bluuebunny/crossref_metadata_2025_split huggingface dataset:
MERLIN_001: A prospective registry study of a primary melanoma gene-signature to predict sentinel node (SN) status and determine its prognostic value for more accurate staging of patients with SN-negative melanoma.
Authors: Hieken Tina J. , Egger Michael Earl , Angeles Christina Vadala , Lowe Michael C. , Burke Erin E. , Bartlett Edmund , Hyngstrom John Robert , Sondak Vernon K. 
Published: June 2022

TPS9606 Background: For patients with cutaneous melanoma, sentinel lymph node biopsy (SLNB) provides important staging and prognostic information that guides surveillance and adjuvant systemic therapy decisions. At most centers, SLNB is indicated for patients with cutaneous melanoma with at least a 5% risk of having nodal metastases, typically melanomas ≥ 0.8 mm in thickness or thinner lesions with high-risk features such as elevated mitotic rate and/or ulceration. SLNB, generally involving a separate incision, does carry a small but measurable risk of complications including seroma, infection and rarely lymphedema, and most patients have negative sentinel lymph nodes. Currently, there is an unmet clinical need to identify patients who may safely forgo SLNB due to a low (<5%) risk of nodal metastasis, who otherwise meet established criteria for SLNB. Previously, a model consisting of gene expression profile (GEP) of the primary tumor combined with clinicopathological features (CP) has been developed to identify melanoma patients with a low risk of having a positive SLNB. The model has also been validated in multiple retrospective studies. The aim of the MERLIN_001 registry study is to prospectively validate the CP-GEP model in an independent multicenter cohort of primary cutaneous melanoma patients who undergo SLNB for standard indications. Methods: In the next two years, a total of 10 centers across the US will enroll 2,340 patients with clinically node-negative cutaneous melanoma undergoing SLNB using current guideline indications and will follow these patients for 5 years (ClinicalTrials.gov identifier: NCT04759781). Enrollment of patients started in September 2021 and 242 patients have been enrolled as of February 1, 2022. FFPE material from the initial melanoma biopsy will be used to assess the GEP of the primary melanoma. The CP-GEP probability scores will be expressed as a binary classification (Low Risk or High Risk for nodal metastasis) and will be compared to SLN pathology. Performance metrics for CP-GEP will be evaluated and will include: Negative Predictive Value, Positive Predictive Value, Sensitivity and Specificity, and the corresponding 95% confidence intervals. Risk for nodal metastasis will be calculated for Low Risk and High Risk CP-GEP patients. Finally, the performance of CP-GEP to stratify patients according to risk of recurrence (local, regional, distant, death) will also be studied, since data will be collected for up to 5 yrs. Clinical trial information: NCT04759781.
Neo-adjuvant T-VEC plus nivolumab combination therapy for resectable early-stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: The NIVEC trial.
Authors: Rohaan Maartje W. , Zijlker Lisanne P. , Stahlie Emma H.A. , Franke Viola , Wilgenhof Sofie , van der Noort Vincent , Van Akkooi Alexander Christopher Jonathan , Haanen John B. A. G. 
Published: June 2022

