bluuebunny/crossref_metadata_2025 huggingface dataset:
Shorter durations of antibiotic therapy in organ transplant
Authors: Alegria William , Medvedeva Natalia , Holubar Marisa
Published: November 2022

Purpose of review

Recent evidence supports shorter courses of antibiotics for several common infections and prophylactic indications. Unfortunately, solid organ transplant patients are often underrepresented or excluded from these studies. As a result, prolonged antibiotic durations are often used in clinical practice despite a lack of demonstrable benefit. This paper reviews recent publications addressing antibiotic duration of therapy in SOT recipients.

Recent findings

Although largely limited to observational studies, longer courses of antibiotics for surgical prophylaxis, urinary tract infections, and bloodstream infections have not demonstrated benefit compared to shorter courses. In some instances, longer courses of therapy have been associated with harm (i.e., adverse drug events and development of resistance).

Although the data remains limited, findings from retrospective studies evaluating shorter courses of antibiotics in SOT patients is encouraging. More robust research is desperately needed to define the optimal duration of antibiotics for common infections in SOT patients.
Liver transplantation and portal vein tumour thrombus: futile enterprise?
Authors: Bhangui Prashant
Published: November 2022

Purpose of review

To summarize recent evidence in literature regarding liver transplantation in patients with hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT) with no extrahepatic disease. In addition, in this review, we have tried to highlight the advances in downstaging with ablative therapies that have made liver transplantation a possibility, and also the key points to focus on when considering liver transplantation in these patients with locally advanced HCC.

Recent findings

Advances in the understanding of technicalities and effectiveness of ablative therapies, including transarterial chemoembolization, stereotactic body radiotherapy and transarterial radioembolization on PVTT have helped successfully downstage patients with HCC and PVTT to within transplant criteria. This provides the opportunity to offer a curative liver transplantation in these patients who are generally managed with systemic or palliative therapy alone with dismal prognosis. Meticulous patient selection based on tumour biology, documented downstaging based on imaging and decrease in tumour marker levels, an adequate waiting period to demonstrate stable disease, liver transplantation with some technical modifications, and a modified immunosuppression protocol may offer long-term survival in a select group of patients treated with initial downstaging therapies in an intention to treat strategy.

In patients with HCC, presence of PVTT is generally considered the end of the road by many. A multidisciplinary approach combining ablation and a curative liver transplantation may offer the best hope of long-term survival in a select group of patients with favourable tumour biology. Although promising, current evidence is limited, and future studies with larger number of patients, and longer follow-up may pave the way for an elaborate selection algorithm to choose the ideal candidates for such a curative strategy in patients with locally advanced HCC with PVTT.
“Autophagy Dysfunction in a Diabetic Peripheral Neuropathy Model”
Authors: Choi Su-Jeong , Kim Sena , Lee Won Suk , Kim Dong Woon , Kim Cuk-Seong , Oh Sang-Ha
Published: November 2022

Background:

The relationship between autophagy and diabetic peripheral neuropathy (DPN) has been highlighted in a only few reports. Using an animal model, we investigated the relationship between autophagy and DPN, and focused particularly on changes in autophagy in Schwann cells.

Methods:

The ultrastructural features of DPN mice were evaluated in vivo using transmission electron microscopy. Dysfunction of autophagy in DPN was evaluated using immunofluorescence microscopy and western blot analysis of autophagy-related proteins, including Beclin1, LC3, and p62. Reactive oxygen species (ROS) levels were measured in vitro in glucose-treated Schwann cells. Dysfunction of autophagy in glucose-treated Schwann cells was examined by immunofluorescence microscopy and western blot analysis.

Results:

Reduced myelin thickness and axonal shrinkage were observed in the sciatic nerves of DPN mice. ROS levels were increased in high glucose-treated Schwann cells (p < 0.05). The expression of Becline1 was increased in DPN mice and high glucose-treated Schwann cells (p < 0.05), whereas the expression of LC3-Ⅱ/LC3-Ⅰ ratio and p62 were decreased in DPN mice and high glucose-treated Schwann cells (p < 0.05).

Conclusions:

Our results suggest that increased levels of ROS induced by high glucose may contribute to autophagy dysfunction in Schwann cells. Autophagy dysfunction especially in Schwann cells may be an underlying cause of DPN.
Ai Chi for Long COVID: Transitioning to a Post-Rehabilitation Community Program
Authors: Pierce Melinda Nygren
Published: November 2022

Background:

As the COVID-19 pandemic continues to impact lives around the world, long COVID symptoms plague a significant number of survivors in their daily lives. Guidelines are available for individualized rehabilitation during acute and subacute phases; however, safe community options are needed for those with lingering symptoms who are transitioning away from formal rehabilitation. A lack of access or resistance to COVID-19 vaccination worldwide, and the emergence of more aggressive coronavirus variants, is predicted to result in many more positive COVID-19 cases and consequentially in more long haulers, increasing the need for community resources.

