bluuebunny/crossref_metadata_2025 huggingface dataset:
Subjective Dry Eye Symptoms in Pregnant Women–A SPEED Survey
Authors: Anantharaman Divya , Radhakrishnan Aiswaryah , Anantharaman Vidhyalakshmi
Published: January 2023

Aim. Multisystemic physiological changes in pregnancy can result in tear film and refractive changes in the eye. We report dry eye prevalence in pregnant women using Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Methods. The SPEED questionnaire was self-administered cross-sectionally to 428 pregnant women (mean age:

26.8
±
4.4

years) with clinically confirmed pregnancy from two obstetric clinics in Chennai, India. Subjects with predisposing risk factors for dry eye were excluded from the study. Subjects were categorized as normal, moderate, and severe dry eye based on the SPEED score. Results. Among the women, 48.5% of the subjects had symptoms like dryness, grittiness or scratchiness, soreness or irritation, burning or watering, or eye fatigue. About 2.3% had moderate dry eye according to SPEED questionnaire criteria. Eye fatigue was the most reported symptom and was present in 76.4% of women. The symptom frequency score and severity score had a strong and significant correlation (

r
=
0.95

,

P
<
.001

). No significant correlation was noted among SPEED score vs age (

r
=
−
0.02

,

P
>
.05

). No significant correlation was found between symptoms of dry eye and gravidity (

ρ
=
−
0.006

,

P
>
.05

) and trimester (

ρ
=
0.38

,

P
>
.05

). Binary logistic regression showed that only occupational status and systemic condition was significantly associated with dry eye symptoms. Conclusion. About half the pregnant women at the visit reported having one or more dry eye-related symptoms. As per the composite SPEED questionnaire score, dry eye was not prevalent among pregnant women irrespective of their age, gravidity, and the trimester, but we found a majority of pregnant women reported to have experienced dry eye-related symptoms, though tolerable. Awareness about dry eye during pregnancy will improve eye care seeking behaviour in pregnant women.
Machine Learning Modeling of Disease Treatment Default: A Comparative Analysis of Classification Models
Authors: Owusu-Adjei Michael , Hayfron-Acquah James Ben , Twum Frimpong , Abdul-Salaam Gaddafi
Published: January 2023

Generally, treatment default of diseases by patients is regarded as the biggest threat to favourable disease treatment outcomes. It is seen as the reason for the resurgence of infectious diseases including tuberculosis in some developing countries. Sadly, its occurrence in chronic disease management is associated with high morbidity and mortality rates. Many reasons have been adduced for this phenomenon. Exploration of treatment default using biographic and behavioral metrics collected from patients and healthcare providers remains a challenge. The focus on contextual nonbiomedical measurements using a supervised machine learning modeling technique is aimed at creating an understanding of the reasons why treatment default occurs, including identifying important contextual parameters that contribute to treatment default. The predicted accuracy scores of four supervised machine learning algorithms, namely, gradient boosting, logistic regression, random forest, and support vector machine were 0.87, 0.90, 0.81, and 0.77, respectively. Additionally, performance indicators such as the positive predicted value score for the four models ranged between 98.72%–98.87%, and the negative predicted values of gradient boosting, logistic regression, random forest, and support vector machine were 50%, 75%, 22.22%, and 50%, respectively. Logistic regression appears to have the highest negative-predicted value score of 75%, with the smallest error margin of 25% and the highest accuracy score of 0.90, and the random forest had the lowest negative predicted value score of 22.22%, registering the highest error margin of 77.78%. By performing a chi-square correlation statistic test of variable independence, this study suggests that age, presence of comorbidities, concern for long queuing/waiting time at treatment facilities, availability of qualified clinicians, and the patient’s nutritional state whether on a controlled diet or not are likely to affect their adherence to disease treatment and could result in an increased risk of default.
Predator Interference in a Predator–Prey Model with Mixed Functional and Numerical Responses
Authors: Alebraheem Jawdat
Published: January 2023

Predator interference refers to the competition effect on individuals of the same species through preventing or limiting access to a resource. In this paper, a novel predator–prey model that includes predator interference is considered. In the novel model, a high prey density is taken into consideration by investigating Crowley–Martin as a numerical response, while the growth rate of prey is logistically described and Holling type II is used as a functional response. In contrast to literature, this model has distinct and notable features: predator and prey species have an intraspecific competition, and this model has a numerical response that generalizes several of the commonly utilized depictions of predator interference. The boundedness of the model is proved. Predator interference effects are theoretically and numerically studied in terms of stability, coexistence, and extinction. Theoretical results show that the system has no effect on coexistence or extinction in these types of models. Numerical simulations present two different dynamics with identical results on the theoretical side of model stabilization for both dynamics. Moreover, the numerical simulations show that there is a change from periodic to steady state dynamics as the value of predator interference increases. This means that the coexistence probability of the model increases. The attained results are explained from both a mathematical and an ecological points of view.
The Relation between ACE Gene Polymorphism and the Severity of COVID-19 Infection
Authors: El-Sayed Marei Yara , Abdallah Bayoumy Ahmed , Mohamed Abulazm Nassar Hassnaa , Mansour Bassam , Bakeir Hamady Asmaa
Published: January 2023

