bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approximation of solutions to integro-differential time fractional order parabolic equations in $L^{p}$-spaces
Authors: Zhao Yongqiang , Tang Yanbin 
Published: November 2023

AbstractIn this paper we study the initial boundary value problem for a class of integro-differential time fractional order parabolic equations with a small positive parameter ε. Using the Laplace transform, Mittag-Leffler operator family, $C_{0}$

C
0

-semigroup, resolvent operator, and weighted function space, we get the existence of a mild solution. For suitable indices $p\in [1,+\infty )$
p
∈
[
1
,
+
∞
)
and $s\in (1,+\infty )$
s
∈
(
1
,
+
∞
)
, we first prove that the mild solution of the approximating problem converges to that of the corresponding limit problem in $L^{p}((0,T), L^{s}(\Omega ))$

L
p

(
(
0
,
T
)
,

L
s

(
Ω
)
)
as $\varepsilon \rightarrow 0^{+}$
ε
→

0
+

. Then for the linear approximating problem with ε and the corresponding limit problem, we give the continuous dependence of the solutions. Finally, for a class of semilinear approximating problems and the corresponding limit problems with initial data in $L^{s}(\Omega )$

L
s

(
Ω
)
, we prove the local existence and uniqueness of the mild solution and then give the continuous dependence on the initial data.
Cardiac protective techniques in left breast radiotherapy: rapid selection criteria for routine clinical decision making
Authors: Kirli Bolukbas Meltem , Karaca Sibel , Coskun Volkan , Kocak Uzel Esengul 
Published: November 2023

Abstract
Objective
In left breast radiotherapy (RT) desired heart doses may be achieved without heart-sparing RT techniques in some patients. We aimed to examine the existence of predictive factors and cutoff points to determine which patients are the main candidates for heart-sparing RT techniques.

Material and method
Dosimetric data for left breast cancer was examined. RT plans were made at conventional doses to the breast and peripheral lymph nodes. Statistical analyses were performed using SPSS 22.0 (SPSS Inc., IBM Corp., Armonk, NY).

Result
114 cases were evaluated by ROC (Receiver operating characteristic) analysis in the breast-conserving surgery (BCS) and mastectomy groups. While only left lung volume (AUC: 0.74, 95% CI 0.61–0.87, p = 0.002) was significant in BCS cases, in cases with mastectomy, left lung volume (AUC: 0.81, 95% CI 0.69–0.94, p = 0.002) and lung/heart volume ratio (AUC: 0.83, 95% CI 0.70–0.96, p = 0.001) had a significant relationship with the relevance of heart doses. The cutoff point of 1.92 was selected for the lung/heart volume ratio for the mastectomized patients. Moreover, the cutoff point 1154 cc and 1208 cc was determined for the left lung volume for the BCS and mastectomized patients, respectively.

Conclusion
Various cutoff points in left breast RT can be used to predict whether RT plans will meet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) heart dose limits. Evaluating only these few cutoff points before planning makes it possible to eliminate 70% of patients with BCS and 40% of patients with mastectomy from respiratory-controlled methods, which require time and effort. Patients with lung volume and lung/heart volume ratio smaller than the cutoff values can be considered primary candidates for heart-sparing techniques.
The effects of chemotherapy on resting energy expenditure, body composition, and cancer-related fatigue in women with breast cancer: a prospective cohort study
Authors: Van Soom Timia , Tjalma Wiebren , Papadimitriou Konstantinos , Gebruers Nick , van Breda Eric 
Published: November 2023

