bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partial replacement of high-fat diet with n-3 PUFAs enhanced beef tallow attenuates dyslipidemia and endoplasmic reticulum stress in tunicamycin-injected rats
Authors: Zheng Jiaxiang , Lee Jisu , Byun Jaemin , Yu Daeung , Ha Jung-Heun 
Published: March 2023

IntroductionMetabolic syndrome (MetS) is considered as a complex, intertwined multiple risk factors that directly increase the risk of various metabolic diseases, especially cardiovascular atherosclerotic diseases and diabetes mellitus type 2. While lifestyle changes, including dietary intervention are effective in mitigating or preventing MetS, there are no specific therapies against MetS. Typical western diets comprise of high saturated fatty acid, cholesterol, and simple sugar; consequently their consumption may increase the potential pathological developmental risk of MetS. Partial replacement of dietary fatty acids with polyunsaturated fatty acids (PUFAs) is widely recommended measure to manage MetS-related disorders.MethodsIn the present study, we used rat model to investigate the role of n-3 PUFA enriched beef tallows (BT) on MetS and tunicamycin (TM)-induced endoplasmic reticulum (ER) stress, by partially replacing dietary fat (lard) with equal amounts of two different BTs; regular BT or n-3 PUFA-enriched BT. The experimental rats were randomly assigned to three different dietary groups (n = 16 per group): (1) high-fat and high-cholesterol diet (HFCD); (2) HFCD partially replaced with regular BT (HFCD + BT1); (3) HFCD partially replaced with n-3 enhanced BT (w/w) (HFCD + BT2). After 10 weeks of dietary intervention, each experimental rodent was intraperitoneally injected with either phosphate-buffered saline or 1 mg/kg body weight of TM.ResultsHFCD + BT2 showed improved dyslipidemia before TM injection, and increased serum high-density lipoprotein cholesterol (HDL-C) levels after TM injection. BT replacement groups had significantly reduced hepatic triglyceride (TG) levels, and decreased total cholesterol (TC) and TG levels in epididymal adipose tissue (EAT). Furthermore, BT replacement remarkably attenuated TM-induced unfolded protein responses (UPRs) in liver, showing reduced ER stress, with BT2 being more effective in the EAT.DiscussionTherefore, our findings suggest that partially replacing dietary fats with n-3 PUFA to lower the ratio of n-6/n-3 PUFAs is beneficial in preventing pathological features of MetS by alleviating HFCD- and/or TM-induced dyslipidemia and ER stress.
An overall survival predictive nomogram to identify high-risk patients among locoregionally advanced nasopharyngeal carcinoma: Developed based on the SEER database and validated institutionally
Authors: Lin Yinbing , Chen Jiechen , Wang Xiao , Chen Sijie , Yang Yizhou , Hong Yingji , Lin Zhixiong , Yang Zhining 
Published: March 2023

ObjectiveLocoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, even at the same stage, have different prognoses. We aim to construct a prognostic nomogram for predicting the overall survival (OS) to identify the high-risk LA-NPC patients.Materials and methodsHistologically diagnosed WHO type II and type III LA-NPC patients in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled as the training cohort (n= 421), and LA-NPC patients from Shantou University Medical College Cancer Hospital (SUMCCH) served as the external validation cohort (n= 763). Variables were determined in the training cohort through Cox regression to form a prognostic OS nomogram, which was verified in the validation cohort, and compared with traditional clinical staging using the concordance index (C-index), Kaplan–Meier curves, calibration curves and decision curve analysis (DCA). Patients with scores higher than the specific cut-off value determined by the nomogram were defined as high-risk patients. Subgroup analyses and high-risk group determinants were explored.ResultsOur nomogram had a higher C-index than the traditional clinical staging method (0.67 vs. 0.60, p&lt;0.001). Good agreement between the nomogram-predicted and actual survival were shown in the calibration curves and DCA, indicating a clinical benefit of the nomogram. High-risk patients identified by our nomogram had worse prognosis than the other groups, with a 5-year overall survival (OS) of 60.4%. Elderly patients at advanced stage and without chemotherapy had a tendency for high risk than the other patients.ConclusionsOur OS predictive nomogram for LA-NPC patients is reliable to identify high-risk patients.
Could S-1-based non-platinum doublet chemotherapy be a new option as a second-line treatment for advanced non-small cell lung cancer patients? A multicenter retrospective study
Authors: Wang Xiangling , Wang Ting , Chu Yunxia , Liu Jie , Yi Cuihua , Yu Xuejun , Wang Yonggang , Zheng Tianying , Cao Fangli , Qu Linli , Yu Bo , Liu Huayong , Ding Fei , Wang Shuang , Wang Xiangbo , Hao Jing , Wang Xiuwen 
Published: March 2023