Introduction. The coronavirus disease 2019 (COVID-19) pandemic, which emerged in China at the end of 2019, rapidly spread worldwide. The angiotensin-converting enzyme (ACE) gene contains an insertion/deletion (I/D) polymorphism that leads to a higher serum ACE level which is associated with several diseases and also with a high mortality rate in SARS. Therefore, this study aimed at assessing the association between ACE gene polymorphism and the risk and severity of COVID-19 disease in patients. Methodology. Forty-five SARS-CoV-2 infected patients and another random control group of 45 healthy individuals were included. The detection of ACE I/D gene polymorphism in both groups was done by PCR. Results. 53% of infected patients with SARS-CoV-2 had an ACE deletion/deletion genotype (D/D), 27% had an ACE deletion/insertion genotype (D/I), and 20% had an ACE insertion/insertion genotype (I/I). On the one hand, the D/D variant was significantly detected in the COVID-19 patients compared to the control subjects, whereas the I/I variant was significantly detected in the control subjects compared to the COVID-19 patients (

p

 = 0.004). The D/D variant subgroup showed the lowest lymphocytic count compared to the D/I or I/I subgroups. In addition, the C-reactive protein was significantly higher and the oxygen saturation was significantly lower in patients with the D/D allele compared to the other subgroups. Conclusions. ACE gene polymorphism, particularly the DD genotype, was observed to affect the severity of COVID-19 infection.
The Oncologic Safety of Sentinel Lymph Node Biopsy in Patients with Node-Positive Breast Cancer with Complete Response to Neoadjuvant Chemotherapy: A Single-Center Experience
Authors: Tercan Ismail Can , Zengel Baha , Ozdemir Ozlem , Cavdar Demet , Tasli Funda , Adibelli Zehra Hilal , Karatas Murat , Simsek Cenk , Durusoy Isabel Raika , Uslu Adam
Published: January 2023

Objective. To evaluate the efficiency and safety of sentinel lymph node biopsy (SLNB) in patients with breast cancer with complete response to neoadjuvant chemotherapy (NAC). Methods. Ninety-two consecutive (T1-4 and N1-2) patients with breast cancer who had pathologic and/or clinical and radiologic axillary lymph node involvement were included. All patients received NAC. Patients with a clinical and radiologic complete response in the axilla after NAC underwent SLNB. Pathologic complete response (ypCR) was defined as the absence of residual invasive and in situ cancer, and near-complete response (ypNCR) represented in situ and/or ≤ 1 mm residual tumor in the breast and/or presence of malignant cell clusters (≤0.2 mm) and/or micrometastases (≤2.0 mm) in the axillary lymph nodes (ALN) (ypTis/T1mi, ypN0i+/pN1mi). Results. The mean age of the 92 patients was 49.6 ± 10.3 years and the mean follow-up was 34.0 ± 17.8 months. With respect to breast tumors, 23 (25.0%) patients had complete and 14 (15.2%) had a near-complete response to NAC. Complete response in ALN was obtained in 39 (42.4%) patients and near-complete in six (6.5%) patients. The overall survival of the 33 patients who achieved ypCR and ypNCR was 100% and the remaining 59 patients with partial or no response to NAC was 83.1% at a mean follow-up of 34 months (

p
=
0.063

). Conclusions. In this study, no event developed in cases with ypCR and ypNCR in the breast and axilla. The persistence of the same results in long-termfollow-ups may enable the use of ypNCR as a positive prognostic marker in addition to ypCR.
Undergraduate Endodontic Training and Its Relation to Contemporary Practice: Multicenter Cross-Sectional Study in Saudi Arabia
Authors: Algahtani Fahda N. , Barakat Reem M. , Alqarni Lujain M. , Alqabbani Alanoud F. , Alkadi Manal F. , Almohareb Rahaf A.
Published: January 2023

Background and Objectives. The aim of this study is to explore the current state of endodontic practical training in Saudi dental schools and its relevance to contemporary endodontic practice. Materials and Methods. An online questionnaire was developed and emailed to all dental schools in Saudi Arabia. This questionnaire was answered by the endodontic undergraduate program director. The data collected were analysed using descriptive statistics. Results. The response rate was 96.15%, which means twenty-five out of twenty-six dental schools participated in the study. The majority of the academic supervisors was endodontists (92%). The use of magnification and ultrasonic tips was not required by 84% and 76% of the dental schools, respectively. The main endodontic treatment techniques were the step-back technique and gates glidden for cleaning and shaping (76%) and cold lateral compaction for obturation (92%). Conclusions. The dental students were supervised by endodontic specialists and trained to use traditional endodontic methods. Encouraging dental educators to train students to use modern technology and equipment would probably improve their graduate clinical skills and performance.
Spinal Manual Therapy for Adolescent Idiopathic Scoliosis: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials
Authors: Sun Yan , Zhang Yong , Ma Haoning , Tan Mingsheng , Zhang Zhihai
Published: January 2023

