bluuebunny/crossref_metadata_2025 huggingface dataset:
The lymphoid microenvironment controls duration of T cell - DC interactions to promote accelerated effector cell generation
Authors: Altenburger Lukas Matthaeus , Harada Yosuke , Dehio Philippe , Ruef Nora , Mehling Matthias , Stein Jens Volker
Published: February 2023

Naïve T cells and dendritic cells (DCs) are drawn to lymphoid tissue by the chemokine receptor CCR7, where its ligands CCL19 and CCL21 are secreted by lymphoid stroma. There, CCR7 fuels the fast migration of naïve T cells to expedite encounters with DCs presenting cognate pMHC, leading to the formation of long-lasting contacts. Direct in situ observations in mouse models have shown that after approximately 12–24 h, activated T cells detach from DCs before undergoing cell division and effector T cell differentiation. Yet, the mechanisms underlying T cell release from DCs, and hence termination of TCR signal integration, are not well understood. Using a reporter system for TCR signaling, we show here that CD8+T cell detachment from DCs does not occur efficiently in the absence of CCR7 ligands, suggesting that T cells do not intrinsically cease TCR signal integration. In contrast, after a short period of unresponsiveness, ex vivo stimulated T cells increasingly separate from DCs in response to CCR7 ligands in line with in vivo kinetics of detachment. Using ex vivo and in vivo imaging, we identify a critical role for phosphoinositide-3-kinase and the Rac activator DOCK2 in calibrating CCR7-dependent duration of T cell-DC interactions. To assess the impact of enforced T cell-DC separation, we examined effector differentiation kinetics as a function of interaction duration with DCs. Environmentally triggered CD8+T cell detachment from DCs positively correlated with their entry into proliferation and granzyme B production while limiting PD-1 expression. In sum, our data assign a novel function to CCR7 ligands secreted by lymphoid stroma to limit the duration of CD8+T cell - DC interactions for accelerated effector T cell generation.
Understanding the role of hnRNPA1 on T cell differentiation
Authors: White Theresa L , Gable Matthew , Jin Ye , Morel Penelope
Published: February 2023

Regulatory T cells (Treg) play a critical role in preventing autoimmunity diseases and maintaining tolerance in various tissues, particularly the gut. Peripheral derived Tregs (pTregs) are especially crucial in gut homeostasis and tolerance to commensal and food antigens. We have previously shown that knockdown of the RNA-binding protein, heterogeneous nuclear ribonucleoprotein (hnRNP) A1, reduces in vitro pTreg induction upon low TCR stimulation. In addition, we have shown that, under conditions of low TCR stimulation, in which pTregs are induced, hnRNP A1 is phosphorylated by Akt. In order to explore the impact of hnRNP A1 phosphorylation by Akt on pTregs induction we have generated a mutant mouse model, hnRNPA1-S199 in which the known Akt phosphorylation site on hnRNP A1 is mutated to Alanine. We have examined the induction of pTregs in vivo using an adoptive transfer model of OT-II TCR transgenic mutant (hnRNPA1-S199A) and wild-type naïve CD4 T cells followed by oral OVA administration. In addition, we are examining the induction of pTregs in vitro using OVA peptide presented by wild-type and mutant (antigen presenting cells) APC from the spleen. Preliminary data showed a decrease in pTreg induction and proliferation when naïve mutant T cells are stimulated either in vitro or in vivo with OVA. Furthermore, we observe that mutant APC have a reduced ability to induce proliferation and pTreg induction in both mutant and WT T cells. These data suggest that hnRNP A1 has important functions in both T cells induction and antigen presentation.
Senescence-associated β-galactosidase activity and other markers of senescence are present in human peripheral blood CD8+ cells during healthy aging
Authors: Dewald Hannah K , Martínez-Zamudio Ricardo Iván , Vasilopoulos Themistoklis , Radeny Joycelyn , Herbig Utz , Fitzgerald-Bocarsly Patricia
Published: February 2023

Aging is associated with a decline in the immune system, termed “immunosenescence”. Cellular senescence is defined by persistent cellular growth arrest and overall loss of function. If immune cells undergo cellular senescence in vivo, and if it has a role in immunosenesence, remains controversial due to the lack of specific markers to identify these cells. Human CD8+ T cells from younger and older donors were isolated from blood and labeled with a fluorescent substrate for senescence-associated b-galactosidase (SA-βGal). CD8+ T cells were sorted based on SA-βGal and analyzed by qRT-PCR, RNA sequencing, and microscopy. We found a higher percentage of CD8+ T cells with high SA-βGal activity in the older cohort. SA-βGal high CD8+ T cells displayed increased p21, p16INK4a, and inflammatory cytokine transcripts. They also had greater DNA damage response foci and p16INK4a protein and had deficient proliferation. SA-βGal increased as T cells matured, which was consistent regardless of age. Intriguingly, a portion of effector cells did not exhibit a senescent phenotype and maintained low SA-βGal. RNA sequencing of CD8+ T cells revealed cells with low, medium, and high SA-βGal had distinct profiles. In addition, SA-βGal high CD8+ T cells had larger mitochondrial mass than cells with low SA-βGal as measured by MitoID staining. This may indicate differences in metabolism, which may contribute to senescence. The presence of p16INK4a, DNA damage, and inflammatory cytokines and deficient proliferation demonstrate that SA-βGal is a strong indicator of cellular senescence in CD8+. T cells. SA-βGal can be leveraged to further identify senescent immune cells and elucidate cellular senescence’s role in immunosenesence.
Anergy-derived Treg cell differentiation in the neonatal mouse hepatic microenvironment
Authors: Morales Milagros Silva , Mueller Daniel L
Published: February 2023

