Anatomical Sites Research Articles

Head and neck sarcomas: Thirty years of experience in a tertiary referral center in Brazil.

This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil. HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow-up information. The Pearson chi-square test, Kaplan-Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors. A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow-up period of 71.9 months, from diagnosis to the last follow-up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow-up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence. In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.

Collateralization of the upper extremity lymphatic system after axillary lymph node dissection.

Lymphatic drainage from the arm may be altered after axillary lymph node dissection (ALND). Understanding these alterations is important as they may change standard surgical and radiation treatment in recurrent breast cancer or upper extremity skin cancers, including melanoma. Utilizing a single-institution planar and single photon emission computed tomography/computed tomography lymphoscintigraphy database, we identified patients with a diagnosis of upper extremity cutaneous melanoma from 2008 to 2023 who previously underwent ALND for cancer treatment and did not develop upper extremity cancer-related lymphedema. ALND patients were matched to control patients presenting with cutaneous melanomas at the same anatomic sites. Sentinel lymph nodes (SLNs) were compared between both groups. Of 3628 upper extremity melanoma cutaneous patients, 934 met inclusion criteria, including 22 ALND and 912 control patients. Level I axillary SLN drainage was observed in 98% of controls and 27% of ALND patients (p < 0.001). Level II axillary SLN drainage was observed in 3% of controls and 27% of ALND patients (p < 0.001). Level III axillary SLN drainage was observed in 1% of controls and 32% of ALND patients (p < 0.001). Epitrochlear SLN drainage was observed in 9% of controls and 32% of ALND patients, respectively (p < 0.046). Brachial SLN drainage was observed in 4% of controls and 23% of ALND patients (p < 0.001). Distinct changes in functional lymphatic drainage were seen between the arms of patients who previously underwent ALND versus control patients. Levels II and III axillary, epitrochlear, and brachial nodes are possible sites of metastatic disease that should be considered in patients with a prior ALND.

Local anesthetic tetracaine hydrochloride induces pyroptosis via caspase-3/gasdermin E in uveal melanoma

BackgroundEvasion of pyroptosis is an effective survival strategy employed by cancer cells to evade immune cell attacks and drug-induced cytotoxicity. Exploring potent molecules capable of inducing pyroptosis in cancer cells has significant clinical implications for the control of cancer progression. Unexpectedly, we found that the local anesthetic tetracaine hydrochloride (TTC) induced pyroptosis, specifically in uveal melanoma but not in acral or cutaneous melanoma. MethodsWe investigated the effects of TTC on various melanoma cell lines and performed transcriptome sequencing of TTC-treated uveal melanoma cells. The role of gasdermin E (GSDME), an executive protein responsible for pyroptosis, was explored using CRISPR-Cas13d knockdown, caspase-3 inhibitor treatment, and western blot analysis. Differential gene expression and pathway enrichment analyses were performed. Furthermore, we used tissue microarrays to assess GSDME expression levels in melanoma tissues from different anatomical sites. ResultsTTC significantly induced pyroptosis specifically in uveal melanoma cells with high GSDME expression levels. TTC treatment could lead to GSDME cleavage by the caspase-3 in uveal melanoma C918 cells. GSDME knockdown or caspase-3 inhibition suppressed TTC-induced pyroptosis. Transcriptome analysis revealed differentially expressed genes enriched in signaling pathways related to pyroptosis, immunity, and cytokines. ConclusionsThis study showed that the local anesthetic TTC effectively induces pyroptosis in uveal melanoma through the caspase-3/GSDME pathway, highlighting its potential application in immunotherapy. Notably, the use of TTC has potential as an agent for inducing pyroptosis and as an adjuvant anticancer therapy in uveal melanoma.