BackgroundFor patients who have contraindications to or have failed checkpoint inhibitors, chemotherapy remains the standard second-line option to treat non-oncogene-addicted advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of S-1-based non-platinum combination in advanced NSCLC patients who had failed platinum doublet chemotherapy.MethodsDuring January 2015 and May 2020, advanced NSCLC patients who received S-1 plus docetaxel or gemcitabine after the failure of platinum-based chemotherapy were consecutively retrieved from eight cancer centers. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. By using the method of matching-adjusted indirect comparison, the individual PFS and OS of included patients were adjusted by weight matching and then compared with those of the docetaxel arm in a balanced trial population (East Asia S-1 Trial in Lung Cancer).ResultsA total of 87 patients met the inclusion criteria. The ORR was 22.89% (vs. 10% of historical control, p &lt; 0.001) and the DCR was 80.72%. The median PFS and OS were 5.23 months (95% CI: 3.91–6.55 months) and 14.40 months (95% CI: 13.21–15.59 months), respectively. After matching with a balanced population in the docetaxel arm from the East Asia S-1 Trial in Lung Cancer, the weighted median PFS and OS were 7.90 months (vs. 2.89 months) and 19.37 months (vs. 12.52 months), respectively. Time to start of first subsequent therapy (TSFT) from first-line chemotherapy (TSFT &gt; 9 months vs. TSFT ≤ 9 months) was an independent predictive factor of second-line PFS (8.7 months vs. 5.0 months, HR = 0.461, p = 0.049). The median OS in patients who achieved response was 23.5 months (95% CI: 11.8–31.6 months), which was significantly longer than those with stable disease (14.9 months, 95% CI: 12.9–19.4 months, p &lt; 0.001) or progression (4.9 months, 95% CI: 3.2–9.5 months, p &lt; 0.001). The most common adverse events were anemia (60.92%), nausea (55.17%), and leukocytopenia (33.33%).ConclusionsS-1-based non-platinum combination had promising efficacy and safety in advanced NSCLC patients who had failed platinum doublet chemotherapy, suggesting that it could be a favorable second-line treatment option.
The temporal trend of women’s cancer in Changle, China and a migrant epidemiological study
Authors: Chen Yu , Song Mengjie , Zhang Yanyu , Yu Xingxing , Zou Shuqing , Zhu Pingxiu , Zhou Yulin , Yang Haomin 
Published: March 2023

BackgroundAlthough the etiology of women’s cancer has been extensively studied in the last few decades, there is still little evidence comparing the temporal pattern of these cancers among different populations.MethodsCancer incidence and mortality data from 1988 to 2015 were extracted from the Changle Cancer Register in China, and cancer incidence data for Los Angeles were extracted from Cancer Incidence in Five Continents plus database. A Joinpoint regression model was used to analyze the temporal trends of incidence and mortality for breast, cervical, corpus uteri and ovarian cancers. The standardized incidence ratios were applied to compare the cancer risk across populations.ResultsAn increasing trend of incidence rate for breast, cervical, corpus uteri and ovarian cancer was observed in Changle, although the rate leveled off for breast and cervical cancer after 2010, although not statistically significant. The mortality rate of breast and ovarian cancer was slightly increased during this period, while we found a decreased mortality of cervical cancer from 2010. The mortality of corpus uteri cancer showed a decreasing and then increasing trend. The incidence of breast, corpus uteri and ovarian cancer in Chinese American immigrants in Los Angeles was significantly higher than indigenous Changle Chinese and lower than Los Angeles whites. However, the incidence of cervical cancer in Chinese American immigrants shifted from significantly exceeding to lower than Changle Chinese.ConclusionThe incidence and mortality of women’s cancers in Changle were generally on the rise, and this study concluded that environmental changes were important factors affecting the occurrence of these cancers. Appropriate preventive measures should be taken to control the occurrence of women’s cancers by addressing different influencing factors.
B cell M-CLL clones retain selection against replacement mutations in their immunoglobulin gene framework regions
Authors: Neuman Hadas , Arrouasse Jessica , Benjamini Ohad , Mehr Ramit , Kedmi Meirav 
Published: March 2023