Objective. We conducted this meta‐analysis to provide better evidence of the efficacy of manual therapy (MT) on adolescent idiopathic scoliosis (AIS). Methods. All RCTs of MT for the management of patients with AIS were included in the present study. The treatment difference between the experimental and control group was mainly MT. The outcomes consisted of the total effective rate, the Cobb angle, and Scoliosis Research Society‐22 (SRS‐22) questionnaire score. Electronic database searches were conducted from database inception to July 2022, including the Cochrane Library, PubMed, Web of Science, Embase, Wanfang Data, CNKI, and VIP. The pooled data were analyzed using RevMan 5.4 software. Results. Four RCTs with 213 patients in the experimental group were finally included. There are 2 studies of standalone MT in the experimental group and 3 studies of MT with identical conservative treatments in the control group. Three trials reported total effective rate, and a statistically significant difference was found (P = 0.004). Three trials reported Cobb angle, and a statistical difference was found (P = 0.01). Then, sensitivity analysis showed that there was a significant difference in the additional MT subgroup (P < 0.00001) while not in the standalone MT subgroup (P = 0.41). Three trials reported SRS‐22 scores (P = 0.55) without significant differences. Conclusion. There is insufficient data to determine the effectiveness of spinal manipulation limited by the very low quality of included studies. High‐quality studies with appropriate design and follow‐up periods are warranted to determine if MT may be beneficial as an adjunct therapy for AIS. Currently, there is no evidence to support spinal manipulation.
β‐Sitosterol Suppresses LPS‐Induced Cytokine Production in Human Umbilical Vein Endothelial Cells via MAPKs and NF‐κB Signaling Pathway
Authors: Bi Yiming , Liang Hongfeng , Han Xin , Li Kongzheng , Zhang Wei , Lai Yigui , Wang Qiang , Jiang Xuefeng , Zhao Xiaoshan , Fan Huijie
Published: January 2023

Atherosclerosis (AS) is an inflammatory disease, whose occurrence and development mechanism is related to a great number of inflammatory cytokines. β‐sitosterol (BS), a natural compound extracted from numerous vegetables and plant medicines, has been suggested to improve AS, but the underlying mechanism remains vague. This work focused on investigating how BS affected the lipopolysaccharide (LPS)‐treated human umbilical vein endothelial cells (HUVECs) and further exploring the potential targets and mechanisms through network pharmacology (NP) and molecular docking (MD). According to in vitro experiments, LPS resulted in an increase in the expression of inflammatory cytokines like tumor necrosis factor‐α (TNF‐α), cyclooxygenase‐2 (Cox‐2), and interleukin‐6 (IL‐6). Besides, secretion of IL‐6, interleukin‐1β (IL‐1β), and TNF‐α also increased in HUVECs, whereas BS decreased the expression and secretion of these cytokines. NP analysis revealed that the improvement effect of BS on AS was the result of its comprehensive actions targeting 99 targets and 42 pathways. In this network, MAPKs signaling pathway was the core pathway, whereas MAPK1, MAPK8, MAPK14, and NFKB1 were the hub targets. MD analysis also successfully validated the interactions between BS and these targets. Moreover, verification test results indicated that BS downregulated the abnormal expression and activation of MAPKs and NF‐κB signaling pathways in LPS‐treated cells, including p38, JNK, ERK, NF‐κB, and IκB‐α phosphorylation expressions. Furthermore, p65 nuclear translocation was also regulated by BS treatment. In conclusion, the BS‐related mechanisms in treating AS are possibly associated with inflammatory response inhibition by regulating MAPKs and NF‐κB signaling pathways.
Dental Caries and Its Management
Authors: Warreth Abdulhadi
Published: January 2023

Objectives. In recent years, the management of dental caries has evolved significantly. Caries prevention, early detection, and a diagnosis based on risk indicators and risk factor assessments are the most current practical approaches. Furthermore, as proposed in minimally invasive dentistry, the new management approaches preserve healthy tissue and maintain pulp vitality. This article overviews the latest minimally invasive dental caries management and treatment options. The information will assist the reader in the early detection, diagnosis, and treatment of dental caries. Materials and Methods. The PubMed (MEDLINE) search engine was used to gather the most relevant information on dental caries. The search was restricted to five years (May 30, 2018–May 29, 2022), and only English-language studies were accessed. A Boolean search of the PubMed data set was implemented to combine a range of keywords. The following filters were applied: abstract, free full text, full text, clinical trial, randomised control trial, systematic review, meta-analysis, and review. More studies were also obtained by manual searches from Google Scholar and textbooks on dental caries. Results. By using this process, 683 articles and studies were obtained. The most relevant published studies were chosen and used in the current review. The selected articles are included in the references list. However, the search extended to cover the last five years as our understanding and management of dental caries have changed significantly. Conclusions. Early detection and diagnosis of caries based on risk indicators and risk factor assessments are effective. Furthermore, minimally invasive restorative techniques are beneficial in managing dental caries and preserving healthy tissue and should be used whenever possible. This new information, knowledge, and materials should encourage professionals to implement this method. Having a strategy and system based on patient-centred care is critical, and our dental responsibilities must prioritise patient-centred care.
Stability Analysis of State Delay Multiagent Systems with Observer-Based Control Protocols
Authors: Li Xingmei , Deng Shasha , Wang Yanhong , Deng Hongyong
Published: January 2023

