bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities
Authors: Falchi Lorenzo , Vardhana Santosha A. , Salles Gilles A. 
Published: November 2022

AbstractTreatment paradigms for B-cell non-Hodgkin lymphomas (B-NHL) have shifted dramatically in the last 2 decades following the introduction of highly active immunotherapies such as rituximab. Since then, the field has continued to witness tremendous progress with the introduction of newer, more potent immunotherapeutics, including chimeric antigen receptor T-cell therapy, which have received regulatory approval for and currently play a significant role in the treatment of these diseases. Bispecific antibodies (BsAb) are a novel class of off-the-shelf T-cell redirecting drugs and are among the most promising immunotherapeutics for lymphoma today. BsAb may target various cell-surface antigens and exist in different formats. Anti-CD20xCD3 BsAb have demonstrated remarkable single-agent activity in patients with heavily pretreated B-NHL with a manageable toxicity profile dominated by T-cell overactivation syndromes. Much work remains to be done to define the optimal setting in which to deploy these drugs for B-NHL treatment, their ideal combination partners, strategies to minimize toxicity, and, perhaps most importantly, pharmacodynamic biomarkers of response and resistance. In this review, we provide an update on BsAb development in B-NHL, from discovery to clinical applications, highlighting the achievements, limitations, and future directions of the field.
A nomogram for predicting cancer-specific survival for elderly patients with gallbladder cancer
Authors: Wen Chong , Tang Jie , Wang Tao , Luo Hao 
Published: November 2022

Abstract
Background
Gallbladder cancer (GBC) is a highly aggressive malignancy in elderly patients. Our goal is aimed to construct a novel nomogram to predict cancer-specific survival (CSS) in elderly GBC patients.

Method
We extracted clinicopathological data of elderly GBC patients from the SEER database. We used univariate and multivariate Cox proportional hazard regression analysis to select the independent risk factors of elderly GBC patients. These risk factors were subsequently integrated to construct a predictive nomogram model. C-index, calibration curve, and area under the receiver operating curve (AUC) were used to validate the accuracy and discrimination of the predictive nomogram model. A decision analysis curve (DCA) was used to evaluate the clinical value of the nomogram.

Result
A total of 4241 elderly GBC patients were enrolled. We randomly divided patients from 2004 to 2015 into training cohort (n = 2237) and validation cohort (n = 1000), and patients from 2016 to 2018 as external validation cohort (n = 1004). Univariate and multivariate Cox proportional hazard regression analysis found that age, tumor histological grade, TNM stage, surgical method, chemotherapy, and tumor size were independent risk factors for the prognosis of elderly GBC patients. All independent risk factors selected were integrated into the nomogram to predict cancer-specific survival at 1-, 3-, and 5- years. In the training cohort, internal validation cohort, and external validation cohort, the C-index of the nomogram was 0.763, 0.756, and 0.786, respectively. The calibration curves suggested that the predicted value of the nomogram is highly consistent with the actual observed value. AUC also showed the high authenticity of the prediction model. DCA manifested that the nomogram model had better prediction ability than the conventional TNM staging system.

Conclusion
We constructed a predictive nomogram model to predict CSS in elderly GBC patients by integrating independent risk factors. With relatively high accuracy and reliability, the nomogram can help clinicians predict the prognosis of patients and make more rational clinical decisions.
Examining socioeconomic status disparities in facility-based childbirth in Kenya: role of perceived need, accessibility, and quality of care
Authors: Kapula Ntemena , Shiboski Stephen , Dehlendorf Christine , Ouma Linet , Afulani Patience A. 
Published: November 2022

Abstract
Background
Giving birth in health facilities with skilled birth attendants (SBAs) is one of the key efforts promoted to reduce preventable maternal deaths in sub-Saharan Africa. However, research has revealed large socioeconomic status (SES) disparities in facility-based childbirth. We seek to extend the literature on the factors underlying these SES disparities. Drawing on the Disparities in Skilled Birth Attendance (DiSBA) framework, we examined the contribution of three proximal factors—perceived need, accessibility, and quality of care—that influence the use of SBAs.

