bluuebunny/crossref_metadata_2025_split huggingface dataset:
Checkpoint inhibitors in metastatic gastric and GEJ cancer: a multi-institutional retrospective analysis of real-world data in a Western cohort
Authors: Schlintl Verena , Huemer Florian , Rinnerthaler Gabriel , Melchardt Thomas , Winder Thomas , Reimann Patrick , Riedl Jakob , Amann Arno , Eisterer Wolfgang , Romeder Franz , Piringer Gudrun , Ilhan-Mutlu Aysegül , Wöll Ewald , Greil Richard , Weiss Lukas 
Published: January 2022

Abstract
Background
Safety and efficacy of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction (GEJ) cancer could be demonstrated in predominantly Asian cohorts, whereas data in Western patients outside of clinical trials are vastly missing.

Methods
In this multi-institutional retrospective analysis conducted at nine oncologic centers in Austria, we tried to assess feasibility of checkpoint inhibitors in advanced gastric/GEJ cancer in a real-world Western cohort.

Results
In total, data from 50 patients with metastatic gastric/GEJ cancer who received nivolumab or pembrolizumab in a palliative setting between November 2015 and April 2020 have been evaluated. The median number of previous palliative therapy lines was two. The median progression-free survival (PFS) and overall survival (OS) were 2.1 (95% CI: 1.4–2.8) and 6.3 (95% CI: 3.3–9.3) months, respectively. There was no statistically significant difference in median OS according to microsatellite or PD-L1 status. However, a trend towards prolonged PFS and OS for the microsatellite instability high subgroup could be observed. Patients with an ECOG Performance Status (PS) ≥ 2 displayed a significantly worse outcome than those with an ECOG PS ≤ 1 (p = .03). Only one patient discontinued immunotherapy due to treatment-related toxicity.

Conclusions
Our results support feasibility of nivolumab and pembrolizumab in pre-treated patients with metastatic gastric and GEJ cancer in a Western real-world cohort. Further phase II/III studies are needed to confirm clinical efficacy.
Assessment of the Cost of the Mediterranean Diet in a Low-Income Region: Adherence and Relationship with Available Incomes
Authors: Rubini Alessia , Vilaplana-Prieto Cristina , Flor-Alemany Marta , Yeguas-Rosa Lorena , Hernández-González Miriam , Félix-García Francisco Javier , Félix-Redondo Francisco Javier , Fernández-Bergés Daniel 
Published: January 2022

Abstract
Background
The Mediterranean Diet (MD) is recognized as heart-healthy, but the economic cost associated with this type of diet has scarcely been studied.
The objective of the present study is to explore the cost and adherence of a low-income region population to the MD and its relationship with income.

Methods
A population-based study was carried out on 2,833 subjects between 25 and 79 years of age, 54% women, selected at random from the municipalities of Vegas Altas, La Siberia and La Serena in the province of Badajoz, Extremadura (Spain).
Average monthly cost of each product included in the MD was computed and related to adherence to the MD using the Panagiotakos Index and average disposable income.

Results
The monthly median cost was 203.6€ (IQR: 154.04-265.37). Food-related expenditure was higher for men (p<0.001), age cohort between 45 and 54 years (p<0.013) and those living in urban areas (p<0.001). A positive correlation between food-related expenditure and the MD adherence was found. Monthly median cost represents 15% of average disposable income, ranging between 11% for the group with low MD adherence and 17% for the group with high MD adherence.

Conclusions
The monthly cost of the MD was positively correlated with the degree of adherence to this dietary pattern. Given that the estimated monthly cost is similar to that of other Spanish regions with a higher income level, the economic effort required to be able to afford the Mediterranean diet is higher. This may represent a barrier to access, which should be analyzed in detail by public decision-makers.
Costs of breast cancer treatment incurred by women in Vietnam
Authors: Ngan Tran Thu , Ngoc Nguyen Bao , Van Minh Hoang , Donnelly Michael , O’Neill Ciaran 
Published: January 2022

Abstract
Background
There is a paucity of research on the cost of breast cancer (BC) treatment from the patient’s perspective in Vietnam.