The consistency problem of multiagent systems with the output feedback and state delay was considered in this paper. First, the reduced-order observer based on the consensus protocol of state delay is designed, and the consensus protocol is proposed by the output information of neighboring agents. Then, by constructing the Lyapunov–Krasovskii functional and combining matrix inequality and the Schur complement lemma, the asymptotic stability of the system can be obtained, and the consistency of state-delay multiagent systems is derived. Finally, the theoretical results are verified by a simulation example.
Molecular Pathways and Mechanisms of TGFβ in Cancer Therapy
Authors: Barcellos-Hoff Mary Helen , Gulley James L.
Published: January 2023

Even though the number of agents that inhibit TGFβ being tested in patients with cancer has grown substantially, clinical benefit from TGFβ inhibition has not yet been achieved. The myriad mechanisms in which TGFβ is protumorigenic may be a key obstacle to its effective deployment; cancer cells frequently employ TGFβ-regulated programs that engender plasticity, enable a permissive tumor microenvironment, and profoundly suppress immune recognition, which is the target of most current early-phase trials of TGFβ inhibitors. Here we discuss the implications of a less well-recognized aspect of TGFβ biology regulating DNA repair that mediates responses to radiation and chemotherapy. In cancers that are TGFβ signaling competent, TGFβ promotes effective DNA repair and suppresses error-prone repair, thus conferring resistance to genotoxic therapies and limiting tumor control. Cancers in which TGFβ signaling is intrinsically compromised are more responsive to standard genotoxic therapy. Recognition that TGFβ is a key moderator of both DNA repair and immunosuppression might be used to synergize combinations of genotoxic therapy and immunotherapy to benefit patients with cancer.
Benign Breast Disease, NSAIDs, and Postmenopausal Breast Cancer Risk in the CPS-II Cohort
Authors: Sherman Mark E. , Vierkant Robert A. , Masters Matthew , Radisky Derek C. , Winham Stacey J. , Degnim Amy C. , Vachon Celine M. , Patel Alpa V. , Teras Lauren R.
Published: January 2023

Nonsteroidal anti-inflammatory agents (NSAID) are associated with modest inconsistent reductions in breast cancer risk in population-based cohorts, whereas two focused studies of patients with benign breast disease (BBD) have found lower risk with NSAID use. Given that BBD includes fibroinflammatory lesions linked to elevated breast cancer risk, we assessed whether NSAID use was associated with lower breast cancer risk among patients with BBD.

Participants were postmenopausal women in the Cancer Prevention Study-II (CPS-II), a prospective study of cancer incidence and mortality, who completed follow-up surveys in 1997 with follow-up through June 30, 2015. History of BBD, NSAID use, and covariate data were updated biennially. This analysis included 23,615 patients with BBD and 36,751 patients with non-BBD, including 3,896 incident breast cancers over an average of 12.72 years of follow-up among participants. NSAID use, overall and by formulation, recency, duration, and pills per month was analyzed versus breast cancer risk overall and by BBD status using multivariable-adjusted Cox models; BBD status and NSAID use were modeled as time-dependent exposures.

Patients with BBD who reported using NSAIDs experienced lower breast cancer risk (HR, 0.87; 95% CI, 0.78–0.97), with similar effects for estrogen receptor (ER)-positive breast cancers [HR, 0.85; 95% confidence interval (CI), 0.74–0.97] and ER-negative breast cancers (HR, 0.87; 95% CI, 0.59–1.29); among women without BBD, NSAID use was unrelated to risk (HR, 1.02; 95% CI, 0.92–1.13; Pinteraction = 0.04). Associations stratified by age, obesity, menopausal hormone use, and cardiovascular disease were similar.

Among patients with BBD, NSAID use appears linked to lower breast cancer risk. Further studies to assess the value of NSAID use among patients with BBD are warranted.

Prevention Relevance:

We examined whether NSAID use, a modifiable exposure, is associated with breast cancer risk in postmenopausal women from the Cancer Prevention Study-II with self-reported benign breast disease, an often inflammatory condition associated with higher rates of breast cancer.
Abstract IA002: Optimizing the public’s health through prevention and early detection (precision and otherwise)
Authors: Rebbeck Timothy
Published: January 2023

Cancer prevention and early detection have the greatest potential for reducing incidence, suffering, and death from cancer of any modality we have available. HPV and HBV vaccination, as well as exposure avoidance (e.g., smoking cessation) are well documented to reduce cancer risks. Approaches such as mammography, colonoscopy and low-dose CT screening clearly provide mortality reductions. While these tools are effective, they are under-used and thus their potential for cancer reduction is sub-optimal. The field is also at a critical phase of development: we have substantial mechanistic understanding of cancer and novel technologies that provide new opportunities for prevention and early detection. We must consider a series of factors in order for effective translation and implementation of this knowledge to occur. Multisector involvement of academia, business, policymakers, biotech, community members, and others are required to build a common language and pathways from discovery to implementation. Diverse data and input from end used communities are required to ensure that these novel approaches do not induce or exacerbate disparities and can benefit all populations equitably. Increased compliance with existing population-based tools that are known to minimize cancer mortality must be improved, while new “precision” methods are developed and implemented. The field has the opportunity to disrupt the landscape of state of cancer by developing and implementing mechanism-based tools and technologies that will be used in novel prevention and early detection strategies.

