bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogeochemical and GIS Analysis of Groundwater Quality for Drinking and Irrigation Purposes in Kuzhithuraiyar Sub-Basin, Kanniyakumari District, Tamil Nadu, India
Authors: Athsha Great Raxana R. , Sellamuthu Venkateswaran , Jothimani Muralitharan
Published: May 2024

A hydrogeochemical analysis was conducted to find the suitability of the groundwater for drinking and irrigation purposes in the Kuzhithuraiyar sub-basin, Kanniyakumari district, Tamil Nadu, India. 48 groundwater samples were collected from the different locations of the study area during both the pre- and postmonsoon periods. This study assesses the groundwater quality for drinking and irrigation purposes based on the analytical results, water quality index, Wilcox plot, and irrigation parameters such as electrical conductance, Kelly’s ratio, sodium absorption ratio values, magnesium hazards, bicarbonate, and the residual sodium carbonate index. The pH values ranged from 8.5 to 6.5, suggesting generally acceptable conditions. TDS concentrations range from 24 to 1277 mg/L, whereas EC values range from 37.50 to 1996 μS/cm. It is observed from the collected samples that the pre-monsoon water samples TDS’ values were exceeded the recommended TDS limits than postmonsoon samples. Water quality indices indicate that 50% of premonsoon samples and 48% of postmonsoon samples are suitable for drinking. In total, 10% of samples are admissible to a doubtful category before and after the monsoon, 6% are good to permissible during the monsoon, and 84% are good to permissible. Kelly’s ratio shows that 56% and 48% of samples collected during the post- and premonsoon are suitable for irrigation, respectively, whereas the remaining samples are not. Due to magnesium hazards, 40% and 44% of pre- and postmonsoon samples are not suitable for irrigation. Overall, the postmonsoon samples exceeded the permissible TDS limit (1000 mg/L) by 10% and the premonsoon samples by 6. 13% of samples obtained after the monsoon and 19% collected before the monsoon have a potential salinity greater than three, indicating that these samples are unacceptable. The sustaining water quality and mitigating possible hazards in the Kuzhithuraiyar sub-basin require continuous monitoring and focused measures.
Malicious Tumor? Pathological Fracture of the Femur in Children Caused by Myelolipoma: A Case Report and Review of Literatures
Authors: Shen Xiaoyu , Yao Qiang , Qi Xiangbei , Ma Lijie
Published: May 2024

Myelolipoma is a kind of benign lipoma containing myeloid cells. It is a rare type of tumor that typically presents as an occasional adrenal tumor, generally manifesting as a nonfunctional adrenal mass. Although it can occur in extra-adrenal tissues, its occurrence in bone tissue is extremely rare. Most cases are discovered accidentally during physical examinations of adults, and there are currently no reports of cases with pathological fractures as the main symptoms. We present a case of a 15-year-old teenager who developed a pathological fracture caused by femoral myelolipoma. The diagnosis of the specific type of bone tumor of the patient was determined through pathology and imaging. To treat the condition, we utilized a technique known as the “soft drill” to fully access the tumor space, remove the bone septum, and scrape away the diseased tissue. The fracture was then stabilized using a hybrid external fixation. After a 2-year follow-up period, there was no recurrence of the bone tumor. This case is the first case of intraosseous myelolipoma that occurred in a minor with the initial symptom of pathological fracture, filling the gap in our existing body of knowledge and providing a reference for the treatment of this type of intraosseous myelolipoma.
Health Risk Assessment of Potentially Toxic Elements Contamination of Commonly Consumed Fruits in Bahir Dar Town, Northwest Ethiopia
Authors: Mekonnen Biset Asrade , Yizengaw Muluabay Getie , Kassahun Haile , Ketema Gebremariam
Published: May 2024

Background. Excess accumulation of potentially toxic elements in frequently consumed fruits is a serious threat to human health. The aim of this study was to determine the levels of cadmium (Cd), chromium (Cr), copper (Cu), and lead (Pb) and to estimate the noncarcinogenic and carcinogenic health risks associated with their daily intake in commonly consumed fruits in Bahir Dar town, northwest Ethiopia. Methods. Three types of fruits (mango, banana, and orange) were collected using a simple random sampling method from open markets in Bahir Dar town. Wet digestion was used, and the concentration of potentially toxic elements was analyzed in the edible portion of the fruits. The average daily intake (ADI), hazard quotient (HQ), hazard index (HI), and target cancer risk (TCR) were estimated to assess the human health risks posed by the intake of those potentially toxic elements from the consumption of the studied fruits. Results. The concentrations of Cr and Cu were lower than the maximum limit of normal values in mango, banana, and orange. However, the Pb and Cd concentrations (mg kg-1) in mango were 0.576 and 1.771, respectively, which exceeded the FAO/WHO recommended permissible limits of 0.3 mg kg-1 and 0.2 mg kg-1, respectively. The ADI of potentially toxic elements was found to be lower than the maximum permitted tolerable daily intake in the studied fruits, and the HI values (mgday-1 kg-1) of all studied potentially toxic elements were lower than one in banana and orange, except mango (3.69). The TCR values for Pb, Cd, and Cr in banana and orange were 7.16×10−4 and 7.15×10−4, respectively, which exceeded the recommended threshold risk limit (>1×10−4), but in mango (1.71×10−3), the level was above the moderate risk limit (>1×10−3). However, the TCR value in all the studied fruits was above the recommended safe limit (ILCR<1×10−6) set by the United States Environmental Protection Agency (US-EPA). Conclusion. The study revealed that the consumption of mango fruit in the studied areas may pose noncarcinogenic and carcinogenic adverse health effects.
Development of Drying Methodology for Intact Whole Buffalo Liver, Its Characterization, Shelf Life, and Evaluation of Palatability as Pet Treat
Authors: Anand T. S. , Ahmad Tanbir , Kumar Devendra , Devadason I. Prince , Mendiratta S. K. , Verma Akhilesh Kumar , Biswas Ashim Kumar , Talukder Suman , Dubal Zunjar B. , Das Asit , Deshpande Aditya D. , Aruna T. S. , Thirupathi Yasotha , Sen A. R.
Published: May 2024