AbstractBackgroundBreast cancer (BC) is the most prevalent tumor in women. Improvements in treatment led to declined mortality, resulting in more survivors living with cancer- or therapy-induced comorbidities. In this study, we investigated the impact of neoplasia and chemotherapy on resting energy expenditure (REE) and body composition, in relation to cancer-related fatigue. Inflammatory parameters were checked as possible explanation for changes in REE.MethodsFifty-six women participated: 20 women with BC and 36 healthy controls. Patients were assessed at baseline (T0) and follow-up (T1) after 12 weeks of chemotherapy. Controls were measured once. REE was assessed with indirect calorimetry: body composition (body weight, fat mass, fat-free mass) by air plethysmography. The multidimensional fatigue index (MFI-20) was used to analyze fatigue. Baseline measurements of patients were compared to results of the healthy controls with the independent-samplesT-test. The paired-samplesT-test investigated the effects of chemotherapy from T0 to T1. A Pearson correlation analysis was conducted between REE, body composition, and fatigue and between REE, body composition, and inflammatory parameters. A linear regression analysis was fitted to estimate the contribution of the significantly correlated parameters. The measured REE at T0 and T1 was compared to the predicted REE to analyze the clinical use of the latter.ResultsAt baseline, patients with BC had significantly higher REE in the absence of differences in body composition. From baseline to T1, REE and body weight did not change. In contrast, fat-free mass declined significantly with concordant increase in fat mass. Fatigue deteriorated significantly. C-reactive protein at baseline predicted the change in energy expenditure. Predicted REE significantly underestimated measured REE.ConclusionsWomen with BC have higher REE in the tumor-bearing state compared to healthy controls. Chemotherapy does not affect REE but alters body composition. Predictive equations are invalid in the BC population. Results of our study can be used to implement personalized nutritional interventions to support energy expenditure and body composition and minimize long-term comorbidities.
The burden of rare variants in DPYS gene is a novel predictor of the risk of developing severe fluoropyrimidine-related toxicity
Authors: De Mattia Elena , Polesel Jerry , Silvestri Marco , Roncato Rossana , Scarabel Lucia , Calza Stefano , Spina Michele , Puglisi Fabio , Toffoli Giuseppe , Cecchin Erika 
Published: November 2023

Abstract
Background
Despite a growing number of publications highlighting the potential impact on the therapy outcome, rare genetic variants (minor allele frequency < 1%) in genes associated to drug adsorption, distribution, metabolism, and elimination are poorly studied. Previously, rare germline DPYD missense variants were shown to identify a subset of fluoropyrimidine-treated patients at high risk for severe toxicity. Here, we investigate the impact of rare genetic variants in a panel of 54 other fluoropyrimidine-related genes on the risk of severe toxicity.

Methods
The coding sequence and untranslated regions of 54 genes related to fluoropyrimidine pharmacokinetics/pharmacodynamics were analyzed by next-generation sequencing in 120 patients developing grade 3–5 toxicity (NCI-CTC vs3.0) and 104 matched controls. Sequence Kernel Association Test (SKAT) analysis was used to select genes with a burden of genetic variants significantly associated with risk of severe toxicity. The statistical association of common and rare genetic variants in selected genes was further investigated. The functional impact of genetic variants was assessed using two different in silico prediction tools (Predict2SNP; ADME Prediction Framework).

Results
SKAT analysis highlighted DPYS and PPARD as genes with a genetic mutational burden significantly associated with risk of severe fluoropyrimidine-related toxicity (Bonferroni adjusted P = 0.024 and P = 0.039, respectively). Looking more closely at allele frequency, the burden of rare DPYS variants was significantly higher in patients with toxicity compared with controls (P = 0.047, Mann–Whitney test). Carrying at least one rare DPYS variant was associated with an approximately fourfold higher risk of severe cumulative (OR = 4.08, P = 0.030) and acute (OR = 4.21, P = 0.082) toxicity. The burden of PPARD rare genetic variants was not significantly related to toxicity. Some common variants with predictive value in DPYS and PPARD were also identified: DPYS rs143004875-T and PPARD rs2016520-T variants predicted an increased risk of severe cumulative (P = 0.002 and P = 0.001, respectively) and acute (P = 0.005 and P = 0.0001, respectively) toxicity.

