Miracle-dz/UniFAR-FTUs huggingface dataset:
Artificial intelligence for HPV status prediction based on disease‐specific images in head and neck cancer: A systematic review and meta‐analysis

Accurate early detection of the human papillomavirus (HPV) status in head and neck cancer (HNC) is crucial to identify at‐risk populations, stratify patients, personalized treatment options, and predict prognosis. Artificial intelligence (AI) is an emerging tool to dissect imaging features. This systematic review and meta‐analysis aimed to evaluate the performance of AI to predict the HPV positivity through the HPV‐associated diseased images in HNC patients. A systematic literature search was conducted in databases including Ovid‐MEDLINE, Embase, and Web of Science Core Collection for studies continuously published from inception up to October 30, 2022. Search strategies included keywords such as “artificial intelligence,” “head and neck cancer,” “HPV,” and “sensitivity & specificity. ” Duplicates, articles without HPV predictions, letters, scientific reports, conference abstracts, or reviews were excluded. Binary diagnostic data were then extracted to generate contingency tables and then used to calculate the pooled sensitivity (SE), specificity (SP), area under the curve (AUC), and their 95% confidence interval (CI). A random‐effects model was used for meta‐analysis, four subgroup analyses were further explored. Totally, 22 original studies were included in the systematic review, 15 of which were eligible to generate 33 contingency tables for meta‐analysis. The pooled SE and SP for all studies were 79% (95% CI: 75−82%) and 74% (95% CI: 69−78%) respectively, with an AUC of 0.83 (95% CI: 0.79−0.86). When only selecting one contingency table with the highest accuracy from each study, our analysis revealed a pooled SE of 79% (95% CI: 75−83%), SP of 75% (95% CI: 69−79%), and an AUC of 0.84 (95% CI: 0.81−0.87). The respective heterogeneities were moderate (I2 for SE and SP were 51.70% and 51.01%) and only low (35.99% and 21.44%). This evidence‐based study showed an acceptable and promising performance for AI algorithms to predict HPV status in HNC but was not comparable to the routine p16 immunohistochemistry. The exploitation and optimization of AI algorithms warrant further research. Compared with previous studies, future studies anticipate to make progress in the selection of databases, improvement of international reporting guidelines, and application of high‐quality deep learning algorithms.
Diagnostic accuracy of HPV16 early antigen serology for HPV‐driven oropharyngeal cancer is independent of age and sex

A growing proportion of head and neck cancer (HNC), especially oropharyngeal cancer (OPC), is caused by human papillomavirus (HPV). There are several markers for HPV‐driven HNC, one being HPV early antigen serology. We aimed to investigate the diagnostic accuracy of HPV serology and its performance across patient characteristics. Data from the VOYAGER consortium was used, which comprises five studies on HNC from North America and Europe. Diagnostic accuracy, that is, sensitivity, specificity, Cohen's kappa and correctly classified proportions of HPV16 E6 serology, was assessed for OPC and other HNC using p16INK4a immunohistochemistry (p16), HPV in situ hybridization (ISH) and HPV PCR as reference methods. Stratified analyses were performed for variables including age, sex, smoking and alcohol use, to test the robustness of diagnostic accuracy. A risk‐factor analysis based on serology was conducted, comparing HPV‐driven to non‐HPV‐driven OPC. Overall, HPV serology had a sensitivity of 86.8% (95% CI 85.1‐88.3) and specificity of 91.2% (95% CI 88.6‐93.4) for HPV‐driven OPC using p16 as a reference method. In stratified analyses, diagnostic accuracy remained consistent across sex and different age groups. Sensitivity was lower for heavy smokers (77.7%), OPC without lymph node involvement (74.4%) and the ARCAGE study (66.7%), while specificity decreased for cases with <10 pack‐years (72.1%). The risk‐factor model included study, year of diagnosis, age, sex, BMI, alcohol use, pack‐years, TNM‐T and TNM‐N stage. HPV serology is a robust biomarker for HPV‐driven OPC, and its diagnostic accuracy is independent of age and sex. Future research is suggested on the influence of smoking on HPV antibody levels.
The human cellular protein NoL12 is a specific partner of the HIV-1 nucleocapsid protein NCp7