The neonatal environment is a natural scenario to study the effects of peripheral self-antigen recognition and induction of immune tolerance within the CD4 T lymphocyte repertoire. Interestingly, we have found that polyclonal Nrp1+ CD73+ anergic conventional CD4 T cells and Foxp3+ regulatory T cells (Tregs) accumulate in the neonatal liver. These observations make the neonatal liver an interesting place to study anergy-derived Foxp3+ Treg cell differentiation. We hypothesize that self-reactive CD4 T cells become anergic in neonates and generate Treg cell progenitors. Furthermore, we predict that unlike secondary lymphoid organs, the neonatal liver microenvironment fails to support anergy maintenance and, therefore, allows anergy-derived Treg cell progenitors to differentiate into Foxp3+Tregs. Accordingly, the objective of this study was to specifically analyze the induction of CD4 T cell anergy and the trans-differentiation of anergic conventional T cells into the Foxp3+ Treg cell lineage within the neonatal liver. We now report that anergic OT-II CD4 T cells partially reverse their anergic phenotype and give rise to Foxp3+Tregs cells within the hepatic environment when transferred into neonatal mice that ubiquitously express an OVA transgene. These findings support the model that a change in the metabolism of anergic CD4 T cells within the neonatal liver leads to cell-cycle progression and chromosomal replication, which then allows for the complete de-methylation of the Foxp3CNS2 locus and differentiation into the Foxp3+ Treg lineage. Future experiments will analyze the importance of enzymes such as DNMT and TET proteins that regulate the epigenetic state of Treg cell progenitors within the anergic cell compartment.
Notch driven mTORC1 signaling enables rapid, division-independent plasma cell division in marginal zone B cells
Authors: Gaudette Brian T. , Roman Carly , Atria Daniela Gomez , Siebel Christian W. , Maillard Ivan , Allman David
Published: February 2023

Lymphocyte differentiation is often tightly linked to mitosis. Clonal bursts due to antigen- or TLR-driven responses increase numbers of responding cells and may also facilitate changes in gene expression and chromatin needed for effector cell differentiation. Alternatively, to guard against rapid infection, lymphocyte pools may also contain cells poised for effector differentiation with minimal proliferation. Since marginal zone (MZ) B cells, which have increased basal mTORC1 activity and c-Myc expression, reside in the marginal sinus of the spleen where they are positioned to respond rapidly to blood borne microbes, we compared their ability to produce plasma cells (PC) with that of follicular B cells in an ex-vivo stimulation assay. We found that MZ B cells are able to produce PCs rapidly and independently of cell division whether exposed to cell cycle inhibitors or with genetic ablation of Cdk1. Furthermore, we found that blockade of Notch signaling rapidly down-regulated c-Myc-driven gene expression and mTORC1 activity in MZ B cells and caused them to adopt differentiation kinetics similar to follicular B cells. Genetic ablation of c-Myc further emphasized the uncoupling of cell division and differentiation in MZ B cells. Whereas acute loss of c-Myc blocked all cell division in ex-vivo stimulation assays, PC differentiation was only blocked with prolonged loss of c-Myc. Finally, using genetic ablation of Tsc1 to disinhibit mTORC1 signaling, we conferred both rapid and division-independent plasma cell differentiation to follicular B cells. These data illustrate that ongoing Notch signaling through c-Myc and mTORC1 allow for rapid division-independent antibody responses in MZ B cells.
Role of the Notch-TRIB2 axis in CD8+ T cell differentiation
Authors: Le Corre Laure , Boulet Salix , De Sousa Dave Maurice , Labrecque Nathalie
Published: February 2023

Following activation, naïve CD8+ T cells expand and differentiate into two effector subpopulations: short-lived effector cells (SLECs) and memory precursor effector cells (MPECs). After the effector response has taken place, SLECs undergo apoptosis, while MPECs mature into memory T cells that protect against reinfection. Notch, a highly conserved pathway, was shown to control SLEC differentiation. Our transcriptomic analysis has revealed that Notch signalling controls the transcription of a large number of genes in activated CD8+ T cells. Among them is Trib2, coding for the pseudokinase Tribbles homolog 2. TRIB2 was reported to activate AKT in some tumour cell lines while Notch-deficient CD8+ T cells show decreased AKT activation, suggesting that Notch transcriptional induction of Trib2 might be important to properly activate AKT and promote SLEC differentiation. Therefore, we hypothesize that induction of TRIB2 expression by Notch signalling promotes SLEC differentiation through AKT activation. To test this, we overexpressed TRIB2 in Notch1–2 deficient CD8+ T cells using retroviral transduction and followed their differentiation after their adoptive transfer into Listeria infected mice. Our results show that overexpression of TRIB2 partially restores SLEC generation in absence of Notch. In conclusion, we uncovered that TRIB2 promotes SLEC differentiation through the Notch pathway. These findings provide a better understanding of the molecular events controlling the differentiation of SLECs, a cell type essential for the elimination of infected cells and cancer.
Regulatory T cell suppressive capacity is governed by synergistic Foxp3 enhancers
Authors: Feng Yongqiang , Zong Xinying
Published: February 2023