Discussion:

Ai Chi is a gentle aquatic body-mind practice employed worldwide by aquatic therapists and trainers to reduce stress, enhance breathing, strengthen core muscles, extend joint range of motion, improve balance, stabilize heart rate, and promote focus and centering. It can address some of the common persisting symptoms in medically stable individuals with long COVID including pain, difficulty breathing, muscle weakness, and stress. While Ai Chi is a promising community aquatic intervention, exercise providers need to be aware of special considerations that may impact this population in community programming, such as postexertional malaise, cardiac impairment, oxygen desaturation, and autonomic nervous system dysfunction when providing exercise programs. Research is needed to validate the effectiveness of Ai Chi with post-rehabilitation COVID long haulers in a community setting.
Artificial Intelligence–Driven Ultra-Fast Superresolution MRI
Authors: Lin Dana J. , Walter Sven S. , Fritz Jan
Published: November 2022

Magnetic resonance imaging (MRI) is the keystone of modern musculoskeletal imaging; however, long pulse sequence acquisition times may restrict patient tolerability and access. Advances in MRI scanners, coil technology, and innovative pulse sequence acceleration methods enable 4-fold turbo spin echo pulse sequence acceleration in clinical practice; however, at this speed, conventional image reconstruction approaches the signal-to-noise limits of temporal, spatial, and contrast resolution. Novel deep learning image reconstruction methods can minimize signal-to-noise interdependencies to better advantage than conventional image reconstruction, leading to unparalleled gains in image speed and quality when combined with parallel imaging and simultaneous multislice acquisition. The enormous potential of deep learning–based image reconstruction promises to facilitate the 10-fold acceleration of the turbo spin echo pulse sequence, equating to a total acquisition time of 2–3 minutes for entire MRI examinations of joints without sacrificing spatial resolution or image quality. Current investigations aim for a better understanding of stability and failure modes of image reconstruction networks, validation of network reconstruction performance with external data sets, determination of diagnostic performances with independent reference standards, establishing generalizability to other centers, scanners, field strengths, coils, and anatomy, and building publicly available benchmark data sets to compare methods and foster innovation and collaboration between the clinical and image processing community. In this article, we review basic concepts of deep learning–based acquisition and image reconstruction techniques for accelerating and improving the quality of musculoskeletal MRI, commercially available and developing deep learning–based MRI solutions, superresolution, denoising, generative adversarial networks, and combined strategies for deep learning–driven ultra-fast superresolution musculoskeletal MRI. This article aims to equip radiologists and imaging scientists with the necessary practical knowledge and enthusiasm to meet this exciting new era of musculoskeletal MRI.
Altered Glucose Metabolism Postchemotherapy Precedes PSMA Expression in Poorly Differentiated Prostate Cancer
Authors: Alabed Yazan Z.
Published: November 2022

A 73-year-old man presented with gastric lesion on upper endoscopy, biopsy-proven as poorly differentiated carcinoma. Staging FDG PET/CT scan showed gastric, intraprostatic, nodal, and extensive osseous lesions. Prostate-specific antigen levels were greater than 1000. The patient was treated as metastatic poorly differentiated prostate cancer with chemotherapy. Posttherapy 18F-PSMA-1007 and FDG PET/CT scans were obtained. PSMA PET/CT scan revealed extensive disease similar in appearance as staging FDG PET/CT scan, indicating no apparent treatment response. FDG PET/CT scan showed partial metabolic response, correlating with improved prostate-specific antigen levels. This case indicates that chemotherapy-induced changes in glucose metabolism likely precede change in PSMA expression in poorly differentiated prostate cancer.
Natural History of Stage IV Pancreatic Cancer. Identifying Survival Benchmarks for Curative-intent Resection in Patients With Synchronous Liver-only Metastases
Authors: Kaslow Sarah R. , Sacks Greg D. , Berman Russell S. , Lee Ann Y. , Correa-Gallego Camilo
Published: November 2022

Objective:

To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients.

Background:

Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups.

Methods:

We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan–Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis.

Results:

We identified 241 patients. Median OS was 7 months (95% CI, 5–9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17–39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR).

Conclusions:

The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.
Applications of Mendelian randomization in psychiatry: a comprehensive systematic review
Authors: Saccaro Luigi F. , Gasparini Simone , Rutigliano Grazia
Published: November 2022

