bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risankizumab as a Therapeutic Approach for Recalcitrant Pyoderma Gangrenosum
Authors: Michelucci Alessandra , Manzo Margiotta Flavia , Granieri Giammarco , Salvia Giorgia , Fidanzi Cristian , Bevilacqua Matteo , Panduri Salvatore , Romanelli Marco , Dini Valentina 
Published: April 2024

ABSTRACT
Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that is challenging to diagnose and treat. Clinicians frequently use fast-acting corticosteroids, which are subsequently combined with slower-acting immunosuppressants to progressively taper the corticosteroid dosage. Current research is focused on the use of monoclonal antibodies (mAbs) directed against target molecules involved in the pathogenesis of PG. However, available data on their efficacy are based on sporadic case reports and clinical experiences, so the authors aimed to evaluate the efficacy of risankizumab, an anti-interleukin-23 mAb, in the management of two complex PG cases.
The authors enrolled two patients with PG who were already treated with immunosuppressive therapies. Their management was based on the off-label use of an mAb directed against the p19 subunit of interleukin-23: risankizumab. Patients received subcutaneous injections of 150 mg at the start of treatment, at week 4, and then every 10 weeks thereafter. Systemic therapy was combined with local management of ulcers, based on the principles of TIME (tissue, infection, moisture balance, and epithelialization) applied to the inflammatory and noninflammatory phases of PG.
Clinical resolution was obtained at week 24 for patient 1 and week 16 for patient 2 and was maintained until week 40, without adverse effects or disease recurrence. These clinical cases demonstrate that risankizumab is a valid tool in terms of efficacy and safety for complicated cases of multirefractory PG when provided in parallel with local personalized wound management.
Follicular (Infundibular–Tricholemmal) Squamous Cell Carcinoma: A New WHO Entity. Clinicopathological Features in 103 Cases, Including Follow-Up and Implications for Patient Management
Authors: Carr Richard A. , Wiggins James , Slater David N. 
Published: April 2024

Aims:
Cutaneous follicular (infundibular–tricholemmal) squamous cell carcinoma (FSCC) is a new World Health Organization entity. We present the largest series of published cases, summarizing clinical data, diagnostic criteria, differential diagnosis, and implications for patient management.

Methods:
Cases were identified from 2004 to 2011. Inclusion criteria included discrete attachment(s) of the tumor to the overlying epidermis via follicular infundibula, tricholemmal keratinization, and cellular pleomorphism. Keratoacanthoma and lesions with adjacent bowenoid epidermal dysplasia were excluded.

Results:
One hundred three cases of FSCC identified. 48.5% demonstrated completely circumscript borders (in situ for practical purposes), 12.6% uncertain for invasion (overwhelmingly pushing borders), and only 38.8% as clearly invasive. Follicular mucin in acantholytic spaces within tumor epithelium was a distinctive finding in 57.2% of cases. Clinical data indicated predominance in elderly (median 78.5 years) men (70.4%), with preferential head and neck location (81.6%). Many were clinically suspected as squamous cell carcinoma (48.5%). However, a significant minority were clinically diagnosed as basal cell carcinoma (40.8%). This may reflect that FSCC commonly presented as a papule or nodule (51.3%). By contrast, keratoacanthoma was less frequently suggested (17.2%) and still fewer lesions were suspected to be actinic keratosis/Bowen's disease (13.6%). Follow-up in 82 cases (median 26.5 months, range 3–144) identified 5 (6.1%) local recurrences. There was no instance of metastasis in the subgroup of lesions with completely circumscript borders. Three of 45 (6.7%) patients, with follow-up, considered to have tumors with invasive pushing, and/or infiltrative borders developed lymph node metastases.

