bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Septic Arthritis in Children Demonstrates Presumed and Confirmed Varieties Which Require Age-specific Evaluation and Treatment Strategies
Authors: Klosterman Mary M. , Villani Mary C. , Hamilton Elizabeth C. , Jo Chanhee , Copley Lawson A. 
Published: September 2021

Background:
There is uncertainty involved in the evaluation and treatment of children suspected to have septic arthritis particularly when no causative pathogen is confirmed. This study evaluates children with primary septic arthritis to refine the processes of evaluation and treatment and improve the rate of pathogen confirmation.

Methods:
Children suspected to have septic arthritis from 2009 to 2019 were retrospectively studied. Diagnosis of primary septic arthritis, defined as hematogenous joint infection without associated osteomyelitis, was established by clinical evaluation, radiology and laboratory results, including joint fluid analysis. Excluded cases were categorized by etiology. Children with primary septic arthritis were divided into confirmed and presumed cohorts for statistical comparison.

Results:
A total of 355 children (average age 4.4 y, range 0.05 to 18 y) were initially treated as septic arthritis. Eighty-seven (24.5%) were excluded due to other conditions, including 34 (9.6%) with noninfectious conditions. Among 268 children with primary septic arthritis, 134 were confirmed and 134 were presumed. A higher rate of 16S polymerase chain reaction (PCR) acquisition (71.6% vs. 45.5%) occurred in the confirmed cohort. Overall yield for various methods of pathogen identification were 27 of 239 (11.3%) by blood culture, 83 of 268 (31.0%) by joint fluid culture and 85 of 157 (54.1%) by PCR. PCR identified a pathogen in 87.5% of children with confirmed septic arthritis. Antibiotic pretreatment was associated with a lower rate of joint fluid culture positivity. Pathogens aggregated within specific age groups. The 4 to 9-year-old age group displayed the widest spectrum of pathogens with limited predictability.

Conclusions:
This study emphasizes the need for systematic processes of evaluation and treatment for children suspected to have primary septic arthritis, including minimization of antibiotic pretreatment, age-based empiric antibiotic selection, and sufficient follow-up to ensure noninfectious conditions are distinguished in culture-negative cases. Extended observation, before intervention, may be appropriate for some children.

Level of Evidence:
Level III—retrospective control study.
Interobserver and Intraobserver Reliability in the Salter Classification of Avascular Necrosis of the Femoral Head in Developmental Dysplasia of the Hip
Authors: Schaeffer Emily K. , Ponton Ethan , Sankar Wudbhav N. , Kim Harry K.W. , Kelley Simon P. , Cundy Peter J. , Price Charles T. , Clarke Nicholas M.P. , Wedge John H. , Mulpuri Kishore 
Published: September 2021

Background:
Avascular necrosis (AVN) of the femoral head is a concerning complication that can result from treatments for developmental dysplasia of the hip (DDH). AVN can lead to degenerative osteoarthritis, persistent acetabular dysplasia, reduced function, and continuing hip pain. The incidence of AVN reported in the DDH literature is widely varied (0% to 73%). This variability may arise from lack of consensus on what constitutes true AVN in this patient population, and lack of clear criteria provided in studies reporting incidence rates.

Methods:
A multicentre, prospective database of infants diagnosed with DDH between 2010 and 2014 from 0 to 18 months of age was analyzed for patients treated by closed reduction (CR). Twelve pediatric orthopaedic surgeons completed 2 rounds of AVN assessments. Deidentified anteroposterior radiographs at most recent follow-up were provided to surgeons along with patient age at radiographic assessment, length of follow-up, ands affected hip. Ten of 12 surgeons completed a third round of assessments where they were provided with 1 to 2 additional radiographs within the follow-up period. Radiographic criteria for total AVN described by Salter and colleagues were used. Surgeons rated the presence of AVN as “yes” or “no” and kappa values were calculated within and between rounds.