Citation Format: Timothy Rebbeck. Optimizing the public’s health through prevention and early detection (precision and otherwise). [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA002.
Abstract IA018: Opportunity for interception as a driver of benefit in cancer early detection: implications for multi-cancer early detection testing
Authors: Etzioni Ruth , Gulati Roman , Owens Lukas , Lange Jane , Ryser Marc D.
Published: January 2023

Early detection cannot succeed unless there is adequate opportunity for cancer to be diagnosed and intercepted within its early preclinical phase. An understanding of opportunity for early detection and interception is therefore critical in predicting potential mortality reduction due to screening. Opportunity is not directly observable but may be learned using data from prospectively screened cohorts and populations. In this presentation I will share a history of methods for learning about early detection opportunity and will present examples of how we have built on this work to study opportunity for early detection in prostate and breast cancer. I will describe a generic model of how opportunity and sensitivity combine to produce stage shift and mortality reduction and will briefly explore whether a lack of opportunity may have been behind the results of the UCKCTOCS trial. I will use this learning to motivate why I believe a prospective study to investigate opportunity for multi-cancer detection and interception is warranted before or alongside ongoing and planned screening trials. This work in in collaboration with Roman Gulat i and Lukas Owens (Fred Hutch), Jane Lange (OHSU) and Marc Ryser (Duke University). We acknowledge funding from the National Cancer Institute and collaboration with and data from the Breast Cancer Surveillance Consortium

Citation Format: Ruth Etzioni, Roman Gulati, Lukas Owens, Jane Lange, Marc D. Ryser. Opportunity for interception as a driver of benefit in cancer early detection: implications for multi-cancer early detection testing. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA018.
Abstract IA022: Assessing implementation of a multi-cancer early detection blood test for population screening in a clinical practice setting: prospective PATHFINDER cohort study
Authors: Klein Eric , Beer Tomasz
Published: January 2023

Background: A validated blood-based multi-cancer early detection (MCED) test uses cfDNA and machine learning to detect a shared cancer signal across >50 cancer types and predict cancer signal origin. PATHFINDER is a prospective study in a screening population to evaluate the clinical feasibility of MCED testing. Methods: Between December 2019 and 2020, 6662 adults aged ≥50 years with or without additional cancer risk factors (smoking history, genetic predisposition, prior cancer diagnosis) were enrolled from 7 US health systems’ outpatient practices. Blood samples were collected, cfDNA was analyzed, and MCED test results were returned. Diagnostic evaluation was conducted at the discretion of the physician. Cancer status was ascertained after one year. Primary outcomes were extent of diagnostic testing and time to diagnostic resolution. Performance measures included signal detection rate, accuracy of predicted cancer signal origin, specificity, and positive and negative predictive values. Findings: Of the 6621 (99.4%) with analyzable samples, cancer signal was detected in 92 (1.4%), 91 reached diagnostic resolution, 90 were evaluable for the primary outcome, and 35 were true positives (TP). Median time to diagnostic resolution was 79 days overall and 57 days in TPs; 73% of TPs achieved resolution in <3 months. Among TPs, signal origin was predicted accurately for 33/34 (97.1%). Specificity was 99.1% (6235/6290), positive predictive value was 38.0% (35/92), and negative predictive value was 98.6% (6235/6321). Adverse events were rare (0.06%); none due to confirmatory diagnostic procedures. Interpretation: A blood-based assay to screen for multiple cancers was safely implemented in adults ≥50 years with and without additional cancer risk. It is feasible to use MCED testing for early detection of cancer in routine outpatient practice.

Citation Format: Eric Klein, Tomasz Beer. Assessing implementation of a multi-cancer early detection blood test for population screening in a clinical practice setting: prospective PATHFINDER cohort study. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr IA022.
Abstract P031: Glycerolipid metabolism is a key early-detection biomarker for spontaneous ovarian cancer onset
Authors: Ellwood Kathryn , Taylor Ashley , Dutta Aditya
Published: January 2023

