bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recurrent paratesticular liposarcoma: a case report
Authors: Blaiech Walid , Ben Othmen Mouna , Ouahchi Ines , Alaya Meriam , Belkacem Oussama , Hmida Wissem , Jaidane Mehdi 
Published: March 2024

Introduction and importance:
Paratesticular liposarcoma (PTL) is a rare condition, with fewer than 200 cases reported worldwide. It is a malignant tumor that originates from fat tissue with high risk of recurrence. Herein, the authors present a contralateral recurrence of a treated PTL. To the best of the authors’ knowledge, in the current literature, there are few cases reported with recurrent PTL.

Case presentation:
The authors report the case of a 62-year-old man who presented with a rapidly growing painless right hemiscrotal swelling. Clinical and radiographic evidence suggested the presence of two paratesticular tumors. The patient underwent a radical orchidectomy with resection of the two tumors through an inguinal approach. The histologic examination revealed a sclerosing, well-differentiated liposarcoma. The decision of the multidisciplinary consultation meeting was not to do adjuvant treatment. A follow-up of 12 months showed recurrence of the contralateral scrotum revealed by an FDG-PET/scan.

Clinical discussion:
PTL, a rare spermatic cord tumor, affects adults aged 50–60, often presenting with scrotal swelling. Diagnosis involves ultrasound, computed tomography, and magnetic resonance imaging. Surgical intervention, including radical orchiectomy and adjuvant radiotherapy, is common for management, while the role of chemotherapy is inconclusive. High-grade subtypes carry a higher recurrence risk.

Conclusion:
PTL is often misdiagnosed preoperatively. It is typically managed through radical orchidectomy, which includes wide excision and high ligation to ensure free surgical margins and avoid recurrence. The role of adjuvant therapy remains debatable. Despite a generally favorable prognosis, long-term follow-up is crucial because of the elevated risk of recurrence.
Aetiology, clinical profile, management and outcome of acute pancreatitis at public hospitals in Addis Ababa, Ethiopia: a prospective observational study
Authors: Hussen Mohammed Seid , Ibrahim Amelmasin Faris , Tekle Yared , Gebremariam Shimelis , Feto Amana Deko , Nida Tamrat , Mohammed Hussen 
Published: March 2024

Background:
Acute pancreatitis (AP) is a rare gastrointestinal pathology that has recently become increasingly common owing to lifestyle changes. Its clinical presentation ranges from mild discomfort to organ failure and death. Previous studies in Ethiopia reported that AP is rare. However, lifestyle changes have recently increased. Therefore, this study aimed to assess the aetiology, clinical profile, management, and outcomes of AP.

Methods:
This prospective observational study included 59 adults diagnosed with AP using the Revised Atlanta Classification between November 2021 and August 2022 at five public hospitals in Addis Ababa. The data were analyzed using SPSS 25. The mean ± standard deviation and adjusted odds ratio (AOR) at 95% CI were used.

Results:
The mean age was 38.2 (SD±11.5 years), mostly aged 30–44, with 67% males and 89.8% patients presenting with new-onset AP. Abdominal pain and nausea were the most common presentations in 93.2% of patients. More than 52.5% of AP cases were caused by alcohol, followed by gallstones (28.8%), and gallstones (47.1%) underwent cholecystectomy during the index admission. One patient (1.7%) died. The length of hospital stay ranges from 1–47 days and increases with the severity of AP. Patients with recurrent AP had a 2.4 folds increase in complications compared to new-onset AP (AOR=2.4, 95% CI=1.38, 15.71).