Conclusions:
FSCC is identified as a common skin cancer, incorporating historical entities, such as infundibular carcinoma and tricholemmal carcinoma, with readily identifiable histologic features. Correct diagnosis has implications for patient management; a significant subgroup of lesions show completely circumscript borders that are considered in situ for practical purposes.
Junctional Epidermolysis Bullosa Linked to Homozygous Mutation in LAMC2 Gene: A Case Report With Eosinophil-Rich Inflammatory Infiltrate
Authors: Haskoloğlu Şule , Öztürk Gökcan , Deveci Demirbaş Nazlı , Akal Can , İslamoğlu Candan , Baskın Kübra , Heper Aylin , Erdeve Ömer , Ceylaner Serdar , Doğu Figen , İkincioğulları Aydan 
Published: April 2024

Abstract:
Junctional epidermolysis bullosa (JEB) is a rare, incurable, devastating, and mostly fatal congenital genetic disorder characterized by painful blistering of the skin and mucous membranes in response to minor trauma or pressure. JEB is classified roughly into 2 subtypes: JEB-Herlitz is caused by mutations on genes encoding laminin-332. The authors present a patient consulted with a suspicion of primary immunodeficiency due to skin sores that started at the age of 1 month and a history of 3 siblings who died with similar sores, who was diagnosed with JEB-Herlitz after detecting a homozygous LAMC2 gene mutation in WES analysis. Microscopic evaluation of hematoxylin and eosin–stained sections showed vesicle formation with subepidermal separation, which is accompanied by striking neutrophil and eosinophil leukocyte infiltration both in the vesicle and papillary dermis (eosinophil-rich inflammatory infiltrate). Such a histopathological finding has been rarely reported in this condition.
Blau Syndrome With Delayed Cutaneous Manifestations: A Case Report
Authors: Panah Elnaz , Garfield Erin , Zahirsha Zisansha , Muhlbauer Aaron , Lake Eden , Speiser Jodi 
Published: April 2024

Abstract:
Blau syndrome is a rare familial autoinflammatory disorder characterized by the triad of granulomatous dermatitis, polyarthritis, and uveitis. Blau syndrome exhibits an autosomal dominant inheritance pattern and can be caused by a gain-of-function mutation in nucleotide-binding oligomerization domain 2 (NOD2), a member of the NOD-like receptor family of pattern recognition receptors. Mutations in NOD2 cause upregulation of inflammatory cytokines and resultant autoinflammation. Because of the rarity of this condition and early onset of symptoms, Blau syndrome may be misdiagnosed as juvenile idiopathic arthritis. We present a case of a 37-year-old male patient with a long-documented history of juvenile idiopathic arthritis and uveitis, who developed an asymptomatic eruption of pink papules on the trunk and upper extremities. A biopsy demonstrated noncaseating, well-formed dermal granulomas with relatively sparse lymphocytic inflammation and Langerhans-type giant cells. Genetic testing confirmed a mutation in NOD2. Based on the patient's clinical history, histologic findings, genetic testing, the diagnosis of Blau syndrome was made.
Rhabdomyomatous Mesenchymal Hamartoma: Report of 4 Cases With Histochemical and Immunohistochemical Findings and Emphasis on Potential Pitfalls
Authors: AbdullGaffar Badr , Keloth Tasnim 
Published: April 2024