Methods
We used data from a survey conducted in Migori County, Kenya in 2016, among women aged 15–49 years who gave birth nine weeks before the survey (N = 1020). The primary outcome is facility-based childbirth. The primary predictors are wealth, measured in quintiles calculated from a wealth index based on principal component analysis of household assets, and highest education level attained. Proposed mediating variables include maternal perceptions of need, accessibility (physical and financial), and quality of care (antenatal services received and experience of care). Logistic regression with mediation analysis was used to investigate the mediating effects.

Results
Overall, 85% of women in the sample gave birth in a health facility. Women in the highest wealth quintile were more likely to give birth in a facility than women in the lowest quintile, controlling for demographic factors (adjusted odds ratio [aOR]: 2.97, 95% CI: 1.69–5.22). College-educated women were five times more likely than women with no formal education or primary education to give birth in a health facility (aOR: 4.96; 95% CI: 1.43–17.3). Women who gave birth in health facilities had higher perceived accessibility and quality of care than those who gave birth at home. The five mediators were estimated to account for between 15% and 48% of the differences in facility births between women in the lowest and higher wealth quintiles.

Conclusion
Our results confirm SES disparities in facility-based childbirth, with the proximal factors accounting for some of these differences. These proximal factors – particularly perceived accessibility and quality of care – warrant attention due to their relationship with facility-birth overall, and their impact on inequities in this care.
Comprehensive analysis of the expression and prognosis for IQ motif-containing GTPase-activating proteins in hepatocellular carcinoma
Authors: Dai Qingqing , Song Fei , Li Xincheng , Huang Fan , Zhao Hongchuan 
Published: November 2022

Abstract
Background
IQ motif-containing GTPase-activating proteins (IQGAPs) are a group of scaffold proteins which have been identified to be involved in tumor initiation and progression in diverse types of cancer. Clinical studies and experimental evidence suggest that IQGAPs play an essential role in hepatocellular carcinoma (HCC) progression and alterations in their expression are closely related to patient prognosis. However, the different expression patterns and prognostic values of all three IQGAP isoforms in HCC have not yet been analyzed simultaneously.

Methods
We analyzed the transcriptional and survival data of IQGAPs in HCC patients using Oncomine, UALCAN, Kaplan–Meier Plotter, cBioPortal, and GeneMANIA. We further examined tumor and adjacent normal tissues from 250 HCC patients using immunohistochemistry to assess the relationship between IQGAPs expression and clinicopathological features and validate the prognostic value of IQGAPs. In addition, we analyzed transcriptional changes of IQGAPs with regards to survival data in HCC patients from the TCGA-LIHC (liver hepatocellular carcinoma) cohort to validate our results.

Results
We found that the expression levels of IQGAP1 and 3 were significantly elevated in HCC tissues than in normal liver tissues, whereas the expression level of IQGAP2 was decreased in the former than in the latter. The clinical data showed that positive IQGAP1 expression was associated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, poor relapse-free survival (RFS), and overall survival (OS), and positive IQGAP3 expression was associated with poorer tumor differentiation, RFS, and OS. Conversely, positive IQGAP2 expression predicted less tumor numbers and microvascular invasion, as well as higher RFS and OS in these patients.

Conclusions
IQGAPs may serve as new prognostic biomarkers and potential targets for precision therapy in HCC.
Paradoxes of breast cancer incidence and mortality in two corners of Europe
Authors: Roginski Mikaela , Sifaki-Pistolla Dimitra , Stomby Andreas , Velivasaki Georgia , Faresjö Tomas , Lionis Christos , Faresjö Åshild 
Published: November 2022

Abstract
Background
Breast cancer incidence is rising globally, while mortality rates show a geographical heterogenous pattern. Early detection and treatment have been proven to have a profound impact on breast cancer prognosis. The aim of his study was to compare breast cancer incidence, mortality, and survival rates in two contrasting corners of Europe, Sweden and Crete, to better understand cancer determinants with focus on disease burden and sociocultural factors.

Methods
Breast cancer data from Sweden and Crete was derived from registries. Incidence and mortality were expressed as Age-Standardized Incidence Rates (ASIR), Age-Standardized Mortality Rates (ASMR).

Findings
Breast cancer incidence has for decades risen in Sweden and on Crete. In 2019, ASIR was 217.5 in Sweden and 58.9 on Crete, (p < 0.001). Mortality rates showed opposite trends. ASMR in Sweden was reduced from 25.5 to 16.8 (2005-2019) while on Crete, ASMR increased from 22.1 to 25.3. A successive rise in survival rate in Sweden with a 5-year survival rate of 92% since 2015, but a converse development on Crete with 85% 5-year survival rate the same year.

