bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of PARP inhibitors beyond BRCA mutation and platinum sensitivity in epithelial ovarian cancer: a meta-analysis of hazard ratios from randomized clinical trials
Authors: Purwar Roli , Ranjan Rakesh , Pal Manjusha , Upadhyay Satyanshu K. , Kumar Tarun , Pandey Manoj 
Published: May 2023

Abstract
Background
PARP inhibitors (PARPi) have a well-established role in platinum-sensitive ovarian cancer (PSOC), in BRCA mutant (BRCAm), and homologous recombination deficiency (HRD) population. However, their role in wild type and homologous recombination proficient population is still not clear.

Methods
A meta-analysis of hazard ratios (HR) of randomized control trials (RCTs) was conducted to study the role of PARPi. The published RCTs comparing the efficacy of PARP inhibitors alone or in combination with chemotherapy and/or target therapies versus placebo/chemotherapy alone/target therapy alone in primary or recurrent ovarian cancer settings were selected. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints.

Results
A total of 14 primary studies and 5 updated studies are considered, consisting of 5363 patients. Overall, HR for PFS was 0.50 [95% CI 0.40–0.62]. HR of PFS was 0.94 [95% CI 0.76–1.15] in the PROC group, 0.41 [95% CI 0.29–0.60] was in HRD with BRCA unknown (BRCAuk), 0.38 [95% CI 0.26–0.57] in HRD with BRCAm, and 0.52 [95% CI 0.38–0.71] in HRD with BRCAwt. In the HRP group, overall HR for PFS was 0.67 [95% CI 0.56–0.80], 0.61 [95% CI 0.38–0.99] in HRD unknown with BRCA wt, and 0.40 [95% CI 0.29–0.55] in BRCAm HR for PFS. Overall, HR for OS was 0.86 [95% CI 0.73–1.031].

Conclusions
The results suggest that PARPi have a meaningful clinical benefit in PSOC, HRD, BRACm, and also in HRP and PROC; however, the evidence is not sufficient to recommend their routine use and further studies are needed to expand their role in the HRP and PROC groups.
Radiation combined with immune checkpoint inhibitors for unresectable locally advanced non-small cell lung cancer: synergistic mechanisms, current state, challenges, and orientations
Authors: Wu Leilei , Zhang Zhenshan , Bai Menglin , Yan Yujie , Yu Jinming , Xu Yaping 
Published: May 2023

AbstractUntil the advent of immune checkpoint inhibitors (ICIs), definitive radiotherapy (RT) concurrently with chemotherapy was recommended for unresectable, locally advanced non-small cell lung cancer (LA-NSCLC). The trimodality paradigm with consolidation ICIs following definitive concurrent chemoradiotherapy has been the standard of care since the PACIFIC trial. Preclinical evidence has demonstrated the role of RT in the cancer-immune cycle and the synergistic effect of RT combined with ICIs (iRT). However, RT exerts a double-edged effect on immunity and the combination strategy still could be optimized in many areas. In the context of LA-NSCLC, optimized RT modality, choice, timing, and duration of ICIs, care for oncogenic addicted tumors, patient selection, and novel combination strategies require further investigation. Targeting these blind spots, novel approaches are being investigated to cross the borders of PACIFIC. We discussed the development history of iRT and summarized the updated rationale for the synergistic effect. We then summarized the available research data on the efficacy and toxicity of iRT in LA-NSCLC for cross-trial comparisons to eliminate barriers. Progression during and after ICIs consolidation therapy has been regarded as a distinct resistance scenario from primary or secondary resistance to ICIs, the subsequent management of which has also been discussed. Finally, based on unmet needs, we probed into the challenges, strategies, and auspicious orientations to optimize iRT in LA-NSCLC. In this review, we focus on the underlying mechanisms and recent advances of iRT with an emphasis on future challenges and directions that warrant further investigation. Taken together, iRT is a proven and potential strategy in LA-NSCLC, with multiple promising approaches to further improve the efficacy.
Evaluation of immunogenicity of gene-deleted and subunit vaccines constructed against the emerging pseudorabies virus variants
Authors: Zhang Hong-liang , Zhang Rui-hua , Liu Gang , Li Gui-mei , Wang Feng-xue , Wen Yong-jun , Shan Hu 
Published: May 2023

Abstract
Background
Pseudorabies (PR) (also called Aujeszky’s disease, AD) is a serious infectious disease affecting pigs and other animals worldwide. The emergence of variant strains of pseudorabies virus (PRV) since 2011 has led to PR outbreaks in China and a vaccine that antigenically more closely matches these PRV variants could represent an added value to control these infections.