Methods
Individual-level data about out-of-pocket (OOP) expenditures on use of services were collected from women treated for BC (n = 202) using an online survey and a face-to-face interview at two tertiary hospitals in 2019. Total expenditures on diagnosis and initial BC treatment were presented in terms of the mean, standard deviation, and range for each type of service use. A generalised linear model (GLM) was used to assess the relationship between total cost and socio-demographic characteristics.

Results
19.3% of respondents had stage 0/I BC, 68.8% had stage II, 9.4% had stage III, none had stage IV. The most expensive OOP elements were targeted therapy with mean cost equal to 649.5 million VND ($28,025) and chemotherapy at 36.5 million VND ($1575). Mean total OOP cost related to diagnosis and initial BC treatment (excluding targeted therapy cost) was 61.8 million VND ($2667). The mean OOP costs among patients with stage II and III BC were, respectively, 66 and 148% higher than stage 0/I.

Conclusions
BC patients in Vietnam incur significant OOP costs. The cost of BC treatment was driven by the use of therapies and presentation stage at diagnosis. It is likely that OOP costs of BC patients would be reduced by earlier detection through raised awareness and screening programmes and by providing a higher insurance reimbursement rate for targeted therapy.
LncRNA TP73‐AS1 promotes nasopharyngeal carcinoma progression through targeting miR-342-3p and M2 polarization via exosomes
Authors: Yao Hongchao , Tian Linli , Yan Bingrui , Yang Like , Li Yushan 
Published: January 2022

Abstract
Background
Nasopharyngeal carcinoma (NPC) is a deadly cancer, mainly presenting in southeast and east Asia. Long noncoding RNAs (lncRNAs) play essential roles in cancer progression. Exosomes are critical for intercellular communication. Thus, the aim of this study was to identify the functional lncRNAs in NPC and its relevant mechanisms.

Methods
Data from public databases were utilized to screen for functional lncRNAs in NPC. Functional and mechanical experiments were performed to determine the role of lncRNAs in NPC and its relative molecular mechanisms. Exosomes derived from NPC cells were isolated to determine their function in tumor-associated macrophages.

Results
LncRNA TP73-AS1 was increased in NPC cells and tissues and was associated with a poor prognosis. TP73-AS1 overexpression promoted proliferation, colony formation, and DNA synthesis of NPC cells while TP73-AS1 knockdown showed opposite roles. TP73-AS1 could directly bind with miR-342-3p. MiR-342-3p overexpression attenuated the effect of TP73-AS1 in NPC cells. Furthermore, TP73-AS1 was transferred by exosomes to promote M2 polarization of macrophages. Lastly, exosomal TP73-AS1 enhanced the motility and tube formation of macrophages.

Conclusions
Together, this study suggests that TP73-AS1 promotes NPC progression through targeting miR-342-3p and exosome-based communication with macrophages and that TP73-AS1 might be an emerging biomarker for NPC.
Animal health is often ignored, but indispensable to the human right to health
Authors: Hartnack Sonja 
Published: January 2022

AbstractAlthough preventable by vaccines, approximately 60′000 humans die due to canine transmitted rabies annually, mostly in Africa and Asia. The aim of this paper is to advocate for including animal health aspects into considerations of human health and human rights, and for equitable access to rabies vaccination for both animals and humans. An infringement of human - in particular of children’s - right to health will be illustrated with the case of rabies and poor dog management in Uganda.
Self-assembling ferritin nanoparticles coupled with linear sequences from canine distemper virus haemagglutinin protein elicit robust immune responses
Authors: Wang Bo , Li Shuang , Qiao Yongbo , Fu Yu , Nie Jiaojiao , Jiang Shun , Yao Xin , Pan Yi , Zhao Linye , Wu Congmei , Shi Yuhua , Yin Yuhe , Shan Yaming 
Published: January 2022

