among patients with colorectal cancer. Screening tests such as immunohistochemistry (IHC) for mismatch repair (MMR) proteins and PREMM5 model help to identify patients at risk of germline pathogenic variants (PVs). However, there has been a disparity in that evaluation of these screening tools and their correlation with pathogenic variants (PVs) has been limited in Hispanic populations. Methods: Patients with colorectal cancer referred for genetic cancer risk assessment were enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) registry from October 2017 to February 2021 at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Genetic testing was performed by full sequencing of the MMR genes ( MLH1, PMS2, MSH2, MSH6 and EPCAM) and other cancer-associated genes ( APC, BRCA1, BRCA2, TP53, NF1, ATM, CHEK2, PALB2, BRIP1) and multiplex ligation dependent probe amplification to detect copy number variants (CNV) was performed for selected genes. Demographic, clinical characteristics and IHC results were obtained from clinical records. MMR PV probability was calculated using PREMM5. Results: Sixty-nine patients with colorectal cancer were included; mean age at diagnosis was 50 (26-82) years and 39/69 (56%) were women. A MMR gene PV was identified in 23/69 patients (33%); most frequently in MLH1 n = 14, followed by MSH2 n = 2, MSH6 n = 2 and PMS2 n = 1. Four recurrent PVs in MLH1 and MSH2 represented 22% of PVs. CNVs were identified in 4/23 (17.4%) patients with LS. PVs in other genes were identified in 8.6% of the cases: 2 ATM, 1 APC, 1 PALB2, 1 BRIP1 and 1 BRCA1. IHC results were available in 52/69 cases (75.4%) and MMR protein deficiency was found in 16/17 (94%) carriers and in 14/31 (45%) non-carriers (sensitivity 94.1% and specificity 54.8%). The area under the ROC curve for PREMM5 score was 0.94 (95% CI 0.88-0.99) with a mean score 31.6 (2.4-50) in patients with LS and 4.1 (0.9-50) in non-carriers. The diagnosis of a second primary colon cancer was more frequent among LS (30% vs 2.5%; p < 0.01). Conclusions: We found a high frequency of MMR gene PVs among patients referred for GCRA with personal history of colon cancer, and only a small proportion with PVs in other genes. Our results showed a good performance of PREMM5 model and a high sensitivity of MMR IHQ in a Mexican population, indicating that these are tools that can be used to prioritize patient selection for germline testing.
Pain among older adults diagnosed with gastrointestinal (GI) malignancies: Results from the cancer and aging resilience evaluation (CARE) registry.
Authors: Al Obaidi Mustafa , Kosmicki Sarah , Harmon Christian , Outlaw Darryl Alan , Gbolahan Olumide B. , Khushman Moh'd M. , Bhatia Smita , Giri Smith , Williams Grant Richard
Published: January 2022

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Background: The impact of pain on functional status and neuropsychological disorders among older adults with cancer is relevant, yet poorly understood. We sought to identify the prevalence of pain at diagnosis in older adults with GI malignancies and evaluate the association between pain and functional status limitations, cognition, and mental health issues. Methods: This study included patients diagnosed with cancer at age ≥60 years and enrolled in the CARE Registry at the University of Alabama at Birmingham (UAB). Patients completed a patient-reported geriatric assessment at their initial visit with a medical oncologist. Patients rated pain on a numeric scale from 0-10. We employed the literature-based cut off for moderate-severe pain of ≥4. Logistic regression modeling was used to determine the association between moderate/severe pain and functional status, falls, cognition, and depression/anxiety. We adjusted the models for sex, race, education, race/ethnicity, marital status, cancer type, and cancer stage. Results: Our cohort included 714 older adults. Median age at diagnosis was 70y (range 60-96) and 59% were male. Median time between diagnosis and study participation was 37 days. Most prevalent diagnoses included colorectal (27.9%), pancreatic (18%), hepatobiliary (11.5%) and gastroesophageal (6.4%) cancers. Overall, 53.1% of the participants reported none/mild (0-3) pain, 25.6% reported moderate (4-7) pain, and 21.4% reported severe (8-10) pain. In univariate analyses, Black patients, lower education, disabled employment, and pancreatic cancer was associated with moderate/severe pain. After multivariate adjusting for covariates, participants with moderate/severe pain were more likely to report limitations in instrumental activities of daily living (adjusted Odds Ratio [aOR] 4.3, 95% confidence interval [CI] 3.1-6.1, p <.001), limitations in activities of daily living (aOR 3.2, 95% CI 2.0-5.1, p <.001), falls (aOR 2.4, 95% CI 1.6-3.6, p <.001), cognitive complaints (aOR 2.9, 95% CI 1.4-6.0, p <.004), anxiety (aOR 2.2, 95% CI 1.4-3.4, p < 0.01), and depression (aOR 3.7, 95% CI 2.2-6.5, p <.001). Conclusions: Pain is common amongst older adults with GI cancers and is associated with functional status limitations, falls, cognitive complaints, and depression/anxiety. Strategies to reduce pain and/or minimize its potential impact on function and mental health warrant future research.