bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of implementing a BRCA screening protocol in primary care
Authors: Rivera-Nunez Yasmin , Smith Diane L. 
Published: July 2023

ABSTRACT
Breast cancer is the second leading cause of cancer death for women, whereas ovarian cancer is the deadliest gynecological cancer. Breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) mutations can increase the risk of developing breast and ovarian cancer. Screening can assist in prevention and early detection. This study aimed to increase provider knowledge of BRCA mutations, the use of BRCA screening tools, and genetic referrals. An Institutional Review Board–approved study was implemented for providers for training on BRCA1 and BRCA2 mutations and the importance of screening and referral for those at risk. Measures included provider confidence and knowledge after training as well as number of patient referrals. A standardized webinar was required with further education provided in multiple modalities. The number of BRCA screenings and referrals for genetic screening was monitored through the electronic health record (EHR). Eight providers including five nurse practitioners and three medical doctors participated in the complete project. As a result, 56 patients were BRCA screened, and four referrals were made to receive genetic counseling. Education enhanced knowledge, increased screening tool use, and resulted in improvement in genetic referrals through the EHR.
Comparison of parathyroid scintigraphy findings in pediatric and adult patients with secondary hyperparathyroidism
Authors: Aktaş Ayşe , Baskin Esra , Gençoğlu Esra Arzu , Çolak Turan 
Published: July 2023

Objectives
Secondary hyperparathyroidism (sHPT) is a compensatory complication of chronic kidney disease. The aim of this study was to compare PS findings in pediatric and adult patients with sHPT.

Methods
This study included 50 pediatric and 50 adult patients with sHPT. Parathyroid scintigraphy was performed with Tc-99m sestamibi. After radiopharmaceutical injection, early-phase (15 min) and late-phase (60–90 min) images were acquired. Planar images were interpreted visually for the presence / number of active foci compatible with a parathyroid lesion, the presence and degree of uptake in skeletal structures, and the degree of thyroid sestamibi uptake. Parathyroid surgery was performed in 21 pediatric and 28 adult patients.

Results
Serum PTH and ALP values were significantly higher in pediatric than in adult patients (P < 0.05 for each). In operated patients, on a lesion-based analysis, the sensitivity of PS in pediatric and adult patients were 40% and 71%, respectively. A nonlocalizing scan was observed in 24% of pediatric patients. Pediatric patients had a higher incidence of reduced thyroid sestamibi uptake (42% versus 2%). Skeletal sestamibi uptake was detected in 40% of pediatric and 30% of adult patients and the degree of uptake was higher in pediatric patients.

Conclusions
The results revealed more significant changes in the biochemical profile of pediatric compared with adult patients with sHPT. The sensitivity of PS was lower, and the likelihood of a nonlocalizing scan was higher in pediatric patients. The results may also suggest more severe skeletal findings in pediatric patients. Reduced thyroid sestamibi uptake in children needs further evaluation.
A review of deep learning and radiomics approaches for pancreatic cancer diagnosis from medical imaging
Authors: Yao Lanhong , Zhang Zheyuan , Keles Elif , Yazici Cemal , Tirkes Temel , Bagci Ulas 
Published: July 2023

Purpose of reviewEarly and accurate diagnosis of pancreatic cancer is crucial for improving patient outcomes, and artificial intelligence (AI) algorithms have the potential to play a vital role in computer-aided diagnosis of pancreatic cancer. In this review, we aim to provide the latest and relevant advances in AI, specifically deep learning (DL) and radiomics approaches, for pancreatic cancer diagnosis using cross-sectional imaging examinations such as computed tomography (CT) and magnetic resonance imaging (MRI).Recent findingsThis review highlights the recent developments in DL techniques applied to medical imaging, including convolutional neural networks (CNNs), transformer-based models, and novel deep learning architectures that focus on multitype pancreatic lesions, multiorgan and multitumor segmentation, as well as incorporating auxiliary information. We also discuss advancements in radiomics, such as improved imaging feature extraction, optimized machine learning classifiers and integration with clinical data. Furthermore, we explore implementing AI-based clinical decision support systems for pancreatic cancer diagnosis using medical imaging in practical settings.SummaryDeep learning and radiomics with medical imaging have demonstrated strong potential to improve diagnostic accuracy of pancreatic cancer, facilitate personalized treatment planning, and identify prognostic and predictive biomarkers. However, challenges remain in translating research findings into clinical practice. More studies are required focusing on refining these methods, addressing significant limitations, and developing integrative approaches for data analysis to further advance the field of pancreatic cancer diagnosis.
Long-term outcomes after tuberculosis for people with HIV in eastern Europe
Authors: Kraef Christian , Bentzon Adrian , Roen Ashley , Bolokadze Natalie , Thompson Magdalena , Azina Inga , Tetradov Simona , Skrahina Alena , Karpov Igor , Mitsura Viktar , Paduto Dmitriy , Trofimova Tatiana , Borodulina Elena , Mocroft Amanda , Kirk Ole , Podlekareva Daria N. 
Published: July 2023