Globally, large quantity of animal byproducts is generated from the slaughter of food animals, but there is lack of research articles related to drying of these byproducts and its use as pet food. Therefore, this study was conducted with the aim of utilization of intact whole buffalo liver by drying for pet treat, evaluating its shelf life and palatability. The intact liver surface was superficially sliced, and the surface was pierced. Thereafter, the livers were pretreated in 3% sugar and 4% salt solution (1 : 3 w/v) for 3 h followed by microwaving for 4 min and hot air drying at 60°C for 40 h (designated as T2L). The livers which were dried the same as T2L except surface piercing were referred as T1L, whereas the livers dried only using hot air oven were referred as control (CL). The moisture and protein contents of the dried CL and T2L were found to be 28.46% and 14.29% and 43.85% and 52.76%, respectively. Sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS-PAGE) image of T2L revealed the presence of few low as well as high molecular weight protein bands which were absent in CL and T1L indicating a comparatively lower level of protein degradation in T2L. The shelf life of T1L and T2L samples based on microbiological and lipid oxidation analyses was found to be more than 60 days at 25 and 4°C. Palatability studies using dogs showed that all dried samples were highly palatable. Thus, it could be concluded that intact buffalo liver could be dried using surface slicing, with/without piercing followed by salt and sugar pretreatment, 4 min microwaving, and hot air drying at 60°C for 40 h. Future study should focus on the sensory properties such as aroma, texture, and flavor and sensory analysis of the dried liver by human.
Statistical Issues on the Neutrino Mass Hierarchy with Δχ2
Authors: Sawy F. , Stanco L.
Published: May 2024

The neutrino mass hierarchy determination (ν MHD) is one of the main goals of the major current and future neutrino experiments. The statistical analysis usually proceeds from a standard method, a single-dimensional estimator 1D−Δχ2 that shows some drawbacks and concerns, together with a debatable strategy. The drawbacks and considerations of the standard method will be explained through the following three main issues. The first issue corresponds to the limited power of the standard method. The Δχ2 estimator provides us with different results when different simulation procedures were used. Regarding the second issue, when χminNH2 and χminIH2 are drawn in a 2D map, their strong positive correlation manifests χ2 as a bidimensional variable, instead of a single-dimensional estimator. The overlapping between the χ2 distributions of the two hypotheses leads to an experiment sensitivity reduction. The third issue corresponds to the robustness of the standard method. When the JUNO sensitivity is obtained using different procedures, either with Δχ2 as one-dimensional or χ2 as two-dimensional estimator, the experimental sensitivity varies with the different values of the atmospheric mass, the input parameter. We computed the oscillation of Δχ2¯ with the input parameter values, Δm2input. The MH significance using the standard method, Δχ2, strongly depends on the values of the parameter Δm2input. Consequently, the experiment sensitivity depends on the precision of the atmospheric mass. This evaluation of the standard method confirms the drawbacks.
Effect of Double Stratification on MHD Williamson Boundary Layer Flow and Heat Transfer across a Shrinking/Stretching Sheet Immersed in a Porous Medium
Authors: Geetha R. , Reddappa B. , Tarakaramu Nainaru , Rushi Kumar B. , Ijaz Khan M.
Published: May 2024

The present study aims to provide a mathematical model of the Williamson fluid flow via a permeable stretching/shrinking sheet in the MHD boundary layer in the presence of a heat source, chemical reaction, and suction. This study is novel because it investigates the physical effects of thermal and solutal stratification on convective heat and mass transport using thermal radiation. The flow’s PDEs are numerically solved using the BVP4c approach and the pertinent similarity variables until a stable solution is found. Through visual analysis, the effects of dimensionless factors on temperature, velocity, and concentration profiles are examined. This encompasses the mass transfer rate, the heat transfer rate, and the coefficient of friction. The results of the present analysis are found to be consistent with those of previously published studies. The findings demonstrate that enhanced temperature and concentration profiles cause the Williamson, magnetic, and permeability parameters to rise in conjunction with a drop in the dimensionless velocity. In relation to temperature, the thermal stratification parameter exhibits the opposite tendency. Regarding the solutal stratification parameter, concentration profiles are seen to show the opposite trend. Lastly, the current work will have important implications for the removal of dust and viruses from viscoelastic fluid in bioengineering, the medical sciences, and medical equipment.
Figure 2 from FUME-TCRseq Enables Sensitive and Accurate Sequencing of the T-cell Receptor from Limited Input of Degraded RNA
Authors: Baker Ann-Marie , Nageswaran Gayathri , Nenclares Pablo , Ronel Tahel , Smith Kane , Kimberley Christopher , Laclé Miangela M. , Bhide Shreerang , Harrington Kevin J. , Melcher Alan , Rodriguez-Justo Manuel , Chain Benny , Graham Trevor A.
Published: May 2024

