bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric conduit reconstruction after esophagectomy
Authors: Watanabe Masayuki , Takahashi Naoki , Tamura Masahiro , Terayama Masayoshi , Kuriyama Kengo , Okamura Akihiko , Kanamori Jun , Imamura Yu
Published: May 2024

A high risk of complications still accompanies gastric conduit reconstruction after esophagectomy. In this narrative review, we summarize the technological progress and the problems of gastric conduit reconstruction after esophagectomy. Several types of gastric conduits exist, including the whole stomach and the narrow gastric tube. The clinical outcomes are similar between the two types of conduits. Sufficient blood supply to the conduit is mandatory for a successful esophageal reconstruction. Recently, due to the availability of equipment and its convenience, indocyanine green angiography has been rapidly spreading. When the blood perfusion of the planning anastomotic site is insufficient, several techniques, such as the Kocher maneuver, pedunculated gastric tube with duodenal transection, and additional microvascular anastomosis, exist to decrease the risk of anastomotic failure. There are two different anastomotic sites, cervical and thoracic, and mainly two reconstructive routes, retrosternal and posterior mediastinal routes. Meta-analyses showed no significant difference in outcomes between the anastomotic sites as well as the reconstructive routes. Anastomotic techniques include hand-sewn, circular, and linear stapling. Anastomoses using linear stapling is advantageous in decreasing anastomosis-related complications. Arteriosclerosis and poorly controlled diabetes are the risk factors for anastomotic leakage, while a narrow upper mediastinal space and a damaged stomach predict leakage. Although standardization among the institutional team members is essential to decrease anastomotic complications, surgeons should learn several technical options for predictable or unpredictable intraoperative situations.
Effects of bark beetle disturbance and fuel types on fire radiative power and burn severity in the Bohemian-Saxon Switzerland
Authors: Beetz Kristina , Marrs Christopher , Busse Annika , Poděbradská Markéta , Kinalczyk Daniel , Kranz Johanna , Forkel Matthias
Published: May 2024

Until recently, forest fires were considered a rare phenomenon in the temperate forests of Central Europe because of the moderate summer temperatures and the humid climate. However, many of those forests (monocultures of Picea abies, Norway Spruce) were affected by bark beetle infestations in the past years and recent fires such as that in the Bohemian-Saxon Switzerland in 2022 raised widespread debates about the effects of forest mortality on fuel accumulation and hence fire occurrence and severity. Here, we aim to investigate the association of fire radiative power (FRP) and burn severity with fuel types during the fire in Bohemian-Saxon Switzerland in 2022. We enhanced a European fuel type classification with a class for dead and dying spruce and mapped pre-fire fuel types using data on habitats, tree species, bark beetle disturbances and tree coverage. FRP was derived from observations of the Visible and Infrared Radiometer Suite (VIIRS) sensors. Burn severity was quantified by the differenced normalized burn ratio (dNBR) through pre- and postfire Landsat 8, 9, and Sentinel-2 images and was assessed in the field using the Composite Burn Index (CBI). We found the highest FRP at sites with dead spruce forests. Burn severity was moderate with high variability across all fuel types but highest severities occurred in dead spruce stands. The dNBR correlated positively with char height and the presence of torched trees (R = 0.48, P < .05), especially in dead spruce stands, likely due to the large amount of dry fine woody debris and the presence of initial natural regeneration. Our results demonstrate that surface fuel accumulation from past bark beetle disturbances resulted in more intense fires (higher FRP, char height and torching) and higher burn severity. The results highlight the need for improved cross-border fire risk management in Central European temperate forests that were previously not considered as fire-prone.
The Locative Function of Situated Art
Authors: Wilder Ken
Published: May 2024

This article proposes a locative function as a defining feature of situated art. All artworks orient their beholders, but situated art is characterized by this context-sensitive orientation entering the work’s content. In so doing, it facilitates ‘here’- and ‘now’-thoughts, not only towards the “real” situation encountered (the work’s outer orientation) but to the work’s “virtual” or “bracketed” realm (its inner orientation). These orientations overlap, but do not necessarily align; indeed, situated works often construct a tension through a deliberate miscalibration of these orientations. But what is the mechanism by which such works afford indexical thought towards their worlds? Drawing upon Gareth Evans’s account of demonstrative content, I contend that sensory imagination—conceived in Evans’s terms as an additional conceptual component—plays a necessary role in negotiating demonstrative thought towards two (or more) separate spaces conceived as “here.” This is something the beholder brings to the work.
Behaviour of Machine Learning algorithms in the classification of energy consumption in school buildings
Authors: Machado José , Chaves António , Montenegro Larissa , Alves Carlos , Durães Dalila , Machado Ricardo , Novais Paulo
Published: May 2024

The significance of energy efficiency in the development of smart cities cannot be overstated. It is essential to have a clear understanding of the current energy consumption (EC) patterns in both public and private buildings. One way to achieve this is by employing machine learning classification algorithms, which offer a broader perspective on the factors influencing EC. These algorithms can be applied to real data from databases, making them valuable tools for smart city applications. In this paper, our focus is specifically on the EC of public schools in a Portuguese city, as this plays a crucial role in designing a Smart City. By utilizing a comprehensive dataset on school EC, we thoroughly evaluate multiple ML algorithms. The objective is to identify the most effective algorithm for classifying average EC patterns. The outcomes of this study hold significant value for school administrators and facility managers. By leveraging the predictions generated from the selected algorithm, they can optimize energy usage and, consequently, reduce costs. The use of a comprehensive dataset ensures the reliability and accuracy of our evaluations of various ML algorithms for EC classification.
An unusual case of gallstone ileus 35 years post-cholecystectomy masked by an incisional hernia
Authors: Gordon Christian I , Molina Gabriel A , Diaz Johann S , Mancero Maria B , Heredia Andrea E , Parrales Diana E , Larco Jesus N
Published: May 2024

