bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optic Perineuritis Associated With Cryptococcal Meningitis Presenting With a “Hot Orbit” in a Patient With Chronic Lymphocytic Leukemia
Authors: Liebman Daniel L. , Tam Emily K. , Lithgow Marie Y. , Kane Joseph E. , Fischbein Nancy J. , Lefebvre Daniel R. , Chwalisz Bart K. , Gaier Eric D. 
Published: April 2022

Abstract:
A 75-year-old man presented with 3 days of progressive left retro-orbital pain, eyelid swelling, tearing, and pain with extraocular movement. His medical history was significant for type II diabetes mellitus and chronic lymphocytic leukemia, stable on no therapy since diagnosis 8 years prior. The initial examination was significant for diffuse restriction of left ocular motility, marked lid edema, and mild dyschromatopsia. Computed tomography demonstrated asymmetric left periorbital soft tissue swelling and intraconal fat stranding with an irregular left optic nerve sheath complex and clear paranasal sinuses. He was hospitalized for orbital cellulitis and treated empirically with broad-spectrum intravenous antibiotics, but his visual acuity declined over the ensuing 2 days. Subsequent MRI demonstrated left-greater-than-right circumferential optic nerve sheath enhancement, and leptomeningeal enhancement. An orbital biopsy demonstrated monoclonal B-cell lymphocyte aggregation, whereas a lumbar puncture was positive for Cryptococcus antigen with subsequent demonstration of abundant Cryptococcus by Papanicolaou stain. The final diagnosis was optic perineuritis secondary to cryptococcal meningitis presenting with orbital inflammation. Although his clinical course was complicated by immune reconstitution inflammatory syndrome, symptoms and signs of optic neuropathy ultimately resolved after 1 month of intensive antifungal therapy.
Impact of Greater Occipital Nerve Block on Photophobia Levels in Migraine Patients
Authors: Membrilla Javier A. , de Lorenzo Íñigo , Sánchez-Casado Lucía , Sastre María , Díaz de Terán Javier 
Published: April 2022

Background:
To study the effect of greater occipital nerve (GON) block on migraine-associated photophobia levels. Photophobia is one of the most bothersome symptoms reported by migraine patients. Studies investigating the impact of migraine treatment on this symptom are scarce.

Methods:
This is an observational prospective case–control study. Patients with migraine and photophobia attending a Headache Clinic were recruited. Cases were defined as patients in whom GON block was performed, following usual clinical practice guidelines. All patients were evaluated with the Hospital Anxiety and Depression Scale, the Migraine Specific Quality of Life Questionnaire, the Utah Photophobia Symptom Impact Scale (UPSIS-12), and the Korean Photophobia Questionnaire (KUMC-8); both in the first visit (V1) and one week after (V2).

Results:
Forty-one patients were recruited, 28 (68.3%) cases and 13 (31.7%) controls. At V1, there were no significant differences in the median [p25-p75] score of UPSIS-12 in cases vs controls (32.0 [21.0–34.0] vs 30.5 [22.0–37.0], P = 0.497) or KUMC-8 (6.5 [5.5–7.0] vs 7.0 [6.0–8.0], P = 0.463). At V2, cases experimented a significant improvement in UPSIS-12 of −5.5 [−8.8 to −1.3] and in KUMC-8 of −0.5 [−2.0 to 0], whereas there were no significant changes in the control group. Migraine with aura patients presented higher UPSIS-12 score at V1 (33.5 [24.5–37.0] vs 26.0 [16.0–35.0]) and lesser improvement at V2 after GON block compared with migraine without aura patients (−4.0 [−6.0 to −1.0] vs −8.0 [−17.0 to −2.0]), although statistical significance was not achieved (P = 0.643 and P = 0.122, respectively). There was no significant variation in the remaining scales.