Conclusion
This work demonstrated that the rare mutational burden of DPYS, a gene strictly cooperating with DPYD in the catabolic pathway of fluoropyrimidines, is a promising pharmacogenetic marker for precision dosing of fluoropyrimidines. Additionally, some common genetic polymorphisms in DPYS and PPARD were identified as promising predictive markers that warrant further investigation.
Diet of Black-backed Jackal (Canis mesomelas, Schreber, 1775), impacts on livelihood and perceptions of farmers in Konasa Pulasa community conserved forest, omo valley of Ethiopia
Authors: Matusal Mesfin , Megaze Aberham 
Published: November 2023

Abstract
Background
Livestock depredation by the black-backed jackal (Canis mesomelas) occurs widely across Africa. The study on human-jackal conflict is important for conservation efforts in Ethiopia. The aim of this study was to investigate the diet of black-backed jackals, to understand their predation effects on domestic livestock and perceptions of farmers’ in the Konasa-Pulasa Community Conserved Forest, Omo Valley of Ethiopia. The study was conducted using scat analysis, questionnaire survey and Focus Group Discussion methods. Livestock depredation and the economic impact of farmers were assessed among 290 randomly selected households. A total of 90 scat samples were collected and analyzed during the dry and wet seasons to identify the diet of jackals.

Results
A total of 624 domestic animals have been lost in the last 5 years (2016–2020). The estimated economic cost of domestic animals lost due to predation by jackals was US $18,180.0 in the last five years, and US $12.5 per year per household. The major diet composition of jackals was of domestic animal origin (45.5%), followed by wild animals (30.8%) in both the dry and wet seasons. However, more prey diversity was recorded during the wet season. The respondents revealed that the causes of black-backed jackal conflict in the study area were higher due to increasing jackal population size (40%). The major traditional mitigation method was guarding (42%). Most of the respondents (48.2%) had negative perceptions towards the conservation of black-backed jackals.

Conclusion
Livestock depredations by black-backed jackals were the major issue of conflict in the study area. Scat analysis showed that large percentage of domestic animal species remain in the scat of jackals. Livestock losses caused by jackals represent an economic concern for livestock owners in the area. Local people close to the forest boundary were highly vulnerable to domestic animal loss due to predation by jackals. Therefore, improved livestock husbandry methods will be implemented by the local people for effective jackal conservation in Konasa-Pulasa Community Conserved Forest. Understanding the ecological and social dimensions of conflict situations in the area may have important ecological and management implications for the country.
Application of Metabolomics to Epidemiologic Studies of Breast Cancer: New Perspectives for Etiology and Prevention
Authors: His Mathilde , Gunter Marc J. , Keski-Rahkonen Pekka , Rinaldi Sabina 
Published: November 2023

PURPOSE To provide an overview on how the application of metabolomics (high-throughput characterization of metabolites from cells, organs, tissues, or biofluids) to population-based studies may inform our understanding of breast cancer etiology. METHODS We evaluated studies that applied metabolomic analyses to prediagnostic blood samples from prospective epidemiologic studies to identify circulating metabolites associated with breast cancer risk, overall and by breast cancer subtype and menopausal status. We provide some important considerations for the application and interpretation of metabolomics approaches in this context. RESULTS Overall, specific lipids and amino acids were indicated as the most common metabolite classes associated with breast cancer development. However, comparison of results across studies is challenging because of heterogeneity in laboratory techniques, analytical methods, sample size, and applied statistical methods. CONCLUSION Metabolomics is being increasingly applied to population-based studies for the identification of new etiologic hypotheses and/or mechanisms related to breast cancer development. Despite its success in applications to epidemiology, studies of larger sample size with detailed information on menopausal status, breast cancer subtypes, and repeated biologic samples collected over time are needed to improve comparison of results between studies and enhance validation of results, allowing potential clinical translation of findings.
Trastuzumab Plus Gemcitabine-Cisplatin for Treatment-Naïve Human Epidermal Growth Factor Receptor 2–Positive Biliary Tract Adenocarcinoma: A Multicenter, Open-Label, Phase II Study (TAB)
Authors: Ostwal Vikas , Mandavkar Sarika , Bhargava Prabhat , Srinivas Sujay , Kapoor Akhil , Shetty Omshree , Kannan Sadhana , Chaugule Deepali , Patil Rajshree , Parulekar Manali , Nashikkar Chaitali , Ankathi Suman Kumar , Baheti Akshay Dwarka , Mehta Daksha , Kaushal Rajiv Kumar , Yadav Subhash , Shah Aekta , Patkar Shraddha , Goel Mahesh , Ramaswamy Anant 
Published: November 2023