MUsculo-Skeleton-Aware (MUSA) deep learning for anatomically guided head-and-neck CT deformable registration

Deep-learning-based deformable image registration (DL-DIR) has demonstrated improved accuracy compared to time-consuming non-DL methods across various anatomical sites. However, DL-DIR is still challenging in heterogeneous tissue regions with large deformation. In fact, several state-of-the-art DL-DIR methods fail to capture the large, anatomically plausible deformation when tested on head-and-neck computed tomography (CT) images. These results allude to the possibility that such complex head-and-neck deformation may be beyond the capacity of a single network structure or a homogeneous smoothness regularization. To address the challenge of combined multi-scale musculoskeletal motion and soft tissue deformation in the head-and-neck region, we propose a MUsculo-Skeleton-Aware (MUSA) framework to anatomically guide DL-DIR by leveraging the explicit multiresolution strategy and the inhomogeneous deformation constraints between the bony structures and soft tissue. The proposed method decomposes the complex deformation into a bulk posture change and residual fine deformation. It can accommodate both inter- and intra- subject registration. Our results show that the MUSA framework can consistently improve registration accuracy and, more importantly, the plausibility of deformation for various network architectures. The code will be publicly available at https://github.com/HengjieLiu/DIR-MUSA.

Abstract A076: Racial disparities in disease-free and overall survival among colorectal cancer patients in the prospective ColoCare cohort

Abstract Background: Despite improvements in screening and treatment, Black and other underserved colorectal cancer survivors continue to experience poorer clinical outcomes. Multicenter prospective cohorts among large cancer centers in the United States (US) offer the unique opportunity to characterize potential multilevel determinants of disparate outcomes while accounting for known contributions of medical access and treatment. We investigated racial and ethnic disparities in disease-free survival (DFS) and overall survival in the ColoCare study, a prospective cohort study of newly diagnosed colorectal cancer patients across six US cancer centers. Method: The ColoCare study population (n=2,471) from six US sites included n=1,950 non-Hispanic White (NHW), n=238 non-Hispanic Black (NHB), and n=114 Hispanic patients. We estimated racial and ethnic differences in baseline patient characteristics using χ2. We investigated disparities in outcomes by estimating associations of race and ethnicity with DFS (among stage I-III) and overall mortality using Cox Proportional Hazards Models, adjusted for sex, stage at diagnosis, age, study center, and anatomic site. Results: The patients were primarily male (53%), had colon tumors (37.5%), with an average age at diagnosis of 58.6 years. Hispanic individuals were on average younger than their counterparts (P=.03), while NHB individuals were more likely to be overweight and obese (P&amp;lt;.01). NHB individuals had statistically significantly poorer DFS than NHW individuals (HR=1.55, 95% CI=1.03-2.32; P=0.03). NHB individuals also had higher risk for overall mortality (HR=1.45, 95% CI=0.97-2.16; P=0.07), though these findings were not statistically significant. Overall, associations of Hispanic ethnicity with DFS and overall survival were close to null. Discussion: NHB individuals had poorer survivorship outcomes in our study despite all patients receiving care at designated comprehensive cancer centers. Our findings highlight the continued need to address disparities in survivorship using targeted, culturally sensitive intervention strategies. Future research efforts should identify actionable factors, such as adiposity, that may disproportionately impact health outcomes among minority colorectal cancer survivors. Citation Format: Esther Jean-Baptiste, Mmadili Ilozumbo, Gazelle Rouhani, Maria F. Gomez, Stephanie R. Hogue, Sheetal Hardikar, Biljana Gigic, Christopher I Li, Jane C Figueiredo, Adetunji T. Toriola, Cornelia M Ulrich, David Shibata, Erin M Siegel, Doratha A. Byrd. Racial disparities in disease-free and overall survival among colorectal cancer patients in the prospective ColoCare cohort [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A076.