Interpretation
The incidence of breast cancer is slowly rising in both studied regions, but mortality increases on Crete in contrast to Sweden with sinking mortality rates. The interpretation of these findings is that differences in health care systems and health policies including differences in early detection like screening programs and early treatment, as well as sociocultural factors in the two countries might play an important role on the differences found in breast cancer burden.
Obesity paradox among patients undergoing total knee arthroplasty: a retrospective cohort study
Authors: Ma Lulu , Yu Xuerong , Weng Xisheng , Lin Jin , Qian Wenwei , Huang Yuguang 
Published: November 2022

AbstractBackgroundObesity has been recognized as the risk factor for postoperative complication for surgical patients. However, recent studies have showed protective effect of obesity in surgical and non-surgical patients. Our study is to examine the association of body mass index(BMI) with early postoperative complications in patients undergoing total knee arthroplasty.Materials and methodsAll patients who had primary total knee arthroplasty between January 2014 and December 2019 were included. Medical records were retrospectively reviewed and BMI was categorized as underweight(BMI < 18.5), normal weight(18.5 < BMI < 24.9), overweight I(25 < BMI < 27.4), overweight II(27.5 < BMI < 29.9), obese I(30 < BMI < 34.9) and obese II(BMI ≥ 35). The association between BMI and occurrence of early postoperative complications was examined and logistic regression was used to calculate relationship between BMI and early postoperative complications.ResultsA total of 2969 patients were included in our analysis. The overall complication rate in patients undergoing total knee arthroplasty was 14.8%, with the highest complication being 22.2% in the underweight group, the second highest in the normal weight group(17.5%), the lowest in the overweight I(13.8%) and obese I(12.0%) group and then higher again in obese II group(16.7%). In multivariable analyses, overweight I (OR 0.737, 95% CI 0.559–0.972,P = 0.031) and obese I (OR 0.631, 95% CI 0.449–0.885,P = 0.008) were associated with lower risk of early postoperative complications after total knee arthroplasty.ConclusionIn this retrospective study, overweight and obese patients had a lower risk of early postoperative complications after total knee arthroplasty. Further studies are necessary to confirm and investigate the mechanism of obesity paradox in this surgical population.Trial registrationThis study had been registrated inwww.chictr.org.cnon 25/10/2021 and the registration ID was ChiCTR2100052408.
Hospital ethical climate survey - selected psychometric properties of the scale and results among polish nurses and midwives
Authors: Dziurka Magdalena , Ozdoba Patrycja , Olson Linda , Jedynak Anna , Ozga Dorota , Jurek Krzysztof , Dobrowolska Beata 
Published: November 2022

Abstract
Background:
The hospital ethical climate affects the quality of nursing care. A positive ethical climate is likely to reduce the proportion of those who consider leaving the profession, so it is necessary to develop tools which will enable assessment and analysis of the hospital ethical climate. The aim of this study was to examine selected psychometric properties of the Polish version of the Hospital Ethical Climate Survey, assess the hospital ethical climate perceived by nurses and midwives from Polish hospitals, and to determine its correlations with job-related variables.

Methods:
A cross-sectional study among 558 nurses and midwives working in hospitals in Poland.

Results:
The 21-item model showed acceptable model fitness between the hypothetical model of ethical climate and the data in the study. Five items with low factor loadings were removed from the study. The internal consistency was satisfactory (0.93). The mean score for the overall hospital ethical climate was 3.62. The highest mean score of hospital ethical climate in the present study was found in the ”peers” subscale and the lowest in the ”physicians” subscale. A positive correlation was found between overall hospital ethical climate and respondents’ satisfaction with work, salary, and working time. The hospital ethical climate was associated with problems found in nurses and midwives’ work, such as: limited time for direct face-to-face care, the lack of equipment and resources to provide high-quality health care, strained relations with hospital managers and other health care professionals, limitations to one’s own competences or those of other medical professionals, moral dilemmas related to patient care, the low prestige of nurses’/midwives‘ work, physical and mental burden, and the risk of making a mistake.