Abstract
Background
Canine distemper virus (CDV), which is highly infectious, has caused outbreaks of varying scales in domestic and wild animals worldwide, so the development of a high-efficiency vaccine has broad application prospects. Currently, the commercial vaccine of CDV is an attenuated vaccine, which has the disadvantages of a complex preparation process, high cost and safety risk. It is necessary to develop a safe and effective CDV vaccine that is easy to produce on a large scale. In this study, sequences of CDV haemagglutinin (HA) from the Yanaka strain were aligned, and three potential linear sequences, termed YaH3, YaH4, and YaH5, were collected. To increase the immunogenicity of the epitopes, ferritin was employed as a self-assembling nanoparticle element. The ferritin-coupled forms were termed YaH3F, YaH4F, and YaH5F, respectively. A full-length HA sequence coupled with ferritin was also constructed as a DNA vaccine to compare the immunogenicity of nanoparticles in prokaryotic expression.

Result
The self-assembly morphology of the proteins from prokaryotic expression was verified by transmission electron microscopy. All the proteins self-assembled into nanoparticles. The expression of the DNA vaccine YaHF in HEK-293T cells was also confirmed in vitro. After subcutaneous injection of epitope nanoparticles or intramuscular injection of DNA YaHF, all vaccines induced strong serum titres, and long-term potency of antibodies in serum could be detected after 84 days. Strong anti-CDV neutralizing activities were observed in both the YaH4F group and YaHF group. According to antibody typing and cytokine detection, YaH4F can induce both Th1 and Th2 immune responses. The results of flow cytometry detection indicated that compared with the control group, all the immunogens elicited an increase in CD3. Simultaneously, the serum antibodies induced by YaH4F and YaHF could significantly enhance the ADCC effect compared with the control group, indicating that the antibodies in the serum effectively recognized the antigens on the cell surface and induced NK cells to kill infected cells directly.

Conclusions
YaH4F self-assembling nanoparticle obtained by prokaryotic expression has no less of an immune effect than YaHF, and H4 has great potential to become a key target for the easy and rapid preparation of epitope vaccines.

Graphical Abstract
Pediatric quality of life multidimensional fatigue scale (PedsQL-MFS) detects the effects of a 3-week Inpatient body weight reduction program for children and adolescents with obesity
Authors: Smout Matthew F. , Manzoni Gian Mauro , Tamini Sofia , Marazzi Nicoletta , De Col Alessandra , Pietrabissa Giada , Castelnuovo Gianluca , Molinari Enrico , Sartorio Alessandro 
Published: January 2022

AbstractBackgroundFatigue is a frequent complaint amongst children and adolescents with obesity, and it interferes with adherence to dietary and exercise regimes that could reduce obesity. The present study evaluated the effect of an inpatient 3-week body weight reduction program on body weight and fatigue.MethodOne hundred children and adolescents with obesity (64% female; aged 11–18 years) undertook an inpatient program of personalized diet, daily exercise, education, and counselling.ResultsThe sample evidenced a mean reduction in body mass (females:ΔM = 4.3 (sd = 2.1) kg,p < .001), males:ΔM = 6.2 (sd = 2.6) kg,p < .001), BMI standard deviation score (females:ΔM = 0.17 (sd = 0.07), males:ΔM = 0.24 (sd = 0.08),p < .001) and fatigue (females:ΔM = 7.8 (sd = 9.7), males:ΔM = 5.0 (sd = 6.9),p < .001) as measured by the Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) and improvements on the Attention problems subscale of the Youth Self Report (total sample:ΔM = 0.89 (sd = 2.44),p < .001). Reliable change analyses revealed fatigue changes were achieved by up to 34% females and 17% males, but the majority did not achieve reliable change and changes in fatigue were not correlated with changes in body mass.ConclusionsThe program achieved clinically significant improvements in some children and adolescents. Future studies should explore predictors of treatment responsiveness.Trial registrationObservational study. Not registered.
Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation
Authors: Dumesic Daniel A. , Padmanabhan Vasantha , Chazenbalk Gregorio D. , Abbott David H. 
Published: January 2022

AbstractAs a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.
Incidence of breast cancer subtypes in immigrant and non-immigrant women in Norway
Authors: Hjerkind Kirsti V. , Johansson Anna L. V. , Trewin Cassia B. , Russnes Hege G. , Ursin Giske 
Published: January 2022

Abstract
Background
Breast cancer incidence differs between non-immigrants and immigrants from low- and middle-income countries. This study investigates whether immigrants also have different subtype-specific incidences.