TPS9607 Background: The prognosis of patients with melanoma is significantly correlated with disease stage and has greatly improved with the introduction of the currently approved therapies. Trials investigating neo-adjuvant treatment with immune checkpoint inhibitors (ICI) have shown high pathologic response rates up to 25-80%, however, still a large group of patients derive no (durable) clinical benefit. Treatment with talimogene laherparepvec (T-VEC), a modified herpes simplex virus type-1, is approved for patients with unresectable stage IIIB-IVM1a melanoma, with high and durable response rates and a mild toxicity profile. Earlier trials have suggested that T-VEC has the capacity to heighten the immune response and to elicit an abscopal effect in melanoma when given in combination with ICI. Combination ICI and intralesional T-VEC has already been investigated in patients with unresectable stage IIIB-IV disease, however, no data is available yet on the potential benefit of this combination therapy in neo-adjuvant setting. This is the first trial investigating the efficacy and safety of neo-adjuvant treatment of T-VEC in combination with nivolumab (anti-PD-1 antibody), followed by surgical resection in patients with resectable stage IIIB-IVM1a melanoma, with the potential of high pathologic response rates and acceptable toxicity. Methods: In this single center, single arm, phase II study, a total of 24 patients ≥18 years of age and a good clinical performance score with treatment naïve, stage IIIB-IVM1a melanoma (AJCC 8th edition) with injectable disease and resectable (sub)cutaneous satellite or in-transit metastases and/or tumor positive lymph nodes, will be included. Patients will receive four courses of T-VEC up to 4mL (first dose as seroconversion dose) and three doses of nivolumab (240mg flatdose) every two weeks, followed by surgical resection in week nine. The primary endpoint of this trial is pathologic response rate, with the aim to show a high major pathologic (near-complete or complete) response rate up to 45%. Secondary endpoints are safety according to CTCAE v5.0, the rate of delay of surgery and event free survival. Additionally, prognostic and predictive biomarker research and health-related quality of life evaluation will be performed. Enrollment started in June 2020 in the Netherlands Cancer Institute, with currently 13 of the 24 planned patients treated. Clinical trial information: NCT04330430.
Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma
Authors: Garcés Juan-Jose , Cedena Maria-Teresa , Puig Noemi , Burgos Leire , Perez Jose J. , Cordon Lourdes , Flores-Montero Juan , Sanoja-Flores Luzalba , Calasanz Maria-Jose , Ortiol Albert , Blanchard María-Jesús , Rios Rafael , Martin Jesus , Martínez-Martinez Rafael , Bargay Joan , Sureda Anna , de la Rubia Javier , Hernandez Miguel-Teodoro , Rodriguez-Otero Paula , de la Cruz Javier , Orfao Alberto , Mateos Maria-Victoria , Martinez-Lopez Joaquin , Lahuerta Juan-Jose , Rosiñol Laura , Blade Joan , San-Miguel Jesus F. , Paiva Bruno 
Published: June 2022

PURPOSE Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined. PATIENTS AND METHODS CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment. RESULTS CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS. CONCLUSION Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.
Cell-Free Tumor DNA Dominant Clone Allele Frequency Is Associated With Poor Outcomes in Advanced Biliary Cancers Treated With Platinum-Based Chemotherapy
Authors: Uson Junior Pedro Luiz Serrano , Majeed Umair , Yin Jun , Botrus Gehan , Sonbol Mohamad Bassam , Ahn Daniel H. , Starr Jason S. , Jones Jeremy C. , Babiker Hani , Inabinett Samantha R. , Wylie Natasha , Boyle Ashton W.R. , Bekaii-Saab Tanios S. , Gores Gregory J. , Smoot Rory , Barrett Michael , Nagalo Bolni , Meurice Nathalie , Elliott Natalie , Petit Joachim , Zhou Yumei , Arora Mansi , Dumbauld Chelsae , Barro Oumar , Baker Alexander , Bogenberger James , Buetow Kenneth , Mansfield Aaron , Mody Kabir , Borad Mitesh J. 
Published: June 2022

PURPOSEThis investigation sought to evaluate the prognostic value of pretreatment of circulating tumor DNA (ctDNA) in metastatic biliary tract cancers (BTCs) treated with platinum-based first-line chemotherapy treatment.MATERIALS AND METHODSWe performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis, we considered the detected gene with highest variant allele frequency as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients' demographics, progression-free survival (PFS), and overall survival (OS).RESULTSThe median age of patients was 67 (27-90) years. Fifty-four (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma, and six gallbladder cancers. Forty-six (68.6%) of the patients were treated with cisplatin plus gemcitabine, and 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations, whereas 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20, or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11, and IDH1 were the genes with highest frequency as DCAF. The median DCAF was 3% (0%-97%). DCAF > 3% was associated with worse OS (median OS: 10.8 v 18.8 months, P = .032). Stratifying DCAF in quartiles, DCAF > 10% was significantly related to worse PFS (median PFS: 3 months, P = .014) and worse OS (median OS: 7.0 months, P = .001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9.CONCLUSIONDCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decreases survival probabilities.
Germline Variant Spectrum Among African American Men Undergoing Prostate Cancer Germline Testing: Need for Equity in Genetic Testing
Authors: Giri Veda N. , Hartman Rebecca , Pritzlaff Mary , Horton Carrie , Keith Scott W. 
Published: June 2022