A, Scatter plot showing V gene usage data from FUME-TCRseq and 5′-RACE ligation (“5′-RACE TCRseq”) methodologies, performed on RNA extracted from a representative whole blood sample. B, Bar plot showing the proportion of each V gene detected by FUME-TCRseq and 5′-RACE ligation. Red bars, highly frequent V genes; blue, less frequent V genes. C, Scatterplot showing overlapping clonotype abundances for the FUME-TCRseq and 5′RACE TCRseq data. Point size is scaled to the geometric mean of clonotype frequency in both samples and axes represent log10 clonotype frequencies in each sample. D, Plot showing the 10 most common clonotypes identified by FUME-TCRseq and the frequencies at which they were detected using 5′-RACE ligation methodology. E, Scatterplot showing overlapping clonotype abundances for technical repeats. Point size is scaled to the geometric mean of clonotype frequency in both samples and axes represent log10 clonotype frequencies in each sample. F, Plot showing the 10 most common clonotypes detected in technical repeats of FUME-TCRseq performed on RNA extracted from an inflammatory polyp.
Table S1 from DNA of Neutrophil Extracellular Traps Binds TMCO6 to Impair CD8+ T-cell Immunity in Hepatocellular Carcinoma
Authors: Song Mengjia , Zhang Chaoqi , Cheng Shaoyan , Ouyang Dijun , Ping Yu , Yang Jieying , Zhang YaoJun , Tang Yan , Chen Hao , Wang Qi-jing , Li Yong-qiang , He Jia , Xiang Tong , Zhang Yizhuo , Xia Jian-Chuan
Published: May 2024

Association of NET expression with clinicopathological features in patients with HCC.
Supplementary Figures from Ketogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy
Authors: Murphy Sean , Rahmy Sharif , Gan Dailin , Liu Guoqiang , Zhu Yini , Manyak Maxim , Duong Loan , He Jianping , Schofield James H. , Schafer Zachary T. , Li Jun , Lu Xuemin , Lu Xin
Published: May 2024

Supplementary FIgure S1, S2, S3, S4, S5, S6
HiChIP-Based Epigenomic Footprinting Identifies a Promoter Variant of UXS1 That Confers Genetic Susceptibility to Gastroesophageal Cancer
Authors: Gnanapragasam Ansley , Kirbizakis Eftyhios , Li Anna , White Kyle H. , Mortenson Katelyn L. , Cavalcante de Moura Juliana , Jawhar Wajih , Yan Yifei , Falter Reilly , Russett Colleen , Giannias Betty , Camilleri-Broët Sophie , Bertos Nicholas , Cools-Lartigue Jonathan , Garzia Livia , Sangwan Veena , Ferri Lorenzo , Zhang Xiaoyang , Bailey Swneke D.
Published: May 2024

Genome-wide association studies (GWAS) have identified more than a hundred single nucleotide variants (SNV) associated with the risk of gastroesophageal cancer (GEC). The majority of the identified SNVs map to noncoding regions of the genome. Uncovering the causal SNVs and genes they modulate could help improve GEC prevention and treatment. Herein, we used HiChIP against histone 3 lysine 27 acetylation (H3K27ac) to simultaneously annotate active promoters and enhancers, identify the interactions between them, and detect nucleosome-free regions (NFR) harboring potential causal SNVs in a single assay. The application of H3K27ac HiChIP in GEC relevant models identified 61 potential functional SNVs that reside in NFRs and interact with 49 genes at 17 loci. The approach led to a 67% reduction in the number of SNVs in linkage disequilibrium at these 17 loci, and at 7 loci, a single putative causal SNV was identified. One SNV, rs147518036, located within the promoter of the UDP-glucuronate decarboxylase 1 (UXS1) gene, seemed to underlie the GEC risk association captured by the rs75460256 index SNV. The rs147518036 SNV creates a GABPA DNA recognition motif, resulting in increased promoter activity, and CRISPR-mediated inhibition of the UXS1 promoter reduced the viability of the GEC cells. These findings provide a framework that simplifies the identification of potentially functional regulatory SNVs and target genes underlying risk-associated loci. In addition, the study implicates increased expression of the enzyme UXS1 and activation of its metabolic pathway as a predisposition to gastric cancer, which highlights potential therapeutic avenues to treat this disease.