Abstract C126: Disparities in time-to-treat insured patients with newly diagnosed cancer in a vertically integrated healthcare system

Abstract Purpose. After a cancer diagnosis, delays in initiating treatment may impact treatment response, disease progression, adverse health events, and overall survival. Race and socioeconomic status (SES) may be factors in initiating cancer treatment. Complicating this issue is the lack of insurance or underinsurance. Thus, the purpose of this study was to assess the influence of race/ethnicity and SES on time to treatments for insured patients diagnosed with cancer in a vertically integrated healthcare system. Methods. We conducted a cross-sectional nested study within a cohort of patients diagnosed with cancer between 2010 and 2018 from Kaiser Permanente Southern California (KPSC), a vertically integrated healthcare system. Patients of all ages and all cancer anatomical sites were included. Patients with in-situ cancers were excluded, with no other exclusion criteria. The main independent variables are race/ethnicity and SES, and the dependent variable is time to initial treatment. All information was pulled from the KPSC Cancer Registry, including race/ethnicity, and treatments (surgical; radiation; chemotherapy; immunotherapy; hormonal). SES was categorized into quintiles based on geocoded expected income using home addresses from census tract data. For each patient, we calculated days from diagnosis to first treatment. Results. We identified 153,270 patients of all ages with cancers of all anatomical sites diagnosed between 2010 and 2018, of which 125,943 received treatment. When examining racial groups, the mean time to treatment for White, Black, Hispanic, Asian/PI, and other patients was 42.5, 52.6, 44.3, 44.1, and 41.2 days, respectively. For White patients, mean time to treatment was 42.4 days in the lower 20% income quintile and 42.7 days in the top 20% income quintile. For Black patients, mean time to treat was 53.9 days in the lower 20% income quintile and 52.8 days in the top 20% income quintile. For Hispanic patients, mean time to treat was 45.8 days in the lower 20% income quintile and 42.1 days in the top 20% income quintile. For Asian/PI patients, mean time to treat was 44.1 days in the lower 20% income quintile and 43.5 days in the top 20% income quintile. For other patients, mean time to treat was 51.4 days in the lower 20% income quintile and 39.2 days in the top 20% income quintile. Within each SES quintile, Black patients consistently started cancer treatment later than other racial/ethnic groups. Conclusion. We found minimal disparities in time to initial treatment based on SES in this vertically integrated system of care. Within each of the White, Black, and Asian racial groups, the difference in time to treatment between the highest and lowest SES groups was less than 2%. This difference was closer to 7% in Hispanic patients. Additional work is necessary to elucidate reasons why Black patients initiate cancer treatments later than other racial groups and if this affects recurrence or survival. Citation Format: Robert Cooper, Reina Haque, Andrea Young, Zimin Zhuang. Disparities in time-to-treat insured patients with newly diagnosed cancer in a vertically integrated healthcare system [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C126.

Mesenchymal Tumors of the Skin: A Review

Mesenchymal tumors of the skin are rare and clinically heterogeneous, and can represent diagnostic challenge for pathologists. Most of these lesions have overlapping clinical and histological features, thus the understanding of architectural patterns, cytoplasmic and stromal features can facilitate proper diagnosis. Anatomic site may be an important factor in the differential diagnosis, as are patient’s age and sex. Ancillary tests are often required and can be useful to rule out other entities. Molecular diagnostics is playing an increasingly important role in the diagnosis of soft tissue neoplasms. Here, we review clinical, histological, and molecular features of some of the most common of these uncommon entities including benign and malignant lesions.

Site-discordant expression of myeloid cell nuclear differentiation antigen in blastic plasmacytoid dendritic cell neoplasm