Abstract:
Rhabdomyomatous mesenchymal hamartoma (RMH) typically presents as a congenital midline head and neck cutaneous polyp in infants. Perianal and mucocutaneous lesions have been reported, and recently, acquired adult-onset variants have been proposed. This makes the true prevalence, etiopathogenesis, and clinicopathologic distribution and classification of RMHs in children compared with those in adults uncertain. We performed a retrospective review to highlight the salient histopathologic, histochemical, and immunohistochemical features in RMHs and to emphasize their specific clinicopathologic criteria to avoid diagnostic pitfalls. We found 4 (0.3%) infants [2 female infants and 2 male infants, average age: 4 months] with mental, nasal, lingual, and perianal midline RMHs (average size: 1.0 cm) of 1303 patients with cutaneous polypoid lesions. Three were isolated, and 1 was associated with Goldenhar syndrome. The cutaneous polyps demonstrated intermixed skeletal muscle, adipose, and fibrocollagenous core stroma that extended into the dermis and around the dermal appendages. The lingual lesion demonstrated skeletal muscle and fibrocollagenous stroma with prominent nerve bundles and little adipose tissue. All showed interstitial loose mesenchyme. Masson trichome demarcated the triphasic stromal components. Alcian blue demonstrated the loose myxoid mesenchyme. Elastic van Gieson did not show elastic fibers. Desmin demonstrated the skeletal muscle bundles, S100 highlighted the adipose tissue lobules and the nerve bundles, and CD34 displayed the mesenchymal stroma. Ki67 showed a low proliferation index in the loose mesenchyme. Smooth muscle actin did not reveal smooth muscle bundles, but with CD31, they highlighted the thick blood vessels. CD117 revealed prominent mast cells. From our retrospective review series, 4 cases that originally diagnosed as RMHs were excluded. Likewise, we found some examples of the reported cases in the English literature that might have been mistaken for RMHs. This is because they did not fulfill the diagnostic clinicopathologic criteria. RMH constitutes a rare entity with specific clinicopathologic features. Most lesions are isolated. Some are associated with congenital anomalies and syndromes. Strict clinicopathologic diagnostic criteria should be applied to avoid mislabeling look-alike lesions for RMHs.
Age-Related Changes in Vancomycin Protein Binding: Is It Time to Take It Seriously?
Authors: Gadsby Jessica , Stachow Lucy , Mulla Hussain 
Published: April 2024

Background:Vancomycin (VAN) protein binding in plasma is influenced by illness and age; hence, doses titrated according to total concentrations are fraught. In this study, model-estimated free VAN concentrations (EFVC) were compared with assumed free VAN concentrations (AFVC) in neonates, children, and adults in the intensive care unit and those on dialysis.Methods:Patient cohorts were identified from the hospital database. Demographics, clinical characteristics, total VAN concentrations, and laboratory variables were obtained from electronic health records. EFVC was derived from 6 models identified in the literature. For all models, total VAN concentration was the most important predictor; other predictors included albumin, total protein, and dialysis status. The AFVC was calculated as 50% of the total concentration (ie, assumption of 50% bound).Results:Differences between EFVC and AFVC in adults were insignificant; however, differences in pediatric intensive care unit patients, according to 2 different models, were significant: mean ± SD = 4.1 ± 1.58 mg/L and 4.7 ± 2.46 mg/L (P< 0.001); the percentages within the free VAN trough range = 30.4% versus 55.1% and 30% versus 55.1%; and the supratherapeutic percentages = 65.2% versus 31.9% and 66.7% versus 31.9%, respectively. In neonates, the difference between EFVC and AFVC was mean ± SD = 6.9 ± 1.95 mg/L (P< 0.001); the percentages within the free VAN trough range for continuous and intermediate dosing were 0% versus 81.3% and 14.3% versus 71.4%, and the supratherapeutic percentages were 100% versus 6.25% and 71.4% versus 0%, respectively.Conclusions:The fraction of free unbound VAN is higher in sick children and neonates than in adults. Therefore, total VAN concentrations do not correlate with the pharmacologically active free VAN concentrations in the same manner as in adults. Adjusting VAN doses in neonates and children to target the same total VAN concentration as the recommended therapeutic range for adults may result in toxicfree concentrations.
Follow the Area Under the Curve Not the Trough Concentration: A Case Study of Tacrolimus Monitoring in a Kidney Transplant Recipient Cotreated With Phenobarbital
Authors: Izarn Oscar , Morin Marie-Pascale , Ntobe-Bunkete Beni , Golbin Léonard , Ferrand-Sorre Marie-José , Tron Camille , Lemaitre Florian 
Published: April 2024