PURPOSE Guidelines for prostate cancer (PCA) germline testing (GT) have expanded, with impact on clinical management and hereditary cancer assessment. African American (AA) men have lower engagement in GT, with concern for widening disparities in genetically informed care. We evaluated the germline spectrum in a cohort of men with PCA enriched for AA men who underwent GT to inform tailored genetic evaluation strategies. METHODS Participants included AA and White men with PCA tested with a 14-gene PCA panel: ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, and TP53. Germline analysis was performed per standard clinical testing and variant classification protocols. Data were compared with Fisher's exact, chi-squared, or two sample t-tests, as appropriate. Multivariable analysis was conducted using Akaike's Information Criterion. The significance level was set a priori at .05. RESULTS The data set included 427 men all tested using the 14-gene PCA panel: AA (n = 237, 56%) and White (n = 190, 44%). Overall, the pathogenic/likely pathogenic (P/LP) variant rate was 8.2%, with AA men having lower rates of P/LP variants then White men (5.91% v 11.05%, respectively; P = .05). Borderline associations with P/LP variant status were observed by race (AA v White; odds ratio = 0.51; P = .07) and age (> 50 v ≤ 50 years; odds ratio = 0.48; P = .06). The P/LP spectrum was narrower in AA men ( BRCA2, PALB2, ATM, and BRCA1) than White men ( BRCA2, ATM, HOXB13, CHEK2, TP53, and NBN). A significant difference was noted in rates of variants of uncertain significance (VUSs) between AA men and White men overall (25.32% v 16.32%; P = .02) and for carrying multiple VUSs (5.1% v 0.53%, P = .008). CONCLUSION Germline evaluation in a cohort enriched for AA men highlights the narrower spectrum of germline contribution to PCA with significantly higher rates of multiple VUSs in DNA repair genes. These results underscore the imperative to engage AA men in GT, the need for larger panel testing in AA men, and the necessity to incorporate novel genomic technologies to clarify VUS to discern the germline contribution to PCA. Furthermore, tailored genetic counseling for AA men is important to ensure understanding of VUS and promote equitable genetics care delivery.
Non-accidental injuries in dogs and cats: review of post-mortem forensic evaluations and the social significance of small animal practice.
Authors: Doukas Dimitrios 
Published: June 2022

The co-existence of animal abuse cases and domestic violence are well established todays. Many studies worldwide have identified that pet dogs and cats are commonly harmed or killed by an abuser who may be a member of the family. In fact, the abuse of pets is an indicator that human members of a family are also at risk. The abusers may show a variety of motivations and mental health disorders, resulting in a variety of abuse forms. The animal victims may be presented alive or dead to a veterinary clinic. The post-mortem differential diagnosis and forensic evaluation of pet dogs and cats with non-accidental injuries (NAI), caused by the physical violence of the abuser and items commonly found in a household environment is presented in the current review, according the main type of abuse: a) blunt force trauma; b) sharp-force injuries; c) gunshot injuries; d) asphyxiation and drowning; e) thermal injuries; and, f) poisoning. The recognition and mandatory report of pet cruelty in the family is a complex issue, causing ethical dilemmas for veterinarians concerning professional confidentiality to the client, duty to protect the human probable victims and how to facilitate prosecution when the law has been broken. The key-role of veterinarians identifying and reporting pet abuse to appropriate state authorities for animal and human welfare is discussed.
Nutritional evaluation of the agro-industrial by-products and waste fruits-vegetable for sustainable ruminant nutrition
Authors: ÜNLÜ Hayrullah Bora , KIRKPINAR Figen , OZDOGAN Mürsel 
Published: June 2022