Abstract Objectives Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic neoplasm that can show clinical, morphologic, and immunophenotypic overlap with acute myeloid leukemia. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed by myelomonocytic cells previously reported to be reliably absent in BPDCN and proposed as a useful adjunct for the distinction of BPDCN and acute myeloid leukemia. We encountered a case of BPDCN that showed strong nuclear expression of MNDA in bone marrow and breast samples and weak to absent expression in skin samples, prompting us to reevaluate the expression of MNDA in BPDCN. Methods We collected all available BPDCN cases from the Stanford University archives collected in the past 10 years and subjected them to MNDA immunohistochemistry. In select cases, molecular profiling by next-generation sequencing was performed. Results We found 4 cases (of 8 total examined [50%]) with convincing site-discordant MNDA expression. This expression was seen in 3 of 6 (50%) bone marrow samples, 1 of 2 (50%) breast soft tissue samples, and 3 of 14 (up to 21%) skin samples and was not obviously predicted by age, sex, history of myeloid neoplasm, or treatment history. In 2 cases, MNDA was strongly expressed in 2 distinct sites (breast/bone marrow, skin/bone marrow) and negative in subsequent samples. Conclusions Our findings suggest that MNDA expression in BPDCN is anatomic site dependent and transient, with noncutaneous infiltrates showing more frequent expression than cutaneous infiltrates. These results caution against the use of MNDA to exclude BPDCN when considering the differential diagnosis of a blastic extramedullary infiltrate.

Incidental finding of intramural splenic heterotopy in the colon mimicking subepithelial neoplasm: a case report

AimThe aim of this case report is describe an unprecedented case with histological and immunohistochemical diagnosis of splenic heterotopy in the colon using material obtained by endoscopic ultrasound-guided biopsy.BackgroundSplenic heterotopia is a benign condition characterized by the implantation of splenic tissue in areas distant from its usual anatomical site, such as the peritoneum, omentum, mesentery, liver, pancreas, and subcutaneous tissue and, more rarely, in locations such as the colon and brain. It is generally associated with a history of splenic trauma or splenectomy and typically does not cause specific symptoms.Case presentationA 35-year-old white male patient who was healthy, with no history of trauma or splenectomy, but had a family history of colorectal neoplasia underwent colonoscopy for screening. The examination revealed a large bulge in the proximal descending colon, covered by normal-appearing mucosa. Endoscopic ultrasound-guided puncture was performed with a 22 gauge fine needle biopsy, and the histopathological and immunohistochemical analysis results were consistent with a heterotopic spleen.ConclusionsThis is the first report of a primary intramural colic splenosis case with histological and immunohistochemical diagnosis of splenic heterotopia in the colon, using material obtained by endoscopic ultrasound and ultrasound-guided biopsy.

Platelet-Rich Plasma in the Prevention and Treatment of Medication-Related Osteonecrosis of the Jaw: A Systematic Review and Meta-Analysis.

Medication-related osteonecrosis of the jaw (MRONJ) is a significant complication associated with bisphosphonates, impacting jaw osteoclasts, and causing altered bone remodelling. Prevention involves stabilizing systemic pathology, considering antiresorptive therapies, and exploring platelet-rich fibrin (PRF) for wound healing and tissue regeneration. The study aims to assess the efficacy of PRF in MRONJ treatment and highlight research gaps for more robust investigations. Following PRISMA and MOOSE guidelines, this systematic review and meta-analysis included English publications from 2013 to 2023, employing a systematic search in databases such as MEDLINE, Scopus, and Web of Science. Quality assessment used the Cochrane Collaboration's tool and the NOS, with the main meta-analysis concentrating on PRF-treated MRONJ cases, assessing resolution rates, and prioritizing healing outcomes and infection absence as primary endpoints. The study, encompassing 11 articles and 480 participants with MRONJ, demonstrated that in stage 1 procedures, PRF significantly outperformed conventional medical treatments (OR: 2.93, 95% CI: 1.54-5.59, P=0.001), particularly at the mandible site (OR: 1.65, 95% CI: 0.86-3.17, P=0.13). PRF also exhibited significantly superior healing outcomes compared with conventional medical treatments (OR: 4.45, 95% CI: 1.58-12.53, P=0.005), supporting its consideration as a valuable alternative in specific MRONJ management scenarios. This study highlights PRF's effectiveness in early MRONJ interventions and specific anatomic sites, despite acknowledged limitations, emphasizing the need for further research, and supporting its consideration in MRONJ surgical management.