Ovarian cancer (OVC) is the fifth leading cause of cancer death in women and the most lethal gynecological cancer due to its inability to be diagnosed early. OVC is very treatable in its early stages, however, it is usually not identified until it’s at a later stage and survivability is low. Early symptoms of OVC such as abdominal pain, bloating, and changes in diet or bathroom habits are nonspecific and thus OVC is a challenge to diagnose early. Identification of early-detection blood biomarker(s) will allow for quicker and more informed treatment decisions and have a direct bearing on enhancing the survival rate. To this end, we use the chicken model of OVC to model spontaneous human OVC initiation and progression. Egg-laying hens develop OVC in much the same way as humans do; spontaneously and without known genetic predisposition. The layer hen has a fully sequenced genome with ~60% gene correspondence and ~99% gene similarity to humans. This combined with reproductive similarities to humans such as repetitive ovulation, gene function, and ovarian cellular makeup are what have validated the hen as an accurate model for OVC study. Moreover, disease presentation and disease grade are highly similar across the two species. Monthly blood draws were performed on specific-pathogen-free (SPF) hens during their entire lifecycle from reproductive prime to spontaneous development of OVC. Blood plasma from young, high laying hens (exhibiting repetitive ovulation, similar to the reproductive prime in women) and older, low-laying hens (those with slowing ovulation, similar to menopausal women) were analyzed for ~550 different metabolites using mass spectrometry. Glycerolipid metabolism was identified as a key early indicator of ovarian health. OVC requires lipid-rich nutrients for growth and spread, as is seen with metastasis often occurring to the omentum, a fat-rich organ. Our results also revealed that steroid biosynthesis was another major pathway in differentiating the cohorts. Upregulated fatty acid metabolism and regulation are associated with increased risk of cancer development as they have roles in cell support, structure, and signaling. Uncovering these early-stage diagnostic and prognostic biomarkers will have a direct bearing on enhancing patient survival rates and improve quality of life.

Citation Format: Kathryn Ellwood, Ashley Taylor, Aditya Dutta. Glycerolipid metabolism is a key early-detection biomarker for spontaneous ovarian cancer onset. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P031.
Genomic Patterns of Malignant Peripheral Nerve Sheath Tumor (MPNST) Evolution Correlate with Clinical Outcome and Are Detectable in Cell-Free DNA
Authors: Cortes-Ciriano Isidro , Steele Christopher D. , Piculell Katherine , Al-Ibraheemi Alyaa , Eulo Vanessa , Bui Marilyn M. , Chatzipli Aikaterini , Dickson Brendan C. , Borcherding Dana C. , Feber Andrew , Galor Alon , Hart Jesse , Jones Kevin B. , Jordan Justin T. , Kim Raymond H. , Lindsay Daniel , Miller Colin , Nishida Yoshihiro , Proszek Paula Z. , Serrano Jonathan , Sundby R. Taylor , Szymanski Jeffrey J. , Ullrich Nicole J. , Viskochil David , Wang Xia , Snuderl Matija , Park Peter J. , Flanagan Adrienne M. , Hirbe Angela C. , Pillay Nischalan , Miller David T. ,   for the Genomics of MPNST (GeM) Consortium
Published: January 2023

Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling and chromosome 8 amplification, and show lower levels of immune cell infiltration. Retention of H3K27me3 leads to extensive genomic instability, but an immune cell-rich phenotype. Specific SCNAs detected in both tumor samples and cell-free DNA (cfDNA) act as a surrogate for H3K27me3 loss and immune infiltration, and predict prognosis.

Significance:

MPNST is the most common cause of death and morbidity for individuals with NF1, a relatively common tumor predisposition syndrome. Our results suggest that somatic copy-number and methylation profiling of tumor or cfDNA could serve as a biomarker for early diagnosis and to stratify patients into prognostic and treatment-related subgroups.

This article is highlighted in the In This Issue feature, p. 517
Integrated Proteomic and Phosphoproteomic Analysis of the Hippocampus in a Mouse Model of Early Life Inflammation
Authors: Wu Xin-miao , Gao Yu-zhu , Zhu Ting-ting , Gu Han-wen , Tong Jian-hua , Sun Jie , Yang Jian-jun , Ji Mu-huo
Published: January 2023

Introduction: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment. Methods: Both female and male mice received a single intraperitoneal injection of 100 μg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining. Results: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis. Conclusions: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.
Prognostic Value of Stress Hyperglycaemia Ratio in Young Patients with Ischaemic Stroke or Transient Ischaemic Attack
Authors: Guo Jiahuan , Jia Jiaokun , Zhang Jia , Liu Xinmin , Li Guangshuo , Zhao Xingquan , Liu Yanfang
Published: January 2023