Methods
The objective of this study was to develop new live attenuated and subunit vaccines against PRV variant strains. Genomic alterations of vaccine strains were based on the highly virulent SD-2017 mutant strain and gene-deleted strains SD-2017ΔgE/gI and SD-2017ΔgE/gI/TK, which constructed using homologous recombination technology. PRV gB-DCpep (Dendritic cells targeting peptide) and PorB (the outer membrane pore proteins of N. meningitidis) proteins containing gp67 protein secretion signal peptide were expressed using the baculovirus system for the preparation of subunit vaccines. We used experimental animal rabbits to test immunogenicity to evaluate the effect of the newly constructed PR vaccines.

Results
Compared with the PRV-gB subunit vaccine and SD-2017ΔgE/gI inactivated vaccines, rabbits (n = 10) that were intramuscularly vaccinated with SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine showed significantly higher anti-PRV-specific antibodies as well as neutralizing antibodies and IFN-γ levels in serum. In addition, the SD-2017ΔgE/gI/TK live attenuated vaccine and PRV-gB + PorB subunit vaccine protected (90–100%) rabbits against homologous infection by the PRV variant strain. No obvious pathological damage was observed in these vaccinated rabbits.

Conclusions
The SD-2017ΔgE/gI/TK live attenuated vaccine provided 100% protection against PRV variant challenge. Interestingly, the subunit vaccines with gB protein linked to DCpep and PorB protein as adjuvant may also be a promising and effective PRV variant vaccine candidate.
Molecular triage of cervical screening samples in women 55–59 years of age: a pilot study
Authors: Helenius Gisela , Lillsunde-Larsson Gabriella , Bergengren Lovisa 
Published: May 2023

Abstract
Background
With HPV screening the specificity of screening positives has decreased, even with a cytological triage test. Increases in colposcopies and detection of benign or low-grade dysplasia are reported, not least in older women. These results highlight the necessity to find other triage tests in HPV screening strategies, so that women can be more accurately selected for colposcopy, thus minimizing the clinically irrelevant findings.

Methods
The study included 55- to 59-year-old women who exited the screening with normal cytology, but later in a follow-up test were positive for the HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 and had a cervical cone biopsy done. To model a screening situation with hrHPV-positive women, three different triage strategies, namely, cytology, genotyping and methylation, were performed. The study considered the effect of direct referral to colposcopy for HPV genotypes 16, 18, 31, 33, 45, 52 and 58, and methylation for FAM19A4 and hsa-mir124-2 and/or any form of abnormal cytology.

Results
Seven out of 49 women aged 55–59 years with hrHPV had a cone biopsy with high-grade squamous intraepithelial lesion. No triage method found all cases, and when comparing positive and negative predictive value and false negative rate, cytology showed better results than genotyping and methylation.

Conclusion
This study does not support a switch in triage strategies from cytology to hrHPV genotyping and methylation for women above 55 years of age yet, but demonstrates the need for more evidence on molecular triage strategies.
Sex-specific associations of matrix metalloproteinases in Alzheimer’s disease
Authors: Aksnes Mari , Edwin Trine H. , Saltvedt Ingvild , Eldholm Rannveig S. , Chaudhry Farrukh A. , Halaas Nathalie B. , Myrstad Marius , Watne Leiv O. , Knapskog Anne-Brita 
Published: May 2023

Abstract
Introduction
Alzheimer’s disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD.

Methods
In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aβ and tau pathology as well as disease progression. Further, we studied sex-specific interactions.