Conclusions:
Greater occipital nerve block improves migraine-associated photophobia, measured with UPSIS-12 and KUMC-8. Patients without aura may exhibit a greater improvement. Physicians could consider GON block for management of photophobia in migraine patients.
The Influence of Pregnancy on PrEP uptake and Adherence Amongst HIV-Negative High-Risk Young Women in Kampala, Uganda: A Qualitative Assessment
Authors: Joshi Shivali , Namuddu Catherine , Kasujja Francis Xavier , Mirembe Miriam , Homsy Jaco , Seeley Janet , King Rachel 
Published: April 2022

ABSTRACTBackgroundPregnant young women who engage in high-risk sexual activity are at elevated biological and social risk for HIV acquisition. PrEP serves as an effective means of HIV prevention, including during pregnancy. This study aimed to explore attitudes, experiences and challenges with PrEP to understand what motivates or limits PrEP uptake and adherence during pregnancy among this population of young women.MethodsSemi-structured interviews were conducted with 23 participants, recruited from the Prevention on PrEP (POPPi) study in the Good Health for Women Project clinic in Kampala, Uganda. POPPi’s inclusion criteria comprised of HIV-uninfected women, aged 15-24, who engaged in high-risk sexual activity. Interviews focused on experience with PrEP and pregnancy. Data were analyzed utilizing a framework analysis approach.FindingsKey themes were comprised of participant barriers to and facilitators of PrEP uptake and adherence. Reasons for PrEP initiation included desire for autonomy and agency, mistrust of partners, and social support. Participants expressed challenges with initiating or sustaining their use of PrEP, including PrEP access and perceived or felt stigma. During pregnancy, participants’ primary motivators for altering PrEP use were either understanding of PrEP safety for their baby or changes in perceptions of their HIV risk. Many of these factors were similar across participants who had experience with pregnancy and those who did not.InterpretationThis study highlights the importance of addressing barriers to and facilitators of PrEP adherence, especially during pregnancy where risk is elevated, with a multi-level approach. Community-oriented education, stigma reduction activities alongside access to PrEP, can serve as means for adherence. The development of robust PrEP adherence support guidelines regarding PrEP use during pregnancy among high-risk women, and strategies for their implementation, are of utmost importance for the control of HIV in key populations and the elimination of mother-to-child transmission of HIV.
The effect of population migration on the diffusion of cholera outbreaks in metapopulations
Authors: Demir Mahir 
Published: April 2022

AbstractIn this study, an improved Susceptible-Infected-Recovered (SIR) epidemic diffusion model for cholera is extended by including migration for susceptible people. This model is applied to a metapopulation that consists of two isolated cities where just susceptible individuals can migrate between the cities. The disease-free equilibrium, the endemic equilibrium points, and the basic reproductive number with unequal migration rates are analyzed for this metapopulation. Firstly, the study showed that the basic reproductive number depends on the migration rates between the cities. Then, showed that when the epidemic SIR system is stable, then the infected cases for cholera outbreak can reach zero in one city, but the infected cases in the other city still can stay positive. Finally, discussed three scenarios that depend on population sizes and migration rates of susceptible people between the cities and showed how important the migration rates are in the diffusion of the cholera outbreak by visualizing these three scenarios.Mathematics Subject ClassificationPrimary: 92B05; Secondary: 92D40
Markers of Fungal Translocation Are Elevated During Post-Acute Sequelae of SARS-CoV-2 Infection and Induce NF-κB Triggered Inflammation
Authors: Giron Leila B. , Peluso Michael J. , Ding Jianyi , Kenny Grace , Zilberstein Netanel F , Koshy Jane , Hong Kai Ying , Rasmussen Heather , Miller Greg , Bishehsari Faraz , Balk Robert A. , Moy James N. , Hoh Rebecca , Lu Scott , Goldman Aaron R. , Tang Hsin-Yao , Yee Brandon C. , Chenna Ahmed , Winslow John W. , Petropoulos Christos J. , Kelly J. Daniel , Wasse Haimanot , Martin Jeffrey N. , Liu Qin , Keshavarzian Ali , Landay Alan , Deeks Steven G. , Henrich Timothy J. , Abdel-Mohsen Mohamed 
Published: April 2022