Gallstone ileus is an uncommon cause of mechanical bowel obstruction in patients with cholecystitis and gallstones who develop a fistula over time. In the post-cholecystectomy patient, the presence of gallstone ileus is extremely rare; these patients have different pathophysiological pathways, such as a spilled gallstone that subsequently erodes into the bowel, subtotal cholecystectomies, and diverticulae that can hold a gallstone for hidden several years. In these patients, the clinical presentations are unique because of their rarity and because the gallbladder had been previously removed. A high index of suspicion by the medical team is needed for diagnosis. We present the case of an 85-year-old male who had a history of cholecystectomy 35 years ago. He presented to the emergency department with intestinal obstruction. Since he had a hernia, it was thought to be the cause of the obstruction; however, during surgery, we were surprised to find a gallstone ileus. After surgery, he fully recovered.
Persistent pneumothorax after laparoscopic appendectomy in a patient who had undergone radical esophagectomy 5 years before: possible relationship with vulnerability of the hiatus after esophagectomy: a case report
Authors: Ishikawa Seiji , Hayashida Masakazu , Satoh Daizo , Mine Shinji , Kawagoe Izumi
Published: May 2024

Postoperative pneumothorax is a well-known but relatively rare complication after laparoscopic surgery. Herein, we report a case of persistent pneumothorax after laparoscopic appendectomy. A 57-year-old male, with a history of minimally invasive esophagectomy and intrathoracic gastric tube reconstruction 5 years before, underwent a laparoscopic appendectomy. A chest X-ray taken on postoperative Day 1 revealed the development of the right pneumothorax, which took more than 3 days to resolve spontaneously. Although the mechanism of postoperative pneumothorax was unclear, it seemed likely that the air that had replaced carbon dioxide in the peritoneal cavity migrated into the thoracic cavity through the esophageal hiatus, which was not covered by the peritoneum or pleura after surgical resection. The present case, together with our previous similar case, suggests that a history of esophageal cancer surgery per se increases the risk of pneumothorax after laparoscopic surgery, probably regardless of when this was performed.
Right paraduodenal hernia presenting with strangulated obstruction with intestinal malrotation: a case report
Authors: Tanaka Hideharu , Mitsutomoe Saki , Nagao Narutoshi , Komori Shuji , Suetsugu Tomonari , Iwata Yoshinori , Watanabe Taku , Tanaka Chihiro , Kawai Masahiko
Published: May 2024

A paraduodenal hernia is a rare cause of an internal hernia that may require massive bowel resection; prompt diagnosis and surgical treatment are essential. In cases of malrotation, strangulation may occur both inside and outside the hernial sac. Strangulation outside the hernial sac makes the preoperative diagnosis more difficult. Herein, we report a patient with a right paraduodenal hernia, intestinal malrotation, and strangulation outside the hernia. An 86-year-old woman was admitted to our hospital with abdominal pain. Enhanced computed tomography showed a closed-loop obstruction of the hypo-enhancing small bowel and absence of a horizontal duodenal leg. The patient underwent an emergency laparotomy and was diagnosed with strangulated bowel obstruction due to a right paraduodenal hernia and malrotation. The patient underwent resection of the ischemic ileum, closure of the hernial orifice, and repositioning of the intestine. The postoperative course was uneventful. The patient reported no abdominal discomfort after 7 months of follow-up.
An idiopathic severe macroglossia in a young adult patient: a rare case
Authors: Al Hariri Bassem , Hassan Muad Abdi , Sharif Muhammad , Mohamed Rawan S , Alsidig Hadil Altaj Altrify , Alsiddig Hind Altag Alteraify , Illahi Memon Noor
Published: May 2024

Macroglossia, an uncommon anatomical anomaly, can manifest as either congenital or acquired. The size of the tongue undergoes variations with age, peaking at 8 years and reaching full maturity at 18 years. Congenital macroglossia stems from diverse conditions, such as muscular hypertrophy, hemangioma, lymphangioma, Down syndrome, and others. Acquired macroglossia can result from malignancies, endocrine and metabolic disorders, chronic infectious diseases, and head and neck infections, among other factors. Additionally, extended-prone surgery can lead to its development. The incidence of macroglossia is likely underreported. This presentation is rare with only six reported cases in the literature.
A rare case of perforated Meckle’s diverticulitis: a case report
Authors: Carlaw Kirsten R , Liyanage Chandika
Published: May 2024