Risk factors for infection after carbapenem-resistant Acinetobacter baumannii colonization

PurposePredicting infection risk in carbapenem-resistant Acinetobacter baumannii (CRAB) colonized patients may help in improving timely appropriate antibiotic therapy. This study aims to explore risk factors for developing infections in hospitalized patients with previous CRAB colonization.MethodsWe performed an observational retrospective cohort study at ASST Sette Laghi-Varese Hospital between January 2020 and December 2022. All consecutive adult (> 18 years old) hospitalized patients with documented colonization by CRAB at any anatomical site or with CRAB infections preceded by CRAB colonization were included. Univariate and multivariate analyses were performed to investigate infection risk factors.ResultsOverall, 144 patients were included in the study: 104 colonized only and 40 infected patients. Colonization and infection rates significantly changed over the years (2020–2022, p < 0.001). The incidence of infections in CRAB carriers was 27.8% (40/144). Median time from colonization to infection was 4 days (IQR 1-8.5). Overall, inhospital mortality was 32.7% and 55.0% in colonized only and infected patients, respectively. At the multivariable logistic regression cardiovascular disease (OR 5.83, 95% CI 1.12–30.43, p = 0.037), COVID-19 (OR 3.72, 95% CI 1.16–11.91, p = 0.027) and intensive care unit (ICU) admission (OR 8.83, 95% CI 2.94–26.51, p < 0.001) were risk factors independently associated with cardiovascular disease CRAB infection after colonization.ConclusionsWe observed an increased infection risk in patients colonized with CRAB with cardiovascular disease, COVID-19 and admitted in ICU setting. Additional evidence is needed to identify predictors of infection in colonized patients.

Children and adolescents assisted in a referral oral medicine diagnostic service: 20 years of experience in Brazil.

Several lesions can affect the oral and maxillofacial region, with trends influenced by lifestyle and age. To investigate the occurrence of oral and maxillofacial lesions in paediatric patients assisted in an oral medicine diagnostic service in Brazil over 20 years. A retrospective cross-sectional study was performed in an oral medicine diagnostic service (1999-2019). Data included sex, age, anatomic site, and diagnosis from clinical records of children (0-9 years) and adolescents (10-19 years). Lesions were diagnosed through clinical examination. Biopsy and histopathologic examination were performed when necessary. Among 10 530 records, 702 (6.67%) were from patients aged 0-19 years diagnosed with oral or maxillofacial lesions. A high frequency of females was observed (58.1%). Reactive/inflammatory lesions were the most common group of lesions (45.2%), followed by abnormalities of teeth/developmental defects (17.8%) and pulpal and periapical diseases (8.5%). Mucocele/ranula was the most common lesion in children (29.3%) and adolescents (25.3%). Lips were the most affected anatomic sites. Most lesions were benign, and mucocele/ranula was the most frequent. Our results did not differ from those of histopathological-based studies, but they provided information on the occurrence of oral and maxillofacial lesions to dentists and paediatricians.