Psychiatric diseases exact a heavy socioeconomic toll, and it is particularly difficult to identify their risk factors and causative mechanisms due to their multifactorial nature, the limited physiopathological insight, the many confounding factors, and the potential reverse causality between the risk factors and psychiatric diseases. These characteristics make Mendelian randomization (MR) a precious tool for studying these disorders. MR is an analytical method that employs genetic variants linked to a certain risk factor, to assess if an observational association between that risk factor and a health outcome is compatible with a causal relationship. We report the first systematic review of all existing applications and findings of MR in psychiatric disorders, aiming at facilitating the identification of risk factors that may be common to different psychiatric diseases, and paving the way to transdiagnostic MR studies in psychiatry, which are currently lacking. We searched Web of Knowledge, Scopus, and Pubmed databases (until 3 May 2022) for articles on MR in psychiatry. The protocol was preregistered in PROSPERO (CRD42021285647). We included methodological details and results from 50 articles, mainly on schizophrenia, major depression, autism spectrum disorders, and bipolar disorder. While this review shows how MR can offer unique opportunities for unraveling causal links in risk factors and etiological elements of specific psychiatric diseases and transdiagnostically, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.
Microbe-derived antimicrobial red pigments for color formation and
microbial growth control in sausage: A mini-review
Authors: Choe Deokyeong
Published: November 2022

Sausage is a popular processed meat product and its consumption has significantly
increased over the past 20 years. Sodium nitrite is used to impart a distinct
red color and cured flavor to sausage during its production. Moreover, sodium
nitrite inhibits lipid oxidation and growth of pathogenic microorganisms in
sausage. Despite these advantages, it is advisable to replace and reduce sodium
nitrite use since sausages with sodium nitrite are classified as a Group 1
carcinogen. The replacement additives should not only impart red color but also
control microbial growth because sausage color is an important factor in its
marketing and the control of initial microbial concentration during sausage
production process is critical for its safety, distribution, and storage.
However, only few sodium nitrite alternatives can impart color while inhibiting
microorganism growth. To address this issue, use of natural red pigments with
antimicrobial activity is being considered. Interest in natural functional
pigments, in particular, microbial pigments with physiological activities, has
spiked due to their various advantages, such as sustainable supply in large
amounts, high yield, and easy down-streaming processing, over those extracted
from plants or insects. This review highlights the characteristics of
microbe-derived antimicrobial red pigments and their potential application as
alternatives to sodium nitrite in sausage processing.
Qualitative evaluation of commercial kimchi
seasoning products
Authors: Chung Young-Bae , Kim Ye-Sol , Chon Seo-Yeong , Choi Yun-Jeong , Min Sung Gi , Seo Hye-Young
Published: November 2022

This study aimed to evaluate the physicochemical and microbiological quality of
kimchi seasoning products purchased from an online shopping mall, using cluster
analysis to inform consumers about the quality of commercial kimchi seasoning
and enable them to make informed purchasing decisions. The clusters were
classified into four groups: CKS02 to 03 (group I), CKS04 to 05 (group II),
CKS07 to 09 (group III), and others (CKS01, CKS06, and CKS10) (group IV).
Principal component analysis (PCA) validated the cluster characteristics and a
strong correlation between the moisture content in group I, salinity in group
II, capsaicinoids content in group III, and pH in group IV. Highly significant
correlations were observed between the L (lightness) and b (yellowness) values,
solid and moisture content, and viscosity and solid content of kimchi seasoning.
The findings of this study provide information on the baseline quality of
commercially available seasoning products, and it is expected that items with a
high correlation among the seasoning qualities can be used as management
indicators to ensure consistency.
Quality characteristics of jeungpyeon with
different additions of won-ju (raw
makgeolli)
Authors: Choi Jin-Hee , Chu Ji-Hye , Choi Hae-Yeon , Jeon Hee-Kyung , Park Jong-Dae , Sung Jung-Min
Published: November 2022

In this study, by replacing makgeolli in
jeungpyeon manufacturing with won-ju (raw
makgeolli) and standardizing the mixing ratio, it was
intended to provide information that could suit consumers’ tastes and
utilize the added value of won-ju (R10, R20, R30, R40 means
amounts of raw makgeolli). Raw makgeolli
content did not significantly differ in moisture content. pH, L value, hardness
and gumminess decreased with increasing addition of raw
makgeolli, while the b value, adhesiveness, springiness,
cohesiveness, and chewiness were increased. The specific volume was the highest
following method R30, and the expansion rate was the lowest following method
R40. The observation with Image J showed that as the amount of raw
makgeolli increased, the pore size became larger, and the
number of pores decreased. As for the sensory evaluation and results of
jeungpyeon, the R30 group showed the highest score in all
items(flavor, appearance, texture, taste, overall acceptability). Therefore,
this study suggests that Jueng-pyun produced with the R30
mixing ratio has excellent quality and sensory characteristics. Furthermore, the
results can be used as foundation data for the standardization of won-ju
jeungpyeon production.
Sentiments and Emotions for Vaccination in 2021: An International Comparison Study
Authors: Liu Xue-Jing
Published: November 2022