Conclusion:
Most AP cases were caused by alcohol consumption, followed by gallstones, smoking, and hypertriglyceridemia. One death in a 60-year-old male with an alcohol and smoking history was diagnosed and triaged as severe AP with persistent multiple organ failure; BISAP score 4, his Creatinine=2.55 mg/dl, haematocrit 72.6%; and left shift of WBC, was associated.
Integration of HIV Testing in a Community Intervention for Tuberculosis Screening Among Household Contacts of Patients with Tuberculosis in Cameroon and Uganda
Authors: Tchakounte Youngui Boris , Atwine Daniel , Otai David , Vasiliu Anca , Ssekyanzi Bob , Sih Colette , Kana Rogacien , Arinaitwe Rinah , Cuer Benjamin , Simo Leonie , Okello Richard , Tchendjou Patrice , Casenghi Martina , Kuate Albert Kuate , Turyahabwe Stavia , Cohn Jennifer , Bonnet Maryline , Tchounga Boris Kevin ,   on behalf of the CONTACT Study Group
Published: March 2024

Introduction:
People living with HIV are considered at higher risk of developing severe forms of tuberculosis (TB) disease. Providing HIV testing to TB-exposed people is therefore critical. We present the results of integrating HIV testing into a community-based intervention for household TB contact management in Cameroon and Uganda.

Methods:
Trained community health workers visited the households of index patients with TB identified in 3 urban/semiurban and 6 rural districts or subdistricts as part of a cluster-randomized trial and provided TB screening to all household contacts. Voluntary HIV counseling and testing were offered to contacts aged 5 years or older with unknown HIV status. We describe the cascade of care for HIV testing and the factors associated with the acceptance of HIV testing.

Results:
Overall, 1983 household contacts aged 5 years or older were screened for TB. Of these contacts, 1652 (83.3%) did not know their HIV status, 1457 (88.2%) accepted HIV testing, and 1439 (98.8%) received testing. HIV testing acceptance was lower among adults than children [adjusted odds ratio (aOR) = 0.35, 95% confidence interval (CI): 0.22 to 0.55], those living in household of an HIV-positive vs HIV-negative index case (aOR = 0.56, 95% CI: 0.38 to 0.83), and contacts requiring a reassessment visit after the initial TB screening visit vs asymptomatic contacts (aOR = 0.20, 95% CI: 0.06 to 0.67) and was higher if living in Uganda vs Cameroon (aOR = 4.54, 95% CI: 1.17 to 17.62) or if another contact of the same index case was tested for HIV (aOR = 9.22, 95% CI: 5.25 to 16.18).

Conclusion:
HIV testing can be integrated into community-based household TB contact screening and is well-accepted.
Risk Factors for Oronasal Fistula in Primary Palatoplasty: A Case-Control Study From a Reference Center in Medellín, Colombia
Authors: Correa Acebedo Esteban , Gallego Gónima Sabrina , Vásquez Sañudo Vanesa , Vélez Toro Juan Sebastián , Salinas Ana María 
Published: March 2024

Background:
Oronasal fistula is one of the most critical complications in primary palatoplasty, with a reported incidence between 5% and 46% with multiple associated risk factors described previously. In addition, in more than half of the patients, it implies additional surgeries, increasing risks for the patient and health care costs. In this case-control study, the authors aim to determine the specific risk factors for oronasal fistula after primary palatoplasty in the study population.

Methods:
A retrospective review was undertaken to identify all patients undergoing primary palatoplasty between 2017 and 2019. Patients who developed oronasal fistula were included (cases) and compared with patients from the same cohort without fistula (controls). Demographic, clinical, and perioperative variables and their association with postoperative fistula presentation were explored through crude and adjusted analysis.

Results:
One hundred thirty-nine patients with a median age of 6 years (5–6) who underwent primary palatoplasty were found. Forty-five presented an oronasal fistula, corresponding to 32% of the population, and 64% required subsequent repair of an oronasal fistula. In the crude analysis, the surgeon’s experience (OR: 0.44) was associated significantly with the outcome. Adjusted analysis showed an association between surgical site infection and syndromic presentation.

Conclusions:
The experience of the surgeon is a protective factor for the oronasal fistula presentation; in addition, the presentation of infection of the operative site, the syndromic presentation, and the clinical follow-up at 1 year were also relevant; the latter, possibly due to the social context of our patients.
The Severity of Initial Unilateral Cleft Lip and Nasal Deformity Predicts Long-Term Postoperative Esthetic Outcome
Authors: Lo Alexis L. , Haley Christopher T. , Jones Christine M. , Brooke Sebastian M. , Long Ross E. , Samson Thomas D. , Mackay Donald R. 
Published: March 2024

Background:
Infantile cleft lip and nasal severity influence the final esthetic result of the repair. Although various authors have described methods of cleft lip and nasal repair, there is a paucity of data that correlates cleft severity with esthetic outcomes. The aim of this study was to examine the correlation between presurgical severity of unilateral cleft deformity and long-term postoperative esthetic outcomes.