PREVALENCE OF PAROTID TUMORS AMONG YEMENI PATIENTS IN SANA'A CITY, YEMEN

Background and aims: Parotid gland tumors (PGT) are a moderately scarce group of tumors with a broad range of histopathological manifestations and clinical characteristics. To date, most epidemiological studies on salivary gland tumors including PGT are limited in Yemen and this is one of the first studies, so the aim of the study was to determine the prevalence of different tumors affecting the parotid glands and the effect of age and sex on their distribution. Methods: Epidemiological information as well as demographic data, anatomical site, and histological analysis of PGT were analyzed. The data analyzed included age, sex, site, and histological diagnosis. Data were collected from all histopathological centers covering the majority of Sana'a city between 2019 and 2023. Results: A total of 284 cases- 69% benign and 31% malignant tumors were examined. Both benign and malignant tumors showed a little male inclination (52.5%) and a peak occurrence between the third and fifth decade. Malignant tumors make up 31% of patients, while benign tumors make up 69%. Mucoepidermoid carcinoma (36.4%) and adenoid cystic carcinoma (11.4%) are two common malignant tumor types. Benign parotid tumors include pleomorphic adenoma (71.4%) and Warthin tumors (11.2%) of benigns. Other malignants and benigns are less frequent. Conclusions: This study presents the first prospective study to date to analyze PGT data from health centers spread across Sana'a city. These results should serve the same as the basis for prospect studies assessing the epidemiological geography of these tumors in Sana'a in particular and Yemen in general. Peer Review History: Received 18 May 2024; Reviewed 12 July 2024; Accepted 23 August; Available online 15 September 2024 Academic Editor: Dr. Nuray Arı, Ankara University, Turkiye, ari@ankara.edu.tr Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewers: Asmaa Ahmed Mohamed Ahmed Khalifa, Pharos University, Alexandria, Egypt, asmaa.khalifa@pua.edu.eg Dr. George Zhu, Tehran University of Medical Sciences, Tehran, Iran, sansan4240732@163.com

PSLBII-7 Meta-analysis of the whole-body microbiota in cattle

Abstract Distinctive and self-sustainable microbial communities are present along the digestive, respiratory, and reproductive tracts, as well as in the mammary gland, and mucosal surfaces of the eye and hoof in cattle. Although the taxonomic and functional features of each of these communities have been relatively well characterized, this has been largely limited to the microbiome of an individual organ/site. However, recent developments suggest the presence of core taxa shared across the gut, respiratory, and reproductive microbiotas in cattle, and there is a need for a more holistic evaluation of microbial communities in and on cattle. Here, we performed a meta-analysis using all publicly available bovine 16S rRNA gene datasets deposited since 2019 to provide a holistic view of the whole-body microbiota. In total, we retrieved 16S rRNA gene sequences from 6,215 samples (53 studies originating from 29 different anatomical sites within beef and dairy cattle from Africa, Asia, Europe, South America, and North America. The 29 different anatomical sites including gut (ruminal fluid, ruminal tissues, feces, ileum, jejunum, cecum, colon and duodenum), respiratory (nasal cavity, deep nasopharynx, trachea and lung tissue), and reproductive tracts (female: vagina, endometrium and uterus; male: semen and prepuce), as well as the mammary gland (udder, teat apex, teat barrel, teat canal), eye (conjunctiva, ocular fluid and ocular surface swab), blood, hoof, joints and liver. Microbial community structure was distinct among different sample types (PERMANOVA, P &amp;lt; 0.05). Microbial richness differed by sample type (P &amp;lt; 0.0001) with mucosal surfaces (e.g. udder, eye and feet) having the greatest microbial richness followed by the gut. The lungs, liver, joints, semen and prepuce had the least microbial richness. Microbial diversity was greatest in the microbiota of the colon, cecum, teat apex, ruminal tissue and duodenum (Shannon diversity index &amp;gt; 5) while the liver (1.5), joint (2.3), and prepuce microbiota (2.7) were the least diverse. Bacillota had the highest relative abundance among phyla in the majority of microbial communities except for in the blood, prepuce, trachea and nasal cavity (dominated by Pseudomonadota), and liver (dominated by Fusobacteriota). The relatively most abundant genera across all samples were Mycoplasma (12.9%), Prevotella (3.9%), Bacteroides (2.4%), Escherichia (2.1%), Fusobacterium (2.0%), Ruminococcaceae UCG-005 (1.9%), Streptococcus (1.8%), Rikenellaceae RC9 (1.6%), and Corynebacterium (1.4%). However, their relative abundance varied greatly by body site, with the ocular and respiratory system samples dominated by Mycoplasma. Fusobacterium was relatively most abundant in the liver and semen, Corynebacterium in the mammary gland-associated samples, Bacteroides in the gut, and Streptococcus in the lower reproductive tract microbiota. Overall, our meta-analysis provides a comprehensive evaluation of the multiple bacterial communities in and on cattle, which will be useful for harnessing the whole-body microbiome to improve animal health and productivity.