PURPOSE Human epidermal growth factor receptor 2 (HER2) overexpression is seen in 4%-16% of biliary tract cancers (BTCs). We aimed to evaluate the clinical activity of gemcitabine-cisplatin (GC) plus anti-HER2 antibody trastuzumab as initial treatment in HER2-positive BTCs. METHODS This study was an investigator-initiated, open-label, single-arm, multi-institutional, phase II trial in adult patients with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+ and fluorescent in situ hybridization–positive), treatment-naïve BTCs. The primary end point of the study was 6-month progression-free survival (PFS). Next-generation sequencing was performed on tissue samples to evaluate mutational status. RESULTS From March 2020 to August 2022, of the 876 screened patients, 118 (13.4%) were found to have HER2-positive status, of whom 90 were enrolled in the study. Most patients had GBC (n = 96; 96%) with two or more sites of metastatic disease (n = 70; 78%). With a median follow-up of 17.3 (95% CI, 15.22 to 19.32) months, 72 patients had disease progression with a median PFS of 7 (95% CI, 6.2 to 7.8) months. The diagnosis to event 6-month PFS rate was 75.6% (95% CI, 66.6 to 84.6). A complete or partial response was seen in 50 (55.5%) patients and 22 (24.4%) patients had stable disease as the best response to treatment, for an overall disease control rate of 80%. The presence of isolated TP53 mutations was associated with inferior PFS compared with other mutations (TERT promoter, HER2, PIK3CA, etc) or no detected mutations (6.51 v 12.02 v 10.58 months; P < .001). CONCLUSION The combination of GC and trastuzumab achieved its primary end point of improving PFS compared with historical data in the treatment-naïve HER2-positive BTC. Evaluating additional mutations such as TP53 and PIK3CA along with HER2 testing may help to preferentially select patients for anti-HER2 therapy in the future (Clinical Trial Registry India number: CTRI/2019/11/021955).
Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer
Authors: Ogobuiro Ifeanyichukwu , Baca Yasmine , Ribeiro Jennifer R. , Walker Phillip , Wilson Gregory C. , Gulhati Prateek , Marshall John L. , Shroff Rachna T. , Spetzler David , Oberley Matthew J. , Abbott Daniel E. , Kim Hong Jin , Kooby David A. , Maithel Shishir K. , Ahmad Syed A. , Merchant Nipun B. , Xiu Joanne , Hosein Peter J. , Datta Jashodeep 
Published: November 2023

PURPOSE Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between patients with young-onset pancreatic cancer (YOPC; younger than 50 years) and patients with average-onset pancreatic cancer (AOPC; 70 years and older). METHODS We analyzed matched whole-transcriptome and DNA sequencing data from 2,430 patient samples (YOPC, n = 292; AOPC, n = 2,138) from the Caris Life Sciences database (Phoenix, AZ). Immune deconvolution was performed using the quanTIseq pipeline. Overall survival (OS) data were obtained from insurance claims (n = 4,928); Kaplan-Meier estimates were calculated for age- and molecularly defined cohorts. Significance was determined as FDR-corrected P values ( Q) < .05. RESULTS Patients with YOPC had higher proportions of mismatch repair–deficient/microsatellite instability-high, BRCA2-mutant, and PALB2-mutant tumors compared with patients with AOPC, but fewer SMAD4-, RNF43-, CDKN2A-, and SF3B1-mutant tumors. Notably, patients with YOPC demonstrated significantly lower incidence of KRAS mutations compared with patients with AOPC (81.3% v 90.9%; Q = .004). In the KRAS wild-type subset (n = 227), YOPC tumors demonstrated fewer TP53 mutations and were more likely driven by NRG1 and MET fusions, whereas BRAF fusions were exclusively observed in patients with AOPC. Immune deconvolution revealed significant enrichment of natural killer cells, CD8+ T cells, monocytes, and M2 macrophages in patients with YOPC relative to patients with AOPC, which corresponded with lower rates of HLA-DPA1 homozygosity. There was an association with improved OS in patients with YOPC compared with patients with AOPC with KRAS wild-type tumors (median, 16.2 [YOPC- KRASWT] v 10.6 [AOPC- KRASWT] months; P = .008) but not KRAS-mutant tumors ( P = .084). CONCLUSION In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.
Recurrent Soft Tissue Infections Associated With Burosumab Therapy in X-Linked Hypophosphatemic Rickets
Authors: Yoon Sean Ho , Passarella Pasquale 
Published: November 2023