Conclusion:
The Polish 21-item version of the Hospital Ethical Climate Survey is a reliable tool. Correlations revealed that relationships with managers and physicians, and working conditions should be improved in order for the hospital ethical climate to improve.
Sclerosing encapsulating peritonitis in a dog with pancreatic ductal adenocarcinoma
Authors: Tsukada Yusuke , Park Young Tae , Mitsui Ikki , Murakami Masahiro , Tsukamoto Atsushi 
Published: November 2022

AbstractBackgroundSclerosing encapsulating peritonitis (SEP) is a rare clinical syndrome characterised by fibrosis and thickening of the peritoneum with massive adhesions of the abdominal organs. In humans, abdominal tumours, such as pancreatic adenocarcinoma, can be underlying diseases of SEP. This report describes a case of SEP in a dog with pancreatic ductal adenocarcinoma.Case presentationAn 11-year-old male neutered French Bulldog presented with chronic vomiting. Ultrasonography revealed a mass in the centre of the abdomen. A small amount of ascites, interpreted as modified transudate, was present in the abdominal cavity. Computed tomography (CT) revealed peritoneal effusion with a thickened peritonium. Laparoscopy revealed a large nodular lesion occupying the central portion of the abdomen, continuous with the falciform ligament. Histological examination of the biopsy specimens of the mass, abdominal wall, and gastric peritoneum revealed marked fibroplasia with mild lymphoplasmacytic infiltrates. Based on these results, a tentative diagnosis of early stage sclerosing encapsulating peritonitis (SEP) was made. Prednisolone and tamoxifen were administered with the expectation of ameliorating SEP, however, the dog died 61 days post diagnosis. At autopsy, the intestinal loop and mesentery were encased in the fibrous membrane, which is a typical finding in SEP. Histopathology and immunohistochemistry of the samples obtained at autopsy supported the diagnosis of pancreatic ductal adenocarcinoma with peritoneal dissemination and distant metastasis with desmoplasia. The unexpectedly hardened skin, where previously laparoscopic ports were inserted, histologically contained the same carcinoma cells with desmoplasia.ConclusionsTo the best of our knowledge, this is the first report of canine SEP with pancreatic ductal adenocarcinoma that also caused metastasis to port insertion sites as well as distant organs.
Extracellular vesicles isolated from hyperuricemia patients might aggravate airway inflammation of COPD via senescence-associated pathway
Authors: Liu Xuanqi , Li Zheng , Zheng Yang , Wang Wenhao , He Peiqing , Guan Kangwei , Wu Tao , Wang Xiaojun , Zhang Xuelin 
Published: November 2022

AbstractBackgroundsChronic obstructive pulmonary disease (COPD) is a major health issue resulting in significant mortality worldwide. Due to the high heterogeneity and unclear pathogenesis, the management and therapy of COPD are still challenging until now. Elevated serum uric acid(SUA) levels seem to be associated with the inflammatory level in patients with COPD. However, the underlying mechanism is not yet clearly established. In the current research, we aim to elucidate the effect of high SUA levels on airway inflammation among COPD patients.MethodsThrough bioinformatic analysis, the common potential key genes were determined in both COPD and hyperuricemia (HUA) patients. A total of 68 COPD patients aged 50—75-year were included in the study, and their clinical parameters, including baseline characteristics, lung function test, as well as blood chemistry test were recorded. These parameters were then compared between the COPD patients with and without HUA. Hematoxylin & Eosin (HE), immunofluorescence (IF), and Masson trichrome staining were performed to demonstrate the pathological changes in the lung tissues. Furthermore, we isolated extracellular vesicles (EVs) from plasma, sputum, and bronchoalveolar lavage fluid (BALF) samples and detected the expression of inflammatory factor (Interleukin-6 (IL-6), IL-8 and COPD related proteases (antitrypsin and elastase) between two groups. Additionally, we treated the human bronchial epithelial (HBE) cells with cigarette smoke extract (CSE), and EVs were derived from the plasma in vitro experiments. The critical pathway involving the relationship between COPD and HUA was eventually validated based on the results of RNA sequencing (RNA-seq) and western blot (WB).ResultsIn the study, the COPD patients co-existing with HUA were found to have more loss of pulmonary function compared with those COPD patients without HUA. The lung tissue samples of patients who had co-existing COPD and HUA indicated greater inflammatory cell infiltration, more severe airway destruction and even fibrosis. Furthermore, the high SUA level could exacerbate the progress of airway inflammation in COPD through the transfer of EVs. In vitro experiments, we determined that EVs isolated from plasma, sputum, and BALF played pivotal roles in the CSE-induced inflammation of HBE. The EVs in HUA patients might exacerbate both systemic inflammation and airway inflammatory response via the senescence-related pathway.ConclusionThe pulmonary function and clinical indicators of COPD patients with HUA were worse than those without HUA, which may be caused by the increased airway inflammatory response through the EVs in the patient's peripheral blood. Moreover, it might mediate the EVs via senescence-related pathways in COPD patients with HUA.
Retrospective observation of subacute thyroiditis before and during the COVID-19 vaccination campaign in a single secondary endocrine centre in the Savona district, Liguria, Italy
Authors: Giusti Massimo , Sidoti Marilena 
Published: November 2022