Background:
Eastern Europe has a high burden of Tuberculosis (TB)/HIV-coinfection with high mortality shortly after TB diagnosis. This study assesses TB recurrence, mortality rates and causes of death among TB/HIV patients from Eastern Europe up to 11 years after TB diagnosis.

Methods:
A longitudinal cohort study of TB/HIV patients enrolled between 2011–2013 (at TB diagnosis) and followed-up until end of 2021. A competing risk regression was employed to assess rates of TB recurrence, with death as competing event. Kaplan-Maier estimates and a multivariable Cox-regression were used to assess long-term mortality and corresponding risk factors. The Coding Causes of Death in HIV methodology was used for adjudication of causes of death.

Results:
375 TB/HIV patients were included. 53 (14·1%) were later diagnosed with recurrent TB (incidence rate 3·1/100 person-years of follow-up (PYFU), 95% CI 2·4–4·0) during a total follow-up time of 1713 PYFU. Twenty-three of 33 patients with data on drug-resistance (69·7%) had MDR-TB. More than half with recurrent TB (n = 30/53, 56·6%) died. Overall, 215 (57·3%) died during the follow-up period, corresponding to a mortality rate of 11·4/100 PYFU (95%CI 10·0–13·1). Almost half of those (48·8%) died of TB. The proportion of all TB-related deaths was highest in the first 6 (n = 49/71; 69·0%; p < 0·0001) and 6 – 24 (n = 33/58; 56·9%; p < 0.0001) months of follow-up, compared deaths beyond 24 months (n = 23/85; 26·7%).

Conclusion:
TB recurrence and TB-related mortality rates in PLWH in Eastern Europe are still concerningly high and continue to be a clinical and public health challenge.
Brain alterations in ovariohysterectomized rats revealed by diffusion tensor imaging
Authors: Wu Chun-Yi , Hsieh Hsin-Hua , Huang Sheng-Min , Chiu Shao-Chieh , Peng Shin-Lei 
Published: July 2023

Objectives
Women undergoing hysterectomy with oophorectomy have an increased risk of Alzheimer’s disease and Parkinson’s disease. However, postoperative neuroimaging data on pathogenic processes in the brain are limited. The aim of this study was to investigate the potential effect of ovariohysterectomy on brain integrity in rat model using diffusion tensor imaging (DTI) technique for the first time.

Methods
We enrolled 13 rats each in the control and ovariohysterectomy groups. Rats in the ovariohysterectomy group underwent the ovariohysterectomy at 7 weeks of age, and all rats underwent DTI scans at 9 weeks of age. The DTI-derived parameters, such as fractional anisotropy and mean diffusivity, were compared between the control and ovariohysterectomy groups.

Results
Compared to the control group, the ovariohysterectomy group showed significantly lower fractional anisotropy in various brain regions, including the corpus callosum, bilateral striatum, and bilateral cortex (all P < 0.05), suggesting neuronal injury in ovariohysterectomized rats. Mean diffusivity did not differ significantly between groups (all P > 0.05).

Conclusion
Rats undergoing ovariohysterectomy had lower fractional anisotropy compared to control in widespread brain regions, suggesting neuronal injury and demyelination. Therefore, neuroimaging should be performed to monitor brain alterations in women after hysterectomy with bilateral oophorectomy in clinical settings.
Identification of Nectin Family Interactive Gene Panel and Stratification of Clinical Outcomes in Patients with Pancreatic Cancer
Authors: Imazu Yuki , Nishiwada Satoshi , Yasuda Satoshi , Nagai Minako , Nakamura Kota , Matsuo Yasuko , Terai Taichi , Yoshida Chieko , Kohara Yuichiro , Sho Masayuki 
Published: July 2023

BACKGROUND:
Although patient-risk stratification is important for selecting individualized treatment for pancreatic ductal adenocarcinoma (PDAC), predicting the oncologic outcomes after surgery remains a challenge. In this study, we identified a nectin family gene panel (NFGP) that can accurately stratify oncologic outcomes in patients with PDAC.