Meckle’s diverticulum is the most common embryological anomaly of the small bowel that is rarely seen in adults. It is caused by the incomplete closure of the vitelline or omphalomesenteric duct. Those who are symptomatic from Meckle’s diverticulum have varied clinical presentations, which raise significant challenges with diagnostic and management options. We report a case of a 47-year-old male who presented to the hospital with clinical signs of appendicitis but was found to have perforated Meckle’s diverticulitis with faecoliths on computed tomography imaging and laparoscopy. Furthermore, histopathology revealed an ectopic gastric tissue cell type, which is a rare finding. This was definitively managed surgically with laparoscopic resection of Meckle’s diverticulum and appendicectomy.
Bilateral tinnitus associated with a diffuse astrocytoma of Heschl’s gyrus: a case report and review of literature
Authors: Aboulhosn Rabii , Bodkin Peter
Published: May 2024

Auditory processing is initiated within the primary auditory cortex, concealed within the sylvian fissure bilaterally on a collection of gyri described as Heschl’s Gyrus (HG). Glial neoplasms localized to or involving HG are rare. The main symptoms of these tumours are complex partial seizures characterized by auditory features. Here, we describe an unusual case of bilateral tinnitus and hemi-paraesthesia associated with a HG diffuse astrocytoma. Bilateral tinnitus secondary to intrinsic brain tumours is atypical. Bilateral tinnitus is frequently observed in patients with noise-induced hearing loss, presbycusis, ototoxic medication, and metabolic and psychiatric disease. In the case we present, the synchronous sensory and auditory symptoms are likely due to seizure activity affecting the primary auditory and somatosensory cortex. In a patient presenting with chronic, bilateral tinnitus with no known underlying otologic disease which is associated with hemi-body paraesthesia, we would advocate for consideration of brain imaging to exclude pathology in HG.
A ruptured mesenteric lymphangioma causing peritonitis: a case report
Authors: Kharkhach Ayoub , Rhoul Chafik , Police Andrea , Mabilia Andrea
Published: May 2024

Cystic lymphangioma is a rare disease that is mainly diagnosed in childhood. When diagnosed, the lesion presents an indication for surgery due to the risk of serious complications. Herein, we report the case of a 32-year-old patient who presented to the emergency room for abdominal pain that developed 2 days before with worsening symptoms and abdominal pain in the last 24 hr. The computed tomography showed diffuse wall thickening of the jejunum and proximal ileum with mesenteric fat infiltration, a mesenteric collection, and a moderate volume of ascites extending into the pelvis. A laparotomy was performed, revealing diffuse chemical peritonitis with a crater-like lesion in the jejunal mesentery, secreting lymphatic fluid. The mesenteric lesion was then excised, and the histological examination showed a ruptured cystic lymphangioma. Lymphangiomas of the small bowel mesentery are rare and may be exceptionally associated with bowel occlusion or peritonitis.
Comprehensive genomic profiling of pediatric peritoneal mesothelioma: case report with a literature review
Authors: Redzepagic Jasmina , Zvizdic Zlatan , Bilalovic Nurija , Milisic Emir , Bukvic Melika , Vranic Semir
Published: May 2024

Malignant peritoneal mesothelioma is an extremely rare and poorly recognized neoplasm in children. A 5-year-old boy presented with a 1-year history of progressive painless abdominal distension. A CT revealed a 19 × 19 × 11 cm3 cystic mass in the right hemiabdomen, without infiltrating the surrounding structures. The tumor was completely removed by surgery. The microscopic and immunohistochemical analyses confirmed peritoneal mesothelioma. Comprehensive genomic profiling revealed no major driving mutations including BAP1, no fusions, but with amplifications of AURKA, AURKC, HLA-1B, ZNF-217, OR5F1 and MEN1 genes. Imaging follow-up 3 months after surgery revealed metastatic disease. The patient died of pneumonia at another hospital shortly after the last follow-up examination at our institution. Pediatric peritoneal mesothelioma is an extremely rare malignancy with limited targeted options and a poor prognosis. Some of the identified molecular genomic biomarkers require further exploration and validation in this cancer.
Amyand’s hernia repair in an asymptomatic patient—a case report and a review of the literature
Authors: Smyrlis Nikolaos V , Mouratidis Stylianos Vladimiros P , Makedos Panagiotis I , Georgakis Konstantinos S
Published: May 2024

Amyand’s hernia is a rare condition, in which the appendix is found in the inguinal hernia sac. Many patients remain asymptomatic and this pathological condition is most commonly diagnosed intraoperatively. We report a case of a 66-year-old male who was admitted to the hospital for an inguinal hernia repair and the presence of the appendix in the inguinal hernia sac was discovered intraoperatively. We performed a reduction of the appendix in the abdominal cavity and a hernia repair with a mesh and a plug. There are few studies in literature about the appropriate method of treatment and, because of that, the therapeutic approach remains controversial. Therefore, we also conducted a review of the literature in order to obtain some conclusions regarding the management of Amyand’s hernia.
Neutropenic Sepsis in the Intensive Care Unit: Differences in Clinical Profile and Outcomes According to the Cause of Neutropenia
Authors: MacPhail Aleece , Dendle Claire , Slavin Monica , Weinkove Robert , Bailey Michael , Pilcher David , McQuilten Zoe
Published: May 2024

Background

Neutropenic sepsis frequently requires admission to an intensive care unit (ICU). Differences between subgroups of patients with neutropenic sepsis are not well characterized.

Aims

To investigate clinical outcomes among patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis.

Methods

Retrospective cohort study of all patients admitted to ICU in Australia or New Zealand between January 2000 and December 2022 with a primary admission diagnosis of sepsis and total white cell count <1.0 × 109 cells/L.