Results:
A total of 69 hips in 60 patients were assessed for AVN a median of 22 months (range: 12 to 36) post-CR. Interobserver kappa values for rounds 1, 2, and 3 were 0.52 (range: 0.11 to 0.90), 0.61 (range: 0.21 to 0.90), and 0.53 (range: 0.10 to 0.79), respectively. Intraobserver agreement for AVN diagnosis was an average of 0.72 (range: 0.31 to 0.96).

Conclusions:
Despite using the most commonly referenced diagnostic criteria, radiographic diagnosis of AVN following CR in DDH patients demonstrated only moderate agreement across surgeons. The addition of sequential radiographs did not improve cross-observer reliability, and while substantial agreement was seen within observers, the range of intraobserver kappa values was large.

Level of Evidence:
Level I—diagnostic study.
Nucleolar protein 6 promotes cell proliferation and acts as a potential novel prognostic marker for hepatocellular carcinoma
Authors: Meng Lei , Xu Kai-Xuan , Zhao Ming-Xi , Li Kang , Zhu Kun , Yuan Da-Wei , Wang Hao-Nan , Dai Peng-Gao , Yan Rong 
Published: September 2021

Abstract

Background:
Nucleolar protein 6 (NOL6) is a nucleolar RNA-associated protein that is highly conserved between species. It has been proved to be associated with the prognosis of liver cancer. However, the underlying mechanism has not been fully established. This study aimed to assess the relationship between NOL6 and liver cancer prognosis.

Methods:
We constructed an NOL6-short hairpin RNA (shRNA)-expressing lentivirus. Through viral transfection, cell growth assay and fluorescence-activated cell sorting, we evaluated the effect of shRNA-mediated NOL6 knockdown on the proliferation, colony formation, and apoptosis of hepatocellular carcinoma (HCC) cells. The relationship between NOL6 expression and HCC patient survival has been established through bioinformatics analysis. We also explored the downstream molecular regulatory network of NOL6 in HCC by performing an Ingenuity Pathway Analysis in the database.

Results:
Increased NOL6 expression was detected in HCC cells compared to normal controls; HCC patients with high NOL6 expression had poorer prognoses than those with low expression. NOL6 knockdown inhibited HCC cell proliferation, apoptosis, and colony formation. Also, MAPK8, CEBPA, and FOSL1 were selected as potential downstream genes of NOL6.

Conclusions:

NOL6 up-regulates HCC cell proliferation and affects downstream expression of related genes. Moreover, NOL6 is considered to be associated with poor prognosis in HCC patients.
In vitro fertilization-embryo transfer in patients with unexplained recurrent pregnancy loss
Authors: Li Tai-Yang , Li Rong , Zeng Lin , Li Li , Qiao Jie , Liu Ping , Wang Hai-Yan 
Published: September 2021

Abstract

Background:
Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.

Methods:
A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.

Results:
The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748–0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887–0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846–0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052–0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770–0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.

Conclusion:
After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.
Chromosomal microarray analysis vs. karyotyping for fetal ventriculomegaly: a meta-analysis
Authors: Sun Yan , Zhang Weiyuan , Wang Zhiwen , Guo Likui , Shi Shaowen 
Published: September 2021

Abstract

Background:
Chromosomal abnormalities are important causes of ventriculomegaly (VM). In mild and isolated cases of fetal VM, obstetricians rarely give clear indications for pregnancy termination. We aimed to calculate the incidence of chromosomal abnormalities and incremental yield of chromosomal microarray analysis (CMA) in VM, providing more information on genetic counseling and prognostic evaluation for fetuses with VM.

Methods:
The Chinese language databases Wanfang Data, China National Knowledge Infrastructure, and China Biomedical Literature Database (from January 1, 1991 to April 29, 2020) and English language databases PubMed, Embase, and Cochrane Library (from January 1, 1945 to April 29, 2020) were systematically searched for articles on fetal VM. Diagnostic criteria were based on ultrasonographic or magnetic resonance imaging (MRI) assessment of lateral ventricular atrium width: ≥10 to <15 mm for mild VM, and ≥15 mm for severe VM. Isolated VM was defined by the absence of structural abnormalities other than VM detected by ultrasonography or MRI. R software was used for the meta-analysis to determine the incidence of chromosomal abnormalities and incremental yield of CMA in VM, and the combined rate and 95% confidence interval (CI) were calculated.