Regulatory T (Treg) cells bearing a diverse antigen receptor repertoire suppress pathogenic T cells and maintain immune homeostasis during their long lifespan. How robust Treg function is determined genetically remains elusive. Here, we investigate the regulatory space of the cis-regulatory elements of Treg lineage–specifying factor Foxp3 known as distinct modules promoting Treg cell induction or lineage stability. Their single deficiencies cause mild, if any, immune dysregulation, leaving the key transcriptional mechanisms of the Foxp3 gene determining Treg suppressive capacity uncertain. Therefore, we examined the collective activities of Foxp3 enhancers and found that they coordinate to maximize Treg cell induction and stability through distinct modes. Thus, the induction and maintenance of a diverse, stable Treg cell repertoire rely on combinatorial Foxp3 enhancers acting in a stage-specific manner, improving our understanding of the genetic determinants of Treg suppressive capacity.
Myosin specific TRM cells mediate increased severity of immune checkpoint inhibitor myocarditis
Authors: Kalinoski Hannah Maryam , Won Taejoon , Rusinkevich Vitali , Talor Monica V , Hughes David M , Wood Megan K , Hooper Jody E , Cihakova Daniela
Published: February 2023

Immune checkpoint blockade has revolutionized the field of cancer immunotherapy; however, it has been also associated with immune-related adverse events (IRAE). Immune checkpoint inhibitor (ICI)-myocarditis occurs in approximately 1% of patients, however, it has a high fatality rate of up to 50%. To prevent life-threatening toxicities, it is imperative to understand what predisposes patients to ICI-myocarditis. We examined if previous cardiac injury increases an individual’s susceptibility to develop ICI-myocarditis. We demonstrated that ischemic injury substantially changes the phenotype of cardiac lymphocytes, causing them to upregulate the well-characterized tissue resident markers such as CD69 and CD103. We were excited to find that these cardiac tissue resident T (TRM) cells express prominent levels of the checkpoint molecule PD-1 and have high TCR specificity for cardiac myosin. TRM cells have been described in the literature to establish residency in non-lymphoid organs where they provide a rapid functional response more efficiently than circulating memory T cells. To investigate the role that cardiac TRM cells play in the occurrence of ICI-myocarditis, we developed a novel two-hit model. In this model cardiac injury is induced through ischemic injury (first hit), mice are allowed to recover before we begin the administration of immune checkpoint antibodies (second hit). Our data suggest that after the administration of PD-1 blocking antibodies, mice with myosin specific TRM cells are more susceptible to ICI-myocarditis. Further characterization of cardiac TRM cells could provide insight into why checkpoint mediated cardiac toxicities are particularly rapid and have high fatality rates.
Non-agonist peptide-MHC engagement triggers TCR proximal signaling distinct from agonists.
Authors: Wolf Gideon S , Singh Nevil J , Douek Daniel C
Published: February 2023

The maintenance of naïve and memory T cell populations, is regulated by signals from cytokines including IL-7 as well as those ensuing from the tonic TCR recognition of endogenous peptide-MHC (pMHC) complexes. These TCR signals are thought to be distinct from typical agonist antigen-driven signals, but the precise biochemistry is poorly understood. In mice, the 5C.C7 TCR transgenic model has well characterized interactions with agonist and non-agonist foreign and self-peptides, respectively. Using these cells, we find that agonist pMHC engagement elicits strong phosphorylation of ERK, actin polymerization, increase of cell size as well as upregulation of surface markers such as CD69. Interestingly, co-culturing 5C.C7 T cells with both the agonist and non-agonist pMHC complexes amplifies these phenotypes of T cell activation when compared to the agonist alone. Additionally, we found that endogenous peptides alone do not directly elicit these downstream cellular responses. In contrast, examination of more TCR proximal signaling suggests that endogenous peptide engagement results in strong LAT phosphorylation comparable to levels triggered by the agonist. These non-agonist-induced phosphorylated LAT levels were present from 30 minutes until 4 hours at a relatively sustained level, compared to the synergistic effects of the downstream signaling (pERK, CD69, etc) which only began to emerge at the 2 hour time point and onwards. These data suggest that TCR signaling after engaging with endogenous self-peptides is uncoupled from agonistic signaling at the level of LAT. This bifurcation may allow T cells to use agonist vs non-agonistic signals for distinct biologic outcomes.
Moderate Malnutrition exacerbates Plasmodium chabaudi induced gut leakage and reduced mucosal Innate Immunity in mice
Authors: Murr Noah Joseph , Olender Tyler , Smith Amari , Opata Michael M.
Published: February 2023

Gastrointestinal problems are among the most reported symptoms in serious cases of malaria infection. While many pathophysiologies including gastric mucosal changes have been reported in serious cases of malaria infection, the influence of moderate malnutrition, common in malaria endemic areas, has not been well explored. Here, we used a rodent mouse model to investigate how moderate malnutrition affects gut integrity and mucosal innate immunity during malaria. Utilizing a well-established low protein diet that is deficient in zinc and iron to induce moderate malnutrition, we investigated mucosal tissue phenotype and integrity, and mucosal innate immunity in the gut. We observed that the infected moderate malnourished mice had lower parasite burden at the peak of infection, but high levels of FITC-Dextran concentration in the blood serum, indicating increased intestinal permeability. The small intestines in the moderate malnourished mice were also shorter after infection with malaria. This was accompanied with lower numbers of CD11b+macrophages, CD11b+CD11c+ myeloid cells, and CD11c+ dendritic cells in the small and large intestines. Despite the lower number of innate immune cells, macrophages in the malnourished mice were highly activated as determined by MHCII expression. Thus, our data suggests that malaria infection may exacerbate the deformities in the gut induced by moderate malnutrition.
Re-thinking the Plasmodium mouse model: using wild derived mice to interrogate asymptomatic malaria
Authors: Cornwall Douglas , Srey Mellina , Maloba Franklin , Evavold Birk , Olatunde Adesola , Jensen Anne , Lamb Tracey J , Evavold Brian D
Published: February 2023