Methods:
This retrospective study, based at a single institution, investigated patients with complete unilateral cleft lip, with or without cleft palate, who underwent repair by a single surgeon, had preoperative infantile facial casts, and had postoperative facial photographs at 6 to 11 years of age (N=31). Preoperative nostril width ratio and columellar angle measurements were taken from facial casts. Postoperative, long-term nasolabial appearance was rated by 5 blinded observers used a modified Kuijpers-Jagtman scale. Linear regression was used to determine the relationship between preoperative cleft severity and postoperative ratings.

Results:
Preoperative nostril width ratio directly correlated with postoperative nasal form score (r=0.40; P=0.026); likewise, preoperative columellar angle predicted postoperative nasal form score (r=0.37; P=0.040). Preoperative cleft severity was not significantly correlated with vermillion border appearance. Cronbach α values of 0.91 (nasal form) and 0.79 (vermillion border) indicated good inter-rater reliability. Kappa values of 0.87 (nasal form) and 0.70 (vermillion border) indicated good intrarater reliability.

Conclusions:
Preoperative unilateral cleft nose severity directly correlates with long-term postoperative nasal appearance in childhood. Outcome studies should present and control for preoperative severity to allow more accurate assessment of repair techniques.
Effects of Danggui Wuji granules on 16S rDNA, metagenome, and metabolome in BDS mice
Authors: Huang Hanhui , Deng Yurong , Chen Shisheng , Li Zongyuan , Li Xiaomin , Sun Jianhui , Hao Liyu , Yu Zeyue , Wang Aoao , Li Jianliang , Huo Hairu , Liu Guimin , Li Hongmei 
Published: March 2024

Abstract
Blood deficiency syndrome (BDS) refers to a pathological state with blood dysfunction and organ dystrophy in traditional Chinese medicine. Danggui Wuji granules (DWG) was developed from a formula containing Angelicae Sinensis Radix and Musculus et Os Galli Domestici. Herein, we investigated the mechanism of DWG in treating BDS by modulating gut microbiota. We found that DWG protected mice from BDS by elevating the levels of red blood cell count, hemoglobin, and hematocrit in peripheral blood and increasing the erythrocyte membrane Na+-K+-ATPase activity. Danggui Wuji granules changed the composition and metabolites of colonic flora. Notably, Lactobacillus, Muribaculaceae, and Alistipes were the main genera showing changes after DWG treatment. Our findings revealed that DWG presented a positive therapeutic effect on BDS in mice by regulating the gut microbiota and metabolites. The protective mechanism of DWG was associated with pathways such as metabolic pathways, biosynthesis of secondary metabolites, ABC transporters, ribosome, thyroid hormone synthesis, lysine degradation, galactose metabolism, tyrosine metabolism, etc.
Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations
Authors: Matejcic Marco , Teer Jamie K. , Hoehn Hannah J. , Diaz Diana B. , Shankar Kritika , Gong Jun , Nguyen Nathalie T. , Lorona Nicole , Coppola Domenico , Fulmer Clifton , Saglam Ozlen , Jiang Kun , Cress Douglas , Muñoz-Antonia Teresita , Flores Idhaliz , Gordian Edna , Oliveras Torres José A. , Felder Seth I. , Sanchez Julian A. , Fleming Jason , Siegel Erin M. , Freedman Jennifer A. , Dutil Julie , Stern Mariana C. , Fridley Brooke L. , Figueiredo Jane C. , Schmit Stephanie L. 
Published: March 2024

AbstractAncestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry.Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression.TP53,APC, andKRASwere the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewerKRAS(OR=0.64, 95%CI=0.41-0.97, p=0.037) andPIK3CAmutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation inKNCN(OR=1.34, 95%CI=1.09–1.66, p=5.74×10-3) andTMEM184B(OR=1.53, 95%CI=1.10–2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status inCDC27(LRT p=0.0084) and betweenSMAD2mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048).Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities.SignificanceOur data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.
Neural mechanisms of disease pathology and cognition in young-onset Alzheimer’s Disease variants
Authors: Sacu Seda , Slattery Catherine F. , Friston Karl J. , Paterson Ross W. , Foulkes Alexander J.M. , Yong Keir , Crutch Sebastian , Schott Jonathan M. , Razi Adeel 
Published: March 2024

AbstractLate-onset Alzheimer’s disease is consistently associated with alterations in the default-mode network (DMN)—a large-scale brain network associated with self-related processing and memory. However, the functional organization of DMN is far less clear in young-onset Alzheimer’s disease (YOAD). We assessed resting-state DMN effective connectivity in two common YOAD variants (i.e., amnestic variant (n = 26) and posterior cortical atrophy (n = 13) and healthy participants (n=24) to identify disease- and variant-specific connectivity differences using spectral dynamic causal modelling. Patients with the amnestic variant showed increased connectivity from prefrontal cortex to posterior DMN nodes relative to healthy controls, whereas patients with posterior cortical atrophy exhibited decreased posterior DMN connectivity. Right hippocampus connectivity differentiated the two patient groups. Furthermore, disease-related connectivity alterations were also predictive of group membership and cognitive performance. These findings suggest that resting-state DMN effective connectivity provides a new understanding of neural mechanisms underlying the disease pathology and cognition in YOAD.
metaGWASmanager: A toolbox for an automated workflow from phenotypes to meta-analysis in GWAS consortia
Authors: Rodriguez-Hernandez Zulema , Gorski Mathias , Plaza Maria Tellez , Schlosser Pascal , Wuttke Matthias 
Published: March 2024

AbstractSummaryThis paper introduces the metaGWASmanager, which streamlines genome-wide association studies within large-scale meta-analysis consortia. It is a toolbox for both the central consortium analysis group and participating studies to generate homogeneous phenotypes, minimize variance from inconsistent methodologies, ensure high-quality association results, and implement time-efficient quality control workflows. The toolbox features a plug-in-based approach for customization.ResultsThe metaGWASmanager toolbox has been successfully deployed in both the CKDGen and MetalGWAS Initiative consortia across hundreds of participating studies, demonstrating its effectiveness in improving the efficiency of GWAS analysis by automating routine tasks and ensuring the value and reliability of association results, thus, ultimately promoting scientific discovery.AvailabilityGitHub:https://github.com/genepi-freiburg/metaGWASmanagerContactpschlos3@jhu.edu,matthias.wuttke@uniklinik-freiburg.de
Cervical collagen network porosity assessed by SHG endomicroscopy distinguishes preterm and normal pregnancy – a pilot study
Authors: Liang Wenxuan , Liu Yuehan , Guan Honghua , Sakulsaengprapha Vorada , Luby-Phelps Katherine , Mahendroo Mala , Li Xingde 
Published: March 2024

Structured AbstractBackgroundPreterm birth (PTB) is a global public health issue affecting millions of newborns every year. Orchestrated remodeling of the cervix is essential for normal pregnancy and birth, while PTB is closely related with premature cervical ripening and loss of cervical mechanical strength. The structure and organization of fibrillar collagen in the extracellular matrix are of vital importance to the biomechanical properties of the cervix. Second harmonic generation (SHG) microscopy has proved capable of revealing the progressive changes in cervical collagen morphology over the course of pregnancy. To translate this promising imaging technology to clinical practice, a flexible SHG endomicroscope has long been envisaged for label-free, non-invasive visualization of cervical collagen architecture and for assessment of PTB risk.ObjectiveTo evaluate the potential of our newly-developed SHG endomicroscope for imaging-based differentiation of cervical collagen architecture between normal pregnant mice and RU486/mifepristone-induced PTB mouse models.Study DesignWe undertook endomicroscopy SHG imaging of cervical collagen on two types ofex vivosamples: 1) frozen cervical tissue sections (∼50 µm thick) and 2) resected intact cervices, and performed SHG-image-based quantitative collagen morphology analysis to distinguish RU486 mouse models from normal pregnant mice.ResultsEndomicroscopic SHG images of cervical tissue sections from mifepristone-treated mouse models exhibit statistically larger collagen fiber diameter, increased pore size, and reduced pore numbers than those of normal pregnant mice. Similar changes are also observed on SHG images of subepithelial collagen fibers acquired from intact cervices by the endomicroscope.ConclusionThe experiment results demonstrated that SHG endomicroscopy along with quantitative image analysis holds promising potential for clinical assessment of cervical collagen remodeling and preterm birth risk.
Inactive Parp2 causes Tp53-dependent lethal anemia by blocking replication-associated nick ligation in erythroblasts
Authors: Lin Xiaohui , Gupta Dipika , Vaitsiankova Alina , Bhandari Seema Khattri , Leung Kay Sze Karina , Menolfi Demis , Lee Brian J. , Russell Helen R. , Gershik Steven , Gu Wei , McKinnon Peter J. , Dantzer Françoise , Rothenberg Eli , Tomkinson Alan E. , Zha Shan 
Published: March 2024