Abstract
Background
Clinicians should be aware that subacute thyroiditis (SAT) might be an under-reported adverse effect of COVID-19 vaccines.

Aim
In records from endocrinological examinations, we reviewed the incidence of diagnoses of SAT from 2000 to 2020 and during the 2021 COVID-19 vaccination campaign.

Methods
Review of electronic records from June to December in each year from 2000 to 2021.

Results
From 2000 to 2020, 51 patients in our centre had SAT (0.6%). From June to December 2021, 7 females were diagnosed with SAT after vaccination. The percentage of SAT in 2021 medical files was 1.5%. SAT diagnoses significantly (P = 0.03) increased in 2021 in comparison with the 2000–2020 period. The median age of SAT patients in 2021 (51 years; IQR 35–66 years) was higher than in the 2000–2020 period (45 years, IQR 38–52 years; P = 0.05).

Conclusion
To date, few cases of SAT after COVID-19 vaccinations have been described in the literature, with sub-clinical, normal or increased thyroid function during 1-3-month follow-up. Our findings indicate that SAT after COVID-19 vaccination occurs more frequently than in other virus-related cases and at a greater age. Our observation of a local increase in SAT during the 2021 COVID-19 vaccination campaign indicates that physicians should be aware of this infrequent side effect, which must be considered and monitored after COVID-19 vaccination.
Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer
Authors: Borneman Rebecca M. , Gavin Elaine , Musiyenko Alla , Richter Wito , Lee Kevin J. , Crossman David K. , Andrews Joel F. , Wilhite Annelise M. , McClellan Steven , Aragon Ileana , Ward Antonio B. , Chen Xi , Keeton Adam B. , Berry Kristy , Piazza Gary A. , Scalici Jennifer M. , da Silva Luciana Madeira 
Published: November 2022

AbstractA leading theory for ovarian carcinogenesis proposes that inflammation associated with incessant ovulation is a driver of oncogenesis. Consistent with this theory, nonsteroidal anti-inflammatory drugs (NSAIDs) exert promising chemopreventive activity for ovarian cancer. Unfortunately, toxicity is associated with long-term use of NSAIDs due to their cyclooxygenase (COX) inhibitory activity. Previous studies suggest the antineoplastic activity of NSAIDs is COX independent, and rather may be exerted through phosphodiesterase (PDE) inhibition. PDEs represent a unique chemopreventive target for ovarian cancer given that ovulation is regulated by cyclic nucleotide signaling. Here we evaluate PDE10A as a novel therapeutic target for ovarian cancer. Analysis of The Cancer Genome Atlas (TCGA) ovarian tumors revealed PDE10A overexpression was associated with significantly worse overall survival for patients. PDE10A expression also positively correlated with the upregulation of oncogenic and inflammatory signaling pathways. Using small molecule inhibitors, Pf-2545920 and a novel NSAID-derived PDE10A inhibitor, MCI-030, we show that PDE10A inhibition leads to decreased ovarian cancer cell growth and induces cell cycle arrest and apoptosis. We demonstrate these pro-apoptotic properties occur through PKA and PKG signaling by using specific inhibitors to block their activity. PDE10A genetic knockout in ovarian cancer cells through CRISP/Cas9 editing lead to decreased cell proliferation, colony formation, migration and invasion, andin vivotumor growth. We also demonstrate that PDE10A inhibition leads to decreased Wnt-induced β-catenin nuclear translocation, as well as decreased EGF-mediated activation of RAS/MAPK and AKT pathways in ovarian cancer cells. These findings implicate PDE10A as novel target for ovarian cancer chemoprevention and treatment.