Significance: Epigenomic footprinting using a histone posttranslational modification targeted 3D genomics methodology elucidates functional noncoding sequence variants and their target genes at cancer risk loci.
Suppl Table S4 from Targeting CCL2/CCR2 Signaling Overcomes MEK Inhibitor Resistance in Acute Myeloid Leukemia
Authors: Modak Rucha V. , de Oliveira Rebola Katia G. , McClatchy John , Mohammadhosseini Mona , Damnernsawad Alisa , Kurtz Stephen E. , Eide Christopher A. , Wu Guanming , Laderas Ted , Nechiporuk Tamilla , Gritsenko Marina A. , Hansen Joshua R. , Hutchinson Chelsea , Gosline Sara J.C. , Piehowski Paul , Bottomly Daniel , Short Nicholas , Rodland Karin , McWeeney Shannon K. , Tyner Jeffrey W. , Agarwal Anupriya
Published: May 2024

Correlation of trametinib AUC and AML feature annotations
Supplementary Table S1 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Immunohistochemical antibodies
Supplementary Figure S8 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S8. STLMS genomic risk stratification for progression-free survival (PFS). A, A 2-tier genomic risk group is proposed for PFS. PFS for 151 patients with primary STLMS from the MSK cohort with low- and high-risk genomic groups is represented by Kaplan-Meier curves.
Supplementary Figure S6 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S6. Oncoprint depicting frequency of TP53, RB1, ATRX, PTEN, and MAP2K4 in the AACR GENIE STLMS cohort.
Supplementary Figure S3 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S3. Overall survival (OS) for 195 STLMS patients from the MSK cohort stratified by in low-, intermediate-, and high-risk genomic groups represented by Kaplan-Meier curves.
Supplementary Figure S11 from Developing Novel Genomic Risk Stratification Models in Soft Tissue and Uterine Leiomyosarcoma
Authors: Dermawan Josephine K. , Chiang Sarah , Singer Samuel , Jadeja Bhumika , Hensley Martee L. , Tap William D. , Movva Sujana , Maki Robert G. , Antonescu Cristina R.
Published: May 2024

Supplementary Figure S11. ULMS genomic risk stratification for progression-free survival (PFS). A, A 3-tier genomic risk group is proposed for PFS. PFS for 238 patients with primary ULMS from the MSK cohort with low-, intermediate- and high-risk genomic groups [co-occurrence of TP53 and ATRX mutations or co-occurrence of TP53 mutation and chr20q amplification (amp20q); intermediate risk – presence of any of the following: TP53 mutation, ATRX mutation or amp20q; low risk – lack of any of these three alterations], as well as stratification by tumor size (B), mitotic rate (C), and necrosis (D) are represented by Kaplan-Meier curves.
Supplementary Table 5 from A Pre-Leukemic DNA Methylation Signature in Healthy Individuals at Higher Risk for Developing Myeloid Malignancy
Authors: Lao Zhentang , Ding Ling-Wen , Sun Qiao-Yang , Jia Li , Yan Benedict , Ng Alvin Yu-Jin , Capinpin Sharah Mae , Wang Renwei , Ying Li , Chng Wee Joo , Koeffler H. Phillip , Koh Woon-Puay , Yuan Jian-Min , Yang Henry , Goh Yeow Tee , Grigoropoulos Nicholas
Published: May 2024

Supplementary Table 5
Supplementary Figure S5 from Targeting SMAD3 Improves Response to Oxaliplatin in Esophageal Adenocarcinoma Models by Impeding DNA Repair
Authors: Ballout Farah , Lu Heng , Bhat Nadeem , Chen Lei , Peng Dunfa , Chen Zheng , Chen Steven , Sun Xiaodian , Giordano Silvia , Corso Simona , Zaika Alexander , McDonald Oliver , Livingstone Alan S. , El-Rifai Wael
Published: May 2024

Supplementary Figure 5. SMAD3 indirectly regulates ATM by interacting with Protein phosphatase 2 (PP2A).
Supplementary Figure S21 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

Dynamic change of circulating CD39+CD103+ T cells in response to the treatment administered.
Supplementary Figure S14 from A Phase II Open-Label Randomized Clinical Trial of Preoperative Durvalumab or Durvalumab plus Tremelimumab in Resectable Head and Neck Squamous Cell Carcinoma
Authors: Kim Chang Gon , Hong Min Hee , Kim Dahee , Lee Brian Hyohyoung , Kim Hyunwook , Ock Chan-Young , Kelly Geoffrey , Bang Yoon Ji , Kim Gamin , Lee Jung Eun , Kim Chaeyeon , Kim Se-Heon , Hong Hyun Jun , Park Young Min , Sim Nam Suk , Park Heejung , Park Jin Woo , Lee Chang Geol , Kim Kyung Hwan , Park Goeun , Jung Inkyung , Han Dawoon , Kim Jong Hoon , Cha Junha , Lee Insuk , Kang Mingu , Song Heon , Oum Chiyoon , Kim Seulki , Kim Sukjun , Lim Yoojoo , Kim-Schulze Seunghee , Merad Miriam , Yoon Sun Och , Kim Hyun Je , Koh Yoon Woo , Kim Hye Ryun
Published: May 2024