IntroductionChronic lymphocytic leukemia (CLL) is the most common adult leukemia, accounting for 30–40% of all adult leukemias. The dynamics of B-lymphocyte CLL clones with mutated immunoglobulin heavy chain variable region (IgHV) genes in their tumor (M-CLL) can be studied using mutational lineage trees.MethodsHere, we used lineage tree-based analyses of somatic hypermutation (SHM) and selection in M-CLL clones, comparing the dominant (presumably malignant) clones of 15 CLL patients to their non-dominant (presumably normal) B cell clones, and to those of healthy control repertoires. This type of analysis, which was never previously published in CLL, yielded the following novel insights. ResultsCLL dominant clones undergo – or retain – more replacement mutations that alter amino acid properties such as charge or hydropathy. Although, as expected, CLL dominant clones undergo weaker selection for replacement mutations in the complementarity determining regions (CDRs) and against replacement mutations in the framework regions (FWRs) than non-dominant clones in the same patients or normal B cell clones in healthy controls, they surprisingly retain some of the latter selection in their FWRs. Finally, using machine learning, we show that even the non-dominant clones in CLL patients differ from healthy control clones in various features, most notably their expression of higher fractions of transition mutations. DiscussionOverall, CLL seems to be characterized by significant loosening – but not a complete loss – of the selection forces operating on B cell clones, and possibly also by changes in SHM mechanisms.
Lymphocyte-activating gene 3 expression in tumor cells predicts immune checkpoint inhibitor response in triple negative breast cancer
Authors: Kim Ji-Yeon , Kim Jeehyun , Cho Eun Yoon , Park Yeon Hee , Ahn Jin Seok , Kim Kyoung-Mee , Im Young-Hyuck 
Published: March 2023

IntroductionImmune checkpoint inhibitor (ICI) is one of the standard treatment strategies in triple negative breast cancer (TNBC). However, the benefit of ICI with chemotherapy is limited in metastatic TNBC. In this study, we evaluated the effect of PD-L1 and LAG-3 expression on tissue microenvironment of mTNBC treated with ICI.MethodsWe reviewed representative formalin-fixed paraffin embedded specimens from metastatic or archival tumor tissues of TNBCs who treated with PD-1/PD-L1 inhibitors in metastatic setting. We used the Opal multiplex Detection kit with six antibodies (anti-PD-L1, anti-LAG-3, anti-CD68, anti-panCK, anti-CD8, anti-CD107a/LAMP antibody).ResultsWe evaluated the association between LAG-3+cells and survival outcome regarding CK expression. Stromal LAG-3+/CK+ and LAG-3+/CK- cells were not associated with ICI-progression free survival(PFS) (P=0.16). However, LAG-3+ cell distributions in the tumor area impacted on ICI-PFS. A high density of LAG-3+CK+ cells was associated with shorter ICI-PFS compared with low densities of both LAG-3+CK+ and LAG-3+CK- cells (1.9 vs. 3.5 months). In addition, a high density of LAG-3+CK- cells had a relatively longer ICI-PFS compared with other groups (P=0.01). In terms of total area, the pattern of densities of LAG-3+CK+ cells and LAG-3+CK- cells were similar to those in the tumor area In addition, ICI-PFS of LAG-3+CK- and LAG-3+CK+ cell densities in the total area was equal to that in the tumor area.DiscussionIn conclusion, our findings revealed tumor-intrinsic LAG-3 expression was the resistance mechanism toward PD-1/PD-L1 inhibitors in mTNBCs. Multivariate analysis also suggested that LAG-3 expression in tumor cells was an independent predictive biomarker.
Examination of cord blood at birth in women with SARS-CoV-2 exposure and/or vaccination during pregnancy and relationship to fetal complete blood count, cortisol, ferritin, vitamin D, and CRP
Authors: Mendenhall Eric , Hogan Mary Beth , Nudelman Matthew , Preston Deborah L. , Weese Hayley , Muckleroy Garrett , Needens Jordan , Addicott Katherine , Haas Jessica Dailey , Roybal Ashlee , Miller Dustin , Cottrell Jesse , Massey Cynthia , Govindaswami Balaji 
Published: March 2023