Abstract:
The authors described tacrolimus dosing in a kidney transplant patient concurrently treated with phenobarbital, where measuring the tacrolimus area under the curve was necessary to achieve adequate drug exposure and improve kidney function.
Understanding the effects of COVID-19 on patients with diabetic nephropathy: a systematic review
Authors: Altoukhi Samar M. , Zamkah Mariam M. , Alharbi Reman A. , Alghamdi Shatha K. , Aldawsari Lama S. , Tarabulsi Muyassar , Rizk Hisham , Sandokji Yousif 
Published: April 2024

Background:
Diabetic nephropathy is one of the consequences of diabetes mellitus that causes a continuous decline in the eGFR. After the COVID-19 pandemic, studies have shown that patients with diabetic nephropathy who had contracted COVID-19 have higher rates of morbidity and disease progression. The aim of this study was to systematically review the literature to determine and understand the effects and complications of SARS-CoV-2 on patients with diabetic nephropathy.

Materials and methods:
The authors’ research protocol encompassed the study selection process, search strategy, inclusion/exclusion criteria, and a data extraction plan. A systematic review was conducted by a team of five reviewers, with an additional reviewer assigned to address any discrepancies. To ensure comprehensive coverage, the authors employed multiple search engines including PubMed, ResearchGate, ScienceDirect, SDL, Ovid, and Google Scholar.

Results:
A total of 14 articles meeting the inclusion criteria revealed that COVID-19 directly affects the kidneys by utilizing ACE2 receptors for cell entry, which is significant because ACE2 receptors are widely expressed in the kidney.

Conclusion:
COVID-19 affects kidney health, especially in individuals with diabetic nephropathy. The mechanisms include direct viral infection and immune-mediated injury. Early recognition and management are vital for improving the outcomes.
Network pharmacology prediction and experiment validation of anti-liver cancer activity of Curcumae Rhizoma and Hedyotis diffusa Willd
Authors: Tie Songyan , Tong Tianhao , Zhan Gangxiang , Li Xin , Ouyang Dan , Cao Jianzhong 
Published: April 2024

Objective:
This study aims to elucidate anti-liver cancer components and potential mechanisms of Curcumae Rhizoma and Hedyotis diffusa Willd (CR-HDW).

Methods:
Effective components and targets of CR-HDW were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Liver cancer-related genes were collected from GeneCards, Gene-Disease Association (DisGeNET), and National Center for Biotechnology Information (NCBI). Protein-protein interaction networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were conducted to analyze the identified genes. Molecular docking was used to simulate binding of the active components and their target proteins. Cell activity assay, western blot, and senescence-associated β-galactosidase (SA-β-gal) experiments were conducted to validate core targets identified from molecular docking.

Results:
Ten active compounds of CR-HDW were identified including quercetin, 3-epioleanic acid and hederagenin. The primary core proteins comprised Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Protein Kinase B(AKT1), etc. The pathways for Phosphoinositide 3-kinase (PI3K)/ AKT, cellular senescence, Fork head boxO (FOXO) were revealed as important for anti-cancer activity of CR-HDW. Molecular docking demonstrated strong binding between liver cancer target proteins and major active components of CR-HDW. In-vitro experiments confirmed that hederagenin and 3-epioleolic acid inhibited HuH-7 cell growth, reduced expression of PI3K, AKT, and mechanistic target of rapamycin (mTOR) proteins. Hederagenin also induced HuH-7 senescence.

Conclusions:
In summary, The authors’ results suggest that the CR-HDW component (Hederagenin, 3-epoxy-olanolic acid) can inhibit the proliferation of HuH-7 cells by decreasing PI3K, AKT, and mTOR. Hederagenin also induced HuH-7 senescence.
Association of Lateral Pelvic Lymph Nodes with Disease Recurrence and Organ Preservation in Patients with Distal Rectal Adenocarcinoma Treated with Total Neoadjuvant Therapy
Authors: Beets Nathalie R. A. , Verheij Floris S. , Williams Hannah , Omer Dana M. , Lin Sabrina T. , Qin Li-Xuan , Beets Geerard L. , Beets-Tan Regina G. H. , Wei Iris H. , Widmar Maria , Pappou Emmanouil P. , Weiser Martin R. , Nash Garrett M. , Smith J. Joshua , Paty Philip B. , Miranda Joao , Kim Tae-Hyung , Gollub Marc J. , Garcia-Aguilar Julio 
Published: April 2024

Objective:
Assess the significance of enlarged lateral lymph nodes (LLN) for disease recurrence, metastasis, and organ preservation in patients with rectal cancer.