ABSTRACTLong COVID, a type of Post-Acute Sequelae of SARS CoV-2 infection (PASC), has been associated with sustained elevated levels of immune activation and inflammation. However, the pathophysiological mechanisms that drive this inflammation remain unknown. Inflammation during acute Coronavirus Disease 2019 (COVID-19) could be exacerbated by microbial translocation (from the gut and/or lung) to the blood. Whether microbial translocation contributes to inflammation during PASC is unknown. We found higher levels of fungal translocation – measured as β-glucan, a fungal cell wall polysaccharide – in the plasma of individuals experiencing PASC compared to those without PASC or SARS-CoV-2 negative controls. The higher β-glucan correlated with higher levels of markers of inflammation and elevated levels of host metabolites involved in activatingN-Methyl-D-aspartate receptors (such as metabolites within the tryptophan catabolism pathway) with established neuro-toxic properties. Mechanistically, β-glucan can directly induce inflammation by binding to myeloid cells (via the Dectin-1 receptor) and activating Syk/NF-κB signaling. Using anin vitroDectin-1/NF-κB reporter model, we found that plasma from individuals experiencing PASC induced higher NF-κB signaling compared to plasma from SARS-CoV-2 negative controls. This higher NF-κB signaling was abrogated by the Syk inhibitor Piceatannol. These data suggest a potential targetable mechanism linking fungal translocation and inflammation during PASC.
Improved MALDI-TOF MS based antimicrobial resistance prediction through hierarchical stratification
Authors: Weis Caroline , Rieck Bastian , Balzer Sebastian , Cuénod Aline , Egli Adrian , Borgwardt Karsten 
Published: April 2022

AbstractMotivationPredicting antimicrobial resistance using MALDI-TOF mass spectrometry based machine learning is a fast-growing field of research. Recent advances in machine learning methods specifically designed for MALDI-TOF mass spectra have outperformed established classification approaches. However, classification performance was observed to have a large standard deviation between different train–test splits. We hypothesise that this variance is caused by the underlying phylogenetic structure between microbial samples, which is implicitly reflected in their MALDI-TOF MS profiles, but not taken into account during the training of a model.ResultsIn this paper, we propose to infer this structure from the dataset—using agglomerative hierarchical clustering—and consider it during the dataset splitting between train and test. We show that incorporating such phylogenetic structure into the antimicrobial resistance prediction scenario leads to an improved classification performance. Average precision was increased from 42.3 to 47.1 for ciprofloxacin resistance prediction in Escherichia coli and from 44.6 to 50.8 for amoxicillin-clavulanic acid resistance prediction in Staphylococcus aureus using a Gaussian process classifier with a MALDI-TOF MS specific kernel. We envision that these results will support the quick and reliable identification of antimicrobial resistances, thus increasing patient well-being and reducing healthcare costs.AvailabilityAll data is available for download and code available as an easy-to-use Python package under https://github.com/BorgwardtLab/maldi_PIKE at branch maldi_stratification.Contactcaroline.weis@bsse.ethz.ch, karsten.borgwardt@bsse.ethz.chSupplementary informationSupplementary information at the end of document.
Murine blastocysts generated by in vitro fertilization show increased Warburg metabolism and altered lactate production
Authors: Lee Seok Hee , Liu Xiaowei , Jimenez-Morales David , Rinaudo Paolo F. 
Published: April 2022

AbstractIn vitro fertilization (IVF) has resulted in the birth of over 8 million children. Although most of IVF-conceived children are healthy, several studies suggest an increased risk of altered growth rate, cardiovascular dysfunction, and glucose intolerance in this population compared to naturally conceived children. However, a clear understanding of how embryonic metabolism is affected by culture condition and how embryos reprogram their metabolism is unknown.Here, we studied oxidative stress and metabolic alteration in blastocysts conceived by natural mating or by IVF and culture in physiologic (5%) or atmospheric (20%) oxygen. We found that IVF-generated blastocyst manifest increased reactive oxygen species, oxidative damage to DNA/lipid/proteins, and reduction in glutathione. Metabolic analysis revealed IVF-generated blastocysts display decreased mitochondria respiration and increased glycolytic activity suggestive of enhanced Warburg metabolism. These findings were corroborated by altered intracellular and extracellular pH and increased intracellular lactate levels in IVF-generated embryos. Comprehensive proteomic analysis and targeted immunofluorescence showed reduction of LDH-B and MCT1, enzymes involved in lactate metabolism. Importantly, these enzymes remained downregulated in tissues of adult IVF-conceived mice, suggesting that metabolic alterations in IVF-generated embryos may result in alteration in lactate metabolism. These findings suggest that alterations in lactate metabolism is a likely mechanism involved in genomic reprogramming and could be involved in the developmental origin of health and disease.
Transcriptomics based prediction of survival and response to therapy in malignant mesothelioma
Authors: Nair Nishanth Ulhas , Jiang Qun , Wei Jun Stephen , Misra Vikram Alexander , Morrow Betsy , Kesserwan Chimene , Hermida Leandro C. , Lee Joo Sang , Mian Idrees , Zhang Jingli , Lebensohn Alexandra , Sengupta Manjistha , Khan Javed , Ruppin Eytan , Hassan Raffit 
Published: April 2022