Introduction: Stress hyperglycaemia is common in stroke. Recently, the stress hyperglycaemia ratio (SHR) has been proposed as a novel marker for stress hyperglycaemia and found to be associated with adverse outcomes in many diseases. However, data regarding the impact of the SHR on ischaemic stroke, especially in young adults, are limited. Therefore, the aim of this study was to investigate whether the SHR is associated with stroke severity and adverse outcomes in young adults with ischaemic stroke or transient ischaemic attack (TIA). Methods: We retrospectively recruited patients aged 18–45 years with acute ischaemic stroke or TIA. The SHR was calculated as fasting blood glucose (FBG) divided by glycated haemoglobin. The primary and secondary outcomes were 90-day poor functional outcomes and stroke severity on admission, respectively. Multivariable logistic regression, restricted cubic spline models, and subgroup analysis were performed to validate the relationship between the SHR and ischaemic stroke or TIA in young adults. Results: A total of 687 young adults (mean age 36.9 years) were recruited. Among them, 119 (17.3%) patients had prior diabetes, and 568 (82.7%) did not. The SHR was significantly associated with stroke severity and poor functional outcome. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have moderate-to-severe stroke. The multivariable-adjusted OR (95% CI) was 1.70 (1.21–2.39) after adjusting for all potential confounders excluding FBG and 1.50 (1.03–2.17) after FBG adjustment. The restricted cubic spline showed a J-shaped association between the SHR and moderate-to-severe stroke. Compared with patients with lower SHR values, patients with higher SHR values were more likely to have poor functional outcome at 90-day follow-up. The multivariable-adjusted OR (95% CI) was 1.95 (1.12–3.41) after adjusting for all potential confounders excluding FBG and 1.84 (1.01–3.36) after FBG adjustment. A J-shaped association was found between the SHR and poor functional outcomes at the 90-day follow-up. In the subgroup analysis, SHR was independently associated with more severe stroke (OR, 1.79, 95% CI, 1.18–2.72) and poor functional outcomes (OR, 2.11, 95% CI, 1.32–3.35) in nondiabetic patients but not in diabetic patients in multivariate logistic analysis. Despite this, the interaction effects of prior diabetes on the association between the SHR and stroke severity and poor functional outcomes did not reach statistical significance. Conclusion: The SHR is independently related to more severe stroke and an increased risk of poor functional outcomes among young adults with ischaemic stroke or TIA.
Effect of Magnesium on Deterioration and Symptomatic Hemorrhagic Transformation in Cerebral Ischemia: An Ancillary Analysis of the FAST-MAG Trial
Authors: Fan Shawn , Jang Michael , Kim-Tenser May , Shkirkova Kristina , Liebeskind David S. , Starkman Sidney , Villablanca Juan Pablo , Hamilton Scott , Naidech Andrew , Saver Jeffrey L. , Sanossian Nerses ,   for the FAST-MAG Investigators and Coordinators
Published: January 2023

Background: Magnesium (Mg) is a neuroprotectant in preclinical models. Lower serum Mg levels have been associated with symptomatic hemorrhagic transformation (HT) in patients with ischemic stroke. Early treatment of acute ischemic stroke with Mg may reduce rates of symptomatic HT. Methods: In this post hoc study of the Field Administration of Stroke Therapy Magnesium (FAST-MAG) trial, 1,245 participants with a diagnosis of cerebral ischemia received 20 g of Mg or placebo initiated in the prehospital setting. Posttreatment serum Mg level was measured for 809 participants. Cases of clinical deterioration, defined as worsening by ≥4 points on the National Institute of Health Stroke Scale (NIHSS), were imaged and evaluated for etiology. Symptomatic HT was defined as deterioration with imaging showing new hemorrhage. Results: Clinical deterioration occurred in 187 and symptomatic HT in 46 of 1,245 cases of cerebral ischemia. Rates of deterioration and symptomatic HT were not significantly lower in those who received Mg (15.7% vs. 14.4%, p = 0.591; 2.8% vs. 4.6%, p = 0.281). In cases where serum Mg level was obtained posttreatment, lower serum Mg level (<1.7 mg/dL) was associated with significantly higher rates of deterioration and symptomatic HT (27.5% vs. 15.5%, p = 0.0261; 11.6% vs. 3.65%, p = 0.00819). Conclusions: Treatment with Mg did not significantly reduce rates of clinical deterioration or symptomatic HT. Future analysis should address whether treatment with Mg could have influenced the subgroup with low serum Mg at baseline.
Laparoscopic versus Open Approach for Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction: A Systematic Review and Meta-Analysis
Authors: Wu Ming , Zhang Wei , Song Yan-Yang
Published: January 2023

Introduction: Due to the specific location, the potential advantages of laparoscopic gastrectomy (LG) compared with open gastrectomy (OG) for Siewert II/III adenocarcinoma of the esophagogastric junction (AEG) remain uncertain. The current study aimed to compare the short- and long-term outcomes of LG versus OG in treating Siewert type II/III adenocarcinoma. Methods: We searched PubMed, Embase, Web of Science, MEDLINE (hosted by Ovid), and the Cochrane Library for publications till July 2022 and then used the RevMan 5.3 software for statistical analysis. Results: Ten publications from 10 medical centers were included, with 1,516 cases from the LG group and 1,219 from the OG group. Meta-analysis results showed that the LG group was superior to the OG group in intraoperative blood loss, hospital stay, lymph nodes retrieved, time to ambulation, time to first flatus, time to diet, 5-year overall survival, and 5-year disease-free survival. There was no significant difference between the two groups in operative time, overall complications, proximal margin, distal margin, pulmonary infection, anastomotic leakage, mortality, ileus, or absolute infection. Conclusions: Compared with OG, LG is associated with better surgical and long-term outcomes in Siewert type II/III AEG. LG is a safe and feasible option for treating Siewert type II/III AEG. However, studies with large sample sizes, long follow-up periods, and rigorous designs are needed for verification.
Saline Vehicle Increases the Ability of Drug Patch Test in Cutaneous Adverse Drug Reactions
Authors: Thaiwat Supitchaya , Prompongsa Sirikarn
Published: January 2023