Background:
Optimal treatment of rectal adenocarcinoma involving LLN is subject to debate.

Methods:
A post hoc analysis of the OPRA trial, a multicenter study of patients with rectal cancer treated with total neoadjuvant therapy (TNT) followed by total mesorectal excision or watch-and-wait management. We analyzed the association of visible LLN (LLN+), LLN≥7 mm (short axis) on baseline MRI, and LLN≥4 mm on restaging MRI with recurrence, metastasis, and rectum preservation.

Results:
At baseline, 57 out of 324 (18%) patients had LLN+. In 30 (53%) of 57 patients with LLN+ on baseline MRI, the LLN disappeared after TNT. Disease recurrence in LLN was rare (3.5% of patients with LLN+ and 0.4% of patients with LLN−). All patients with recurrence in LLN also had distant metastasis. The rate of organ preservation was significantly lower in patients with LLN≥4 mm on restaging MRI (P=0.013). We found no significant differences in rates of local recurrence or metastasis between patients with LLN+ vs. LLN− and in patients with LLN≥7 vs.<7 mm on baseline MRI. LLN dissection was performed in 3 patients; 2 of them died of distant metastasis.

Conclusions:
LLN involvement is not associated with disease recurrence or metastasis, but persistence of LLN≥4 mm after TNT is negatively associated with rectum preservation in patients with locally advanced rectal cancer treated with TNT. Dissection of lateral nodes likely benefits few patients.
Periprosthetic Femoral Fractures in Total Hip Arthroplasty
Authors: Dauder-Gallego Cristina , López-Hualda Alvaro , Ferreño-Márquez David Manuel , Sosa-Reina María Dolores , Villafañe Jorge Hugo , Martínez-Martín Javier 
Published: April 2024

Objective:
This study aimed to analyze the occurrence of periprosthetic fractures (PPFs) in patients who underwent total hip arthroplasty.

Methods:
The researchers conducted a retrospective review of 447 patients (494 hips) who received a hip replacement with an ESOP stem. The average follow-up period was 12.33 ± 5.2 years. The study population comprised 248 men with 276 hips and 203 women with 220 hips, with a mean age of 65.7 ± 11.6 years.

Results:
We found 42 PPFs, 15 of them taking place intraoperatively. Regarding the postoperative fractures, 3 of them happened during the first month and the rest of them afterward. There were 3 deaths directly related to the PPF episode. We found a higher risk of fractures among the female, population older than 65 years, and among those with total hip arthroplasty following hip fracture. This population showed a higher incidence of complications and mortality rate. The cumulative percentage probability of periprosthetic femoral fracture was 3.2% (95% confidence interval, 2-5.6) at 10 years, and 10.3% (95% confidence interval, 7-20) at 20 years after surgery.

Conclusions:
Our findings indicate that periprosthetic femoral fracture incidence increases significantly after the first decade. The use of modular stems did not modify this behavior, similar to other nonmodular or anatomical stems.
Efficacy of Rehabilitative Intervention on Pain and Function in Patients With Upper Limb Complex Regional Pain Syndrome
Authors: Buraschi Riccardo , Ranica Giorgia , Nicassio Filippo , Falso Maurizio Vincenzo , Pollet Joel 
Published: April 2024

Aim:
Investigate the efficacy of physical therapy in the management of complex regional pain syndrome (CRPS)

Methods:
We conducted a systematic review on 3 databases: MEDLINE, EMBASE, and CENTRAL. The applied methods are stated in the protocol and registered in OSF: 10.17605/OSF.IO/SF49B.