ABSTRACTMalignant mesothelioma is an aggressive cancer with limited treatment options and poor prognosis. Better understanding of mesothelioma genomics and transcriptomics could advance novel therapies. We performed whole-exome and RNA-sequencing of germline and tumors of 122 patients with pleural, peritoneal, and tunica-vaginalis mesothelioma. We identify a 48 gene prognostic signature that is highly predictive of mesothelioma patient survival including CCNB1, whose expression is highly predictive of patient survival on its own. Using a synthetic-lethality (SL) based pipeline for analyzing the patients’ transcriptomic data, we identified SL-based signatures predictive of response to an anti-PD1 immune checkpoint inhibitor and combination therapies with pemetrexed. These SL-profiles successfully predict the overall patient-response observed across targeted, immuno- and chemotherapies in 11 independent mesothelioma clinical trials spanning 7 different treatments. These findings lay a basis for future studies aimed specifically at testing the ability of these SL profiles to serve as treatment biomarkers in mesothelioma.
Genomic analyses of wild and cultivated bacanora agave (Agave angustifoliavar.pacifica) reveal inbreeding, few signs of cultivation history and shallow population structure
Authors: Klimova Anastasia , Mondragón Karen Y. Ruiz , Freaner Francisco Molina , Aguirre-Planter Erika , Eguiarte Luis E. 
Published: April 2022

AbstractDue to the recent increase in demand for agave-based beverages, many wild agave populations have experienced rapid decline and fragmentation; whereas cultivated plants are now managed at monocultural plantations, in some cases involving clonal propagation. We examined the relative effect of migration, genetic drift, natural selection and human activities on the genetic repertoire ofAgave angustifolia var. pacifica, an agave used for bacanora (an alcoholic spirit similar to tequila) productionin northwesternMexico. We sampled 34 wild and cultivated sites and used over eleven thousand genome-wide SNPs. We found shallow genetic structure among wild samples, although, detected differentiation between coastal and inland sites. Surprisingly, no differentiation was found between cultivated and wild populations. Moreover, we detected moderate inbreeding (FIS∼ 0.13) and similar levels of genomic diversity in wild and cultivated agaves. Nevertheless, the cultivated plants had almost no private alleles and presented evidence of clonality. The overall low genetic structure inA. angustifoliavar.pacificais apparently the result of high dispersibility promoted by pollinators and possibility of clonal reproduction. Incipient cultivation history and reliance on wild seeds and plants are probably responsible for the observed patterns of high genetic connectivity and considerable diversity in cultivated samples.
Speed and correctness guarantees for programmable enthalpy-neutral DNA reactions
Authors: Wang Boya , Thachuk Chris , Soloveichik David 
Published: April 2022

AbstractMolecular control circuits embedded within chemical systems to direct molecular events have transformative applications in synthetic biology, medicine, and other fields. However, it is challenging to understand the collective behavior of components due to the combinatorial complexity of possible interactions. Some of the largest engineered molecular systems to date have been constructed from DNA strand displacement reactions, in which signals can be propagated without a net change in base pairs. For linear chains of such enthalpy-neutral displacement reactions, we develop a rigorous framework to reason about interactions between regions that must be complementary. We then analyze desired and undesired properties affecting speed and correctness of such systems, including the spurious release of output (leak) and reversible unproductive binding (toehold occlusion), and experimentally confirm the predictions. Our approach, analogous to the rigorous proofs of algorithm correctness in computer science, can guide engineering of robust and efficient molecular algorithms.
Free fatty acid receptor 4 (FFAR4) regulates cardiac oxylipin balance to promote inflammation resolution in a model of heart failure preserved ejection fraction secondary to metabolic syndrome
Authors: Zhang Naixin , Murphy Katherine A. , Harsch Brian , Zhang Michael , Gyberg Dylan J. , Wagner Brandon M. , Mendelson Jenna , Patterson Michael T. , Orchard Devin A. , Healy Chastity L. , Williams Jesse W. , Shearer Gregory C. , O’Connell Timothy D. 
Published: April 2022