BackgroundSARS-CoV-2 is known to manifest a robust innate immune response. However, little is known about inflammatory influences from maternal SARS-CoV-2 infection or maternal mRNA vaccination upon the fetus. In addition, it is unknown if Vitamin D deficiency influences fetal homeostasis or if an anti-inflammatory mechanism to the development of possible innate cytokines or acute phase reactants by the maternal/fetal dyad, in the form of cortisol elevations, occur. In addition, effects on Complete Blood Count (CBC) are not known.ObjectiveTo evaluate the neonatal acute phase reactants and anti-inflammatory responses after maternal SARS-CoV-2 disease or mRNA vaccination.MethodsSamples and medical records reviews from mother/baby dyads (n = 97) were collected consecutively, and were categorized into 4 groups; no SARS-CoV-2 or vaccination exposure (Control), Vaccinated mothers, maternal SARS-CoV-2 disease positive/IgG titer positive fetal blood, and maternal SARS-CoV-2 positive/IgG titer negative fetal blood. SARS-CoV-2 IgG/IgM/IgA titers, CBC, CRP, ferritin, cortisol, and Vitamin D were obtained to examine the possible development of an innate immune response and possible anti-inflammatory response. Student's t-test, Wilcoxon rank-sum, and Chi-squared with Bonferroni corrections were used to compare groups. Multiple imputations were performed for missing data.ResultsCortisol was higher in babies of both mothers who were vaccinated (p = 0.001) and SARS-CoV-2 positive/IgG positive (p = 0.009) as compared to the control group suggesting an attempt to maintain homeostasis in these groups. Measurements of ferritin, CRP, and vitamin D did not reach statistical significance. CBC showed no variation, except for the mean platelet volume (MPV), which was elevated in babies whose mothers were vaccinated (p = 0.003) and SARS-CoV-2 positive/IgG positive (p = 0.007) as compared to the control group.ConclusionAcute phase reactant elevations were not noted in our neonates. Vitamin D levels were unchanged from homeostatic levels. Cord blood at birth, showed Cortisol and MPV higher in vaccinated and SARS-CoV-2 IgG positive mother/baby dyads as compared to the Control group, indicating that possible anti-inflammatory response was generated. The implication of possible inflammatory events and subsequent cortisol and/or MPV elevation effects upon the fetus after SARS-CoV-2 disease or vaccination is unknown and merits further investigation.
Red blood cell transfusion-related eicosanoid profiles in intensive care patients—A prospective, observational feasibility study
Authors: Raeven Pierre , Hagn Gerhard , Niederstaetter Laura , Brugger Jonas , Bayer-Blauensteiner Sophia , Domenig Christoph , Hoetzenecker Konrad , Posch Martin , Leitner Gerda , Gerner Christopher , Baron David M. 
Published: March 2023

Introduction: Eicosanoids are bioactive lipids present in packed red blood cells (PRBCs), and might play a role in transfusion-related immunomodulation (TRIM). We tested the feasibility of analyzing eicosanoid profiles in PRBC supernatant and in plasma samples of postoperative intensive care unit (ICU) patients transfused with one unit of PRBCs.Methods: We conducted a prospective, observational feasibility study enrolling postoperative ICU patients: 1) patients treated with acetylsalicylic acid following abdominal aortic surgery (Aorta); 2) patients on immunosuppressants after bilateral lung transplantation (LuTx); and 3) patients undergoing other types of major surgery (Comparison). Abundances of arachidonic acid (AA) and seven pre-defined eicosanoids were assessed by liquid chromatography and tandem mass spectrometry. PRBC supernatant was sampled directly from the unit immediately prior to transfusion. Spearman’s correlations between eicosanoid abundance in PRBCs and storage duration were assessed. Patient plasma was collected at 30-min intervals: Three times each before and after transfusion. To investigate temporal changes in eicosanoid abundances, we fitted linear mixed models.Results: Of 128 patients screened, 21 were included in the final analysis (Aorta n = 4, LuTx n = 8, Comparison n = 9). In total, 21 PRBC and 125 plasma samples were analyzed. Except for 20-hydroxyeicosatetraenoic acid (HETE), all analyzed eicosanoids were detectable in PRBCs, and their abundance positively correlated with storage duration of PRBCs. While 5-HETE, 12-HETE/8-HETE, 15-HETE, 20-HETE, and AA were detectable in virtually all plasma samples, 9-HETE and 11-HETE were detectable in only 57% and 23% of plasma samples, respectively.Conclusions: Recruitment of ICU patients into this transfusion study was challenging but feasible. Eicosanoid abundances increased in PRBC supernatants during storage. In plasma of ICU patients, eicosanoid abundances were ubiquitously detectable and showed limited fluctuations over time prior to transfusion. Taken together, larger clinical studies seem warranted and feasible to further investigate the role of PRBC-derived eicosanoids in TRIM.
Identification of the protonation and oxidation states of the oxygen-evolving complex in the low-dose X-ray crystal structure of photosystem II
Authors: Saito Keisuke , Nakao Shu , Ishikita Hiroshi 
Published: March 2023