STUDY DESIGN:
Comprehensive analysis of the expression of 9 nectin family genes identified the NFGP, which was assessed for predictive performance in 2 independent public cohorts (The Cancer Genome Atlas [TCGA] n = 176; International Cancer Genome Consortium [ICGC] n = 89). It was subsequently trained and validated for the in-house training cohort without neo-adjuvant therapy (NAT, n = 213) and the validation cohort with NAT (n = 307).

RESULTS:
Using the Cox regression model, NFGP derived from 9 nectin family genes accurately stratified overall survival (OS) in TCGA (p = 0.038) and ICGC (p = 0.005). We subsequently optimized NFGP, which robustly discriminated postoperative prognosis, OS (p = 0.014) and relapse-free survival ([RFS] p = 0.006) in the training cohort. The NFGP was successfully validated in an independent validation cohort (OS: p < 0.001; RFS: p = 0.004). Multivariate analysis demonstrated the NFGP was an independent prognostic factor for OS and RFS in the training (p = 0.028 and 0.008, respectively) and validation (p < 0.001 and 0.013, respectively) cohorts. The subcohort analyses showed that the predictive performance of NFGP is applicable to the patients’ subcohort according to resectability or adjuvant therapy status. Additionally, a combination model of NFGP score and CA19-9 level emerged with improved accuracy for predicting prognosis.

CONCLUSIONS:
This study established the predictive significance of NFGP for oncologic outcomes after surgery in PDAC. Our data demonstrate its clinical impact as a potent biomarker for optimal patient selection for individualized treatment strategies.
Miniaturized microscope for non-invasive imaging of leukocyte-endothelial interactions in human microcirculation
Authors: Bagramyan Arutyun , Lin Charles P. 
Published: July 2023

ABSTRACTWe present a miniature oblique back-illumination microscope (mOBM) for imaging the microcirculation of human oral mucosa, enabling real-time, label-free phase contrast imaging of leukocyte rolling and adhesion, the initial steps in leukocyte recruitment that is a hallmark of inflammation. Imaging cell motion can provide new diagnostic information (time course of disease progression, response to therapy, etc.) that is not available using traditional static diagnostic parameters such as cell number and morphology.
Translational impact of basic science promotes a new era of precision medicine for migraine
Authors: Porreca Frank , Navratilova Edita , Hirman Joe , MaassenVanDenBrink Antoinette , Lipton Richard B. , Dodick David W. 
Published: July 2023

AbstractPrecision medicine has emerged as a powerful approach to improve treatment outcomes for many medical conditions by consideration of the genetic characteristics of the patient. Migraine is likely to be the world’s most common neurological disorder affecting over 1 billion people, approximately 700 million of whom are women. Yet, patient sex, the most basic genetic difference, is rarely considered in selection of therapies for people with migraine. Preclinical studies reveal that calcitonin gene-related peptide (CGRP), a neurotransmitter thought to be causal in promoting migraine in many patients, elicits female selective pain and headache-like responses. Consistent with this, we report a subgroup analysis of publicly available clinical data evaluating small molecule CGRP receptor antagonists for the acute migraine revealing preferential efficacy in women. Analyses of human post-mortem sensory neurons from male and female donors reveal sexual dimorphism at transcript, protein and functional levels. These findings raise the possibility that regardless of common diagnosis and phenotype, mechanisms promoting migraine pain may differ between sexes. Such qualitative sex differences suggest that clinical trials should include sex-specific analyses, that sex stratified treatment guidelines may improve treatment outcomes in migraine and that the uniform therapeutic approach to pain-related disorders in men and women requires reassessment.
Phenotypic grouping of Catheter-AssociatedEscherichia colifrom COVID-19 isolation wards using Hierarchical clustering in Surabaya, Indonesia
Authors: Edbert Daniel , Mertaniasih Ni Made , Endraswari Pepy Dwi 
Published: July 2023