ABSTRACT The human immunodeficiency virus-1 (HIV-1) nucleocapsid protein (NCp7) is a nucleic acid chaperone protein with two highly conserved zinc fingers. To exert its key roles in the viral cycle, NCp7 interacts with several host proteins. Among them, the human NoL12 protein (hNoL12) was previously identified in genome wide screens as a potential partner of NCp7. hNoL12 is a highly conserved 25 kDa nucleolar RNA-binding protein implicated in the 5′end processing of ribosomal RNA in the nucleolus and thus in the assembly and maturation of ribosomes. In this work, we confirmed the NCp7/hNoL12 interaction in cells by Förster resonance energy transfer visualized by Fluorescence Lifetime Imaging Microscopy and co-immunoprecipitation. The interaction between NCp7 and hNoL12 was found to strongly depend on their both binding to RNA, as shown by the loss of interaction when the cell lysates were pretreated with RNase. Deletion mutants of hNoL12 were tested for their co-immunoprecipitation with NCp7, leading to the identification of the exonuclease domain of hNoL12 as the binding domain for NCp7. Finally, the interaction with hNoL12 was found to be specific of the mature NCp7 and to require NCp7 basic residues. IMPORTANCE HIV-1 mature nucleocapsid (NCp7) results from the maturation of the Gag precursor in the viral particle and is thus mostly abundant in the first phase of the infection which ends with the genomic viral DNA integration in the cell genome. Most if not all the nucleocapsid partners identified so far are not specific of the mature form. We described here the specific interaction in the nucleolus between NCp7 and the human nucleolar protein 12, a protein implicated in ribosomal RNA maturation and DNA damage response. This interaction takes place in the cell nucleolus, a subcellular compartment where NCp7 accumulates. The absence of binding between hNoL12 and Gag makes hNoL12 one of the few known specific cellular partners of NCp7. HIV-1 mature nucleocapsid (NCp7) results from the maturation of the Gag precursor in the viral particle and is thus mostly abundant in the first phase of the infection which ends with the genomic viral DNA integration in the cell genome. Most if not all the nucleocapsid partners identified so far are not specific of the mature form. We described here the specific interaction in the nucleolus between NCp7 and the human nucleolar protein 12, a protein implicated in ribosomal RNA maturation and DNA damage response. This interaction takes place in the cell nucleolus, a subcellular compartment where NCp7 accumulates. The absence of binding between hNoL12 and Gag makes hNoL12 one of the few known specific cellular partners of NCp7.
Commentary on Viewpoint: Exercise and cardiovascular risk reduction: time to update the rationale for exercise?

TO THE EDITOR: We believe the recent Viewpoint article by Green et al. (1) to be a timely and important one. While the focus was primarily on direct effects on the vasculature, we wish to offer further comment on the central nervous system (CNS)’s role. A neural role in beneficial changes due to exercise training (ET) is not new, but is beginning to be elucidated as CNS neuroplastic changes (2). Our recent research demonstrated that sympathoexcitatory sites show changes consistent with the observed decrease in sympathoexcitation (SE) with ET and which are also consistent with the time course of ET and detraining (4). We caution that linkage between a decrease in dendritic arborizations in these areas and its ultimate expression in reducing SE has yet to be directly demonstrated. While cardiovascular risk in myocardial infarction was a principal focus of the article, another line of research which has shown that CNS changes appear to be important in a reduction of SE with ET is demonstrated by the work of Zucker et al. (5) in heart failure. Still another effect with an underlying reduction of SE is the central theme of the work by Billman et al. (2) that emphasizes that ET is a potent antiarrhythmic intervention. This aspect has a neural and, as shown in their recent report (2), a peripheral component. Probable linkage between the CNS and the periphery is clear and if other effector systems are any guide, possibly not all related to simple neural activity.
Critical test of the assumption that the hypothalamic entopeduncular nucleus of rodents is homologous with the primate internal pallidum

The globus pallidus (GP) of primates is divided conventionally into distinct internal and external parts. The literature repeats since 1930 the opinion that the homolog of the primate internal pallidum in rodents is the hypothalamic entopeduncular nucleus (embedded within fiber tracts of the cerebral peduncle). To test this idea, we explored its historic fundaments, checked the development and genoarchitecture of mouse entopeduncular and pallidal neurons, and examined relevant comparative connectivity data. We found that the extratelencephalic mouse entopeduncular structure consists of four different components arrayed along a dorsoventral sequence in the alar hypothalamus. The ventral entopeduncular nucleus (EPV), with GABAergic neurons expressing Dlx5&6 and Nkx2‐1, lies within the hypothalamic peduncular subparaventricular area. Three other formations—the dorsal entopeduncular nucleus (EPD), the prereticular entopeduncular nucleus (EPPRt), and the preeminential entopeduncular nucleus (EPPEm)—lie within the overlying paraventricular area, under the subpallium. EPD contains glutamatergic neurons expressing Tbr1, Otp, and Pax6. The EPPRt has GABAergic cells expressing Isl1 and Meis2, whereas the EPPEm population expresses Foxg1 and may be glutamatergic. Genoarchitectonic observations on relevant areas of the mouse pallidal/diagonal subpallium suggest that the GP of rodents is constituted as in primates by two adjacent but molecularly and hodologically differentiable telencephalic portions (both expressing Foxg1). These and other reported data oppose the notion that the rodent extratelencephalic entopeduncular nucleus is homologous to the primate internal pallidum. We suggest instead that all mammals, including rodents, have dual subpallial GP components, whereas primates probably also have a comparable set of hypothalamic entopeduncular nuclei. Remarkably, there is close similarity in some gene expression properties of the telencephalic internal GP and the hypothalamic EPV. This apparently underlies their notable functional analogy, sharing GABAergic neurons and thalamopetal connectivity.
Calcium Signaling in MR1-Dependent Antigen Presentation of Mycobacterium tuberculosis