Malaria is a major world health issue, with over 200 million clinical cases per year that lead to over 200,000 deaths. Though there have been advances in treatment and control of malaria in symptomatic patients, nearly 60–75% of Plasmodium infections are asymptomatic (no overt symptoms), leading to a large proportion of ignored infections that have a large influence on transmission. However, the term asymptomatic is misleading, as many of these individuals display evidence of mild anemia and vascular activation, leading to a higher risk for co-morbidities such as infection with typhoidal Salmonella. Unfortunately, the immunological mechanisms governing the asymptomatic phenotype are poorly understood, partially due to a lack of reliable immunologically intact asymptomatic animal models. Here, we utilize a unique genetically diverse wild-derived mouse model to address the immunological underpinnings of asymptomatic malaria. This model allows us to disentangle the relative roles of the genetics and environment in the generation of immune responses to Plasmodium infections. Results show the wild-derived mice have varying levels of anemia associated with Plasmodium yoelii XNL infection, with some mice exhibiting an asymptomatic phenotype with mild anemia independent of parasitemia. Anemia levels positively correlate with the production of TNF-a and IL-10, which is consistent with patterns seen in children in Cameroon. Furthermore, the CD4 T cells producing IL-10 and IFN-g were also correlated with the severity of anemia, also a pattern seen in human malaria. These results demonstrate that the wild-derived mice can be used to model asymptomatic malaria and allow us to interrogate the immune mechanisms leading to anemia.
Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling on intestinal epithelial cells
Authors: El-Naccache Darine W. , Chen Fei , Palma Mark J , Lemenze Alexander , Wu Wenhui , Mishra Pankaj Kumar , Eltzschig Holger , Robson Simon C. , Di Virgilio Francesco , Hasko George , Gause William C
Published: February 2023

Intestinal nematode infections trigger potent type 2 immune responses, although the mechanisms that initiate these host protective responses against multicellular parasites remain uncertain. We have previously reported that A2BAR deficient mice (A2BAR−/−) have an impaired type 2 immune response and delayed helminth expulsion during Heligmosomoides polygyrus bakeri (Hpb) infection. However, the cell types expressing A2BAR receptors that participate in this initiation and how the adenosine-A2BAR axis drives memory type 2 immune responses in helminth infections remains unknown. We now report that mice lacking A2BAR specifically on intestinal epithelial cells (VillinCre-A2BARfl/fl), but not on myeloid cells (LysMCre-A2BARfl/fl) show increased worm metabolism and delayed worm expulsion after Hpb secondary inoculation. We further show, the transfer of Hpb primed CD4+ T cells from WT but not from VillinCre-A2BARfl/fl can rescue the impaired immune response in recipient VillinCre-A2BARfl/fl mice. Moreover, the transfer of Hpb primed CD4+ T cells from WT but not from IL-4−/− mice into IL-4−/− mice rescued the protective memory type 2 immune response. During the primary response, type 2 immunity was dependent on epithelial A2BAR signaling as early as 24 hours after inoculation and was associated with marked increases in eATP production. Furthermore, mice lacking CD39 exhibited similarly impaired type 2 immunity to Hpb, indicating that extracellular ATP is metabolized to adenosine, which then acts as an essential endogenous danger signal. Our data thus demonstrate a key role for intestinal epithelial cell-specific A2BAR signaling in the development of host protective CD4+ IL-4 expressing memory T cells during helminth infection.
Understanding the role of peptidoglycan and associated protein NapA in Lyme disease pathogenesis
Authors: McClune Mecaila E. , Davis Mari , Jutras Brandon
Published: February 2023

Lyme disease is the most common vector-borne illness in the United States with 400,000 estimated new cases annually. Borrelia burgdorferi (Bb), the causative agent, causes severe clinical manifestations, but lacks classical virulence factors. The primary cause for patient symptomology is unknown. Peptidoglycan (PG) serves as both a protective barrier from osmotic pressure and a pathogen associated molecular pattern (PAMP). In diderms, this structure resides between the outer and inner membrane. Bb is an atypical Gram-negative bacterium. It contains L-ornithine in its PG peptide stem and lacks a PG recycling pathway. The collective results are an atypical pathogen that sheds unusual PG fragments into its extracellular environment.

We have recently shown that these PG fragments reside in the human host, well after acute infection in Lyme arthritis patients. Also, when injected into a mouse, Bb PG is capable of causing acute arthritis that mimics that of Lyme arthritis. Here, we probed the pathogenic properties of Bb PG chemistry. Comparative RNA-seq analysis from human PBMCs stimulated with PG fragments isolated from different bacteria demonstrate a surprising and unique immunological response that appears to be dictated by the chemical features unique to Bb PG.