High-dimensional profiling of CD8+ T cells.
Supplementary Figure S6 from Biomarkers of Efficacy and Safety of the Academic BCMA-CART ARI0002h for the Treatment of Refractory Multiple Myeloma
Authors: Oliver-Caldes Aina , Español-Rego Marta , Zabaleta Aintzane , González-Calle Verónica , Navarro-Velázquez Sergio , Inogés Susana , de Cerio Ascensión López-Díaz , Cabañas Valentín , López-Muñoz Nieves , Rodríguez-Otero Paula , Reguera Juan Luis , Moreno David F. , Martínez-Cibrian Nuria , López-Corral Lucía , Pérez-Amill Lorena , Martin-Antonio Beatriz , Rosiñol Laura , Cid Joan , Tovar Natalia , Sáez-Peñataro Joaquín , López-Parra Miriam , Olesti Eulalia , Guillén Elena , Varea Sara , Rodríguez-Lobato Luis Gerardo , Battram Anthony M. , González Marta Sonia , Sánchez-Salinas Andrés , González-Navarro Azucena , Ortiz-Maldonado Valentín , Delgado Julio , Prósper Felipe , Juan Manel , Martínez-López Joaquín , Moraleda José M. , Mateos Maria Victoria , Urbano-Ispizua Álvaro , Paiva Bruno , Pascal Mariona , Fernández de Larrea Carlos
Published: May 2024

Figure 6. Impact of ARI0002h persistence in duration of response, progression-free and overall survival.
Supplementary Table S3 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

Percentage of reads matching with mouse DNA
Supplementary Figure S6 from Integrative Molecular Analyses of the MD Anderson Prostate Cancer Patient-derived Xenograft (MDA PCa PDX) Series
Authors: Anselmino Nicolas , Labanca Estefania , Shepherd Peter D.A. , Dong Jiabin , Yang Jun , Song Xiaofei , Nandakumar Subhiksha , Kundra Ritika , Lee Cindy , Schultz Nikolaus , Zhang Jianhua , Araujo John C. , Aparicio Ana M. , Subudhi Sumit K. , Corn Paul G. , Pisters Louis L. , Ward John F. , Davis John W. , Vazquez Elba S. , Gueron Geraldine , Logothetis Christopher J. , Futreal Andrew , Troncoso Patricia , Chen Yu , Navone Nora M.
Published: May 2024

Comparison between adenocarcinoma and neuroendocrine carcinoma
Data from Onvansertib in Combination with FOLFIRI and Bevacizumab in Second-Line Treatment of KRAS-Mutant Metastatic Colorectal Cancer: A Phase Ib Clinical Study
Authors: Ahn Daniel H. , Barzi Afsaneh , Ridinger Maya , Samuëlsz Errin , Subramanian Ramanand A. , Croucher Peter J.P. , Smeal Tod , Kabbinavar Fairooz F. , Lenz Heinz-Josef
Published: May 2024

AbstractPurpose:
Onvansertib is a highly specific inhibitor of polo-like kinase 1 (PLK1), with demonstrated safety in solid tumors. We evaluated, preclinically and clinically, the potential of onvansertib in combination with chemotherapy as a therapeutic option for KRAS-mutant colorectal cancer.
Patients and Methods:
Preclinical activity of onvansertib was assessed (i) in vitro in KRAS wild-type and -mutant isogenic colorectal cancer cells and (ii) in vivo, in combination with irinotecan, in a KRAS-mutant xenograft model. Clinically, a phase Ib trial was conducted to investigate onvansertib at doses 12, 15, and 18 mg/m2 (days 1–5 and 14–19 of a 28-day cycle) in combination with FOLFIRI/bevacizumab (days 1 and 15) in patients with KRAS-mutant metastatic colorectal cancer who had prior oxaliplatin exposure. Safety, efficacy, and changes in circulating tumor DNA (ctDNA) were assessed.
Results:
In preclinical models, onvansertib displayed superior activity in KRAS-mutant than wild-type isogenic colorectal cancer cells and demonstrated potent antitumor activity in combination with irinotecan in vivo. Eighteen patients enrolled in the phase Ib study. Onvansertib recommended phase II dose was established at 15 mg/m2. Grade 3 and 4 adverse events (AE) represented 15% of all treatment-related AEs, with neutropenia being the most common. Partial responses were observed in 44% of patients, with a median duration of response of 9.5 months. Early ctDNA dynamics were predictive of treatment efficacy.
Conclusions:
Onvansertib combined with FOLIFRI/bevacizumab exhibited manageable safety and promising efficacy in second-line treatment of patients with KRAS-mutant metastatic colorectal cancer. Further exploration of this combination therapy is ongoing.