Comprehending how individuals feel when they discuss the vaccine is important for the immunization campaign and outbreak management during a health emergency. Online conversations provide useful information for assessing sentimental and emotional reactions to the evolutions of the pandemic and immunization program. In this study, we employ a corpus of around 58 million English tweets from users in 17 countries that discuss vaccine-related topics in the year 2021. We apply Soft Dynamic Time Warping algorithm and Time Lag Cross-Correlation approach and find that the evolutions of sentiments closely mirror the pandemic statistics. We also examine five topics connected to vaccination and discover that trust is the most predominate feeling, followed by fear, anger, and joy. Some countries reported higher emotional scores on a theme than others (people in Cuba and the United States exhibit higher levels of trust, Pakistanis and Indians express higher levels of joy, Australians and Chinese express higher levels of fear, and Japanese and British people express higher levels of anger). This study report offers a viewpoint on the public’s response to the epidemic and vaccination and aids policy-makers with preventive strategies for a future crisis.
Immune landscape of isocitrate dehydrogenase stratified human gliomas
Authors: Gupta Pravesh , Dang Minghao , Oberai Shivangi , Peshoff Mekenzie , Milam Nancy , Ahmed Aml , Bojja Krishna , Tran Tuan M. , Cox Kathryn , Shehwana Huma , Kamiya-Matsuoka Carlos , Li Jianzhuo , Gumin Joy , Goldman Alicia , Seth Sameer A. , Maheshwari Atul , Lang Frederick F. , Navin Nicholas E. , Heimberger Amy B. , Clise-Dwyer Karen , Wang Linghua , Bhat Krishna P.
Published: November 2022

The brain tumor immune microenvironment (TIME) continuously evolves during glioma progression, but only a limited view of a highly complex glioma associated immune contexture across isocitrate dehydrogenase mutation (IDH) classified gliomas is known. Herein, we present an unprecedentedly comprehensive view of myeloid and lymphoid cell type diversity based on our single cell RNA sequencing and spectral cytometry-based interrogation of tumor-associated leukocytes from fifty-five IDH stratified primary and recurrent human gliomas and three non-glioma brains. Our analyses revealed twenty-two myeloid and lymphoid cell types within and across glioma subtypes. Glioma severity correlated with microglial attrition concomitant with a continuum of invading monocyte-derived microglia-like and macrophages amongst other infiltrating conventional T and NK lymphocytes and unconventional mucosa associated invariant T (MAIT) cells. Specifically, certain microglial and monocyte-derived subpopulations were associated with antigen presentation gene modules, akin to cross-presenting dendritic cells (DCs). Furthermore, we identified phagocytosis and antigen presentation gene modules enriched in Triggering receptor expressed on myeloid (TREM)-2+cells as a putative anti-glioma axis. Accelerated glioma growth was observed inTrem2deficient mice implanted with CT2A glioma cells affirming the anti-glioma role of TREM2+myeloid cells. In addition to providing a comprehensive landscape of glioma-specific immune contexture, our investigations discover TREM2 as a novel immunotherapy target for brain malignancies.
Automatic brain categorization of discrete auditory emotion expressions
Authors: Talwar Siddharth , Barbero Francesca M. , Calce Roberta P. , Collignon Olivier
Published: November 2022

Seamlessly extracting emotional information from voices is crucial for efficient interpersonal communication. However, it remains unclear how the brain categorizes vocal expressions of emotion beyond the processing of their acoustic features. In our study, we developed a new approach combining electroencephalographic recordings (EEG) in humans with an oddball frequency tagging paradigm to automatically tag neural responses to specific emotion expressions. Participants were presented with a periodic stream of heterogeneous non-verbal emotional vocalizations belonging to five emotion categories (Anger, Disgust, Fear, Happiness, Sadness) at 2.5 Hz. Importantly, unbeknown to the participant, a specific emotion category appeared at an oddball presentation rate at 0.83 Hz that would elicit an additional response in the EEG spectrum only if the brain discriminates the target emotion category from other emotion categories and generalizes across heterogeneous exemplars of the target emotion category. Stimuli were matched across emotion categories for harmonicity-to-noise ratio, spectral center of gravity, pitch, envelope, and early auditory peripheral processing via the simulated output of the cochlea. Additionally, participants were presented with a scrambled version of the stimuli with identical spectral content and periodicity but disrupted intelligibility. We observed that in addition to the responses at the general presentation frequency (2.5 Hz) in both intact and scrambled sequences, a peak in the EEG spectrum at the oddball emotion presentation rate (0.83 Hz) and its harmonics emerged in the intact sequence only. The absence of response at the oddball frequency in the scrambled sequence in conjunction to our stimuli matching procedure suggests that the categorical brain response elicited by a specific emotion is at least partially independent from low-level acoustic features of the sounds. Further, different topographies were observed when fearful or happy sounds were presented as an oddball that supports the idea of different representations of distinct discrete emotions in the brain. Our paradigm revealed the ability of the brain to automatically categorize non-verbal vocal emotion expressions objectively (behavior-free), rapidly (in few minutes of recording time) and robustly (high signal-to-noise ratio), making it a useful tool to study vocal emotion processing and auditory categorization in general in populations where brain recordings are more challenging.
Elasticity control of entangled chromosomes: crosstalk between condensin complexes and nucleosomes
Authors: Yamamoto Tetsuya , Kinoshita Kazuhisa , Hirano Tatsuya
Published: November 2022