SummaryPARP1&2 enzymatic inhibitors (PARPi) are promising cancer treatments. But recently, their use has been hindered by unexplained severe anemia and treatment-related leukemia. In addition to enzymatic inhibition, PARPi also trap PARP1&2 at DNA lesions. Here, we report that unlikeParp2-/-mice, which develop normally, mice expressing catalytically-inactive Parp2 (E534A,Parp2EA/EA) succumb toTp53-andChk2-dependent erythropoietic failurein utero, mirroringLig1-/-mice. While DNA damage mainly activates PARP1, we demonstrate that DNA replication activates PARP2 robustly. PARP2 is selectively recruited and activated by 5’-phosphorylated nicks (5’p-nicks) between Okazaki fragments, typically resolved by Lig1. Inactive PARP2, but not its active form or absence, impedes Lig1- and Lig3-mediated ligation, causing dose-dependent replication fork collapse, particularly harmful to erythroblasts with ultra-fast forks. This PARylation-dependent structural function of PARP2 at 5’p-nicks explains the detrimental effects of PARP2 inhibition on erythropoiesis, revealing the mechanism behind the PARPi-induced anemia and leukemia, especially those with TP53/CHK2 loss.SignificanceThis work shows that the hematological toxicities associated with PARP inhibitors stem not from impaired PARP1 or PARP2 enzymatic activity but rather from the presence of inactive PARP2 protein. Mechanistically, these toxicities reflect a unique role of PARP2 at 5’-phosphorylated DNA nicks during DNA replication in erythroblasts.
Unexpected transformations during pyrroloiminoquinone biosynthesis
Authors: Figueroa Josseline Ramos , Zhu Lingyang , van der Donk Wilfred A. 
Published: March 2024

AbstractPyrroloiminoquinone containing natural products have long been known for their biological activities. They are derived from tryptophan, but their biosynthetic pathways have remained elusive. Studies on the biosynthetic gene cluster (BGC) that produces the ammosamides revealed that the first step is attachment of Trp to the C-terminus of a scaffold peptide in an ATP and tRNA dependent manner catalyzed by a PEptide Amino-acyl tRNA ligase (PEARL). The indole of the Trp is then oxidized to a hydroxyquinone. We previously proposed a chemically plausible and streamlined pathway for converting this intermediate to the ammosamides using additional enzymes encoded in the BGC. In this study, we report the activity of four additional enzymes that show that the proposed pathway is incorrect and that Nature’s route towards pyrroloiminoquinones is much more complicated. We demonstrate that, surprisingly, the amino groups in pyrroloiminoquinones are derived from three different sources, glycine, asparagine, and leucine, all introduced in a tRNA dependent manner. We also show that an FAD-dependent putative glycine oxidase is required for the process that incorporates the nitrogens from glycine and leucine, and that a quinone reductase is required for the incorporation of the asparagine. Additionally, we provide the first insights into the evolutionary origin of the PEARLs as well as related enzymes such as the glutamyl-tRNA dependent dehydratases involved in the biosynthesis of lanthipeptides and thiopeptides. These enzymes appear to all have descended from the ATP-GRASP protein family.