Background: Drug patch test to identify cutaneous adverse drug reactions (CADRs) has been widely reported. Appropriate vehicles can improve the ability of drug delivery and significantly increase positive reaction of drug patch tests. Objective: The aim of this study was to evaluate the efficacy of drug patch tests using 0.9% saline vehicle in comparison with other traditional vehicles in CADRs. Method: All patients were patch tested with suspected drugs using 10–30% concentration of the commercialized form of drugs diluted in 0.9% saline, petrolatum, and water. Result: Of 100 patients with CADRs, 54 of those had at least one positive drug patch test. In terms of vehicles used, 43 patients had positive drug patch test with saline as compared to 35 with water (p = 0.485) and 25 with petrolatum (p = 0.007). Among CADRs subgroup, saline rendered significantly higher positive rate when compared with petrolatum in drug rash with eosinophilia and systemic symptom (DRESS) (70% vs. 20%, p = 0.025), maculopapular rash (MP) (52.4% vs. 31%, p = 0.046), and lichenoid drug eruption (46.7% vs. 0.0%, p = 0.002). 12/54 (22.2%) of CADRs patients had positive reaction with saline alone. Among these patients, 4/12 (33.3%) were lichenoid drug reaction, 3/12 (25%) were DRESS, and 2/12 (16.7%) were MP rash. Allopurinol was the drug giving positive patch test only with saline. Conclusion: Appropriate vehicles are essential to obtain the positive drug patch test. Using saline as a vehicle can increase the positive reaction of drug patch test, particularly in lichenoid drug eruption. We recommend the use of saline as another traditional vehicle in drug patch test.
Chondroblastoma: Cytomorphologic Analysis of 10 Cases with Review of the Literature
Authors: Saoud Carla , Wakely Jr. Paul E. , Pantanowitz Liron , Siddiqui Momin T. , Ali Syed Z.
Published: January 2023

Introduction: Chondroblastoma (CB) is a rare, benign cartilage-producing tumor, typically affecting the epiphysis of long bones in skeletally immature individuals. There have been only limited case reports describing the cytomorphologic features of this tumor, and thus the cytopathologic diagnostic criteria are controversial. Herein, we report the cytologic findings of 10 CB cases, discuss the diagnostic criteria and critical differential diagnosis, along with a comprehensive review of the literature. Methods: We performed a retrospective search of our cytopathology and surgical pathology databases for cases diagnosed as CB that had corresponding cytology specimens from four large medical institutions. All available cytopathology specimens were retrieved and reviewed. Clinicopathologic and radiologic data were recorded. Results: Ten cases were retrieved from 8 patients aged 15–42 years (mean, 24 years), five of whom were males. Eight cases represented primary tumors while 2 cases were recurrences. Three cases occurred in the femur, two cases occurred in the humerus, while 1 case occurred in each of the glenoid, talus, and proximal phalanx of the 3rd toe. The cytologic diagnosis of CB was achieved in 7 cases. The neoplastic mononuclear cells were present in all cases and their cytologic features were similar. These cells displayed round to oval eccentric nuclei, evenly distributed chromatin, and inconspicuous nucleoli; few of which had nuclear indentations. Multinucleated giant cells were present in 9 cases (90%). Fragments of chondromyxoid matrix were present in 4 cases on cytologic preparations (40%). Cell blocks were available in 8 cases. Mononuclear and multinucleated giant cells were present in all adequate cell blocks and their cytologic features were identical to those seen in the smears. The chondroid matrix was present in only three of the adequate cell blocks (43%). Conclusion: We concluded that with the appropriate clinical and radiologic setting, the diagnosis of CB can be achieved on cytology if characteristic chondroblasts are present. The presence of chondromyxoid matrix is a helpful clue but is not necessary for the diagnosis. As in surgical pathology, cytologic evaluation of bone tumors should be interpreted in conjunction with clinical and radiologic findings.
Reproductive notes and larval development of Macrogenioglottus alipioi (Anura: Odontophrynidae) from the northern Atlantic forest
Authors: Nascimento Filipe Augusto C. , Aguilar Anyelet Valencia , Pansonato André , Lisboa Barnagleison S. , Vilela Bruno
Published: January 2023

The neotropical monotypic genus Macrogenioglottus, described to enclose M. alipioi, is a forest leaf litter frog with a wide geographic distribution in eastern Brazil, despite being considered a rare species. Herein, we present some reproductive data of this species from a population of the north of the São Francisco River, Northeastern Brazil. We present information on the amplexus, egg clutch, advertisement, and release calls, along with a description of its larval development. Adults were observed only after heavy and continuous rains, in a temporary pond located inside the forest. Males call in chorus at the edge of the pond. The advertisement call consists of a pulsatile single note, with no substantial variation in relation to the other population of the species, but which promptly differs this genus from the remaining Odontophrynidae. The amplexus is axillary. One female deposited 298 pigmented eggs in a plastic bag. The tadpole reaches its larger size at Stage 39, being the largest tadpole within the family. At the end of metamorphosis, the froglet snout–vent length is equivalent to tadpole total length at stage 26–27, indicating substantial postmetamorphic growth until adulthood. Data on body size of males and females are also provided. The uniqueness of some larval traits and mainly on some call attributes supports the systematic distinction of Macrogenioglottus.