IntroductionModerate to critical COVID-19 patients may be indicated for urinary catheter use due to the risk of immobility and ventilator or oxygen use. In intensive care units, 18-81.7% of all patients use a urinary catheter. Almost all patients with urinary catheters suffered from bacteriuria within 30 catheter-days. Hospital-associated isolate tracing is mainly performed using complex molecular tests that are not vastly available. This study aims to trace catheter-associated urinary tract infection (CAUTI) isolates using a common hierarchical clustering method that is vastly availableMethodsThis is a descriptive study presenting a collection ofEscherichia coliculture data performed by dr. Soetomo Public Hospital microbiology laboratory from March, 26th2020 to March, 31st2021. Hierarchical clustering was performed using statistical software using Ward’s clustering method.ResultsThere are 36E.coliassociated with CAUTI. Isolate biochemistry profile and minimum inhibitory concentrations profiles were clustered into 3 clades for each profile. A total of 9 cluster combinations were found. Cluster-ID 1 was melibiose fermenters, Cluster ID 2 was a non-Arginine utilizer, and Cluster ID-3 was an Arginine utilizer. Cluster MIC A consists of third-generation Cephalosporin resistant isolates, Cluster MIC C was multi-susceptible isolates. The Chi-square test between cluster ID and MIC showed no significant differences between the number of isolates per group (X2, p = .430, CI = 95%).ConclusionCAUTI associatedE.coliis divided into 9 clusters. This indicates no cluster dominates the isolates, thus CAUTI is not caused by hospital transmission but by normal flora carried by the admitted patient.
Trends and Factors associated with Neonatal Mortality among Neonates Hospitalized at the Women and Newborn Hospital in Lusaka Zambia
Authors: Tembo Deborah , Kaonga Patrick , Mweene Cheelo , Jacobs Choolwe 
Published: July 2023

AbstractBackgroundNeonatal mortality is a global problem especially in resource-poor settings such as sub-Saharan African Countries. Trends and factors associated with neonatal mortality vary in different settings. This cross-sectional study investigated trends and factors that are associated with increased neonatal mortality among hospitalised neonates with a view of identifying pointers that can be modified to help improve neonatal survival.MethodsMedical records for all neonates admitted to the NICU in 2018 and 2019 were reviewed for the study. The Mortality rates were calculated using WHO standard and Microsoft excel 2010 used to construct monthly trends analysis using monthly totals. Univariate and multivariate logistic regression analysis to determine the factors associated with neonatal deaths at the tertiary facility using Stata version 14.2. Model fit was evaluated using Hosmer and Lemeshow test (chi2=13.90, P =0.0845), implies the model’s estimates fit the data at an acceptable level.ResultsA total of 7,581 admissions were seen and 2340 files were extracted for analysis, of which 940 (40.2%) died. The overall Neonatal mortality percentage during the study period was 31.8%. Relatively similar trends were observed during the study period with differences in case fatality rates. Factors associated with an increased odds of dying were not attending antenatal care (AOR=2.09, 95% CI [1.46 - 2.99] p <0.0001), parity (AOR=1.09, 95% CI [1.02 – 1.16] p=0.0013) and age of the neonate in days (AOR=0.92, 95% CI [0.91- 0.94] p <0.0001).ConclusionNeonatal mortality is high among hospitalized neonates at the Women and New-born Hospital in Zambia. Associated Factors included no antenatal attendance, increased parity, and early age of the neonate. This has detrimental effects; hence emphasis is on early Antenatal Care for easy monitoring of mother and neonates for fast actions in case of complications
Understanding the Immunomodulatory Effects of Bovine Colostrum: Insights into IL-6/IL-10 Axis-Mediated Inflammatory Control
Authors: Grigaleviciute Ramune , Matusevicius Paulius , Planciuniene Rita , Stankevicius Rolandas , Radzeviciute-Valciuke Eivina , Baleviciute Austeja , Zelvys Augustinas , Zinkeviciene Aukse , Zigmantaite Vilma , Kucinskas Audrius , Kavaliauskas Povilas 
Published: July 2023