Methods
We used national health registries in Norway and calculated subtype-specific incidence rate ratios (IRRs) for invasive breast cancer among women aged 20–75 and 20–49 years between 2005 and 2015. Immigrant groups were classified by country of birth broadly defined based on WHO regional groupings. Subtype was defined using estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) status as luminal A-like (ER+ PR+ HER2-), luminal B-like/HER2- (ER+ PR- HER2-), luminal B-like/HER2+ (ER+ PR any HER2+), HER2+ (ER-PR-HER2+) and triple-negative breast cancer (TNBC) (ER-PR-HER2-).

Results
Compared to non-immigrants, incidence of the luminal A-like subtype was lower in immigrants from Sub-Saharan Africa (IRR 0.43 95% CI 0.28–0.66), South East Asia (IRR 0.63 95% CI 0.51–0.79), South Asia (IRR 0.67 95% CI 0.52–0.86) and Eastern Europe (IRR 0.86 95% CI 0.76–0.99). Immigrants from South Asia had higher rates of HER2 + tumors (IRR 2.02 95% CI 1.26–3.23). The rates of TNBC tended to be similar regardless of region of birth, except that women from South East Asia had an IRR of 0.54 (95% CI 0.32–0.91).

Conclusions
Women from Eastern Europe, Sub-Saharan Africa and Asia had different subtype-specific incidences compared to women from high-income countries (including non-immigrants). These differences in tumor characteristics between immigrant groups should be taken into consideration when planning preventive or screening strategies.
Luteolin increases susceptibility to macrolides by inhibiting MsrA efflux pump in Trueperella pyogenes
Authors: Guo Yuru , Huang Chengcheng , Su Hongyu , Zhang Zehui , Chen Menghan , Wang Ruxia , Zhang Dexian , Zhang Luyao , Liu Mingchun 
Published: January 2022

AbstractTrueperella pyogenes (T. pyogenes) is an opportunistic pathogen associated with a variety of diseases in many domestic animals. Therapeutic treatment options for T. pyogenes infections are becoming limited due to antimicrobial resistance, in which efflux pumps play an important role. This study aims to evaluate the inhibitory activity of luteolin, a natural flavonoid, on the MsrA efflux pump and investigate its mechanism. The results of antimicrobial susceptibility testing indicated that the susceptibility of msrA-positive T. pyogenes isolates to six macrolides increased after luteolin treatment, while the susceptibility of msrA-negative isolates showed no change after luteolin treatment. It is suspected that luteolin may increase the susceptibility of T. pyogenes isolates by inhibiting MsrA activity. After 1/2 MIC luteolin treatment for 36 h, the transcription level of the msrA gene and the expression level of the MsrA protein decreased by 55.0–97.7% and 36.5–71.5%, respectively. The results of an affinity test showed that the equilibrium dissociation constant (KD) of luteolin and MsrA was 6.462 × 10–5 M, and hydrogen bonding was predominant in the interaction of luteolin and MsrA. Luteolin may inhibit the ATPase activity of the MsrA protein, resulting in its lack of an energy source. The current study illustrates the effect of luteolin on MsrA in T. pyogenes isolates and provides insight into the development of luteolin as an innovative agent in combating infections caused by antimicrobial-resistant bacteria.
Neurological management and work-up of neurotoxicity associated with CAR T cell therapy
Authors: Möhn Nora , Bonda Viktoria , Grote-Levi Lea , Panagiota Victoria , Fröhlich Tabea , Schultze-Florey Christian , Wattjes Mike P. , Beutel Gernot , Eder Matthias , David Sascha , Körner Sonja , Höglinger Günter , Stangel Martin , Ganser Arnold , Koenecke Christian , Skripuletz Thomas 
Published: January 2022

Abstract
Introduction
Treatment with CD19 chimeric antigen receptor (CAR) T cells is an innovative therapeutic approach for patients with relapsed/refractory diffuse large B cell lymphoma (r/rDLBCL) and B-lineage acute lymphoblastic leukemia (r/rALL). However, convincing therapeutic response rates can be accompanied by cytokine release syndrome (CRS) and severe neurotoxicity termed immune effector cell-associated neurotoxicity syndrome (ICANS).