We also provide evidence that Bb PG is not alone in eliciting this unique response. Our recent, unpublished studies show that NapA— Neutrophil Attracting Protein A— is physically linked to Bb PG and contributes to this atypical PG response. Using molecular and cellular studies, including a novel microfluidic chamber, we show that the unique PG-NapA linkage augments the production of IL-17 and recruits the frontline of the innate immune system in response towards this unusual PAMP.
Age-associated defects in the adaptive immune response to Clostridium difficile infection impair the development of a protective immune response in the elderly
Authors: Bell Matthew , Bernui Mariana , Shah Neev , Kutzler Michele A.
Published: February 2023

Clostridium difficile is the number one cause of healthcare-associated infection in the United States and the most lethal acute enteric pathogen. The elderly (≥65) have the greatest risk of C. difficile infection (CDI) and severe morbidity and mortality due to CDI. Additionally, most recurrent CDIs occur within the elderly. To better understand why the elderly are at greater risk of severe and recurrent CDI, our lab has conducted a longitudinal study of the aging immune response to primary and recurrent CDI in patients at Hahnemann University Hospital. Both elderly and young CDI patients were enrolled in the study, and stool and blood samples were collected at enrollment and 12 days after diagnosis of CDI. Analysis of the samples looking at the humoral response in elderly versus young CDI patients shows that the early humoral response in elderly patients is impaired when compared to young CDI patients. In addition, recurrent CDI patients have similarly defective humoral responses. Finally, preliminary work in an aging mouse model of CDI further supports that age-related defects within the adaptive immune response impair the development of a protective immune response. Since the adaptive immune response to CDI plays an important role in neutralizing toxins produced by C. difficile, an impaired humoral response in both aged and recurrent CDI patients may contribute to the increased risk of infection, morbidity, and mortality observed in elderly patients. Future studies will seek to further characterize the aging immune response using patient samples as well as aging mouse models of CDI.
IL-17A or IL-17F is sufficient to maintain innate response and control of H. pylori immunopathogenesis
Authors: Algood Holly Marie Scott , Dixon Beverly R.E.A. , Lee Tiffany J , Piazuelo M. Blanca
Published: February 2023

Interleukin-17 receptor (IL-17R) signaling is required for control of many extracellular pathogens due to its impact on neutrophil recruitment and antimicrobial responses. Infection with the extracellular pathogen Helicobacter pylori results in Th1 and Th17 cell activation and a chronic inflammatory process which can lead to adverse outcomes such as gastric cancer. Previously, we identified IL-17RA as a requirement for the recruitment of neutrophils. Surprisingly, H. pylori infected IL-17RA−/− mice had significantly more chronic inflammation than H. pylori infected WT mice. In the current study, in vitro human epithelial cell cultures and in vivo mouse models were used to investigate differential roles for IL-17A, IL-17F and IL-17A/F during H. pylori infection. The data indicate generally that epithelial cells responded to IL-17A or IL-17A/F better than IL-17F. Increased gene expression of some factors, such as Cxcl8, required a co-stimulus such as H. pylori, TNF or IL-22 in epithelial cells, but expression of Pigr and Nox1 were induced by IL-17A alone. In vivo deficiencies of IL-17A or IL-17F alone did not significantly change the immunopathological response to H. pylori, but if both cytokines were absent, a hyperinflammatory lymphocytic response developed similar to what was observed in IL-17RA−/− mice. These data imply that IL-17A and IL-17F may have some overlapping role or compensatory roles in maintenance of the gastric mucosal response to infection which is required for preventing immunopathology.
A georeferenced dataset of Italian occurrence records of the phylum Rotifera
Authors: Ferrari Vittoria , Gualdi Arianna , Bertani Isabella , Fontaneto Diego , Kamburska Lyudmila , Karimullah Karimullah , Marrone Federico , Obertegger Ulrike , Rossetti Giampaolo , Tiberti Rocco , Cancellario Tommaso
Published: February 2023

We report a dataset of known and published occurrence records of Italian taxa from species (and subspecies) to family rank of the phylum Rotifera; we considered only Bdelloidea, Monogononta, and Seisonacea, and did not include Acanthocephala. The dataset includes 15,525 records (12,015 of which with georeferenced coordinates) of 584 valid species and subspecies names, gathered from 332 published papers. The published literature spans the period from 1838 to 2022, with the lowest number of papers published during the Second World War followed by an increasing number of papers, from 20 to more than 60 in each decade. The Italian regions with the highest number of records and species are Emilia-Romagna, Lombardy, and Piedmont, whereas no records are known for Molise. The number of species known from each region mostly mirrors sampling efforts, measured as the number of publications per region. The dataset is available through the Open Science Framework (OSF), and all the georeferenced occurrence data have been uploaded to the Global Biodiversity Information Facility (GBIF).
Impulse oscillometry system as a new diagnostic tool in patients with chronic obstructive pulmonary disease
Authors: Elzahapy Nehal A. , Sharshar Ragia S. , Mohamed Ahmed S. , El-Shimy Wafaa S.
Published: February 2023

Background

Both diagnosis and assessment of chronic obstructive pulmonary disease (COPD) are based mainly on pulmonary-function tests that are of very important significance in COPD. Impulse oscillometry is a noneffort-dependent method to assess the mechanical structure of the respiratory system.

Objectives

The study aims to evaluate impulse oscillometry system (IOS) as a diagnosis tool of COPD, in a trial to clarify the sensitivity and correlations of IOS parameters with COPD severity.

Patients and methods

The study included 30 healthy volunteers, group I (control group): 15 smokers, 15 nonsmokers, and 60 patients with COPD, group II: 30 patients with mild-to-moderate COPD, and group III: 30 patients with severe COPD. All participants were sequentially assessed by IOS to detect impedance, after this, spirometry was done, and both were repeated 15–45 min after the first dose of inhalation therapy (salbutamol). IOS is more sensitive in detecting small-airway affection in mild-to-moderate COPD than spirometry.

