bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparing the Laboratory for Neoadjuvant Cancer Immunotherapy: Insights from a Pathology Learning Collaborative
Authors: Schulte J J , Zhang W , Rosa M , Hernandez S A , Al Salihi S , Green L K , Ibrahim D Y , Luo W , Mettman D , Ussakli C , Kelly M , Kim J , Mani M , Jani J 
Published: October 2024

Abstract

Introduction/Objective
Neoadjuvant immunotherapy (NIT) is an emerging strategy to treat multiple types of early- stage resectable cancers by inducing a systemic anti-tumor immune response and increasing the likelihood of complete pathological response (pCR). The evaluation of pathological response following NIT is challenging and requires specific expertise. Traditional response criteria may be difficult to apply since immunotherapy may lead to unique changes in the tumor bed. Moreover, many laboratories may not feel prepared to evaluate pathologic response following immunotherapy given their lack of experience and the time required to accurately assess specimens and report findings.

Methods/Case Report
To explore ways to help laboratories prepare for these challenges, the American Society for Clinical Pathology (ASCP) formed an immuno-oncology learning collaborative to engage pathologists from different institutions and subspecialties. The group met over six months to review and discuss the implications of relevant literature, guideline recommendations, and emerging trends such as tumor-specific recommendations (eg, IASLC Neoadjuvant Therapy Pathologic Response Initiative) to pan-tumor immune-related pathologic response criteria (irPRC). ASCP then developed a series of educational resources based on recommendations made by the group.

Results (if a Case Study enter NA)
Members of the ASCP learning collaborative identified and prioritized several topics to help laboratories prepare and equip their teams to perform pathologic assessment after neoadjuvant immunotherapy in routine clinical practice. These included: definition and classification of pathological response criteria, assessing unique changes in the tumor bed (ie, regression bed), interpreting data from clinical trials, reporting results in routine clinical practice, organizing educational resources, and staffing workload. The group also emphasized the importance of collaborating with oncologists and surgeons and promoting communication about these topics within each institution.

Conclusion
Based on promising results from neoadjuvant immunotherapy clinical trials, we can expect more FDA approvals for neoadjuvant indications and a growing number of patients receiving this treatment. Pathologists and laboratory professionals need to prepare their institutions for a future where the assessment of pathological response in routine clinical practice will impact treatment decisions following surgical resection.
Reporting a Rare HLA Allele with Sequence Analysis Prevents Potentially Lethal Allopurinol Hypersensitivity Reaction
Authors: Patel L R , Morris A B , Achram R , Yurekci E , Sullivan H C , Bray R A 
Published: October 2024

Abstract

Introduction/Objective
In addition to their essential role in histocompatibility testing, human leukocyte antigen (HLA) alleles have informative pharmacogenomic and disease associations. For example, HLA-B*58:01 carriers have 100- fold greater risk of allopurinol hypersensitivity syndrome (AHS), a lethal T-cell mediated Type IV reaction with a 20- 25% mortality rate. To prevent AHS, patients are tested for carrier status before treatment.

Methods/Case Report
Patient presented for workup of intermittently flaring right knee pain and uricemia. Uric acid is elevated, plain film imaging is ordered, arthrocentesis is planned, and HLA testing is performed to inform uricemia treatment. Next generation sequencing (NGS) typing reveals the patient carries HLA-B*58:11. Sequence analysis demonstrates the allele’s open reading frame differs from HLA-B*58:01 by a single I194V substitution. Amino acid sequences of peptide binding regions (PBR) encoded by these alleles are identical. Presentation of allopurinol/oxypurinol peptides to T-cells by B*58:01 is the putative mechanism underlying AHS pathogenesis.
Identical protein sequence in the PBR of B*58:11 favors similar function. Findings are reported and treatment with allopurinol foregone.