Results:
At the end of the screening process, 12 RCTs were included. Included studies presented heterogeneous and multicomponent interventions. Physical therapy interventions resulted valuable in the management of CRPS. Motor imagery and some physical agents therapies are effective in reducing pain and for functional improvements.

Conclusion:
Physiotherapy is a central treatment for patients with CRPS.
Lifting the curse from high dimensional data: Automated projection pursuit clustering for the variety of biological data modalities
Authors: Simpson Claire , Tabatsky Evgeniy , Rahil Zainab , Eddins Devon J. , Tkachev Sasha , Georgescauld Florian , Papalegis Derek , Culka Martin , Levy Tyler , Gregoretti Ivan , Chernyshev Andrei , Koeppen Hartmut , Walther Guenther , Ghosn Eliver E. B. , Orlova Darya 
Published: April 2024

AbstractUnsupervised clustering is a powerful machine-learning technique widely used to analyze high-dimensional biological data. It plays a crucial role in uncovering patterns, structure, and inherent relationships within complex datasets without relying on predefined labels. In the context of biology, high-dimensional data may include transcriptomics, proteomics, and a variety of single-cell omics data. Most existing clustering algorithms operate directly in the high-dimensional space, and their performance may be negatively affected by the phenomenon known as the curse of dimensionality. Here, we show an alternative clustering approach that alleviates the curse by sequentially projecting high-dimensional data into a low-dimensional representation. We validated the effectiveness of our approach, named APP, across various biological data modalities, including flow and mass cytometry data, scRNA-seq, multiplex imaging data, and T-cell receptor repertoire data. APP efficiently recapitulated experimentally validated cell-type definitions and revealed new biologically meaningful patterns.
Generative Modelling of Oncogene-carrying Extrachromosomal Circular DNA Biogenesis and Dynamics in Cells
Authors: Haskó János , Feng Weijia , Arshadi Aram , Tolomeo Doron , Hembo Chuang Sun , Petersen Trine Skov , Lv Wei , Han Peng , Zeng Yuchen , Wang Fei , Bolund Lars , Lin Lin , Regenberg Birgitte , Storlazzi Clelia Tiziana , Luo Yonglun 
Published: April 2024

ABSTRACTExtrachromosomal circular DNAs (ecDNA) are focal gene amplifications frequently associated with cancer development and often indicating a poor prognosis. To understand the early dynamics of oncogene-carrying ecDNAs, we previously developed CRISPR-C, a tool for precise ecDNA generation by deleting specific chromosomal regions. Here, we adapted CRISPR-C to recreate tumor ecDNAs. This method also allowed us to enhance ecDNA generation efficiency by directly delivering Cas9 protein and sgRNAs as a ribonucleoprotein complex. By using the modified CRISPR-C, we successfully generated ecDNAs carrying oncogenes (EGFR, CDK4, MDM2, MYC, MYCN, FGFR2, ABCB1,andDHFR) in various human cell types. Furthermore, we demonstrated that our method could generate chimeric ecDNAs composed of target sequences from distant intra or inter-chromosomal regions. Using these generative ecDNA cell models, we studied the oncogene ecDNA expression and stability. TheMDM2expression was increased after CRISPR-C, whileCDK4was decreased indicating genomic-context dependent effect. The copy number of CRISPR-C generatedCDK4was ecDNA increased in cells after a long period of treatment with theCDK4inhibitor palbociclib. Unlike CDK4, the CRISPR-C generatedABCB1ecDNA was unstable in cells under normal growth conditions, but is stably retained when the cells were treated with colcemid, a recognized substrate for ABCB1. We thus provide valuable tools and an attractive platform for studying ecDNA biogenesisy and in vitro drug screening on ecDNA stability.