In photosystem II (PSII), the O3 and O4 sites of the Mn4CaO5 cluster form hydrogen bonds with D1-His337 and a water molecule (W539), respectively. The low-dose X-ray structure shows that these hydrogen bond distances differ between the two homogeneous monomer units (A and B) [Tanaka et al., J. Am Chem. Soc. 2017, 139, 1718]. We investigated the origin of the differences using a quantum mechanical/molecular mechanical (QM/MM) approach. QM/MM calculations show that the short O4-OW539 hydrogen bond (~2.5 Å) of the B monomer is reproduced when O4 is protonated in the S1 state. The short O3-NεHis337 hydrogen bond of the A monomer is due to the formation of a low-barrier hydrogen bond between O3 and doubly-protonated D1-His337 in the overreduced states (S−1 or S−2). It seems plausible that the oxidation state differs between the two monomer units in the crystal.
AtCIPK16, a CBL-interacting protein kinase gene, confers salinity tolerance in transgenic wheat
Authors: Imtiaz Khadija , Ahmed Moddassir , Annum Nazish , Tester Mark , Saeed Nasir A. 
Published: March 2023

Globally, wheat is the major source of staple food, protein, and basic calories for most of the human population. Strategies must be adopted for sustainable wheat crop production to fill the ever-increasing food demand. Salinity is one of the major abiotic stresses involved in plant growth retardation and grain yield reduction. In plants, calcineurin-B-like proteins form a complicated network with the target kinase CBL-interacting protein kinases (CIPKs) in response to intracellular calcium signaling as a consequence of abiotic stresses. The AtCIPK16 gene has been identified in Arabidopsis thaliana and found to be significantly upregulated under salinity stress. In this study, the AtCIPK16 gene was cloned in two different plant expression vectors, i.e., pTOOL37 having a UBI1 promoter and pMDC32 having a 2XCaMV35S constitutive promoter transformed through the Agrobacterium-mediated transformation protocol, in the local wheat cultivar Faisalabad-2008. Based on their ability to tolerate different levels of salt stress (0, 50, 100, and 200 mM), the transgenic wheat lines OE1, OE2, and OE3 expressing AtCIPK16 under the UBI1 promoter and OE5, OE6, and OE7 expressing the same gene under the 2XCaMV35S promoter performed better at 100 mM of salinity stress as compared with the wild type. The AtCIPK16 overexpressing transgenic wheat lines were further investigated for their K+ retention ability in root tissues by utilizing the microelectrode ion flux estimation technique. It has been demonstrated that after 10 min of 100 mM NaCl application, more K+ ions were retained in the AtCIPK16 overexpressing transgenic wheat lines than in the wild type. Moreover, it could be concluded that AtCIPK16 functions as a positive elicitor in sequestering Na+ ions into the cell vacuole and retaining more cellular K+ under salt stress to maintain ionic homeostasis.
Mentalizing the therapist – Therapist experiences with short-term mentalization-based therapy for borderline personality disorder: A qualitative study
Authors: Søndergaard Amanda Ark , Juul Sophie , Poulsen Stig , Simonsen Sebastian 
Published: March 2023

BackgroundMentalization-Based Therapy (MBT) was originally developed as a structured psychotherapy approach developed to treat borderline personality disorder (BPD) lasting up to 18 months in outpatient settings. However, a short-term (5 months) MBT program has recently been developed. No studies have investigated how MBT therapists experience the shift towards conducting short-term MBT for BPD.ObjectiveThe objective of this study was to explore therapist experiences with conducting short-term MBT for outpatients with BPD in the Danish mental health services.MethodsSemi-structured qualitative interviews were conducted with seven therapists about their experiences with short-term MBT after a one-year pilot phase. The interviews were verbatim transcribed and analyzed using thematic analysis.ResultsThe following four major themes from the therapists’ experiences with short-term MBT were found in the qualitative analysis: (1) The longer the better, (2) Change processes can be intellectual or experiential, (3) Short-term therapy is hard work, and (4) Termination is more challenging in short-term MBT.ConclusionMost therapists were overall reluctant towards changing from long-term to short-term MBT. These therapist experiences could inform implementation of short-term MBT in mental health settings in the future.