MR1 is a ubiquitously expressed MHC-Ib molecule that presents microbial metabolites to MR1-restricted T cells, but there are differences in the antigen presentation pathway of an intracellular microbe compared to exogenous antigen. We have shown the importance of endosomal trafficking proteins in MR1-dependent presentation of Mycobacterium tuberculosis (Mtb). Two pore channels (TPCs) are endosomal calcium channels that regulate endosomal trafficking. Due to their location on endosomes, we hypothesized that TPCs could be required for MR1-dependent presentation of antigens derived from the intracellular microbe Mtb. We found that TPCs are critical for the presentation of Mtb by MR1; inhibition of TPCs had no effect on MR1 presentation of extracellular (exogenous) antigens, HLA-B presentation, or HLA-II presentation. Finally, we found that the calcium sensitive trafficking protein Synaptotagmin 7 was also key in the presentation of Mtb by MR1. This calcium-dependent endosomal pathway is a novel mechanism by which the immune system can sample intracellular antigens.
Subsurface petroleum geology of Santa Rosa Sandstone (Triassic), northeast New Mexico

The Santa Rosa Sandstone (Triassic) occurs at depths of less than 2,000 ft over most of northeast New Mexico. Although the Santa Rosa Sandstone is currently not producing, two major petroleum accumulations are known to exist in it. One accumulation is located approximately 6 mi north of Santa Rosa, where oil-impregnated Santa Rosa Sandstone crops out; these outcrops of oil-impregnated sandstone are known as the Santa Rosa tar sands. The oil in the tar sands is viscous and heavy. The Santa Rosa tar sands were mined in the 1930's for road-surfacing material, but presently are not being worked. The other known petroleum accumulation in the Santa Rosa Sandstone is a pool of heavy oil that occurs at depths of 400-800 ft in northeast Guadalupe County. Attempts are being made to recover the heavy oil with steamflooding in two small pilot fields, the O'Connell Ranch field and the T-4 Ranch field. In northeast New Mexico the Santa Rosa Sandstone is 67-350 ft thick. It rests on the Artesia Group (Permian) with angular unconformity and is subdivided into three regionally recognizable units: a lower sandstone unit 18-140 ft thick, a middle mudstone unit 0144 ft thick, and an upper sandstone unit 7-150 ft thick. The lower and upper sandstone units are blanket deposits composed mostly of fine- to medium-grained porous sandstones and minor red siliciclastic mudstones. The middle mudstone unit is a blanket deposit composed chiefly of red siliciclastic mudstones and minor lenticular sandstones. The lower and upper sandstone units were deposited by braided streams that flowed southeast toward a large Santa Rosa-age lake that was centered in west-central Texas. The middle mudstone unit is of lacustrine origin and was deposited during a high stand of the lake. Structures on the Santa Rosa Sandstone are mostly gentle northwest-to northeast-trending folds. The heavy oil in the tar-sand deposit at Santa Rosa Lake and the heavy oil near Newkirk both occur in the upper sandstone unit. Shows of asphaltic hydrocarbons have been encountered in the lower unit. Stratigraphic and petrographic studies indicate that good reservoirs are widespread in the lower and upper sandstone units in northeast New Mexico. The blanket geometry of the lower and upper sandstone units indicates that structure probably plays an important or even dominant role in the trapping of any undiscovered hydrocarbons in the Santa Rosa. Oil proximal to the outcrop belt of the Santa Rosa Sandstone has probably been flushed by recently recharged, fresh ground water. Although the source of the oil in Santa Rosa Sandstone is not definitely known, geochemical studies point to the San Andres Formation (Permian) or possibly Pennsylvanian rocks.
Hydroxytyrosol produced by engineered Escherichia coli strains activates Nrf2/HO-1 pathway: An in vitro and in vivo study