AbstractBovine colostrum (COL), the first milk secreted by lactating cows postpartum, is a rich source of bioactive compounds that exert significant role on the survival, growth, and immune development of neonatal calves [9,10]. This study investigated the immunomodulatory effects of COL on cytokine productionin vitrousing a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA). COL pretreatment significantly reduced IL-6 production induced by PMA, while increasing IL-10 production. Further investigations revealed that the IL-6 suppressive effect of colostrum was heat-sensitive and associated with components of higher molecular mass (100 kDa). Moreover, colostrum primarily influenced THP-1 macrophages rather than Caco-2 epithelial cells. The effects of colostrum on IL-6 production were associated with reduced NF-κB activation in THP-1 macrophages. In calf-FMT transplanted C57BL/6 murine model, colostrum decreased intestinal permeability, reduced immune cell infiltration, and suppressed IL-6 production duringS. typhimuriuminfection. These results highlight the immunomodulatory activity of bovine colostrum and its potential therapeutic applications in inflammatory disorders. Further studies are needed to elucidate the underlying mechanisms and validate the findings in bovine models.Simple SummaryThis study explores the immunomodulatory properties of bovine colostrum (COL), the initial milk produced by lactating cows, on cytokine productionin vitroand in a novel murine calf-FMT model. The researchers utilized a Caco-2/THP-1 macrophage co-culture model stimulated with Phorbol 12-myristate 13-acetate (PMA) to investigate the effects of COL on cytokine production. The findings indicate that COL pretreatment significantly reduced IL-6 production while enhancing IL-10 production. The IL-6 suppressive effect was heat-sensitive and associated with components of higher molecular mass (100 kDa). Colostrum demonstrated decreased intestinal permeability, reduced immune cell infiltration, and suppressed IL-6 production duringS. typhimuriuminfection. These results highlight the immunomodulatory potential of bovine colostrum and its prospective therapeutic applications in inflammatory disorders. Further research is necessary to elucidate the underlying mechanisms and corroborate the findings in bovine models.
Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase
Authors: Lin Folan , Zhang Ruxin , Shao Weihan , Lei Cong , Zhang Ying , Ma Mingxi , Wen Zengqi , Li Wanqiu 
Published: July 2023

AbstractHistone lysine methyltransferase of SUV420H1, which is responsible for site-specific di-/tri-methylation of histone H4 lysine 20 (H4K20), has crucial roles in DNA-templated processes, including DNA replication, DNA damage repair and chromatin compaction. Its mutations frequently occur in human cancers. Nucleosomes containing the histone variant H2A.Z enhance the catalytic activities of SUV420H1 in H4K20 di-methylation deposition, regulating early replication origins. However, the molecular mechanism of how H4K20 methyl marks are deposited on nucleosomes by SUV420H1 remains poorly understood. Here we report the cryo-electron microscopy (cryo-EM) structures of SUV420H1 associated with canonical nucleosome core particles (NCPs) or H2AZ containing NCPs. We find that SUV420H1 make extensive site-specific contacts with histone and DNA regions. SUV420H1 C-terminal domain recognizes the H2A-H2B acidic pocket of NCPs through its two arginine anchors, thus enabling H4K20 insertion for catalysis specifically. We also identify important residues increasing the catalytic activities of SUV420H1 bound to H2A.Z NCPs. In vitro and in vivo functional analysis reveal that multiple disease associated mutations at the interfaces are essential for its catalytic activity and chromatin states regulation. Together, our study provides molecular insights into the nucleosome-based recognition and methylation mechanisms of SUV420H1, and a structural basis for understanding SUV420H1-related human disease.
Region-specific reversal of epidermal planar polarity in the fancyrosettemouse
Authors: Cetera Maureen , Sharan Rishabh , Hayward-Lara Gabriela , Phillips Brooke , Biswas Abhishek , Halley Madalene , Beall Evalyn , vonHoldt Bridgett , Devenport Danelle 
Published: July 2023

AbstractThe planar cell polarity (PCP) pathway collectively orients thousands of cells with respect to a body axis to direct cellular behaviors that are essential for embryonic morphogenesis. Hair follicles of the murine epidermis provide a striking readout of PCP activity in their uniform alignment along the entire skin surface. Here, we characterize, from the molecular to tissue-scale, PCP establishment in therosettefancy mouse, a natural variant with posterior-specific whorls in its fur, to understand how epidermal polarity is coordinated across the tissue. We find that embryonic hair follicles ofrosettemutants emerge with reversed orientations specifically in the posterior region, creating a mirror image of epidermal polarity. Therosettetrait is associated with a missense mutation in the core PCP geneFzd6, which alters a consensus site for N-linked glycosylation and inhibits its membrane localization. Unexpectedly, this defect in Fzd6 trafficking, observed across the entire dorsal epidermis, does not interfere with the ability of other core PCP proteins to localize asymmetrically. Rather, the normally uniform axis of PCP asymmetry is disrupted and rotated in the posterior region such that polarity is reflected on either side of a transition zone. The result is a reversal of polarized cell movements that orient nascent follicles, specifically in the posterior of the embryo. Collectively, our multiscale analysis of epidermal polarity reveals PCP patterning can be regionally decoupled to produce the unique posterior whorls of the fancyrosettemouse.SummaryRegion-specific rotation of the Planar Cell Polarity axis reverses posterior hair follicles in the fancyrosettemouse.