See related commentary by Stebbing and Bullock, p. 2005
Long-term Remissions Following CD20-Directed Chimeric Antigen Receptor–Adoptive T-cell Therapy
Authors: Mo George , Lee Sang Y. , Coffey David G. , Voillet Valentin , Kirsch Ilan R. , Gottardo Raphael , Smythe Kimberly S. , Yeung Cecilia C.S. , Greenbaum Adam , Green Damian J. , Maloney David G. , Till Brian G.
Published: May 2024

Chimeric antigen receptor (CAR) T-cell therapy produces high response rates in refractory B-cell non–Hodgkin lymphoma, but long-term data are minimal to date. In this study, we present long-term follow-up of a pilot trial testing a CD20-targeting third-generation CAR in patients with relapsed B-cell lymphomas following cyclophosphamide-only lymphodepletion. Two of the three patients in the trial, with mantle cell lymphoma and follicular lymphoma, had remissions lasting more than 7 years, though they ultimately relapsed. The absence of B-cell aplasia in both patients suggested a lack of functional CAR T-cell persistence, leading to the hypothesis that endogenous immune responses were responsible for these long-term remissions. Correlative immunologic analyses supported this hypothesis, with evidence of new humoral and cellular antitumor immune responses proximal to clinical response time points. Collectively, our results suggest that CAR T-cell therapy may facilitate epitope spreading and endogenous immune response formation in lymphomas.

Significance: Two of three patients treated with CD20-targeted CAR T-cell therapy had long-term remissions, with evidence of endogenous antitumor immune response formation. Further investigation is warranted to develop conditions that promote epitope spreading in lymphomas.
Supplementary Figure S1 from Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: May 2024

Shows the levels of cytokines/chemokines/growth factors released by TKTB34-RAS and TKTB34-PIK3CA cells. Related to Figure 6 of the main manuscript.
Supplementary Data S1 from Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: May 2024

Unprocessed western blot images and Ponceau S staining used to generate figures in the main manuscript
FIGURE 2 from Mutant RAS-driven Secretome Causes Skeletal Muscle Defects in Breast Cancer
Authors: Wang Ruizhong , Khatpe Aditi S. , Kumar Brijesh , Mang Henry Elmer , Batic Katie , Adebayo Adedeji K. , Nakshatri Harikrishna
Published: May 2024

The effects of PDXs on plasma miR-486 and functional markers in skeletal muscle. A, A significant decline in circulating miR-486 levels was observed across all PDX subtypes. B, Differential effects of PDX subtypes on miR-486 in skeletal muscles of mice. C, Differential impact of PDXs on skeletal muscle Pax7. D, Differential impact of PDXs on skeletal muscle MyoD. E, The effect of PDXs on skeletal muscle Myh1. F, The effect of PDXs on skeletal muscle p53. G, ER+/PR+ and ER+/PR− tumor-derived PDXs increased skeletal muscle Pdk4, compared with TNBC PDXs.
Intracranial Arachnoid Cyst in Children: Clinical Presentation and Risk Factors for Surgical Intervention
Authors: Talreja Raghav , Fonseca Laura Daniela , Chikkannaiah Mahesh , Kumar Gogi
Published: May 2024

Introduction: Intracranial arachnoid cysts (IAC) in children are a common incidental finding on imaging. Most IACs are asymptomatic and can be monitored; however, a small percentage may enlarge and require surgical intervention. This study aimed to identify clinical risk factors in patients with IAC who underwent surgery versus those who did not. Methods: We conducted a retrospective chart review from 2009 to 2021 at a free-standing children’s hospital. A total of 230 patients diagnosed with an IAC aged 0–21 years of age were included in the study. Data on demographics, imaging, and neurological follow-up were analyzed. Results: Out of 230 patients, 45 (19.6%) underwent surgery. At time of IAC diagnosis, the surgical patients were younger (median age 1.1 years), and their median cyst volume was larger (41.7 cm3), compared to nonsurgical patients (median age 5.9 years, volume 11.8 cm3, respectively). Headache was the most common reason for initial imaging in nonsurgical patients (54/185, 29.2%) while prenatal ultrasound (11/45, 24.4%) and macrocephaly (11/45, 24.4%) were the most common reasons for surgical patients. The majority of both surgical and nonsurgical patients had the IAC incidentally found (41/45, 91.1% and 181/185, 97.8%, respectively). Surgery relieved symptoms in 38/45 (84.4%) patients. Cyst volume and age were predictors of increased odds of having surgery. Discussion/Conclusion: Patients who underwent surgery were younger and had larger cyst volumes at time of diagnosis. The majority of the IAC were found incidentally and remained stable over prolonged follow-up. The majority of the patients experienced relief of symptoms postsurgical intervention. There is a greater odds of having surgical treatment with decreased age and greater cyst volume at diagnosis, and therefore these patients should be monitored closely for development of symptoms indicating need for surgical intervention.
Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes Using Low-Cost Dual Dye Technique: Identifying Factors Associated with Adequate False Negative Rate Threshold
Authors: Yadav Sanjay Kumar , Chavda Jayesh , Mishra Arpan , Sharma Dhananjaya , Rawat Shyam Ji , Jain Rajesh
Published: May 2024