This study explores the biological effects of hydroxytyrosol (HT), produced by the metabolic engineering of Escherichia coli, in a series of in vitro and in vivo experiments. In particular, a metabolically engineered Escherichia coli strain capable of producing HT was constructed and utilized. HEK293 and HeLa cells were exposed to purified HT to determine non-toxic doses that can offer protection against oxidative stress (activation of Nrf2/HO-1 signaling pathway). Male CD-1 mice were orally supplemented with HT to evaluate (1) renal and hepatic toxicity, (2) endogenous system antioxidant response, and (3) activation of Nrf2/HO-1 system in the liver. HT protected cells from oxidative stress through the activation of Nrf2 regulatory network. Activation of Nrf2 signaling pathway was also observed in the hepatic tissue of the mice. HT supplementation was safe and produced differential effects on mice’s endogenous antioxidant defense system. HT biosynthesized from genetically modified Escherichia coli strains is an alternative method to produce high-quality HT that exerts favorable effects in the regulation of the organism’s response to oxidative stress. Nonetheless, further investigation of the multifactorial action of HT on the antioxidant network regulation is needed.
Effect of Hydroxyurea Therapy on Growth Parameters in Older Children (6-15 Year-Old) with Sickle Cell Disease: Low Dose Versus High Dose

Abstract Growth impairment is a known complication of sickle cell disease (SCD). Few studies explored the potential effects of hydroxyurea (HU) on growth in children with SCD in relation to HU dose and response. This is a prospective study conducted at Sultan Qaboos University Hospital, Oman, and included 91 SCD patients with age below 16 years when started on HU, aiming to explore the potential effect/s of HU on growth parameters of older children with SCD in relation to their clinical improvement and the dose required for this improvement. Weight, height, and body mass index (BMI) were collected at baseline, 6 and 18 months after initiation. Anthropometric data were compared to WHO standards. Initial height and BMI Z scores (HAZ and WAZ) were lower compared to WHO norms. HAZ and WAZ did not change significantly after 6 and 18 months on HU therapy. However, BMI Z-scores improved significantly after 6 and 18 months of follow-up (p value 0.044 and 0.028 respectively). No significant changes were observed in WAZ or HAZ among patients on low dose versus those on high dose. BMI Z score improved significantly after 18 months of low dose group (p = 0.014) but did not change in those on high dose HU. In conclusion, HU therapy did not adversely affect weight and height growth in older children with SCD. BMI Z scores improved at 18 months in patients on low dose but not in those on high dose (p = 0.014).
Recent developments in the pathology of primary pulmonary salivary gland‐type tumours

Primary pulmonary salivary gland‐type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland‐type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial‐myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland‐type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland‐type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type‐tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high‐grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland‐type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland‐type tumours of the lung and those primary to other sites.
Potential impact of mesenchymal stem cells on nephrotoxicity induced by gamma irradiation and antiepileptic drugs cotherapy in rats

The goal of this study was to assess the influence of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) on the nephrotoxicity induced by fractionated doses of gamma irradiation (Rad) and the cotherapy of levetiracetam and oxcarbazepine in male rats. Adult rats were randomly divided into four groups. Group I: Control, Group II: antiepileptic drugs (AEDs), Group III: AEDs +Rad and Group IV: AEDs + Rad + MSCs. Rats treated with AEDs and exposed to fractionated doses of γ‐irradiation displayed a discernible increase in serum urea, creatinine, kidney injury marker, kidney malondialdehyde, transforming growth factor beta (TGF‐β) and the relative expression of Smad3 along with a decrease in the relative expression of Smad7 and glutathione level. Alternatively, groups treated with BM‐MSCs with AEDs and Rad showed a substantial modification in the majority of the evaluated parameters and looked to be successful in reducing the hazards of the combination therapy of AEDs and radiation. The reno‐histopathological study supports the biochemical analysis. In conclusion, BM‐MSCs exhibited therapeutic potential against nephrotoxicity induced by fractionated doses of γ‐irradiation and AEDs. The outcome was brought about by the downregulation of the TGF‐β/Smad pathway. BM‐MSCs might be suggested as a valuable therapeutic strategy to overcome kidney injury induced by gamma irradiation during AEDs cotherapy.
Contrast-enhanced and conventional ultrasound images of renal wounds after partial nephrectomy.

OBJECTIVES To observe the features of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) images of renal wounds after minimally-invasive partial nephrectomy (MIPN) and evaluate their severity using these two modalities. METHODS This prospective, observational study included 120 patients who underwent MIPN from April to December 2019 in our hospital. The postoperative US images were evaluated and classified, and contrast extravasation characteristics of CEUS were recorded. The correlation between the classification system and perioperative factors was analyzed. RESULTS Eighty-five patients underwent US and CEUS after MIPN. Conventional US images were classified into three grades according to the surface morphology of renal wounds and overall shape of the kidney around the incision. Univariable and multivariable analyses indicated that the N component of the R.E. N.A. L. score and the resection range were preoperative and intraoperative factors, respectively, related to the US image grades (UIGs). A deep location and expanded excision contributed to an increased UIG. The extravasation rate increased with the UIG (Spearman correlation rho=0.247, P=0.022), and a higher UIG prolonged the length of extravasation. The depth of the tumor and resection range were related to the UIG. CONCLUSIONS US and CEUS were feasible and repeatable methods that reflect the morphologic changes of renal wounds after MIPN and may be useful for evaluating their severity.