Results

We identified 8617 ICU admissions with neutropenic sepsis (hematological malignancy n = 4660; metastatic solid cancer n = 1034; no cancer n = 2800). Patients with hematological malignancy were younger (median, 61.5 years) with low rates of chronic comorbidities (4.7%) and were usually admitted to ICU from the ward (67.4%). Mechanical ventilation rates were 20.2% and in-hospital mortality was 30.6%. Patients with metastatic solid cancers were older (median, 66.3 years), with higher rates of chronic comorbidities (9.9%), and were usually admitted to the ICU from the emergency department (50.8%). Mechanical ventilation rates were 16.9% and in-hospital mortality was 42.4%. Patients with no documented cancer had highest rates of mechanical ventilation (41.7%) and mortality (46.3%). Neutropenia was independently associated with mortality among patients with solid cancers or no cancer but did not confer increased risk among patients with hematological malignancy (odds ratio, 0.98; 95% confidence interval, .90–1.06; P = .60).

Conclusions

Patients with neutropenic sepsis and hematological malignancy, metastatic solid cancer, or no cancer diagnosis constitute 3 distinct clinical groups. Management approaches should be tailored accordingly.
Learning to learn: Single session acquisition of new rules by freely moving mice
Authors: Levi Amir , Aviv Noam , Stark Eran
Published: May 2024

Learning from examples and adapting to new circumstances are fundamental attributes of human cognition. However, it is unclear what conditions allow for fast and successful learning, especially in nonhuman subjects. To determine how rapidly freely moving mice can learn a new discrimination criterion (DC), we design a two-alternative forced-choice visual discrimination paradigm in which the DCs governing the task can change between sessions. We find that experienced animals can learn a new DC after being exposed to only five training and three testing trials. The propensity for single session learning improves over time and is accurately predicted based on animal experience and criterion difficulty. After establishing the procedural learning of a paradigm, mice continuously improve their performance in new circumstances. Thus, mice learn to learn.
Impact of the 2022 African Cup of Nations mass-gathering event on the COVID-19 epidemic in Garoua, Cameroon
Authors: Berland Jean-Luc , Njifon Hermann , Westeel Emilie , Moumbeket Henri , Komurian-Pradel Florence , Ilouga Pauliana , Njouom Richard , Perraut Ronald
Published: May 2024

Background

The 2022 African Cup of Nations (AFCON) took place in Cameroon from January 9th to February 5th, 2022, including Garoua in the north. We aimed to measure the impact of this event on the local COVID-19 epidemic given the implementation of a preventive strategy based on a health pass.

Methods

All players, staff and fans involved in the AFCON event were screened with PCR tests. Symptomatic cases were also continuously monitored in the general population and screened for variants of concern. Daily numbers of confirmed cases were compared to neighboring countries numbers retrieved from a public domain source.

Results

In total, 1479 and 2481 tests were performed in the general population and on asymptomatic AFCON attendees, respectively. From the latter, 12.5% were PCR-positive; 97% were infected with Omicron, with no significant difference compared to the passive program (G-test, P value = 0.162). Surveillance indicated the AFCON did not increase the number of symptomatic PCR-positive cases in the general population compared to neighboring countries.

Conclusions

Though the COVID-19 epidemic was fueled by asymptomatic cases infected with the Omicron variant at the time, the non-therapeutic preventive measures implemented for AFCON mitigated an increase in the epidemic in the local population.
Arbutin abrogates cisplatin-induced hepatotoxicity via upregulating Nrf2/HO-1 and suppressing genotoxicity, NF-κB/iNOS/TNF-α and caspase-3/Bax/Bcl2 signaling pathways in rats
Authors: Okkay Irmak Ferah , Famurewa Ademola , Bayram Cemil , Okkay Ufuk , Mendil Ali Sefa , Sezen Selma , Ayaz Teslime , Gecili Ibrahim , Ozkaraca Mustafa , Senyayla Selcuk , Hacimuftuoglu Ahmet
Published: May 2024

Background: Cisplatin is a potent anticancer agent widely employed in chemotherapy. However, cisplatin leads to toxicity on non-targeted healthy organs, including the liver. We investigated the hepatoprotective mechanism of arbutin (ARB), a glycosylated hydroquinone, against cisplatin-induced hepatotoxicity. Methods: Rats were orally administered with ARB (ARB1 = 50 mg/kg; ARB2 = 100 mg/kg) for 14 consecutive days against hepatotoxicity induced by a single dose of cisplatin (10 mg/kg) on day 15. Three days after the intraperitoneal cisplatin injection, serum and liver tissue were collected for subsequent analyses. Results: Cisplatin triggered marked increases in serum AST, ALT, and ALP activities, hepatic malondialdehyde (MDA) and reactive oxygen species (ROS) coupled with a considerable diminution in hepatic activities of superoxide dismutase (SOD), catalase (CAT) and the concentration of reduced glutathione (GSH). The gene expressions of interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and IL-6 were notably increased. The pre-administration of ARB1 and ARB2 reduced AST, ALT and ALP in serum and restored SOD, CAT, GSH, ROS, MDA and cytokine levels which was also evidenced by alleviated hepatic lesions. Further, cisplatin-induced prominent alterations in the gene expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), iNOS, NF-κB, Bax, Bcl-2, caspase-3 and 8-OHdG in the liver. Interestingly, ARB protected the liver and mitigated the cisplatin-induced alterations in serum AST, ALT, ALP, and reduced hepatic redox markers, 8-OdG, inflammatory markers and gene expressions. Conclusion: The findings demonstrate that ARB is a potential protective adjuvant against cisplatin-induced hepatotoxicity via inhibition of hepatic oxidative stress, inflammation, and apoptosis.
Enhancing Gene Expression Representation and Drug Response Prediction with Data Augmentation and Gene Emphasis
Authors: Lu Diyuan , Pamar Daksh P.S. , Ohnmacht Alex J. , Kutkaite Ginte , Menden Michael P.
Published: May 2024