The growing consumption of ruminant animal products gives rise to a huge demand of animal feed in growing countries. By-product feeds, waste fruits-vegetables, and crop residues should be considered as a valuable alternative feed resource in ruminant nutrition. This waste can be reutilized and converted by ruminants to valuable products for human benefits as a new resource and in return to increase the effectiveness of limited feed sources. But, there are limited new information and research regarding the nutritive value of this waste for ruminants. For this purpose, the experiment was conducted to evaluate the nutritional potential of some agro-industrial by-products, waste fruits-vegetable, and crop residue for ruminants specifically. Fourteen by-products, waste fruits-vegetable and crop residue were collected from the west part regions of Turkey. Nine by-product feeds (whole cottonseed, rice bran, soybean hull, apple pomade, citrus pulp, grape pomade, tomato pomade, grape stalk, rice hull), three waste fruits (dry grape, dry fig, carrot), one waste vegetable (potato) and also one crop residue (cornstalk) were analyzed for nutritional composition and metabolizable energy values were calculated by crude nutrients for ruminants. Further, energy, DMD, and OMD of these samples were investigated by using the cellulose enzyme method. All samples were analyzed the macro minerals (Ca, P, Na, K, and Mg) and the microelements (Fe, Cu, Mn, and Zn) contents. In the research, all samples regarding the parameters in DM, ash, OM, CP, EE, CF, NFE, NSC, NDF, ADF, starch, sugar, Ca, P, Na, K, Mg, Fe, Cu, Mn, Zn, DMD, OMD, MECN, and MECEL were different (P<0.05). The study showed that the waste fruits, vegetable, and by-products have valuable sugar (grape, fig, and carrot), starch (potato, rice bran), NSC (citrus pulp), and oil (cottonseed) content that is the main compounds making them high energetic feeds for ruminants. Also, most of these research materials have enough or much more macro and micro mineral concentrations for ruminant nutrition.
Protective Effect of Spirulina against Aspartame Induced Oxidative Stress and Molecular Gene Brain damage
Authors: Attiya Hamam 
Published: June 2022

Spirulina and lipoic acid has been considered as one of the most effective in ant oxidative stress and anti-inflammatory activity.Aspartame (ASP) is one of the mostwidely used (artificial sweeteners)used in a variety of foods and feeds.This study was conducted to evaluate the possible protective effect of Spirulina and alpha-lipoic acid against aspartame induced oxidative stress and brain damage in rabbits. Forty two white male New-Zealand Rabbits were classified into seven equal groups. Group I: (Control group) received no drugs. Group II: rabbits administered with aspartame (250 mg/kg b. wt/day). Group III: rabbits received alpha- lipoic acid (100 mg/kg b. wt/day). Group IV: rabbits received spirulina platensis (1500 mg/kg. b. wt/day). Group V: rabbits received aspartame (250 mg mg/kg b. wt) and treated with alpha- lipoic acid (100 mg/kg b. wt). Group VI: rabbits received aspartame (250 mg mg/kg b.wt) and treated with spirulina platensis (1500 mg/kg b. wt). Group VII: rabbits received aspartame (250 mg mg/kg b.wt) and treated daily with alpha- lipoic acid (100 mg/kg b. wt) and spirulina platensis (1500 mg/kg b. wt) for 8 weeks. At the end of experiment brain tissue were isolated and analyzed for determination of L-malondialdehyde (L-MDA), Catalase (CAT) and reduced glutathione (GSH) in addition to Anti-inflammatory cytokines: Interlukin-10 (IL-10),Activator Protein-1(AP-1),Bax gene expression and DNA damage. The obtained results showed a significant up-regulation of Activator Protein-1(AP-1),Bax gene expression level and a significant down-regulation of Interlukin-10 (IL-10) and marked increase in L-MDA and DNA damage that was indicated by an increase in tail length and tail DNA percent in brain tissue of aspartame treated rabbits. However, brain CAT activity andGSH concentration were markedly decreased when compared with control group.Coad ministration of spirulinaand alpha lipoic acid protect aspartame induced brain damage in rabbits caused a significant improvement of all previous parameters and attenuate DNA changes. Conclusively, spirulina platensis and alpha-lipoic acid exerts a protective effect against DNA damage and oxidative stress in brain of aspartameusage through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidants defense system mechanisms.
Dofinansowanie przedsięwzięć niskoemisyjnych z Funduszu Termomodernizacji i Remontów – zagadnienia materialnoprawne i proceduralne
Authors: Ofiarska Małgorzata 
Published: June 2022