Abstract
X-linked hypophosphatemic rickets (XLH) is a genetic disorder characterized by elevated fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and inadequate bone mineralization. Burosumab, a monoclonal antibody that inhibits FGF23 activity, has shown promise in improving renal phosphate reabsorption and clinical outcomes in XLH patients. However, the potential side effects of burosumab, particularly its impact on immune function and susceptibility to infections, remain a subject of concern. In this case report, we describe a 57-year-old male individual with XLH who experienced recurrent soft tissue infections while receiving burosumab therapy. The infections included an olecranon abscess, a cervical retropharyngeal phlegmon with a sternocleidomastoid abscess, and suprapubic cellulitis, all of which were treated with antibiotic therapy. Following discontinuation of burosumab therapy, the patient did not experience further soft tissue infections. These observations suggest a potential association between burosumab therapy and an increased risk of soft tissue infections. Mechanistically, disruption of the FGF23-Klotho signaling axis may lead to impaired humoral immunity mediated by B lymphocytes and compromised innate immune response mediated by macrophages. Further investigation is warranted to better understand the immunological effects of burosumab and its implications for infectious complications in XLH patients.
Initiation of Continuous rhPTH Infusion With Insulin Pump in an Inpatient Setting
Authors: Lindsay Mart Faith , Winer Karen K , Johnson Karla , Wasserman Halley 
Published: November 2023

Abstract
Hypoparathyroidism is one of the few remaining hormonal insufficiencies not treated with replacement of its missing hormone. Conventional therapy involves multiple daily oral doses of calcium, active vitamin D, and magnesium, which is not only cumbersome for patients, but carries risk of nephrocalcinosis and is inadequate in patients with enteral malabsorption. Subcutaneous parathyroid hormone 1-34 (PTH[1-34]) has been tested as a hormonal replacement therapy for treatment of hypoparathyroidism. PTH(1-34) delivered by continuous infusion via insulin pump decreases or eliminates the need for oral medications, stabilizes serum and urine calcium at normal levels with minimal fluctuation, and significantly reduces PTH doses. In this case report, we describe the clinical application of PTH(1-34) via insulin pump in an adolescent with autoimmune polyendocrinopathy syndrome type 1 (APS1). Transition to a PTH pump reduced hospital admissions for calcium abnormalities and allowed our patient to discontinue all scheduled daily conventional therapy.
Pre-gelation staining expansion microscopy for visualisation of the Plasmodium liver stage
Authors: Atchou Kodzo , Berger Bianca Manuela , Heussler Volker , Ochsenreiter Torsten 
Published: November 2023

ABSTRACT
Fluorescence and light microscopy are important tools in the history of natural science. However, the resolution of microscopes is limited by the diffraction of light. One possible method to circumvent this physical restriction is the recently developed expansion microscopy (ExM). However, the original ultrastructure ExM (U-ExM) protocol is very time-consuming, and some epitopes are lost during the process. In this study, we developed a shortened pre-gelation staining ExM (PS-ExM) protocol and tested it to investigate the Plasmodium liver stage. The protocol presented in this study allows expanding of pre-stained samples, which results in shorter incubation times, better preservation of some epitopes and the advantage that non-expanded controls can be performed alongside using the same staining protocol. The protocol applicability was accessed throughout the Plasmodium liver stage, showing isotropic five-fold expansion. Furthermore, we used PS-ExM to visualise parasite mitochondria as well as the association of lysosomes to the parasitophorous vacuole membrane (PVM) as an example of visualising host–pathogen interaction. We are convinced that this new tool will be helpful for a deeper understanding of the biology of the Plasmodium liver stage.