Results:
Twenty-three articles involving 1635 patients were included. The incidence of chromosomal abnormalities in VM was 9% (95% CI: 5%–12%) and incremental yield of CMA in VM was 11% (95% CI: 7%–16%). The incidences of chromosomal abnormalities in mild, severe, isolated, and non-isolated VM were 9% (95% CI: 4%–16%), 5% (95% CI: 1%–11%), 3% (95% CI: 1%–6%), and 13% (95% CI: 4%–25%), respectively.

Conclusions:
Applying CMA in VM improved the detection rate of abnormalities. When VM is confirmed by ultrasound or MRI, obstetricians should recommend fetal karyotype analysis to exclude chromosomal abnormalities. Moreover, CMA should be recommended preferentially in pregnant women with fetal VM who are undergoing invasive prenatal diagnosis. CMA cannot completely replace chromosome karyotype analysis.
Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration
Authors: Xing Chen , Liu Xiao-Feng , Zhang Chun-Feng , Yang Liu 
Published: September 2021

Abstract

Background:
Age-related macular degeneration (AMD) is the leading cause of vision loss worldwide. However, the mechanisms involved in the development and progression of AMD are poorly delineated. We aimed to explore the critical genes involved in the progression of AMD.

Methods:
The differentially expressed genes (DEGs) in AMD retinal pigment epithelial (RPE)/choroid tissues were identified using the microarray datasets GSE99248 and GSE125564, which were downloaded from the gene expression omnibus database. The overlapping DEGs from the two datasets were screened to identify DEG-related biological pathways using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The hub genes were identified from these DEGs through protein-protein interaction network analyses. The expression levels of hub genes were evaluated by quantitative real-time polymerase chain reaction following the induction of senescence in ARPE-19 with FK866. Following the identification of AMD-related key genes, the potential small molecule compounds targeting the key genes were predicted by PharmacoDB. Finally, a microRNA-gene interaction network was constructed.

Results:
Microarray analyses identified 174 DEGs in the AMD RPE compared to the healthy RPE samples. These DEGs were primarily enriched in the pathways involved in the regulation of DNA replication, cell cycle, and proteasome-mediated protein polyubiquitination. Among the top ten hub genes, HSP90AA1, CHEK1, PSMA4, PSMD4, and PSMD8 were upregulated in the senescent ARPE-19 cells. Additionally, the drugs targeting HSP90AA1, CHEK1, and PSMA4 were identified. We hypothesize that Hsa-miR-16-5p might target four out of the five key DEGs in the AMD RPE.

Conclusions:
Based on our findings, HSP90AA1 is likely to be a central gene controlling the DNA replication and proteasome-mediated polyubiquitination during the RPE senescence observed in the progression of AMD. Targeting HSP90AA1, CHEK1, PSMA4, PSMD4, and/or PSMD8 genes through specific miRNAs or small molecules might potentially alleviate the progression of AMD through attenuating RPE senescence.
C4d as a Practical Marker for Cutaneous Amyloidosis
Authors: Yaman Banu , Kumbaracı Banu Sarsık , Gómez González Claudia A. , Akalın Taner , Şen Sait 
Published: September 2021