W opracowaniu przedstawiono istotę, normatywną strukturę oraz zasady co do zasady bezzwrotnego wpierania gmin w realizacji przedsięwzięć niskoemisyjnych, których realizacja może być dofinansowana z Funduszu Termomodernizacji i Remontów zasilanego przede wszystkim dotacjami z budżetu państwa. Wspierane w tym trybie mogą być tylko przedsięwzięcia niskoemisyjne wykonywane w domach jednorodzinnych lub lokalach mieszkalnych znajdujących się w takich domach, a ich beneficjentami powinny być w szczególności osoby fizyczne uprawnione do korzystania ze świadczeń pieniężnych pomocy społecznej. Przyjęty przez ustawodawcę normatywny schemat udzielenia wsparcia złożony jest z kilku podstawowych elementów: tzw. uchwały antysmogowej podjętej przez sejmik województwa, porozumienia w sprawie realizacji przedsięwzięć niskoemisyjnych zawieranego przez Narodowy Fundusz Ochrony Środowiska i Gospodarki Wodnej z gminą, umowy o wykonanie konkretnego przedsięwzięcia zawieranej między gminą i osobą fizyczną spełniającą warunki formalne, trybu weryfikacji i kontroli efektów wykonanego przedsięwzięcia. Ustanowiono w ten sposób finansowy mechanizm wsparcia, w stosunkowo wąsko wyznaczonym obszarze, działań mających doprowadzić do poprawy jakości powietrza. W opracowaniu pozytywnie zweryfikowano tezę o potrzebie stosowania takiej formy wsparcia, ale jednocześnie krytycznie oceniono nadmierną ostrożność ustawodawcy, polegającą na ustaleniu wąskich pod względem podmiotowo-przedmiotowym granic programu działań na rzecz poprawy jakości powietrza w Polsce.
Dotacja żłobkowa jako instrument samodzielności legislacyjnej i wydatkowej samorządu gminnego
Authors: Ostrowska Anna 
Published: June 2022

Uchwalona w 2011 r. ustawa o opiece nad dziećmi w wieku do lat 3 przyniosła niemal rewolucyjne zmiany nie tylko w strukturze ustrojowej i własnościowej placówek świadczących opiekę żłobkową, ale także w sferze aktywności legislacyjnej i dotacyjnej samorządów gminnych. Na jej podstawie rady gmin uzyskały bowiem delegację ustawową do określania w drodze aktu prawa miejscowego wysokości, zasad ustalania oraz rozliczania dotacji celowej udzielanej z budżetu gminy podmiotom prowadzącym żłobek lub klub dziecięcy, dziennym opiekunom lub osobom zatrudniającym dziennych opiekunów. Ta sfera samorządowego dotowania ujawnia niezwykłą „pomysłowość” rad gmin przy określaniu powyższych zasad, która dość często spotyka się z nadzorczą reakcją ze strony regionalnej izby obrachunkowej. Artykuł ma na celu uzasadnienie tezy badawczej twierdzącej, iż udzielanie dotacji żłobkowej z budżetu gminy stanowi przykład jej najszerszej samodzielności dotacyjnej występującej w zakresie aktywności legislacyjnej i wydatkowej organów gminy. W celu udowodnienia powyższej tezy przeprowadzone badania objęły analizę porównawczą dotacji żłobkowej z innymi dotacjami udzielanymi z budżetów jednostek samorządu terytorialnego (w szczególności z dotacją oświatową), a także analizę orzeczeń nadzorczych i sądowych zapadłych w sprawach uchwał rad gmin podejmowanych na podstawie upoważnienia z art. 60 ust. 2 powyższej ustawy. W celu zobrazowania aktywności wydatkowej gminy w tym zakresie posłużono się także metodą ilościową poprzez przedstawienie analizy wydatków budżetu jednego z miast wojewódzkich na dotacje żłobkowe. Przyjmując bowiem, iż w mieście na prawach powiatu będącym jednocześnie stolicą województwa powinny funkcjonować wszystkie formy opieki nad dziećmi do lat 3, w artykule przeprowadzono analizę wydatków budżetu takiego miasta na opiekę żłobkową. Analiza ta ukazała rozmiar i strukturę udzielanych przez powyższe miasto dotacji żłobkowych, które z kolei potwierdziły istnienie samodzielności gminy w tym zakresie. Wyniki przeprowadzonych w artykule analiz odniesiono także do zagadnień związanych z udzielaniem dotacji żłobkowych w okresach kryzysu pandemicznego i kryzysu uchodźczego.