ABSTRACTFree fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor for long-chain fatty acids that improves metabolism and attenuates inflammation. Heart failure preserved ejection fraction (HFpEF) is a complex clinical syndrome, but a predominant subset of patients has meta-bolic syndrome (MetS). Mechanistically, systemic, non-resolving inflammation associated with MetS might promote HFpEF. Interestingly, we recently demonstrated that Ffar4 is cardioprotective in pressure overload. The beneficial effects of Ffar4 on metabolism/inflammation, the high incidence of MetS in HFpEF patients, and the cardioprotective effects of Ffar4 led us to hypothesize that loss of Ffar4 would worsen remodeling in HFpEF secondary to MetS (HFpEF-MetS). To test this, mice with systemic deletion of Ffar4 (Ffar4KO) were fed a high-fat/high-sucrose diet with L-NAME in their water (HFpEF-MetS diet) to induce HFpEF-MetS. In male Ffar4KO mice, the HFpEF-MetS diet induced similar metabolic deficits, but worsened diastolic function and microvascular rarefaction compared to wild-type mice. Conversely, in female Ffar4KO mice, the diet produced greater obesity but no worsening of HFpEF. Loss of Ffar4 in males altered the balance of inflammatory oxylipins in the heart, decreasing the eicosapentaenoic acid derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE), while increasing the arachadonic acid derived, proinflammatory oxylipin 12-hydroxyeicosatetraenoic acid (12-HETE). This increased 12-HETE/18-HEPE ratio, reflecting a more proinflammatory state, was associated with increased macrophage numbers, which in turn correlated with worsened ventricular remodeling in male Ffar4KO hearts. In summary, our data suggest that Ffar4 controls the pro/anti-inflammatory oxylipin balance in the heart to modulate macrophage function and attenuate HFpEF remodeling.
A structural database of chain-chain and domain-domain interfaces of proteins
Authors: Sen Neeladri , Madhusudhan M.S. 
Published: April 2022

AbstractIn this study, we have mined the PDB and created a structural library of 178,465 interfaces that mediate protein-protein or domain-domain interactions. Interfaces involving the same CATH fold(s) were clustered together. Our analysis of the entries in the library reveals the similarity between chain-chain and domain-domain interactions. The library also illustrates how a single protein fold can interact with multiple folds using similar interfaces. The library is hence a useful resource to study the types of interactions between protein folds. Analyzing the data in the library reveals various interesting aspects of protein-protein and domain-domain interactions such as how proteins belonging to folds that interact with many other folds also have high EC values. These data could be utilized to seek potential binding partners. It can also be utilized to investigate the different ways in which two or more folds interact with one another structurally. We constructed a statistical potential of pair preferences of amino acids across the interface for chain-chain and domain-domain interactions separately. They are quite similar further lending credence to the notion that domain-domain interfaces could be used to study chain-chain interactions. Lastly and importantly, the library includes predicted small molecule binding sites at the protein-protein interfaces. This has applications as interfaces containing small molecule binding sites can be easily targeted to prevent the interaction and perhaps form a part of a therapeutic strategy.
ModA phasevarions regulate adherence of non-typeableHaemophilus influenzaeto the host airway in a tissue-specific manner
Authors: Garai Preeti , Atack John M. , Wills Brandon M. , Jennings Michael P. , Bakaletz Lauren O. , Brockman Kenneth L. 
Published: April 2022

AbstractAdherence of non-typeableHaemophilus influenzae(NTHi) to the host airway is an essential initial step for asymptomatic colonization of the nasopharynx, as well as development of disease. NTHi relies on strict regulation of multiple adhesins for its pathogenesis. The ModA phasevarion is a bacterial regulatory system important for virulence of NTHi. However, the role of the ModA phasevarion in adherence of NTHi to the host airway is not understood well. This study addressed the role of the ModA phasevarion in the regulation of adherence of NTHi to multiple substrates of the host airway. Assessment of adherence of themodAvariants of four clinical isolates of NTHi showed that ModA phasevarions regulated adherence of NTHi to mucus, middle ear epithelial cells, and vitronectin in a substrate-specific manner. The adhesins Protein E and P4 were found to contribute to the ModA-regulated adherence of NTHi to distinct substrates. A better understanding of such tissue-specific regulation of NTHi adherence by the ModA phasevarion will allow identification of virulent NTHi populations at the site of disease within the host airway and facilitate more directed development of vaccines or therapeutics.