Representation learning for tumor gene expression (GEx) data with deep neural networks is limited by the large gene feature space and the scarcity of available clinical and preclinical data. The translation of the learned representation between these data sources is further hindered by inherent molecular differences. To address these challenges, we propose GExMix (GeneExpressionMixup), a data augmentation method, which extends the Mixup concept to generate training samples accounting for the imbalance in both data classes and data sources. We leverage the GExMix-augmented training set in encoder-decoder models to learn a GEx latent representation. Subsequently, we combine the learned representation with drug chemical features in a dual-objective enhanced gene-centric drug response prediction, i.e., reconstruction of GEx latent embeddings and drug response classification. This dual-objective design strategically prioritizes gene-centric information to enhance the final drug response prediction. We demonstrate that augmenting training samples improves the GEx representation, benefiting the gene-centric drug response prediction model. Our findings underscore the effectiveness of our proposed GExMix in enriching GEx data for deep neural networks. Moreover, our proposed gene-centricity further improves drug response prediction when translating preclinical to clinical datasets. This highlights the untapped potential of the proposed framework for GEx data analysis, paving the way toward precision medicine.
CPT2 mediated fatty acid oxidation is dispensable for humoral immunity
Authors: Li Meilu , Zhou Xian , Zhu Xingxing , Li Yanfeng , Hitosugi Taro , Li Yuzhen , Zeng Hu
Published: May 2024

B cell activation is accompanied by dynamic metabolic reprogramming, supported by a multitude of nutrients that include glucose, amino acids and fatty acids. While several studies have indicated that fatty acid mitochondrial oxidation is critical for immune cell functions, contradictory findings have been reported. Carnitine palmitoyltransferase II (CPT2) is a critical enzyme for long-chain fatty acid oxidation in mitochondria. Here, we test the requirement of CPT2 for humoral immunity using a mouse model with a lymphocyte specific deletion of CPT2. Stable13C isotope tracing reveals highly reduced fatty acid-derived citrate production in CPT2 deficient B cells. Yet, CPT2 deficiency has no significant impact on B cell development, B cell activation, germinal center formation, and antibody production upon either thymus-dependent or –independent antigen challenges. Together, our findings indicate that CPT2 mediated fatty acid oxidation is dispensable for humoral immunity, highlighting the metabolic flexibility of lymphocytes.
XistDeletion in B Cells Results in Systemic Lupus Erythematosus Phenotypes
Authors: Lovell Claudia D. , Jiwrajka Nikhil , Amerman Hayley K. , Cancro Michael P. , Anguera Montserrat C.
Published: May 2024

Systemic lupus erythematosus (SLE) is an autoimmune disease preferentially observed in females. X-linked gene expression in XX females is normalized to that of XY males by X-Chromosome Inactivation (XCI). However, B cells from female SLE patients and mouse models of SLE exhibit mislocalization of Xist RNA, a critical regulator of XCI, and aberrant expression of X-linked genes, suggesting that impairment of XCI may contribute to disease. Here, we find that a subset of female mice harboring a conditional deletion ofXist in B cells (“Xist cKO”) spontaneously develop SLE phenotypes, including expanded activated B cell subsets, disease-specific autoantibodies, and glomerulonephritis. Moreover, pristane-induced SLE-like disease is more severe in Xist cKO mice. Activated B cells from Xist cKO mice with SLE phenotypes have increased expression of proinflammatory X-linked genes implicated in SLE. Together, this work indicates that impaired XCI maintenance in B cells directly contributes to the female-bias of SLE.
Single-cell phylodynamic inference of tissue development and tumor evolution with scPhyloX
Authors: Wang Kun , Lu Zhaolian , Yao Zeqi , He Xionglei , Hu Zheng , Zhou Da
Published: May 2024

Phylodynamics inference (PI) is a powerful approach for quantifying population dynamics and evolutionary trajectories of natural species based on phylogenetic trees. The emergence of single-cell lineage tracing technologies now enables the reconstruction of phylogenetic trees for thousands of individual cells within a multicellular organism, opening avenues for employing PI methodologies at the cellular level. However, the intricate process of cell differentiation poses challenges for directly applying current PI frameworks in somatic tissues. Here, we introduce a novel computational approach called single-cell phylodynamic explorer (scPhyloX), designed to model structured cell populations in various cell states, by leveraging single-cell phylogenetic trees to infer dynamics of tissue development and tumor evolution. Our comprehensive simulations demonstrate the high accuracy of scPhyloX across various biological scenarios. Application of scPhyloX to three real datasets of single-cell lineage tracing unveils novel insights into somatic dynamics, such as the overshoot of cycling stem cell populations in fly organ development, clonal expansion of multipotent progenitors of hematopoiesis during human aging, and pronounced subclonal selection in early colorectal tumorigenesis. Thus, scPhyloX is an innovative computational method for investigating the development and evolution of somatic tissues.
The cornerstone of early diagnosis and immunotherapy of prostate cancer:screening characteristic genes
Authors: Shao Bo , Wu Kaixiu , Wan Shui , Sun Pingping , Zuo Yanggen , Xiao Li , Pi Jinbo , Fan Zhengkai , Han Zhongxiong
Published: May 2024

Background

Prostate cancer (PCA) has become a common malignant tumor globally, posing a substantial risk to the health of middle-aged and elderly men. However, there is still a lack of effective strategies for early detection and treatment of prostate cancer. The introduction of gene therapy in recent years has shown promise as a potential approach for cancer diagnosis and treatment.