Results
MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aβ biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women.

Conclusion
Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.
Identification and validation of CCL2 as a potential biomarker relevant to mast cell infiltration in the testicular immune microenvironment of spermatogenic dysfunction
Authors: Dong Fan , Ping Ping , Wang Si-Qi , Ma Yi , Chen Xiang-Feng 
Published: May 2023

Abstract
Background
Spermatogenic dysfunction is an important cause of azoospermia. Numerous studies have focused on germ-cell-related genes that lead to spermatogenic impairment. However, based on the immune-privileged characteristics of the testis, the relationship of immune genes, immune cells or immune microenvironment with spermatogenic dysfunction has rarely been reported.

Results
Using integrated methods including single-cell RNA-seq, microarray data, clinical data analyses and histological/pathological staining, we found that testicular mast cell infiltration levels were significantly negatively related to spermatogenic function. We next identified a functional testicular immune biomarker, CCL2, and externally validated that testicular CCL2 was significantly upregulated in spermatogenic dysfunctional testes and was negatively correlated with Johnsen scores (JS) and testicular volumes. We also demonstrated that CCL2 levels showed a significant positive correlation with testicular mast cell infiltration levels. Moreover, we showed myoid cells and Leydig cells were two of the important sources of testicular CCL2 in spermatogenic dysfunction. Mechanistically, we drew a potential “myoid/Leydig cells-CCL2-ACKR1-endothelial cells-SELE-CD44-mast cells” network of somatic cell–cell communications in the testicular microenvironment, which might play roles in spermatogenic dysfunction.

Conclusions
The present study revealed CCL2-relevant changes in the testicular immune microenvironment in spermatogenic dysfunction, providing new evidence for the role of immunological factors in azoospermia.
ScRNA-seq revealed an immunosuppression state and tumor microenvironment heterogeneity related to lymph node metastasis in prostate cancer
Authors: Xin Shiyong , Liu Xiang , Li Ziyao , Sun Xianchao , Wang Rong , Zhang Zhenhua , Feng Xinwei , Jin Liang , Li Weiyi , Tang Chaozhi , Mei Wangli , Cao Qiong , Wang Haojie , Zhang Jianguo , Feng Lijin , Ye Lin 
Published: May 2023

Abstract
Background
Metastasis is a crucial aspect of disease progression leading to death in patients with prostate cancer (PCa). However, its mechanism remains unclear. We aimed to explore the mechanism of lymph node metastasis (LNM) by analyzing the heterogeneity of tumor microenvironment (TME) in PCa using scRNA-seq.

Methods
A total of 32,766 cells were obtained from four PCa tissue samples for scRNA-seq, annotated, and grouped. InferCNV, GSVA, DEG functional enrichment analysis, trajectory analysis, intercellular network evaluation, and transcription factor analysis were carried out for each cell subgroup. Furthermore, validation experiments targeting luminal cell subgroups and CXCR4 + fibroblast subgroup were performed.

Results
The results showed that only EEF2 + and FOLH1 + luminal subgroups were present in LNM, and they appeared at the initial stage of luminal cell differentiation, which were comfirmed by verification experiments. The MYC pathway was enriched in the EEF2 + and FOLH1 + luminal subgroups, and MYC was associated with PCa LNM. Moreover, MYC did not only promote the progression of PCa, but also led to immunosuppression in TME by regulating PDL1 and CD47. The proportion of CD8 + T cells in TME and among NK cells and monocytes was lower in LNM than in the primary lesion, while the opposite was true for Th and Treg cells. Furthermore, these immune cells in TME underwent transcriptional reprogramming, including CD8 + T subgroups of CCR7 + and IL7R+, as well as M2-like monocyte subgroups expressing tumor-associated signature genes, like CCR7, SGKI, and RPL31. Furthermore, STEAP4+, ADGRF5 + and CXCR4+, and SRGNC + fibroblast subgroups were closely related to tumor progression, tumor metabolism, and immunosuppression, indicating their contributions in PCa metastasis. Meanwhile, The presence of CXCR4 + Fibroblasts in PCa was confirmed by polychromatic immunofluorescence.