Condensin-mediated loop extrusion is now considered as the main driving force of mitotic chromosome assembly. Recent experiments have shown, however, that a class of mutant condensin complexes deficient in loop extrusion can assemble chromosome-like structures inXenopusegg extracts, although these structures are somewhat different from those assembled by wild-type condensin complexes. In the absence of topoisomerase II (topo II), the mutant condensin complexes produce an unusual round-shaped structure termed a ‘bean’, which consists of a DNA-dense central core surrounded by a DNA-sparse halo. The mutant condensin complexes accumulate in the core whereas histones are more concentrated in the halo than in the core. We consider that this peculiar structure serves as a model system to study how DNA entanglements, nucleosomes, and condensin functionally crosstalk with each other. To gain insight into how the bean structure is formed, here we construct a theoretical model. Our theory predicts that the core is formed by attractive interactions between mutant condensin complexes whereas the halo is stabilized by the energy reduction through the selective accumulation of nucleosomes. The formation of the halo increases the elastic free energy due to the DNA entanglement in the core, but the latter free energy is compensated by condensin complexes that suppress the assembly of nucleosomes.
TREM1+regulatory myeloid cells expand in steatohepatitis-HCC and associate with poor prognosis and therapeutic resistance to immune checkpoint blockade
Authors: Giraud Julie , Chalopin Domitille , Ramel Eloïse , Boyer Thomas , Zouine Atika , Derieppe Marie-Alix , Larmonier Nicolas , Adotevi Olivier , Bail Brigitte Le , Blanc Jean-Frédéric , Chiche Laurence , Nikolski Macha , Saleh Maya
Published: November 2022

Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Immune checkpoint blockade primarily benefits patients with viral HCC. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance in the steatohepatitis setting. Here, we present a high resolution atlas of hepatic innate immune cells from patients with HCC that unravels a steatohepatitis contexture characterized by the emergence of high entropy myeloid cell states and myeloid-biased NK cell differentiation. We identify a discrete population of tumor-infiltrating myeloid cells, predominant in the steatohepatitis setting, that expresses a variety of myeloid lineage-affiliated genes, including granulocyte, macrophage and dendritic cell features, and can be identified in HCC tumors based on selective dual expression ofTREM1andCD163. Functional characterization reveals that TREM1+CD163+myeloid cells highly express TGFβ and IL-13RA, localize to HCC fibrotic lesions, and potently suppress T cell effector functionsex vivo, a function further potentiated by TREM1 engagement. We refer to this population as TREM1+CD163+regulatory myeloid cells (TREM1+CD163+Mreg). Deconvolution analyses in large cohorts of patients with HCC and other solid tumors reveals that the density of TREM1+CD163+Mregincreases in advanced stages, associates with poor prognosis, and therapeutic resistance to PD-1 blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC and identify TREM1 as a therapeutic target.

HIGHLIGHTS

Atlas of hepatic innate immune cells (100,000 transcriptomes) from patients with HCC

Core signatures to identify, discriminate and localize innate lymphoid and myeloid cells

A population of TREM1+CD163+myeloid cells, referred to as TREM1+CD163+Mreg, expands in steatohepatitis HCC

TREM1+CD163+Mregexpress granulocyte- and macrophage/dendritic cell-lineage genes

TREM1+CD163+Mregpotently suppress T cell effector functions, which is potentiated by TREM1 engagement by cognate ligands

TREM1+CD163+Mregproduce high levels of TGFβ and populate fibrotic lesions

The density of TREM1+CD163+Mregincreases in advanced HCC and associate with poor patient survival

The density of TREM1+CD163+Mregassociates with resistance to immune checkpoint blockade in other solid tumors
Gac is a transcriptional repressor of the Lyme disease spirochete’s OspC virulence-associated surface protein
Authors: Castro-Padovani Tatiana N. , Saylor Timothy C. , Husted Olivia T. , Krusenstjerna Andrew C. , Jusufovic Nerina , Stevenson Brian
Published: November 2022

The OspC outer-surface lipoprotein is essential for the Lyme disease spirochete’s initial phase of vertebrate infection. Bacteria within the midguts of unfed ticks do not express OspC, but produce high levels when ticks begin to ingest blood. Lyme disease spirochetes cease production of OspC within 1-2 weeks of vertebrate infection, and bacteria that fail to downregulate OspC are cleared by host antibodies. Thus, tight regulation of OspC levels is critical for survival of Lyme borreliae, and therefore an attractive target for development of novel treatment strategies. Previous studies determined that a DNA region 5’ of theospCpromoter, theospCoperator, is required for control of OspC production. Hypothesizing that theospCoperator may bind a regulatory factor, DNA affinity pulldown was performed, and identified binding by the Gac protein. Gac is encoded by the C-terminal domain of thegyrAopen reading frame, from an internal promoter, ribosome-binding site, and initiation codon. Our analyses determined that Gac exhibits a greater affinity forospCoperator and promoter DNAs than for other tested borrelial sequences. In vitro and in vivo analyses demonstrated that Gac is a transcriptional repressor ofospC. These results constitute a substantial advance to our understanding the mechanisms by which the Lyme disease spirochete controls production of OspC.