Results

In COPD, a significant increase in IOS-resistant parameters (R5, R5–20), reactance parameter (AX), and a decrease in reactance (X5) parameter was observed in two groups of COPD (groups II and III) if compared with control group I. IOS parameters significantly correlated with spirometric parameters, particularly large-airway parameters (R5 correlated with forced expiratory volume in the first second postbronchodilator in group II and group III), small-airway parameters (R5–20, X5, and AX correlated with maximal mid-expiratory flow postbronchodilator in group III).

Conclusions

IOS is very useful in detecting small-airway affection in mild and moderate COPD and could be done as an alternative to spirometric tests in severe COPD patients with more accurate grading.
Utility of lung ultrasound in adjustment of the initial mechanical ventilation settings in patients with acute respiratory distress syndrome
Authors: Mohamed Menna A.M. , Khalil Magdy M. , Diab Haytham S. , EL-Maraghy Ashraf A.S.
Published: February 2023

Background

Bedside lung ultrasound (US) is an essential tool in assessing lung aeration in severely ill patients.

Aim

The goal of this study was to determine the use of lung US in evaluating changes in lung aeration in dependent lung areas during positive end expiratory pressure (PEEP) titration in patients with acute respiratory distress syndrome (ARDS).

Patients and methods

A total of 52 mechanically ventilated patients with ARDS admitted in the ICU of Abbassia Chest Hospital were enrolled in this study. Transthoracic sonography was performed at the posterior axillary line on either side after 30 min of initial ventilator settings; recruitment at the end of expiration was sonographically assessed while changing PEEP. Arterial blood gases were performed before and after recruitment maneuver along with continuous monitoring of hemodynamics and oxygen saturation throughout the procedure. The procedure was terminated if the plateau pressure exceeded 30 cmH2O or if there was hemodynamic compromise.

Results

A total of 52 mechanically ventilated patients with ARDS were enrolled in the study. Overall, 80% had severe ARDS. Initial US assessments were done, and subpleural consolidation (C) was found in 18 patients, whereas exaggerated B lines (B) were found in 33 patients. After PEEP titration, under US guidance, 13 patients changed the US pattern from C to B and 22 patients changed from B to A (A-line pattern). These results correlated with improvement of PaO2/FiO2 ratio from 69.98 ± 27.93 to 86.21 ± 31.64 and increased compliance from 26.49 ± 8.63 to 28.73 ± 8.74. However, there was an increase in plateau pressure from 25.12 ± 3.88 to 27.98 ± 3.18, and also PaCO2 increased from 51.00 ± 16.05 to 58.52 ± 15.93. The mean arterial blood pressure decreased from 84.87 ± 7.91 to 81.60 ± 8.72.

Conclusion

US is an effective tool in achieving PEEP titration in mechanically ventilated patients with ARDS. US finding of aeration correlates well with improvement in oxygenation and compliance. However, the patients should be monitored for safe limits of pressures, hemodynamics, and PaCO2 level that may rise.
Pulmonary sarcomatoid carcinoma revealed by gingival metastases
Authors: Imen Bachouch , Belloumi Nidhal , Racha Smaoui , Yoldez Houcine , Habouria Chaima , Sonia Jrad , Fatma Chermiti , Faouzi El Mezni , Soraya Fenniche
Published: February 2023

Oral soft tissue metastases may be presented as rapidly progressive hyperplasic growths mimicking benign processes. Gingival metastases from pulmonary sarcomatoid carcinoma are extremely rare and have poor prognosis. We report in this publication a case of a 65-year-old male patient, presenting asarcomatoid carcinoma of the right upper pulmonary lobe. Clinical examination found a gingival swelling initially considered as a benign lesion. Gingival biopsy showed aspects of undifferentiated sarcomatoid carcinoma of pulmonary origin according to the immunohistochemical staining. Even rarely described, benign-mimiking lesions may be the first sign of an aggressive underlying malignancy, and, therefore, periodontists should be vigilant. Any abnormal lesion must be evaluated by histopathological investigations.
Evaluation of Ventilatory Functions in Hypothyroid Patients
Authors: Garg Nitika , Kumar Vipul , Gupta Krishnan B. , Garg Sumit
Published: February 2023

Introduction

Respiratory muscle weakness is proportional to the degree of thyroid function and is reversible by replacement therapy with thyroxine.

Aim

To evaluate the changes in pulmonary functions in newly diagnosed hypothyroid patients as compare with healthy controls by spirometry and to observe the improvement in pulmonary functions after hormone replacement therapy.

Patients and methods

A total of 30 newly diagnosed hypothyroid patients and 30 healthy controls of age between 18 to 50 years of either sex were included in our study. Clinical criteria and biochemical tests were registered, and spirometry was done.

Results

Approximately 17% of the hypothyroid patients were normal, whereas 33% had mild restrictive lung impairment and the rest 50% had moderate to severe restrictive impairment on spirometry.

Conclusion

On comparing the hypothyroid patients with normal healthy person of same age group through spirometer, the ventilatory functions were diminished and these pulmonary functions improved after levothyroxine therapy for 6 months but could not reach the normal healthy values. A spirometric evaluation should be considered in hypothyroid patients, even in the absence of respiratory illness.
Role of lung point navigation bronchoscopy in diagnosis of peripheral pulmonary lesions
Authors: Allam Amira H. , Eisa Sherif A. , El-Sayed Abd El-Rahim Mahmoud , Amin Nashwa A.
Published: February 2023

Background

Cancer of the lung is the leading cause of mortality worldwide. There is a continuing problem to treat patients with pulmonary lesions in the peripheral lung. Technology like virtual bronchoscopic imaging is based on assisted-computed tomography pictures that lead the bronchoscopist to the target peripheral lesion.