Conclusions
The significant heterogeneity of luminal, immune, and interstitial cells in PCa LNM may not only directly contribute to tumor progression, but also indirectly result in TME immunosuppression, which may be the cause of metastasis in PCa and in which MYC played an role.
Risk factors for school-based presenteeism in children: a systematic review
Authors: Woodland Lisa , Brooks Samantha K. , Webster Rebecca K. , Amlôt Richard , Rubin G. James 
Published: May 2023

IntroductionChildren attending school whilst unwell, known as school-based presenteeism, results in negative impacts on education and mental and physical health. We aimed to identify the risk factors for this behaviour.MethodWe conducted a systematic search of five databases (11 July 2022) using words associated with school (e.g., school and childcare) and presenteeism (e.g., presenteeism and sick leave). The studies are synthesised according to the risk factors associated with school-based presenteeism and are grouped into themes by related topics.ResultsOur review included 18 studies, with quantitative, qualitative, and mixed-method study designs. Children, parents, and school staff reported past incidents and intentions for future presenteeism. We identified five themes from these reports: perceptions about the illness / signs and symptom(s); children’s characteristics; children’s and parents’ motivations and attitudes towards school; organisational factors; and school sickness policy. Increased risk of school-based presenteeism was commonly linked to symptoms that were perceived low in severity and unidentifiable, children with a high school absence record, disbelief in children’s illness, unsupportive employers, vague school policies and financial consequences.ConclusionsSchool-based presenteeism is complex due to the competing interests of the multiple individuals involved, such as children, parents, and school staff. Sickness policies need to include clear and specific guidance about illness and the signs and symptoms of diseases and should be communicated to all relevant individuals to mitigate against discrepancies in how the policy is interpreted. Furthermore, parents and school staff need support, such as financial and childcare, to be able to manage children when they are unwell.
A pilot screening for cognitive impairment through voice technology (WAY2AGE)
Authors: Moret-Tatay Carmen , Iborra-Marmolejo Isabel , Jorques-Infante María José , Bernabé-Valero Gloria , Beneyto-Arrojo María José , Irigaray Tatiana Quarti 
Published: May 2023

AbstractVoice technology has grown exponentially, offering an opportunity to different fields, such as the health area. Considering that language can be a sign of cognitive impairment and most screening tools are based on speech measures, these devices are of interest. The aim of this work was to examine a screening tool for Mild Cognitive Impairment (MCI) through voice technology. For this reason, the WAY2AGE voice Bot was tested across Mini-Mental (MMSE) scores. The main results depict a strong relationship between MMSE and WAY2AGE scores, as well as a good AUC value to discriminate between no cognitive impairment (NCI) and MCI groups. However, a relationship between age and WAY2AGE scores, but not between age and MMSE scores, was found. This would indicate that, even if WAY2AGE seems sensitive to detect MCI, the voice tool is age-sensitive and not as robust as the traditional MMSE scale. Future lines of research should look more deeply into parameters that distinguish developmental changes. As a screening tool, these results are of interest for the health area and for at-risk older adults.
Canadian women in otolaryngology: Head and neck surgery part 2—challenges in family planning, fertility, and lactation
Authors: Naismith Kendra , Ioanidis Khrystyna , Dzioba Agnieszka , MacNeil S. Danielle , Paradis Josee , Nayan Smriti , Strychowsky Julie E. , Graham M. Elise 
Published: May 2023