Results (if a Case Study enter NA)
NA

Conclusion
High resolution HLA testing is essential to appropriately interpret and report results for disease risk and pharmacogenomics assessments. However, NGS detects rare alleles that have yet to be associated with a disease process. When pathogenesis is thought to be linked to the PBR, rare HLA alleles with identical or similar PBR to disease associated alleles may confer similar risk. In this case, NGS identified PBR similarity between the patient’s allele and an established AHS risk allele. Although B*58:11 has not been shown to be associated with AHS, likely due to low prevalence, the risk was deemed sufficient to select an alternative therapy and potentially prevent a lethal drug reaction.
Exploring the link between COVID-19 and gut microbiome at the community level
Authors: Li B , Terwilliger A , Maresso A , Britton R , Yousefipour Z , Donnachie E , Lyu Z 
Published: October 2024

Abstract

Introduction/Objective
Monitoring SARS-CoV-2 virus through wastewater has been adopted as an effective surveillance approach for combating the COVID-19 pandemic. To understand the interplay between this virus and the human microbiome, this study examined the longitudinal co-dynamics between the virus and the microbiome across various sewage samples representing diverse demographic populations in Houston.

Methods/Case Report
We collected wastewater through manholes and the viral RNA levels of SARS-CoV-2 were monitored from December 2020 to 2021. The sampling sites serve nursing homes, rehabs, and shelters across the metro Houston area, respectively. The viral load was analyzed by the gold standard RT-qPCR method, and the microbiome load and composition by qPCR and amplicon sequencing of the 16S and ITS DNA.

Results (if a Case Study enter NA)
Preliminary results on the dynamics of SARS-CoV-2 viral load indicated diverse trends among sampling sites. These viral trends could be classified into three basic categories: flat, up and down, and up, suggesting disparities in COVID-19 infections among communities. A full analysis of the microbiome is underway, but a preview of the data revealed that bacteria and fungi commonly seen in the human gut predominated the wastewater samples. This paves the way to exploring the link between COVID-19 and the gut microbiome, which could shed light on the observed COVID-19 disparities.

Conclusion
As a proof-of-concept, our sewage bio-monitoring program was able to capture COVID-19 viral, bacterial, and fungal signals longitudinally from manholes serving a wide range of communities. Because these signals are predominantly human-associated, further analysis of these signals could offer insight on COVID-19 related disparities among these communities.
DNA fragmentation of sperm and microdeletions in the long arm of the Y chromosome in male infertility patients from private fertilization units of Barquisiemto, Lara State
Authors: Alamo T G 
Published: October 2024

Abstract

Introduction/Objective
Figures for infertility area increasing worldwide, with a large share of causes related to the male gender. The objective of this study is to relate the frequency of abnormal sperm DNA fragmentation and the frecuency of microdeletions in the long arm of Y chromosome (Yq) in patients with male infertility from private fertilitation units of Barquisimeto, Lara, during the 2010-2012 period.

Methods/Case Report
We analyzed 38 samples of semen from infertile male patients to measure DNA fragmentation index (FI) by TUNEL technique, and 36 semen samples from patients with male infertility to measure FI employing SCD method. To dertermine the frecuency of Yq microdeletions by polymerase chain reaction (PCR), samples of peripheral blood from 33 patients with male infertility were evaluated. Among the 38 patients in whom the FI was measured by TUNEL technique, eight(8) of them were also tested for detection of Yq microdeletions, and one (1) of these patients performed SCD test for medical reasons.

Results (if a Case Study enter NA)
The frecuency of abnormal fragmentation index of sperm DNA, determined by the TUNEL technique in patients with male infertility was 47.37%. The frecuency of abnormal fragmentation index of sperm DNA determoined by SCD method in infertile male patients was 22.22%. And the frecuency of microdeletions of the long arm of the Y chromosome in patients with male infertility was 9.09%. All microdeletions were found at DAZSY208 in AZFc region and in one case there was also detected a microdeletion at DAZSY255.

Conclusion
It was also showed that, sperm DNA fragmentation is not depending on the existence of Yq microdeletions.
Exploring Molecular Signatures in Early-Stage Pancreatic Ductal Adenocarcinoma: Implications for Patient Management and Therapeutic Strategies
Authors: Mousavi S , Salehiazar S , Mirzaei Baboli K 
Published: October 2024

Abstract

Introduction/Objective
Pancreatic ductal adenocarcinoma (PDAC) poses significant challenges to patient survival, predominantly due to its tendency for late-stage diagnosis and high rates of post-surgical cancer recurrence.
Therefore, a comprehensive understanding of the molecular characteristics associated with the early stages of PDAC is imperative. This understanding holds the potential to improve patient treatment strategies by enabling targeted interventions and personalized therapies.