Abstract:Cutaneous amyloidosis (CA) is defined by the accumulation of amyloid in the dermis; it might be primary or secondary. The diagnosis is based on histopathological findings with the demonstration of amyloid deposits, confirmed by Congo red stain under the polarized light. Studies on other diagnostic markers are ongoing in the literature. The aim of this study was to demonstrate the utility of C4d staining in the recognition of amyloid in CA and using it as an alternative or substitute marker for the diagnosis. In this retrospective study, 199 skin biopsies with a clinical provisional diagnosis of CA were analyzed, the Congo red stain was performed, and, in a subgroup (n = 97) with histopathological findings probably for CA, C4d immunohistochemistry was assessed. Forty-eight cases of CA were detected. Congo red birefringence was positive in all cases, whereas in 14 cases, it was faded. In these 14 cases, the diagnosis of CA was made by means of Congo red fluorescence and Thioflavin T because the histopathological findings were highly suggestive for CA. All CA cases were positive with C4d, and in 12 of the 49 inflammatory dermatoses, C4d was positive. The interpretation of C4d immunohistochemistry can be performed more easily and rapidly than Congo red evaluation. The sensitivity and specificity of C4d were 100% and 75.5%, respectively. In our experience, C4d staining was a useful method for detecting amyloid deposits in CA. Although Congo red staining is the gold standard for amyloid detection, we propose C4d immunohistochemistry as a routine screening method or hybrid transition while further investigations are completed.
Utility of Cyclin D1 Immunostaining in Cutaneous Xanthogranuloma
Authors: Sharma Anurag , McAfee John , Wang Lin , Cook Eleanor , Ababneh Emad , Bergfeld Wilma F. 
Published: September 2021

Abstract:
Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase pathway activation has recently been found to be associated with almost all Langerhans cell histiocytosis cases. In BRAF V600E mutation–positive cases, this activation is seen as a downstream activation. In addition, cyclin D1 is a downstream target of the MAPK pathway. Recent studies have argued in favor of using cyclin D1 as a potential neoplastic marker to differentiate Langerhans cell histiocytosis from other reactive Langerhans cell proliferations in the skin and lymph nodes. Therefore, we chose to study the immunohistochemical expression of cyclin D1 in cutaneous xanthogranuloma (XG) cases. Fifteen XG cases were retrieved and stained for cyclin D1, BRAF (v-raf murine sarcoma viral oncogene homolog B1), CD1a, and langerin (CD207). Twelve cases showed strong and diffuse nuclear positivity for cyclin D1, both in the XG cells and in the multinucleated osteoclast-like giant cells. Three cases showed focal weak nuclear staining for cyclin D1. All 15 cases showed negative immunoreactivity for BRAF, CD1a, and CD207. Although limited by small sample size, we conclude that most cases of cutaneous XG should show at least weak nuclear staining with cyclin D1. The histogenesis of XG is still largely unknown, and the finding of cyclin D1 positivity in a majority of cases may indicate a role for the MAPK/extracellular signal-regulated kinase pathway in cutaneous XG.
Diagnostic Value of Plasmacytoid Dendritic Cells in Differentiating Pityriasis Lichenoides et Varioliformis Acuta From Lymphomatoid Papulosis
Authors: Brem Candice E. , Abbas Ossama , Bhawan Jag 
Published: September 2021

Abstract:
Pityriasis lichenoides et varioliformis acuta (PLEVA) and lymphomatoid papulosis (LyP) can often demonstrate clinical and histopathologic overlap. A recent study demonstrated significant plasmacytoid dendritic cell (pDC) recruitment in lesions of PLEVA, whereas another study reported minimal pDC recruitment in lesions of LyP. To confirm the possible diagnostic value of pDCs in differentiating PLEVA and LyP, we compared the presence and distribution of pDCs and myxovirus protein A (MxA) expression (an indirect assessment of pDC activity). In total, 19 cases of PLEVA (16 patients) and 14 cases of LyP (11 patients) were examined using immunohistochemical stains for anti–blood-derived dendritic cell antigen-2 and MxA. Individual semiquantitative scoring systems were used to assess the immunohistochemical results, and a Mann–Whitney test with a subsequent 2-tailed P test was performed for statistical analysis. No statistically significant difference in the number of pDCs in both groups was found. However, most PLEVA cases (84%) demonstrated intense and diffuse MxA expression, whereas LyP cases (71%) demonstrated weak patchy staining (P < 0.007). Our study suggests that although additional studies may be needed to determine whether pDCs are more relevant to the pathogenesis of PLEVA or LyP, pDC activity through MxA staining may play a role in differentiating PLEVA from LyP and may serve as a platform for additional studies.
CD8+ Lymphogranulomatous Dermatitis as a Manifestation of Malignancy-Associated Immunodeficiency: Rethinking Paraneoplastic Granulomas
Authors: Stonesifer Connor J. , Trager Megan H. , Magro Cynthia M. , Geskin Larisa J. 
Published: September 2021