Objectives

The purpose of this research was to evaluate the safety and effectiveness of the lung point navigation system in the identification of peripheral pulmonary lesions.

Patients and methods

A total of 20 patients took part in this cross-sectional investigation, which used analytical methods. Finally, tissue samples from peripheral pulmonary lesions were collected using virtual bronchoscopic navigation.

Results

Overall, 90% of the cases analyzed were correctly diagnosed using lung point navigation, whereas 10% of the cases were incorrectly diagnosed. The lesion was on average 22.4 mm×23 mm in size, 17.2 mm away from the costal border, and 102.5 mm away from the diaphragm. The average navigation time was 7.4 min, whereas the average planning time was 5 min, and the overall examination duration was 31 min.

Conclusion

The navigation bronchoscopic method is a promising innovation in the field of lung disease diagnostics. Cost, operational skills, and the learning curve have all conspired to keep it from being widely used thus far.
Necrotizing dacryometaplasia – A needle in haystack of necrotizing sialometaplasia
Authors: Khetwani Dhwanit Sureshkumar , Tanwar Meghana , Kim Usha R. , Radhakrishnan Santhi S
Published: February 2023

Necrotizing dacryometaplasia (ND) is a rare entity which can mimic an aggressive malignant tumor. It seems to be analogous to necrotizing sialometaplasia which generally affects the salivary glands and is an inflammatory condition. There is scarce information about this entity as only two case reports have been reported in the last two decades. Due to the presence of adjacent bony erosion, it may mimic an aggressive malignant tumor. Here, we report a 27-year-old male who presented with right upper eyelid swelling for 2 months, which clinically and radiologically pointed to be a malignancy turned out to be ND.
Proposed predictive score for visual outcome in cataracts with comorbidities following small-incision cataract surgery
Authors: Shah Mehul , Shah Shreya , Kataria Apeksha , Korane Ashvini
Published: February 2023

Introduction:

Cataract with comorbidity having poor prognosis, it is important to predict visual outcome in these eyes.

Materials and Methods:

This was a prospective cohort study to develop scoring system to predict visual outcome in case of cataracts with comorbidities. We enrolled all cataracts with comorbidities fulfilling inclusion criteria between August 2019 and 2020. For all enrolled cases, data were collected in pretested online format in electronic medical records. A specially designed form was used to calculate preoperative score which was categorized and compared with postoperative visual outcome. All data were exported and analyzed with SPSS 22 using descriptive, cross-tabulation, and one-sample test functions.

Results:

Our cohort consisted of 230 eyes of 230 patients with a mean age of 44 ± 21.22 years with 121/230 (52.6%) females and 109/230 (47.4%) males. Out of total 230 eyes Traumatic cataracts were in 64, cataract with corneal opacity in 45, postuveitic cataract in 43, neglected cataracts in 39 eyes. We found a significant difference in pre- and postoperative visual outcome. When we studied preoperative score, we found a significant difference between outcomes.

Conclusion:

Preoperative score for cataracts with comorbidities undergoing small-incision cataract surgery SICS is a very useful tool to predict visual outcome and universalize for comparison.
Fahr's syndrome and optic nerve head calcification in young
Authors: Bhardwaj Rahul , Dhawan Aeshvarya , Singh Sindhuja , Saha Indranil , Singh Anupam
Published: February 2023

Fahr's syndrome, a rare disease, is characterized by symmetrical and bilateral intracranial calcification. Here, we present the case of a 25-year-old female. She presented with progressive diminution of vision, dysarthria, and slowness of movements and had a history of seizures. Neurological examination revealed Parkinsonian features and episodes of stiffness all over the body. Right eye ultrasound-B scan and swept-source optical coherence tomography revealed optic nerve head (ONH) calcification, which is not a common finding. A computed tomography scan of the brain revealed bilateral, symmetrical, large areas of calcification over the basal ganglia, thalamus, and globus pallidus. In our patient, age and ONH calcification were two uncommon presentations.
Management of an intrastromal corneal foreign body
Authors: Darade Dnyanoba M. , Naik Hrishikesh D.
Published: February 2023

A 27-year-old male presented with complaints of irritation and watering in the left eye following injury by a shrub. These symptoms subsided on rubbing the eyes and an eyewash. Slit-lamp bio-microscopy revealed an edematous cornea with vegetative foreign bodies embedded in the stroma, which were confirmed by anterior-segment optical coherence tomography. Antimicrobial therapy and immediate foreign body removal was undertaken. The patient was discharged the next day, with regular follow-ups. Foreign bodies either get embedded on the corneal surface or penetrate into the anterior chamber; it is rare for them to be retained intracorneally. The patient made a full and uneventful recovery following surgery.
Amalric triangular sign
Authors: Bindra Chahveer Singh , Bindra Parminder Singh , Preeti Bindra
Published: February 2023

A 55-year-old female patient presented with no light perception and features suggestive of central retinal artery occlusion (CRAO) and posterior ciliary artery occlusion. Multimodal imaging analysis revealed retinal thickening, cherry-red spot, pallid optic disc with choroidal infarction (Amalric sign), and macular edema. Carotid Doppler disclosed 70% stenosis of the right common carotid artery. Systemic investigations showed elevated erythrocyte sedimentation rate, total cholesterol, and low-density lipoprotein level. The Amalric triangular sign with CRAO may present with macular edema. Prompt cardiac and carotid evaluation with appropriate management should be done.
Posterior lens capsular neovascularization in the absence of any risk factors
Authors: Krishna Chaitanya Y. V. , Shyamsundar K. , Kumar Poninder , Kaushik Jaya , Agrawal Mohini , Moosa Mandhoof
Published: February 2023