Methodology & Theoretical Orientation

The training set data GSE45016, GSE46602, and GSE69223 from the Gene Expression Omnibus (GEO) dataset, along with validation training set data GSE17951, were utilized. Differentially expressed genes (DEGs) between normal individuals and tumor patients were identified by combining the training set data. Subsequent analyses including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were conducted on the DEGs. WGCNA analysis was then performed on the gene expression matrix to identify module genes highly correlated with PCA, followed by the application of the LASSO algorithm to obtain PCA candidate genes. The candidate genes were validated using the area under the receiver operating characteristic (ROC) curve (AUC) to determine key feature genes. Finally, the relationship between key characteristic genes and immune cells was explored.

Findings

A total of 54 DEGs were identified, with 26 down-regulated genes and 28 up-regulated genes. The GO function analysis revealed enrichment in processes such as ‘establishment of protein localization to membrane’ and ‘protein targeting to membrane’. KEGG analysis showed enrichment in pathways like ‘eutrophil degranulation’, ‘neutrophil activation involved in immune response’, and ‘regulation of cell morphogenesis’. GSEA analysis highlighted enrichment in pathways like ‘CTRL_VS_ACT_IL4 AND ANTI_IL12_12H_CD4_TCELL_DN’. Through WGCNA and LASSO regression analysis, key characteristic genes MARCKSL1, TMTC4, and TTLL12 were identified, with AUC values greater than 0.8 in both the training and validation sets, and were found to be closely associated with immune cell infiltration.

Conclusion & Significance

MARCKSL1, TMTC4, and TTLL12 emerge as crucial genes in the process of PCA, showing significant relevance to immune cell infiltration.this study offers valuable clinical insights into the diagnosis and treatment of prostate cancer through the identification of specific genes associated with the disease.
Frequencies of house fly proto-Y chromosomes across populations are predicted by temperature heterogeneity within populations
Authors: Foy Patrick D. , Loetzerich Sara R. , Boxler David , Burgess Edwin R. , Trout Fryxell R. T. , Gerry Alec C. , Hinkle Nancy C. , Machtinger Erika T. , Olds Cassandra , Tarone Aaron M. , Watson Wes , Scott Jeffrey G. , Meisel Richard P.
Published: May 2024

Sex chromosomes often differ between closely related species and can even be polymorphic within populations. Species with polygenic sex determination segregate for multiple different sex determining loci within populations, making them uniquely informative of the selection pressures that drive the evolution of sex chromosomes. The house fly (Musca domestica) is a model species for studying polygenic sex determination because male determining genes have been identified on all six of the chromosomes, which means that any chromosome can be a “proto-Y” chromosome. In addition, chromosome IV can carry a female-determining locus, making it a W chromosome. The different proto-Y chromosomes are distributed along latitudinal clines on multiple continents, their distributions can be explained by seasonality in temperature, and they have temperature-dependent effects on physiological and behavioral traits. It is not clear, however, how the clinal distributions interact with the effect of seasonality on the frequencies of house fly proto-Y chromosomes across populations. To address this question, we measured the frequencies of house fly Y and W chromosomes across nine populations in the United States of America. We confirmed the clinal distribution along the eastern coast of North America, but it is limited to the eastern coast. In contrast, annual mean daily temperature range is significantly correlated with proto-Y chromosome frequencies across the entire continent. Our results therefore suggest that temperature heterogeneity can explain the distributions of house fly proto-Y chromosomes in a way that does not depend on the cline. These results contribute to our understanding of how ecological factors affect sex chromosome evolution.
mosGraphGen: a novel tool to generate multi-omics signaling graphs to facilitate integrative and interpretable graph AI model development
Authors: Zhang Heming , Cao Dekang , Chen Zirui , Zhang Xiuyuan , Chen Yixin , Sessions Cole , Cruchaga Carlos , Payne Philip , Li Guangfu , Province Michael , Li Fuhai
Published: May 2024