Importance

Borrelia burgdorferi(sensu lato) requires its surface-exposed OspC protein in order to establish infection of humans and other vertebrate hosts. Bacteria that either do not produce OspC during transmission, or fail to repress OspC after infection is established, are rapidly cleared by the host. Herein, we identified a borrelial protein, Gac, that exhibits preferential affinity to theospCpromoter and 5’ adjacent DNA. A combination of biochemical analyses and investigations of genetically-manipulated bacteria demonstrated that Gac is a transcriptional repressor ofospC. This is a substantial advance toward understanding how the Lyme disease spirochete controls production of the essential OspC virulence factor, and identifies a novel target for preventative and curative therapies.
Jointly aligning cells and genomic features of single-cell multi-omics data with co-optimal transport
Authors: Demetci Pinar , Tran Quang Huy , Redko Ievgen , Singh Ritambhara
Published: November 2022

The availability of various single-cell sequencing technologies allows one to jointly study multiple genomic features and understand how they interact to regulate cells. Although there are experimental challenges to simultaneously profile multiple features on the same single cell, recent computational methods can align the cells from unpaired multi-omic datasets. However, studying regulation also requires us to map the genomic features across different measurements. Unfortunately, most single-cell multi-omic alignment tools cannot perform these alignments or need prior knowledge. We introducescootr, a co-optimal transport-based method, which jointly aligns both cells and genomic features of unpaired single-cell multi-omic datasets. We applyscootrto various single-cell multi-omic datasets with different types of measurements. Our results show thatscootrprovides quality alignments for unsupervised cell-level and feature-level integration of datasets with sparse feature correspondences (e.g., one-to-one mappings). For datasets with dense feature correspondences (e.g., many-to-many mappings), our joint framework allows us to provide supervision on one level (e.g., cell types), thus improving alignment performance on the other (e.g., genomic features) or vice-versa. The unique joint alignment framework makesscootra helpful hypothesis-generation tool for the integrative study of unpaired single-cell multi-omic datasets.

Available at:https://github.com/rsinghlab/SCOOTR.
Standardization of laboratory practices for the study of the human gut microbiome
Authors: Kool Jolanda , Tymchenko Liza , Shetty Sudarshan , Fuentes Susana
Published: November 2022

Technical advances in next-generation sequencing (NGS) have made it more accessible to study the human microbiome, resulting in more available data and knowledge. As a result of this expansion of data, the need to obtain comparable and reproducible data has become one of the most important challenges facing microbiome research nowadays. In this study, we aim to contribute to existing knowledge to promote high quality microbiome data and minimize bias introduced by technical variation throughout studies, from sample collection, storage, to sequencing strategies. While immediate freezing upon sampling has been the “golden standard” in the field, this method is often logistically difficult and expensive, becoming a limiting factor when conducting large scale studies or in regions where maintenance of the cold-chain presents difficulties. Therefore, we compared the immediately frozen method to storage at room temperature for 3 – 5 days in two commercially available stabilization solutions (Omnigene gut and Zymo Research) as well as without buffer. Other important aspects were tested, such as DNA extraction, bacterial DNA input or number of PCR cycles. Method choice for cell disruption resulted in the biggest difference in compositional profiles. The changes observed in microbiome profiles in samples stored at RT without stabilization solution was prevented by the use of these. For library preparation and sequencing, we found the highest heterogeneity in the DNA extraction step, followed by the use of different Illumina barcodes, indicating that both of these steps have an impact during library preparation. We did not observe a batch effect between the different sequencing runs. Standardized methods are important to allow comparison of results between different research groups worldwide and reliably expand microbiome data to a broad range of diseases, ethnical backgrounds and geographic locations. A more global perspective will increase our understanding of the human microbiome around the world.
Massive proteogenomic reanalysis of publicly available proteomic datasets of human tissues in search for protein recoding via adenosine-to-inosine RNA editing
Authors: Levitsky Lev I. , Ivanov Mark V. , Goncharov Anton O. , Kliuchnikova Anna A. , Bubis Julia A. , Lobas Anna A. , Solovyeva Elizaveta M. , Pyatnitskiy Mikhail A. , Ovchinnikov Ruslan K. , Kukharsky Mikhail S. , Farafonova Tatiana E. , Novikova Svetlana E. , Zgoda Victor G. , Tarasova Irina A. , Gorshkov Mikhail V. , Moshkovskii Sergei A.
Published: November 2022