Neovascularization of the posterior capsule after uncomplicated cataract surgery is a rare occurrence. This case entails a similar presentation, however, in the absence of any known predisposition. An 80-year-old male presented with painless progressive diminution of vision in his right eye after having undergone uncomplicated cataract surgery with good visual recovery 3 years back. He had a visual acuity of counting fingers close to face with accurate projection of rays with no further improvement. He was found to have posterior capsular opacification with capsular neovascularization. He was managed with intravitreal ranibizumab followed 2 weeks later by neodymium: yttrium-aluminum-garnet capsulotomy clearing the visual axis. His visual acuity improved; however, the best-corrected visual acuity was 6/60 due to an epiretinal membrane.
Acute myeloid leukemia and myelofibrosis
Authors: Nalluru Swarna Sri , Efe Orhan , Chen Yayan , Trivedi Nitin
Published: February 2023

Essential thrombocytosis (ET) is usually an indolent disease but can uncommonly evolve into acute myeloid leukemia (AML) with a grim prognosis of 2–7 months. Studies report a lower incidence of leukemic transformation when compared to fibrotic transformation. The risk of transformation depends on the age, duration of disease, and tumor biology. Hydroxyurea, a cytoreductive agent, is generally associated with minimal adverse reactions; however, there are conflicting data on its effect on leukogenecity. We describe a rare case of a 79-year-old female developing disseminated intravascular coagulation due to the transformation of ET to both AML and myelofibrosis while being treated with hydroxyurea for 8 years.
Intratumoral heterogeneity contributes to the chemotherapy prognosis of breast cancer
Authors: Li Yang , Wang Maohua , Yang Siyuan , Kuang Licheng , Tao Xinling , Yang Jilan , Zhao Wentao , Zhang Ji
Published: February 2023

Context:

Previous studies have shown that intratumoral heterogeneity (ITH) is associated with poor clinical outcomes and is thought to be a mechanism of resistance to chemotherapy and radiotherapy.

Aims:

We aimed to determine how ITH affects the response to drug therapy in breast cancer (BC).

Settings and Design:

We assessed ITH using mutated allele tumor heterogeneity (MATH) data from BC patients in the TCGA database.

Methods and Material:

The study enrolled 515 patients with BC treated with chemotherapy from the TCGA database who had available data on survival, whole-exome sequencing, and genome-wide transcriptome sequencing. Additionally, 399 MSK-BRCA cohort patients were treated with chemotherapy.

Statistical Analysis Used:

All statistical analyses were conducted using R. All comparisons were made using the two-sided Mann–Whitney test, Pearson's Chi-squared test, and the Kruskal–Wallis test. Statistical significance was defined as P values less than 0.05 (*P < 0.05). The survival package in R was used to conduct the analysis.

Results:

Additional analysis was performed on 515 BC patients receiving adjuvant chemotherapy. MATH was associated with overall survival (OS) in multivariate analysis (hazard ratio (HR), 1.432; 95% confidence interval, 1.073–1.913; P = 0.015). Pathway enrichment and immune cell analysis revealed that the low MATH group had significantly higher infiltration of 24 different types of immune cells than the high MATH group.

Conclusions:

Individuals with low MATH scores had a longer OS than those with high MATH scores. Immune responses were significantly enhanced in breast cancer patients with low MATH scores.
Necrosis onstaging 18F FDG PET/CT is associated with worse progression-free survival in patients with stage IIIB non-small cell lung cancer
Authors: Eren Gulnihan , Kupik Osman
Published: February 2023

Objective:

The presence of pathological necrosis in the tumor is known to be a factor indicating worse survival. Our study defined necrosis in staging 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in patients with stage IIIB non-small-cell lung cancer (NSCLC) to investigate whether this is a poor prognostic marker.

Methodology:

A total of 77 patients with NSCLC were evaluated. To evaluate necrosis on 18F FDG PET/CT, we drew a region of interest (ROI) in the area showing visually very low/or no FDG uptake on PET and PET/CT fusion images. If SUVmax was less than blood pool SUVmax and showed significantly less attenuation [10 to 30 Hounsfield units (HUs)] than surrounding tissue on low-dose correlative CT with non-intravenous contrast, we defined it as necrotic (PETNECROSIS). We evaluated the relationship of SUVmax, tumor size, and PETNECROSIS with progression-free survival (PFS) using a Cox proportional hazard regression model.

Results:

A PFS analysis was performed on 16 patients treated with standard chemoradiotherapy (CRT) regimen. Tumor size ≤42 mm versus >42 mm (P = 0.044, HR: 6.103, 95 CI%: 1.053–35.358) and PETNECROSİS presence/absence (P = 0.027, HR: 6.719, 95 CI%: 1.245–36.264) were independent predictors for PFS. Patients with tumor size ≤42 mm and PETNECROSİS absence were associated with higher 1-year PFS rate than patients with tumor size >42 mm and PETNECROSİS presence (86% vs. 63.5% P = 0.005 and 87.5% vs. 29%, P = 0.001, respectively).

Conclusion:

PETNECROSİS is helpful to distinguish the patients who would suffer worse survival in stage IIIB NSCLC.