Expansion of tumor-reactive CD8+ T cell clonotypes occurs in the spleen in response to immune checkpoint blockade.

Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8+ T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8+ T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB.

Trends of chlamydia and gonorrhea infections by anatomic sites among men who have sex with men in south China: a surveillance analysis from 2018 to 2022

BackgroundChlamydia and gonorrhea notifications are rapidly rising in men who have sex with men (MSM). Currently, there are limited data on the prevalence of chlamydia and gonorrhea across various anatomical sites. Our study aimed to explore the prevalence, association and changing trends of urethral and rectal chlamydia and gonorrhea among MSM in Guangdong Province, China.MethodsWe analyzed data among MSM attending sexually transmitted infections (STI) clinics in the Guangdong governmental sentinel network between 2018 and 2022. Chi-square tests were used to compare the difference, Join-point regressions for analyzing changing trends, and multivariate logistic regressions for examining associated factors.ResultsWe included 4856 men in the analysis. Rectal chlamydia significantly increased from 13.8% to 26.4% over the past 5 years (average annual percentage change [AAPC] 19.2%, 95%CI 1.0-40.6, p = 0.043). After adjusting for covariates, chlamydia infection positively associated with main venue used to seek sexual partners (aOR = 2.31, 95%CI 1.17–4.55), having regular sexual partners in the past 6 months (aOR = 3.32, 95%CI 1.95–5.64), receiving HIV counselling and testing services (aOR = 2.94, 95%CI 1.67–5.17), receiving peer education (aOR = 1.80, 95%CI 1.14–2.83), infection with syphilis (aOR = 2.02, 95%CI 1.02–4.01) and infection with gonorrhea (aOR 7.04, 95% CI 3.01–16.48). Gonorrhea infection positively associated with having regular sexual partners in the past 6 months (aOR = 3.48.95%CI 1.16–10.49), and infection with chlamydia (aOR 7.03, 95% CI 2.99–16.51).ConclusionsTo conclude, our findings reveal a high prevalence of chlamydia infections among MSM, particularly in the rectal area. Comprehensive chlamydia and gonorrhea health services are necessary for MSM to improve sexual health.

Autonomic nervous system and viscera-related responses to manual therapy: A narrative overview

BackgroundManual therapy (MT) has long-held that it physiologically impacts autonomic nervous system (ANS) and viscera-related function. This narrative review is intended to serve as a consolidated interdisciplinary resource of original studies related to physiological effects of MT as it relates to the ANS for MT clinicians and researchers new to this MT-related topic. ObjectiveThis review seeks to identify ANS and viscera-related physiological responses to MT interventions using search terms commonly used by chiropractic, massage, osteopathic, physical therapy, and structural integration clinicians and to provide a quick reference resource of original MT-related studies investigating ANS effects. MethodsFor this interdisciplinary review, the search was limited to the largest and most commonly used database (PubMed) between years 2000 and 2024, with a focus on direct ANS-related physiological outcomes. Unlike systematic reviews, assessment of scientific rigor and potential bias of included articles was beyond the scope and purpose of the current work. ResultsOriginal MT-related studies provide mixed evidence with regards to immediate and/or short term ANS and/or viscera-related responses on blood pressure, heart rate variability, skin conductance/temperature, respiratory and lymphatic changes. ConclusionsThis review identified a large number of MT and ANS-related original research in PubMed. Careful study of original MT-related research is needed with particular attention focused on the standardization of MT methodological approaches, appropriate controls, study design, appropriate populations, MT techniques, and anatomical site delivery so as to design more rigorous studies in order to arrive at definitive conclusions regarding direct effects of MT on the ANS.