The proteogenomic search pipeline developed in this work has been applied for re-analysis of 40 publicly available shotgun proteomic datasets from various human tissues comprising more than 8,000 individual LC-MS/MS runs, of which 5442 .raw data files were processed in total. The scope of this re-analysis was focused on searching for ADAR-mediated RNA editing events, their clustering across samples of different origin, and classification. In total, 33 recoded protein sites were identified in 21 datasets. Of those, 18 sites were detected in at least two datasets representing the core human protein editome. In agreement with prior art works, neural and cancer tissues were found being enriched with recoded proteins. Quantitative analysis indicated that recoding of specific sites did not directly depend on the levels of ADAR enzymes or targeted proteins themselves, rather it was provided by differential and yet undescribed regulation of interaction of enzymes with mRNA. Nine recoding sites conservative between human and rodents were validated by targeted proteomics using stable isotope standards in murine brain cortex and cerebellum, and an additional one was validated in human cerebrospinal fluid. In addition to previous data of the same type from cancer proteomes, we provide a comprehensive catalog of recoding events caused by ADAR RNA editing in the human proteome.
High Throughput Chromosome Conformation Capture identifies differential genome organization in virulent and avirulent strains ofMycobacterium tuberculosis
Authors: Mishra Mohit , Arya Ajay , Malik Md. Zubbair , Bhatnagar Rakesh , Hasnain Seyed E. , Ahmad Shandar , Chaturvedi Rupesh
Published: November 2022

Recent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization inMycobacterium tuberculosis (M. tuberculosis), the etiologic agent of tuberculosis, remains unknown. On the other hand, exact mechanism of differential pathogenesis in the canonical strains ofM. tuberculosisH37Rv and H37Ra remains poorly understood in terms of their raw sequences. In this context, a detailed contact map from a Hi-C experiment is a candidate for what bridges the gap. Here we present the first comprehensive report on genome-wide contact maps between regions of H37Rv and H37Ra genomes. We tracked differences between the genome architectures of H37Rv and H37Ra, which could possibly explain the virulence attenuation in H37Ra. We confirm the existence of a differential organization between the two strains most significantly a higher Chromosome Interacting Domain (CID) size in attenuated H37Ra strain. CID boundaries are also found enriched with highly expressed genes and with higher operon density in H37Rv. Furthermore, most of the differentially expressed PE/PPE genes were present near the CID boundaries in H37Rv and not in H37Ra. Collectively our study proposes a differential genomic topological pattern between H37Rv and H37Ra, which could explain the virulence attenuation in H37Ra.
Establishing the Median Infectious Dose (ID50) and Characterizing the Clinical Manifestations of Mouse, Rat, Cow, and HumanCorynebacterium bovisIsolates in Select Immunocompromised Mouse Strains
Authors: Mendoza Gerardo , Cheleuitte-Nieves Christopher , Lertpiriyapong Kvin , Wipf Juliette R.K. , Arbona Rodolfo J. Ricart , Miranda Ileana C. , Lipman Neil S.
Published: November 2022

Corynebacterium bovis(Cb), the etiology of hyperkeratotic dermatitis in various immunocompromised mouse strains, significantly impacts research in which infected mice are used. Although Cb has been isolated from a variety of species, including mice, rats, cows, and humans, little is known about the differences in the infectivity and clinical disease in mice associated with unique isolates. The infectious dose yielding colonization of 50% of the exposed population (ID50) and any associated clinical disease was determined for mouse (n=3), rat (n=1), cow (n=1), and human (n=2) Cb isolates in athymic nude mice (Hsd:Athymic Nude-Foxn1nu). The same investigations were undertaken comparing 2 of these murine isolates in 2 furred immunocompromised mouse strains (NSG [NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz] and NSG-S [NOD.Cg-PrkdcscidIl2rgtm1WjlTg(CMV-IL3,CSF2,KITLG)1Eav/MloySzJ]). To determine the ID50, mice (n=6/dose; 3 of each sex) were inoculated topically with 1 to 108bacteria (10-fold increments) of each Cb isolate. Mice were scored (0 to 5) daily based on the severity of clinical signs for 14 days. On day 7 and 14 post-inoculation (PI), buccal and dorsal skin swabs were evaluated by aerobic culture to determine infection status. The mouse isolates yielded a lower ID50(58 to 1,000 bacteria) as compared to the bovine (6,460 to 7,498 bacteria) and rat (10,000 bacteria) Cb isolates. Mice were not colonized and disease did not result when inoculated with human isolates. Mouse isolates produced varying clinical disease severity in nude mice (max score/isolate: 0 to 5). Despite significant immunodeficiency, furred NSG and NSG-S mice required a considerably higher (1,000- to 3,000-fold) inoculum to become colonized as compared to athymic nude mice. Once colonized, clinically detectable hyperkeratosis did not develop in these strains until 18 to 22 days PI. In contrast, in athymic nude mice that developed clinically detectable disease, hyperkeratosis was observed 6 to 14 days PI. In conclusion, there are significant differences in Cb’s ID50, disease course, and severity between Cb isolates and among immunodeficient mouse strains.
Determination against all odds? A story from Waste4Change
Authors: Adhariani Desi , Dewi Miranti Kartika
Published: November 2022