Multi-omics data, i.e., genomics, epigenomics, transcriptomics, proteomics, characterize cellular complex signaling systems from multi-level and multi-view and provide a holistic view of complex cellular signaling pathways. However, it remains challenging to integrate and interpret multi-omics data for mining key disease targets and signaling pathways. Graph AI models have been widely used to analyze graph-structure datasets, and are ideal for integrative multi-omics data analysis because they can naturally integrate and represent multi-omics data as a biologically meaningful multi-level signaling graph and interpret multi-omics data via graph node and edge ranking analysis. However, it is non-trivial for graph-AI model developers to pre-analyze multi-omics data and convert the data into biologically meaningful graphs, which can be directly fed into graph-AI models. To resolve this challenge, we developedmosGraphGen(multi-omics signaling graph generator), generating Multi-omics Signaling graphs (mos-graph) of individual samples by mapping multi-omics data onto a biologically meaningful multi-level background signaling network with data normalization by aggregating measurements and aligning to the reference genome. With mosGraphGen, AI model developers can directly apply and evaluate their models using these mos-graphs. In the results, mosGraphGen was used and illustrated using two widely used multi-omics datasets of TCGA and Alzheimer’s disease (AD) samples. The code of mosGraphGen is open-source and publicly available via GitHub:https://github.com/FuhaiLiAiLab/mosGraphGen
Exploring the dynamic ticks-camel-pathogens interaction
Authors: Makwatta JohnMark O. , Ndegwa Paul N. , Oyieke Florence A. , Ahuya Peter , Masiga Daniel K. , Getahun Merid N.
Published: May 2024

The ability of ticks to interact and adapt to different ecologies and hosts determines their vectorial competence for various pathogens, however ticks-livestock-pathogens interaction studies are limited. With our ticks-hosts-pathogens interface studies, we found 14 species of ticks feeding on various livestock. Ticks showed a strong preference for one-humped camels (Camelus dromedarius). The camel nostril was the most preferred predilection site. The most prevalent tick species on camels wasHyalomma rufipes. We found two novelAmblyomma gemmavariants which are distinct both morphologically and genetically from previously describedAmblyomma gemma. The signature odors from camel breath and body were attractive toH. rufipes; demonstrating ticks utilize camel-derived metabolites to find their host. Our research shows thatH. rufipesand camel hosts have unique and shared pathogens showingH. rufipes’ vector and camel’s reservoir host qualities. Our study unravels the dynamic interactions between ticks, pathogens, and camels that all influence the likelihood of pathogen adaptation and transmission dynamics.

IMPORTANCE

Ticks are obligatory hematophagous arachnids, serving as vectors for a wide array of pathogens that can be transmitted to animals and humans. The ability of ticks to acquire and transmit various pathogens depends on its attraction to quality reservoir host and the survival of the pathogens in ticks’ gut and other tissues. However, the complex dynamics of tick-pathogens interaction and host-seeking behavior remains understudied. This investigation revealed notable variation in tick preference for domestic animals, camel being the most preferred host. Moreover, our spatial analysis about tick attachment sites showed nostril is the most preferred sites by various tick species. Our epidemiology data showed variation in the pathogens harbored by camel (host) and vector (H. rufipes), demonstrating the camel’s efficiency as reservoir host and ticks’ vector competence for various pathogens. With our behavioral experiment usingH. rufipesand its preferred host’s (camel) breath and body signature odors, we identified novel attractants forH. rufipes, thus offering new avenues for combating TBDs. Overall, our study presents novel insights into how multiple factors shape tick-host-pathogens interaction.
Automated Prediction of Fibroblast Phenotypes Using Mathematical Descriptors of Cellular Features
Authors: Khang Alex , Barmore Abigail , Tseropoulos Georgios , Bera Kaustav , Batan Dilara , Anseth Kristi S.
Published: May 2024

Fibrosis is caused by pathological activation of resident fibroblasts to myofibroblasts that leads to aberrant tissue stiffening and diminished function of affected organs with limited pharmacological interventions. Despite the prevalence of myofibroblasts in fibrotic tissue, existing methods to grade fibroblast phenotypes are typically subjective and qualitative, yet important for screening of new therapeutics. Here, we develop mathematical descriptors of cell morphology and intracellular structures to identify quantitative and interpretable cell features that capture the fibroblast-to-myofibroblast phenotypic transition in immunostained images. We train and validate models on features extracted from over 2,500 primary heart valve interstitial cells (VICs) and test their predictive performance on VICs treated with the small molecule drug 5-azacytidine, which inhibited myofibroblast activation. Collectively, this work introduces an analytical framework that unveils key features associated with distinct fibroblast phenotypes via quantitative image analysis and is broadly applicable for high-throughput screening assays of candidate treatments for fibrotic diseases.
IB-DNQ and Rucaparib dual treatment alters cell cycle regulation and DNA repair in triple negative breast cancer cells
Authors: Runnebohm Avery M. , Wijeratne H.R. Sagara , Peck Justice Sarah A. , Wijeratne Aruna B. , Roy Gitanjali , Singh Naveen , Hergenrother Paul , Boothman David A. , Motea Edward A. , Mosley Amber L.
Published: May 2024

Background

Triple negative breast cancer (TNBC), characterized by the lack of three canonical receptors, is unresponsive to commonly used hormonal therapies. One potential TNBC-specific therapeutic target is NQO1, as it is highly expressed in many TNBC patients and lowly expressed in non-cancer tissues. DNA damage induced by NQO1 bioactivatable drugs in combination with Rucaparib-mediated inhibition of PARP1-dependent DNA repair synergistically induces cell death.

Methods

To gain a better understanding of the mechanisms behind this synergistic effect, we used global proteomics, phosphoproteomics, and thermal proteome profiling to analyze changes in protein abundance, phosphorylation and protein thermal stability.