Abstract:
Paraneoplastic granulomatous disease occurs in approximately 7.3% of patients with non-Hodgkin lymphoma, most commonly among patients with chronic lymphocytic leukemia (CLL). These lesions are often reported to appear similar to sarcoidosis in clinical presentation and under light microscopy. However, comprehensive descriptions of the cytomorphologic characteristics of these paraneoplastic granulomas are lacking, and the mechanisms involved in their formation remain ill-defined. Noninfectious dermal granulomatous reactions have also been reported in many primary immunodeficiencies, including common variable immune deficiency and ataxia-telangiectasia. We present a case of noninfectious CD8+ predominant granulomatous dermatitis with ocular involvement occurring in the setting of CLL and marked hypogammaglobulinemia. Based on the analysis of shared factors in patients with primary immunodeficiencies and CLL, we conclude that the presence of pan-humoral immunodeficiency could itself be a risk factor for developing a CD8+ lymphogranulomatous reaction. This report and associated discussion evince that CD8+ predominant granulomatous reactions, distinct from sarcoidosis, may represent a previously unappreciated segment of the paraneoplastic granulomas observed in hematologic malignancies.
Lymphocyte-Peppered Sclerotic Collagen: An Additional Histological Clue in Lichen Sclerosus, Morphea, and Systemic Sclerosis
Authors: Yadav Deepika , Agarwal Shipra , Thakur Shilpi , Ramam M. 
Published: September 2021

Background:
“Line sign,” “cookie cutter sign,” “square biopsy sign,” “high eccrine glands sign” have been previously described in morphoea and lichen sclerosus. We found focal areas of thickened collagen bundles with lymphocytes interspersed between them in several biopsies of these conditions.

Materials and Methods:
We reviewed slides of sclerosing disorders obtained from the archives of the pathology department in our hospital for the period 2013–2019.

Results:
A total of 73 slides including 40 of lichen sclerosus, 24 of morphea, 2 of lichen sclerosus-morphea overlap, and 7 of systemic sclerosis were evaluated. Lymphocytes were noted between sclerotic collagen bundles in 46 (63%) slides, being most common in lichen sclerosus (80%, 32/40) followed by morphea (50%, 12/24), whereas it was seen in one case each of lichen sclerosus with morphea overlap (50%, 1/2) and systemic sclerosis (14.3%, 1/7). The finding was noted in the upper dermis in 20 of 32 (62.5%) slides of lichen sclerosus and in both the superficial and deep dermis in 11 (91.7%) of 12 slides of morphea.

Conclusion:
Lymphocyte-peppered sclerotic collagen may be a useful histological clue to the diagnosis of lichen sclerosus, morphea, and systemic sclerosis.
Squamoid Eccrine Ductal Carcinoma: Treatment and Outcomes
Authors: Lim Megan M. , Macdonald Jillian A. 
Published: September 2021

Background:
Squamoid eccrine ductal carcinoma (SEDC) represents a subtype of eccrine carcinomas that are diagnostically challenging for both clinicians and dermatopathologists.

Objective:
To provide an updated review of SEDC and examine patient outcomes with different treatment modalities.

Methods:
A review of Ovid MEDLINE was performed to review the English language medical literature of SEDC.

Results:
A comprehensive review of clinical presentation, histologic findings, rates of lymphovascular and metastatic disease, treatment modalities and recurrence rates are reviewed.

Limitations:
There is a limitation on available data because of the rare incidence.

Conclusions:
SEDC is a rare adnexal neoplasm with a relatively high rate of local recurrence, lymphovascular invasion, perineural invasion, and metastases. Clinicians should be aware of this entity as close follow-up is essential to detect recurrence and metastatic disease. Mohs micrographic surgery seems to result in superior patient outcomes.