Background Previous literature demonstrates that female surgeons face difficulties in family planning, meeting breastfeeding goals, leadership and advancement opportunities. These issues have received limited attention in Canadian surgeons despite different maternity leave patterns compared to the general Canadian population. We sought to describe the experience of otolaryngologist-head and neck surgeons in family planning, fertility, and lactation and to identify the role of gender and career stage in these experiences. Methods A RedCAP® survey was disseminated to Canadian otolaryngology–head and neck surgeons and residents from March to May of 2021 through social media and the national listserv. This survey examined fertility, pregnancy losses, and infant feeding. Major independent variables include gender and career stage (faculty and resident). Dependent variables include respondent experiences with fertility, number of children, and length of parental leave. Responses were tabulated and presented descriptively to communicate the experience of Canadian otolaryngologists. Further, statistical comparisons such as chi-square and t-tests were employed to identify relationships between these variables. Thematic analysis was conducted for narrative comments. Results We received 183 completed surveys (22% response rate). 54% of females versus 13% of males agreed that career influenced their ability to have children ( p = 0.002). 74% of female respondents without children have concerns about future fertility compared to 4% of men ( p < 0.001). Furthermore, 80% of women versus 20% of men have concerns about future family planning ( p < 0.001). The average maternity leave was 11.5 weeks for residents, and 22.2 weeks for staff. Additionally, significantly more women than men stated that maternity leave impacted advancement opportunities (32% vs. 7%) and salary/remuneration (71% vs. 24%) ( p < 0.001). Over 60% of those choosing to pump breastmilk at work reported having inadequate time, space, and breastmilk storage. In total, 62% of breastfed infants were receiving breastmilk at 1 year. Conclusion Canadian female otolaryngologists-head and neck surgeons face challenges in family planning, ability to conceive, and breastfeeding. Focused effort is required to provide an inclusive environment that helps all otolaryngologists-head and neck surgeons achieve both their career and family goals, regardless of gender or career stage. Graphical Abstract
Safety injections of nuclear medicine radiotracers: towards a new modality for a real-time detection of extravasation events and 18F-FDG SUV data correction
Authors: Iori Mauro , Grassi Elisa , Piergallini Lorenzo , Meglioli Greta , Botti Andrea , Sceni Giada , Cucurachi Noemi , Verzellesi Laura , Finocchiaro Domenico , Versari Annibale , Fraboni Beatrice , Fioroni Federica 
Published: May 2023

Abstract
Background
18F-FDG PET/CT imaging allows to study oncological patients and their relative diagnosis through the standardised uptake value (SUV) evaluation. During radiopharmaceutical injection, an extravasation event may occur, making the SUV value less accurate and possibly leading to severe tissue damage. The study aimed to propose a new technique to monitor and manage these events, to provide an early evaluation and correction to the estimated SUV value through a SUV correction coefficient.

Methods
A cohort of 70 patients undergoing 18F- FDG PET/CT examinations was enrolled. Two portable detectors were secured on the patients' arms. The dose-rate (DR) time curves on the injected DRin and contralateral DRcon arm were acquired during the first 10 min of injection. Such data were processed to calculate the parameters ΔpinNOR = (DRinmax- DRinmean)/DRinmax and ΔRt = (DRin(t) − DRcon(t)), where DRinmax is the maximum DR value, DRinmean is the average DR value in the injected arm. OLINDA software allowed dosimetric estimation of the dose in the extravasation region. The estimated residual activity in the extravasation site allowed the evaluation of the SUV's correction value and to define an SUV correction coefficient.

Results
Four cases of extravasations were identified for which ΔRt [(390 ± 26) µSv/h], while ΔRt [(150 ± 22) µSv/h] for abnormal and ΔRt [(24 ± 11) µSv/h] for normal cases. The ΔpinNOR showed an average value of (0.44 ± 0.05) for extravasation cases and an average value of (0.91 ± 0.06) and (0.77 ± 0.23) in normal and abnormal classes, respectively. The percentage of SUV reduction (SUV%CR) ranges between 0.3% and 6%. The calculated self-tissue dose values range from 0.027 to 0.573 Gy, according to the segmentation modality. A similar correlation between the inverse of ΔpinNOR and the normalised ΔRt with the SUV correction coefficient was found.

Conclusions
The proposed metrics allowed to characterised the extravasation events in the first few minutes after the injection, providing an early SUV correction when necessary. We also assume that the characterisation of the DR-time curve of the injection arm is sufficient for the detection of extravasation events. Further validation of these hypotheses and key metrics is recommended in larger cohorts.