Results

Very few protein abundance changes resulted from single or dual agent treatment; however, protein phosphorylation and thermal stability were impacted. Histone H2AX was among several proteins identified to have increased phosphorylation when cells were treated with the combination of IB-DNQ and Rucaparib, validating that the drugs induced persistent DNA damage. Thermal proteome profiling revealed destabilization of H2AX following combination treatment, potentially a result of the increase in phosphorylation. Kinase substrate enrichment analysis predicted altered activity for kinases involved in DNA repair and cell cycle following dual agent treatment. Further biophysical analysis of these two processes revealed alterations in SWI/SNF complex association and tubulin / p53 interactions.

Conclusions

Our findings that the drugs target DNA repair and cell cycle regulation, canonical cancer treatment targets, in a way that is dependent on increased expression of a protein selectively found to be upregulated in cancers without impacting protein abundance illustrate that multi-omics methodologies are important to gain a deeper understanding of the mechanisms behind treatment induced cancer cell death.
Method for isolation of small extracellular vesicles from different biofluids and workflow for Mass Spectrometry based-shotgun proteomics and RNA isolation
Authors: Sharma Pratibha , Dhamija Rajinder K
Published: May 2024

Small extracellular vesicles (sEVs) or exosomes are small-sized (30-150 nm), nanoparticles that are released from almost all cells under normal and pathophysiological conditions. The sEVs have a vital role in biological systems as they communicate and transfer their contents, such as proteins, lipids, and nucleic acids, from the cells of origin to nearby or distant cells. In recent years, there has been a growing interest in isolating sEVs for use in disease mechanisms, clinical diagnoses, and therapeutics. Due to their small size sEVs can be observed using electron microscopy. The size distribution and concentration were checked by Nanoparticle Tracking Analysis. Western blotting confirmed the presence of exosome markers. The ease of obtaining patient samples from biofluids like plasma, saliva, and urine makes them a valuable source for diagnostic purposes by isolating sEVs to diagnose and predict diseases early. However, there is no specific protocol to perform it altogether. We have developed an improved ultracentrifugation method using gradient ultracentrifugation and ultrafiltration, which results in higher sEVs purity and yield. We have tested this method on plasma, saliva, and urine at a single platform, and we have isolated proteins and RNA from exosomes for their downstream applications. Our method is simple to use and can be utilized for clinical research biomarker applications, in understanding disease mechanisms and monitoring its progressions from biofluid sample collections.
Endemic demographics of the Jomon people estimated based on complete mitogenomes reveal their regional diversity
Authors: Yoshida Koki , Wakiyama Yoshiki , Valverde Guido , Tanino Akio , Waku Daisuke , Katsumura Takafumi , Ogawa Motoyuki , Nagaoka Tomohito , Hirata Kazuaki , Koganebuchi Kae , Watanabe Yusuke , Ohashi Jun , Yoneda Minoru , Takahashi Ryuzaburo , Oota Hiroki
Published: May 2024

The Jomon culture that spread across Japanese archipelago began about 16,000 years ago and lasted for over 10,000 years. The genetic diversity of the Jomon people, prehistoric hunter-gatherers bearing the Jomon culture, is of great interest in understanding prehistoric East Eurasians. Until now, their demographic history has been estimated using archaeological sites and present-day genomes, but detailed studies using Jomon genomes have been insufficient. To investigate the Jomon demography, we determined the complete mitochondrial genome (mitogenome) sequences from 13 Jomon individuals and conducted population genetic analysis on 40 Jomon genomes including previously published data. Our results revealed an effective population size increase during the Incipient – Initial phase of the Jomon period, which had not been observed in analysis of mitogenome sequences from present-day Japanese populations. This endemic demographic pattern is pronounced in the eastern part of the archipelago, under the assumption of no gene flow between the Eastern and Western Jomon.
Optimizing Peptide Crosslinks for Cell-Responsive Hydrogels
Authors: Wu Yingjie , Rozans Samuel J. , Moghaddam Abolfazl Salehi , Pashuck E. Thomas
Published: May 2024

Cells dynamically modify their local extracellular matrix by expressing proteases that degrade matrix proteins. This enables cells to spread and migrate within tissues, and this process is often mimicked in hydrogels through the incorporation of peptide crosslinks that can be degraded by cell-secreted proteases. However, the cleavage of hydrogel crosslinks will also reduce the local matrix mechanical properties, and most crosslinking peptides, such as the widely used GPQGIWGQ “PanMMP” sequence, lead to bulk degradation of the hydrogel. A subset of proteases are localized to the cell membrane and are only active in the pericellular region in the immediate vicinity of the cell surface. These membrane-type proteases have important physiological roles and enable cells to migrate within tissues. In this work we developed an approach to identify and optimize peptide sequences that are specifically degraded by membrane-type proteases. We utilized a proteomic screen to identify peptide targets, and coupled this with a functional assay that both quantifies peptide degradation by individual cell types and can elucidate whether the peptides are primarily cleaved by soluble proteases or membrane-type proteases. We then used a split-and-pool synthesis approach to generate more than 300 variants of the target peptide to improve the degradation behavior. We identified an optimized peptide sequence, KLVADLMASAE, which is primarily degraded by membrane-type proteases, but enables both endothelial cells and stem cells grown in KLVADLMASAE-crosslinked hydrogels to spread and have viabilities similar to the gels crosslinked by the PanMMP peptide. Notably, the biological performance of the KLVADLMASAE peptide-cross linked gels was significantly improved from the initial peptide target found in the proteomic screen. This work introduces a functional approach to identifying and refining protease-substrate peptides as a way to enhance the properties of hydrogel matrices.