Methods/Case Report
Initially, RNA-seq datasets of early-stage PDAC cases (stages IA, IB, IIA, and IIB, all without distant metastasis; M0) were extracted from the GEO database. Subsequently, the datasets were analyzed in four distinct groups, and differentially expressed genes were identified within each group. Group 1 compared T1T2 cases with T3 cases (T: primary tumor), irrespective of N status (N: regional lymph nodes), while group 2 compared N0 cases with N1 cases, regardless of T status. Group 3 included comparisons between T1T2N0 cases and T3N0 cases, and group 4 compared T1T2N1 cases with T3N1 cases. Utilizing a Venn diagram, commonalities between gene expression profiles were isolated. Afterward, gene ontology and signaling pathways were determined using KEGG and Enrichr. Finally, a protein network was constructed, and the proteins were evaluated using the GEPIA and TCGA clinical databases.

Results (if a Case Study enter NA)
The study encompassed a total of 43 cases, with 25 (58.1%) being male and 18 (41.9%) female. The mean age of the participants was 64.4 years. In group 1, the expression levels of MUC5AC, AKAP13, and SPG7 were significantly upregulated in T3 cases. In group 2, STAB1, PDLIM1, and MTUS1 emerged as the top upregulated genes in N1 cases. Group 3 exhibited notable upregulation of CCNL2, CEACAM6, and TSPAN3 in T3N0 cases, while group 4 demonstrated marked upregulation of LTBR, AKAP12, and BOP1 in T3N1 cases. These genes exhibited diverse functions in PDAC progression. They contributed to the regulation of gene expression and cell cycle progression, modulating cell proliferation, inhibiting tumor growth, regulating cell signaling, and were involved in cytoskeletal organization.

Conclusion
The upregulated genes in cases with the T3 and/or N1 staging components may shed light on the potential mechanisms of progression from stage IA/B to stage IIA/B in PDAC cases. Furthermore, the identified genetic alterations may hold potential therapeutic and prognostic applications for future use in the early stages of PDAC.
Social Media and Pathology: A Powerful Intersection for Visibility
Authors: Buckelew H , Crowe C 
Published: October 2024

Abstract

Introduction/Objective
The employment of social media usage for visibility efforts in the field of pathology is a relatively new practice, yet this strategy for both individual practitioners and departmental promotion is growing each day. Social media is being implemented for use in recruiting faculty, staff, and trainees, sharing cases and educational resources, establishing communities, and serving as a source of news for research breakthroughs and accolade recognition. A deeper look into one pathology department’s usage of social media across several platforms lends broad insight into the distinction of which forms of content perform well more consistently on each platform, and how these analytics continue to expand. The current study will examine the growth of one pathology department over the course of six months and determine which content forms made the most impact in increasing departmental visibility.

Methods/Case Report
The use of Instagram, X, LinkedIn, and Facebook is examined over the course of six months. Two reporting periods of three-month intervals are used for comparison: October–December 2023 and January–March 2024. The social media management system Sprout Social is used to gather reports of change in metrics over these periods.

Results (if a Case Study enter NA)
The audience growth rate increased 4.3% in the second reporting period (January-March 2024), with a 34.7% increase in net audience growth rate (total gained followers), an 8.6% increase in published posts, a 16.1% increase in impressions and a 55.3% increase in engagements.

Conclusion
Based on the data analysis provided above, trainee content and cases of the week perform best on X. On Instagram, reels excel in performance. On LinkedIn, faculty accolades, research news, and group photos perform best. People-centered content and educational resources increase audience, impressions, engagement, and, in turn, departmental visibility. A focus on this content and an increase in total posts is the definitive cause for growth in the second reporting period.
Comparative Study of GPT-4Vision and Convolutional Neural Networks in Histopathological Image Analysis
Authors: Koga S , Ono D , Dickson D 
Published: October 2024

Abstract

Introduction/Objective
Recent advancements in artificial intelligence (AI), particularly with Large Language Models like ChatGPT-4Vision (GPT-4V), have expanded the potential for automated interpretation of medical images. This study evaluates the diagnostic accuracy of GPT-4V in histopathological analysis of neurodegenerative diseases and compares its performance with traditional Convolutional Neural Networks (CNNs).