Universal penalized regression (Elastic-net) model with differentially methylated promoters for oral cancer prediction

BackgroundDNA methylation showed notable potential to act as a diagnostic marker in many cancers. Many studies proposed DNA methylation biomarker in OSCC detection, while most of these studies are limited to specific cohorts or geographical location. However, the generalizability of DNA methylation as a diagnostic marker in oral cancer across different geographical locations is yet to be investigated.MethodsWe used genome-wide methylation data from 384 oral cavity cancer and normal tissues from TCGA HNSCC and eastern India. The common differentially methylated CpGs in these two cohorts were used to develop an Elastic-net model that can be used for the diagnosis of OSCC. The model was validated using 812 HNSCC and normal samples from different anatomical sites of oral cavity from seven countries. Droplet Digital PCR of methyl-sensitive restriction enzyme digested DNA (ddMSRE) was used for quantification of methylation and validation of the model with 22 OSCC and 22 contralateral normal samples. Additionally, pyrosequencing was used to validate the model using 46 OSCC and 25 adjacent normal and 21 contralateral normal tissue samples.ResultsWith ddMSRE, our model showed 91% sensitivity, 100% specificity, and 95% accuracy in classifying OSCC from the contralateral normal tissues. Validation of the model with pyrosequencing also showed 96% sensitivity, 91% specificity, and 93% accuracy for classifying the OSCC from contralateral normal samples, while in case of adjacent normal samples we found similar sensitivity but with 20% specificity, suggesting the presence of early disease methylation signature at the adjacent normal samples. Methylation array data of HNSCC and normal tissues from different geographical locations and different anatomical sites showed comparable sensitivity, specificity, and accuracy in detecting oral cavity cancer with across. Similar results were also observed for different stages of oral cavity cancer.ConclusionsOur model identified crucial genomic regions affected by DNA methylation in OSCC and showed similar accuracy in detecting oral cancer across different geographical locations. The high specificity of this model in classifying contralateral normal samples from the oral cancer compared to the adjacent normal samples suggested applicability of the model in early detection.

Prospective multicenter study using artificial intelligence to improve dermoscopic melanoma diagnosis in patient care

BackgroundEarly detection of melanoma, a potentially lethal type of skin cancer with high prevalence worldwide, improves patient prognosis. In retrospective studies, artificial intelligence (AI) has proven to be helpful for enhancing melanoma detection. However, there are few prospective studies confirming these promising results. Existing studies are limited by low sample sizes, too homogenous datasets, or lack of inclusion of rare melanoma subtypes, preventing a fair and thorough evaluation of AI and its generalizability, a crucial aspect for its application in the clinical setting.MethodsTherefore, we assessed “All Data are Ext” (ADAE), an established open-source ensemble algorithm for detecting melanomas, by comparing its diagnostic accuracy to that of dermatologists on a prospectively collected, external, heterogeneous test set comprising eight distinct hospitals, four different camera setups, rare melanoma subtypes, and special anatomical sites. We advanced the algorithm with real test-time augmentation (R-TTA, i.e., providing real photographs of lesions taken from multiple angles and averaging the predictions), and evaluated its generalization capabilities.ResultsOverall, the AI shows higher balanced accuracy than dermatologists (0.798, 95% confidence interval (CI) 0.779–0.814 vs. 0.781, 95% CI 0.760–0.802; p = 4.0e−145), obtaining a higher sensitivity (0.921, 95% CI 0.900–0.942 vs. 0.734, 95% CI 0.701–0.770; p = 3.3e−165) at the cost of a lower specificity (0.673, 95% CI 0.641–0.702 vs. 0.828, 95% CI 0.804–0.852; p = 3.3e−165).ConclusionAs the algorithm exhibits a significant performance advantage on our heterogeneous dataset exclusively comprising melanoma-suspicious lesions, AI may offer the potential to support dermatologists, particularly in diagnosing challenging cases.

Distribution of Chlamydia trachomatis ompA-genotypes over three decades in Portugal

ObjectivesChlamydia trachomatis is classified into 15 major genotypes, A to L3, based on the diversity of ompA gene. Here, we evaluated and characterised the distribution and diversity of ompA-genotypes over...