Background: In this study, we evaluated the feasibility of the sentinel lymph node (SLN) identification rate (SLN-IR) of fluorescein-guided sentinel lymph node biopsy (SLNB) in combination with methylene blue dye (MBD) and factors which can lead to a false negative rate (FNR) threshold of 10%. Methods: This was a prospective cross-sectional non-randomized validation study in patients with post-neoadjuvant chemotherapy (NACT) clinically node negative axilla who were node positive prior to start of NACT. Patients underwent validation of SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and FNR were assessed and compared with various molecular subtypes. Results: The SLNs were identified in 102 out of 120 (85%) post-NACT patients. The median number of sentinel lymph nodes identified was 2 (range 1–3). The SLN-IR using MBD was 85%, FD was 82.5%, and combined MBD FD was 85%. Two or more SLNs were removed in 72 patients and 11 patients had tumor in the rest of the axilla, resulting in an FNR of 17.4%. An FNR was 25% in case only one SLN was found, and it was 11.42% if two or more than two SLNs were excised. Conclusions: This cohort study found that use of low-cost dual dyes in patients with positive axillary disease, rendered cN0 with NACT, with 2 or more negative SLNs with SLNB alone, results in an FNR of 11.4%. Her 2 positive and TNBC with 2 or more negative SLNs are associated with an FNR of <10%. However, the number of such patients was small and further studies with larger sample size are warranted to confirm these findings.
Laser Doppler Fluximetry in Cutaneous Vasculature: Methods for Data Analyses
Authors: Huang Sophie J.Y. , Wang Xuan , Halvorson Brayden D. , Bao Yuki , Frisbee Stephanie J. , Frisbee Jefferson C. , Goldman Daniel
Published: May 2024

Introduction: Acquisition of a deeper understanding of microvascular function across physiological and pathological conditions can be complicated by poor accessibility of the vascular networks and the necessary sophistication or intrusiveness of the equipment needed to acquire meaningful data. Laser Doppler fluximetry (LDF) provides a mechanism wherein investigators can readily acquire large amounts of data with minor inconvenience for the subject. However, beyond fairly basic analyses of erythrocyte perfusion (fluximetry) data within the cutaneous microcirculation (i.e., perfusion at rest and following imposed challenges), a deeper understanding of microvascular perfusion requires a more sophisticated approach that can be challenging for many investigators. Methods: This manuscript provides investigators with clear guidance for data acquisition from human subjects for full analysis of fluximetry data, including levels of perfusion, single- and multiscale Lempel-Ziv complexity (LZC) and sample entropy (SampEn), and wavelet-based analyses for the major physiological components of the signal. Representative data and responses are presented from a recruited cohort of healthy volunteers, and computer codes for full data analysis (MATLAB) are provided to facilitate efforts by interested investigators. Conclusion: It is anticipated that these materials can reduce the challenge to investigators integrating these approaches into their research programs and facilitate translational research in cardiovascular science.
Clinimetric Properties of the “FIND-NEEDS” to Screen Geriatric Conditions
Authors: Chang Chia-Ming , Lin Chung-Ying , -Hu Fang-Wen , Wang Ying-Wei , Huang Chi-Chang , Lo Yu-Tai , Wu Chien-Yuan , Chung Yuan-Fang , Kang Chiu-Chen , Chen Yi-Jung , Yang Yi-Ching , Liu Li-Fan , Griffiths Mark D. , Lin Dai-Chan , Shen Meng-Ru
Published: May 2024

Introduction: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic “FIND-NEEDS” was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. Methods: The participants comprised first-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) who were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). Results: The mean age of the 114 outpatients was 78.3 ± 7.6 years, and 79 (69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r = 0.494; p < 0.001), and the binary score showed excellent correlation (r = 0.944; p < 0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). Discussion/Conclusion: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.
The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID
Authors: Anastassopoulou Cleo , Davaris Nikolaos , Ferous Stefanos , Siafakas Nikolaos , Boufidou Fotini , Anagnostopoulos Konstantinos , Tsakris Athanasios
Published: May 2024

Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.
On the Text and Interpretation of Accius 306-307 Dangel
Authors: Nelis Basil L.P.
Published: May 2024

This article argues that the text of Accius 306-307 Dangel, as transmitted, cannot stand on grammatical grounds. It aims to clarify the use of the word cuiatis, propose an emendation of the text, and suggest a new explanation of the metre of the fragment.
The Decentralised Governance in Kenya: Implications on Citizen Participation in the Local Governance
Authors: Onyalo Paul Otieno
Published: May 2024

This study sought to examine the extent to which decentralisation efforts have affected citizen participation in local governance in Kenya. Survey research designs was employed. 371 questionnaires were administered and 16 interview conducted with key stakeholders. The findings revealed that decentralisation influences citizen participation in devolved Governance. 77.3% of the respondents agreed decentralization had promoted political entrepreneurship while 75% contended that decentralization had influenced citizen participation in development of policies and legislation. Moreover, 57.2% of the respondents felt that citizen participation in decentralized policy-making was high while 69% of the respondents were satisfied that decentralization had made it possible for citizens to participate in county budgeting. Only 49% approved the effectiveness of decentralization in promoting citizen participation in participatory budgeting and planning process. The national and county governments should put in place measures to safeguard the independence of the counties in realizing the objective of citizen participation in governance.
A new freshwater species Achnanthes licunese sp. nov. (Achnanthaceae, Bacillariophyta) from pebbles of Licun River, Shandong Province, China
Authors: CHEN WEI , YU PAN , SONG GAOFEI , ABATE REDIAT
Published: May 2024