Methods/Case Report
We utilized 1515 histopathological images, including hematoxylin and eosin (H&E) staining and tau immunohistochemistry, from patients with various neurodegenerative diseases, such as Alzheimer’s disease, progressive supranuclear palsy, and corticobasal degeneration. GPT-4V’s performance was assessed through multi- step prompts to assess how textual context influences the image interpretation. In the quantitative analysis, the diagnostic accuracy of GPT-4V and the CNN-based model YOLOv8 was assessed for classifying three tau lesions—astrocytic plaques, neuritic plaques, and tufted astrocytes. The analysis used both zero-shot and few-shot learning methods, where GPT-4V and YOLOv8 were evaluated on their ability to distinguish these lesions using ten hold-out test images and 490 training images per lesion.

Results (if a Case Study enter NA)
GPT-4V accurately recognized Lewy bodies in all cases, but it showed limited accuracy in identifying neurofibrillary tangles (20%) and Pick bodies (0%) on H&E slides. Notably, GPT-4V often suggested Alzheimer’s disease as a potential diagnosis, relying more on contextual clues, such as the prevalence of certain diseases, rather than direct image analysis. In the tau immunohistochemical analysis, GPT-4V’s diagnoses were strongly influenced by additional information about staining and brain region. However, few-shot learning markedly improved GPT-4V’s diagnostic capabilities from 40% accuracy with zero-shot learning to 90% with few-shot learning, reaching best accuracy with 20-shot learning. This performance compared favorably against YOLOv8, which also achieved 90% accuracy but required 100-shot learning.

Conclusion
While GPT-4V faces challenges in independently interpreting histopathological images, few-shot learning significantly improves its accuracy. This approach is particularly promising for neuropathology, where acquiring extensive labeled datasets is challenging. The findings highlight the need for ongoing refinement of AI applications in pathology, emphasizing balanced integration of textual and visual data to optimize diagnostic efficacy and reliability.
Uncommon Presentation of Pulmonary Adenoid Cystic Carcinoma: A Case of Brain Metastasis in a Young Smoker
Authors: Liu J , Yeon S , Valyi-Nagy T , Garzon S 
Published: October 2024

Abstract

Introduction/Objective
Pulmonary adenoid cystic carcinoma (PACC) is a rare entity, accounting for only 0.04-0.2% lung cancers, and mainly originating from the small salivary glands in the tracheobronchial tree. Due to slow-growing pattern and unspecific symptoms, the diagnosis is often delayed. While metastasis in PACC is uncommon, reports of brain metastasis are exceedingly rare. We present a case of PACC with metastasis to the brain in a young smoker.

Methods/Case Report
A 29-year-old female with history of smoking presented with headache, hypersomnia, episodes of vomiting and falling. Physical examination revealed multiple palpable nodes on the mid head, left temporal and right parietal area, left shoulder area were found. CT scan demonstrated complex cystic mass with a mural nodule within the left cerebellar hemisphere, with displacement of the cerebellar tonsils, as well as a 7.4 cm left infrahilar mass with heterogenous enhancement. Patient underwent craniotomy with tumor resection and left lower lobe endobronchial biopsy.
Touch smear of the brain lesion showed clusters of hyperchromatic cells with myxoid like and hyalinized stroma. H&E stain showed cords of neoplastic cells embedded in a basophilic/myxoid stroma. Lung biopsy showed similar histological patterns. IHC stain showed the tumor cells were positive for epithelial and myoepithelial cells markers(CAM5.2, CK7, p63, Sox 10), retained INI1/BAF47 and BRG1 expression, negative for NUT and BCOR. Salivary Gland NGS Fusion Panel was performed and detected a MYBL1::NFIB [t(8;9)(8q13.1;9p23)] fusion alteration, which confirmed the diagnosis of adenoid cystic carcinoma. Considering no lesion was found in the patient’s head and neck, diagnosis of PACC was made.