Methods
Single center, prospective observational study of fifteen consecutive r/r DLBCL patients treated with Tisagenlecleucel within 1 year at Hannover Medical School. Extensive neurological work-up prior to CAR T cell infusion included clinical examination, cognitive testing (Montreal-Cognitive-Assessment), brain MRI, electroencephalogram, electroneurography, and analysis of cerebrospinal fluid. After CAR T cell infusion, patients were neurologically examined for 10 consecutive days. Afterwards, all patients were assessed at least once a week.

Results
ICANS occurred in 4/15 patients (27%) within 6 days (4–6 days) after CAR T cell infusion. Patients with ICANS grade 2 (n = 3) exhibited similar neurological symptoms including apraxia, expressive aphasia, disorientation, and hallucinations, while brain MRI was inconspicuous in either case. Treatment with dexamethasone rapidly resolved the clinical symptoms in all three patients. Regarding baseline parameters prior to CAR T cell treatment, patients with and without ICANS did not differ.

Conclusions
In our cohort, ICANS occurred in only every fourth patient and rather low grade neurotoxicity was found during daily examination. Our results demonstrate that a structured neurological baseline examination and close monitoring are helpful to detect CAR T cell related neurotoxicity already at an early stage and to potentially prevent higher grade neurotoxicity.
Phase II Trial of Inotuzumab Ozogamicin in Children and Adolescents With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: Children's Oncology Group Protocol AALL1621
Authors: O'Brien Maureen M. , Ji Lingyun , Shah Nirali N. , Rheingold Susan R. , Bhojwani Deepa , Yuan Constance M. , Xu Xinxin , Yi Joanna S. , Harris Andrew C. , Brown Patrick A. , Borowitz Michael J. , Militano Olga , Kairalla John , Devidas Meenakshi , Raetz Elizabeth A. , Gore Lia , Loh Mignon L. 
Published: January 2022

PURPOSE Children's Oncology Group trial AALL1621 was conducted to prospectively determine the safety and efficacy of inotuzumab ozogamicin (InO) in pediatric and adolescent patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). PATIENTS AND METHODS This single-arm phase II trial enrolled patients age 1-21 years with R/R CD22-positive B-ALL. In cycle 1, InO dosing was 0.8 mg/m2 intravenously on day 1 and 0.5 mg/m2 on days 8 and 15 of a 28-day cycle with response evaluation at day 28. Using a two-stage design, the trial was continuously monitored for dose-limiting toxicities and sinusoidal obstruction syndrome (SOS). CD22 expression was retrospectively evaluated by central flow cytometry. RESULTS Forty-eight patients were evaluable for response and toxicity; 19 had complete response (CR) and nine CR with incomplete count recovery (CRi) after cycle 1 (CR/CRi rate: 58.3%; two-sided 90% CI, 46.5 to 69.3). Twenty-seven of 28 patients with CR or CRi had minimal residual disease measured by flow cytometry; 18 (66.7%) had minimal residual disease < 0.01%. Seven of 28 patients (25%) with CR or CRi had delayed count recovery past day 42 in cycle 1. Three (6.3%) patients had grade 3 ALT elevation and one patient had grade 3 hyperbilirubinemia in cycle 1. Of 21 patients undergoing hematopoietic stem-cell transplantation after InO, 6 (28.6%) developed grade 3 SOS. Partial CD22 expression and lower CD22 site density were associated with lower likelihood of response to InO. CONCLUSION InO is effective and well tolerated in heavily pretreated children and adolescents with R/R CD22-positive B-ALL. SOS after hematopoietic stem-cell transplantation and prolonged cytopenias were notable. CD22 modulation was identified as a mechanism of resistance. Expanded study of InO combined with chemotherapy is underway.