A new freshwater diatom species, Achnanthes licunese sp. nov., was found on pebble samples collected from Licun River in Shandong Province, China. The various taxonomic characteristics of Achnanthes licunese sp. nov. is observed under light and scanning electron microscope. The living cells of A. licunese sp. nov. possesses two chloroplasts. Its valves exhibit a linear to linear-lanceolate outline, slightly constricted in the middle part, with uniseriate striae. The central area of the raphid valves is expanded into a linear and thickened stauros, and the raphe is filiform. On the araphid valves, there is no central area, and the axial area (sternum) is located in the valve margin. The valve of the A. licunese sp. nov. possesses the marginal spines, but no marginal ridge and terminal orbiculi. By comparing the new species with similar Achnanthes species, A. licunese sp. nov. was confirmed to be sufficiently different regarding valve size, striae density, and the presence of marginal spines. The discovery of this species increases the diversity of freshwater diatoms.
Referral Contagion: Downstream Benefits of Customer Referrals
Authors: Gershon Rachel , Jiang Zhenling
Published: May 2024

Companies often invest in referral reward programs to incentivize their current customers to spread word of mouth. Previous work has documented that referred customers tend to be more valuable than nonreferred customers through their purchases or engagement with the company. The authors propose a previously overlooked benefit of encouraging referrals: Referred customers are also more valuable because they make more referrals. Using a large-scale field dataset, the authors show that referred customers make 31%–57% more referrals than nonreferred customers conditional on purchase activities. Using preregistered lab experiments, they replicate the main effect and propose one underlying mechanism: Referred customers perceive referring to be more socially appropriate than nonreferred customers do. In a field experiment, the authors build on previous work on norm salience and show that reminding referred customers that they joined through a referral further boosts their referral likelihood by 21%. These results advance the understanding of the social motives that contribute to referral decisions and illustrate that promoting referrals is substantially more valuable than previously estimated.
Preparation and properties of PP/SEBS foam materials
Authors: Tian Zhao , Wu Zhiqiang , Wang Yunfei , Shen Chunhui , Gao Shanjun
Published: May 2024

In this study, styrene-ethylene-butene-styrene block copolymer (SEBS) is blended with polypropylene (PP) to improve the melt strength of PP. Azodicarbonamide (AC) is used as a chemical foaming agent to prepare PP foaming materials with good mechanical properties by moulding foaming. The melt strength of the material, the content of the nucleating agent and the concentration of the foaming agent will affect the foaming effect of the material. Orthogonal optimization experiments are designed for these three factors to explore the best ratio of foaming materials. The results show that when PP:SEBS = 85:15, the addition amount of nano-SiO2 is 3%, and the content of AC foaming agent is 5%, the cell structure of the foaming material is the best. The cell structure is observed by SEM,the average cell diameter is reduced to 45.73 μm, and the cell density is increased to 4.12 × 106 cells cm−3. The apparent density of the material is measured to be 0.62 g cm−3, which is 32% lower than that of pure PP (0.91 g·cm−3). The tensile strength of PP/SEBS foamed composites is lower than that of pure PP and pure PP foamed materials, but its elongation at break is 124.3% higher than that of pure PP, and 238.8% higher than that of pure PP foamed materials. The bending strength of PP/SEBS foamed material is lower than that of pure PP and pure PP foamed material. The impact strength of PP/SEBS is only 8.4 % lower than that of pure PP, and 60.8 % higher than that of pure PP foamed material.
Exploring structure/property relationships to health and environmental hazards of polymeric polyisocyanate prepolymer substances-3. Aquatic exposure and hazard of aliphatic diisocyanate-based prepolymers
Authors: West Robert J , Jarrom Rebecca , Kelly Mitch , Simon Glenn S , Snyder Stephanie A
Published: May 2024

The water extractability and acute aquatic toxicity of seven aliphatic diisocyanate-based prepolymer substances were investigated to determine if lesser reactivity of the aliphatic isocyanate groups, as well as increased ionization potential of the expected (aliphatic amine-terminated) polymeric hydrolysis products, would influence their aquatic behavior compared to that of previously investigated aromatic diisocyanate-based prepolymers. At loading rates of 100 and 1,000 mg/L, only the substances having log Kow ≤9 exhibited more than 1% extractability in water, and a maximum of 66% water extractability was determined for a prepolymer having log Kow = 2.2. For the more hydrophobic prepolymer substances (log Kow values from 18–37), water extractability was negligible. High-resolution mass spectrometric analyses were performed on the water-accommodated fractions (WAF) of the prepolymers, which indicated the occurrence of primary aliphatic amine-terminated polymer species having backbones and functional group equivalent weights aligned to those of the parent prepolymers. Measurements of reduced surface tension and presence of suspended micelles in the WAFs further supported the occurrence of these surface-active cationic polymer species as hydrolysis products of the prepolymers. Despite these characteristics, the water-extractable hydrolysis products were practically non-toxic to Daphnia magna. All of the substances tested exhibited 48-h EL50 values of >1,000 mg/L, with one exception of EL50 = 157 mg/L. The results from this investigation support a grouping of the aliphatic diisocyanate-based prepolymers as a class of water-reactive polymer substances having predictable aquatic exposure and a uniformly low hazard potential, consistent with that previously demonstrated for the aromatic diisocyanate-based prepolymers.