Results (if a Case Study enter NA)
NA

Conclusion
PACC manifests three histologic subtypes: cribriform (most common), trabecular, and solid. In this case, brain and lung lesions exhibited similar patterns - nests of small, monomorphic cells within a myxoid-like and basophilic stroma background, consistent with trabecular pattern. Cytologically, densely packed cellular clusters were embedded in a myxoid like matrix.
Distinguishing PACC from other salivary gland tumors is challenging. Immunostains for epithelial and myoepithelial cells, along with morphology, aid in diagnosis. The MYB::NFIB fusion helps differentiate from other lung salivary gland malignancies, but is found in a lower percentage of PACC cases (~40%) compared to other primary adnoid cystic carcinoma (~85%).
An Economic Model for Rapid On-Site Evaluation (ROSE) Telecytology to Improve Remote Access and Pathology Practice
Authors: Petersen J M , Jhala A 
Published: October 2024

Abstract

Introduction/Objective
Rapid On-Site Evaluation (ROSE) is an integral part of the fine needle aspiration (FNA) procedure to inform on the diagnostic adequacy of the passes already taken. However, traditional ROSE is not accessible in rural areas and takes valuable cytopathologist time to travel to attend the procedure on site.
Telecytology has the promise to allow remote access with equivalent accuracy, though an economic benefit model based on the literature is sparse.

Methods/Case Report
Mean traditional ROSE times for cytopathologists and mean telecytology ROSE times from two institutions each from the literature were reviewed. The savings by telecytology ROSE was then modeled using the 2019 Medscape Physician Compensation Report (MPCR). Literature review of the nondiagnostic rate both with and without ROSE and costs reported from the University of Pennsylvania were used to model savings from increased accessibility of ROSE to remote settings by telecytology.

Results (if a Case Study enter NA)
Telecytopathologist traditional ROSE time (20.95 minutes and 56.2 minutes) and telecytology ROSE time (2.91 minutes and 7.5 minutes) was noted. The average pathologist salary per the 2019 MPCR was $120 per hour. The preceding corresponds to monetary savings of $26.90 to $106.58 per case. At one of the reviewed institutions, this would correspond to $23,672 to $93,790.40 in yearly savings. An average reported non- diagnostic rate of 20% (without ROSE with cost of $3,096 per FNA procedure) versus 0.98% (with ROSE with cost of $3327 per procedure) was noted, which if each non-diagnostic FNA results in a repeat procedure, leads to $32,186 in savings per 100 patients.

Conclusion
Telecytology has promise in not only improving economic efficiency of the ROSE procedure over traditional ROSE, but also in cost savings in remote settings that would otherwise not have access to ROSE at all. Therefore, there are economic savings that could be realized by improving access to telecytology across settings.
Don’t omit a urine culture when a urinalysis is suspicious for asymptomatic bacteriuria during pregnancy
Authors: Bergbower S B 
Published: October 2024

Abstract

Introduction/Objective
Investigation of a clinical problem using steps of evidence-based practice (EBP) led to the development of a recommendation submitted for Choosing Wisely consideration.
The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is between 2-15%. ASB may be a concern in pregnancy because of its capacity for association with adverse outcomes, namely preterm delivery, low birthweight, and possible progression to pyelonephritis. Screening and treatment may reduce the risks of adverse outcomes, but data is not current. A point-of-care urine dipstick is low cost and commonly used at routine obstetrician clinic visits to screen for ASB. The urinalysis dipstick is associated with high false-positive and false-negative rates as compared to the gold standard urine culture. Some providers make the decision to treat ASB given a positive urinalysis screen without ordering a follow-up culture. Such practice could lead to overtreatment of the patient and poor antibiotic stewardship.

Research question
Is a urinalysis without culture sufficient for diagnosis and treatment of ASB during pregnancy?

Methods/Case Report
Laboratory Medicine Best Practices A-6 steps of Ask, Acquire, Appraise, Apply, Analyze, and Assess were utilized to develop an appropriate and relevant clinical question, collect literature, determine evidence value, assign ratings, implement into practice, and evaluate outcomes. During appraisal, six selected articles were graded according to study rating, practice, measures, and results, further including the final rating and effect size rating. Consistency and overall strength of the evidence were analyzed.

Results (if a Case Study enter NA)
Each evidence study demonstrated final ratings between 8 and 10, a rating of “Good,” and an effect size rating of “Substantial.” Consistency leads to a “High” overall strength among the body of evidence.

Conclusion
Obtain a urine culture if routine prenatal point-of-care dipstick urinalyses have findings consistent with asymptomatic bacteriuria. Urinalyses are limited as screening due to low sensitivity and specificity for bacteriuria. Positive urinalysis dipstick results should be neither the sole basis for diagnosis nor decision to treat.