Learning outcomes

This case aims to help students achieve the following learning objectives: ■ to apply the Emergence of Social Enterprise in Europe (Emergence des Enterprises Sociales en Europe – EMES) Network definitional framework to the case, and in doing so, have a useful framework to define social enterprises in emerging markets; ■ to identify the factors that can play important role in making strategic decisions in social enterprises; ■ to evaluate the sustainability of a social enterprise; and ■ to address the unique funding and financial challenges faced by social enterprises.

Case overview/synopsis

This case study discusses the dilemmas related to business expansion faced by Waste4Change (W4C), a waste management organization based in Bekasi, Jakarta, Indonesia. W4C was founded in 2014 by a group of young men who shared the idealism of changing the world by doing the right things. This principally involved protecting the environment and educating communities while maintaining economic profitability. However, idealism can sometimes create dilemmas within decision-making as an organization attempts to prevent market logic from dictating its direction. This case examines two different types of decision: the problem of securing a waste management contract when a permit had not been granted by the local government; and the problem of selecting the appropriate funding sources to enable the organization to grow. The first decision occurred in the context of a dilemma in 2017 when W4C expanded their waste management services to several regions in Indonesia but without having succeeded in securing a permit from the local government to provide such services. Attempts to provide such services without a formal legal permit would have been considered a violation of the law, even though the clients needed them (be it residents or companies) and the nature of the service in question had a positive connotation (i.e. maintaining the cleanliness of the city through waste management).The second decision concerned W4C’s plan to go public around 10 years from now. The CEO, Mohamad Bijaksana Junerosano, also known as Sano, has been considering this option since 2020 in a bid to grow the social enterprise. W4C differed from other startups; however, in the sense that while many startups will approach a plan to go public as an exit strategy, Sano wanted to preserve the idealism that had been a cornerstone of the enterprise since its inception. In other words, for W4C, going public was not just a means to an end.

Complexity academic level

Undergraduate as well as graduate courses that focus on sustainability, accounting, financing and strategy.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 1: Accounting and Finance.
Status and determinants of poverty among women-owned micro-businesses in Wolaita zone, southern Ethiopia
Authors: Ergo Alemayehu Elda , Connor Deirdre O’ , Mega Tekle Leza
Published: November 2022

Purpose

Micro-businesses contribute to economic development by improving individual welfare. Women are the primary drivers and owners of such businesses in urban Ethiopia. The purpose of this study is to investigate the poverty status and determinants among women-owned micro-businesses.

Design/methodology/approach

The basic study units were women who owned micro-businesses. A sample of 384 women-owned micro-business was chosen using a stratified and systematic random sampling technique. Thirty-six participants were purposely chosen for in-depth interviews and focus group discussions. Questionnaires, in-depth interviews and focus group discussions were used to collect data. The poverty head count, poverty gap and poverty severity indices were computed to estimate poverty status. The major determinants of women’s poverty were investigated using a logistic regression model.

Findings

The overall poverty incidence, gap and severity were estimated to be 24.27%, 3.85%, and 1.11% respectively, among the women who owned micro-businesses. Eight of the 14 poverty determinants, including age, dependents, savings, remittance and the number of days and hours women work in their businesses, were found to have a significant effect on women’s poverty. The results suggest that local governments, technical and vocational training institutions should work together to reduce the impact of poverty-aggravating factors on women and increase the contribution of women-owned micro-businesses to poverty reduction.

Originality/value

This study addressed the poverty status of women who run micro-businesses, which is a crucial issue in Ethiopia’s urban context. It adds new knowledge to the issue of gendered economic participation, poverty reduction and poverty determinants in the Ethiopian context.
Biogeographical patterns of abundant and rare bacterial biospheres in paddy soils across East Asia
Authors: Luan Lu , Shi Guangping , Zhu Guofan , Zheng Jie , Fan Jianbo , Dini‐Andreote Francisco , Sun Bo , Jiang Yuji
Published: November 2022

Soil bacterial communities play fundamental roles in ecosystem functioning and often display a skewed distribution of abundant and rare taxa. So far, relatively little is known about the biogeographical patterns and mechanisms structuring the assembly of abundant and rare biospheres of soil bacterial communities. Here, we studied the geographical distribution of different bacterial sub‐communities by examining the relative influence of environmental selection and dispersal limitation on taxa distributions in paddy soils across East Asia. Our results indicated that the geographical patterns of four different bacterial sub‐communities consistently displayed significant distance–decay relationships (DDRs). In addition, we found niche breadth and dispersal rates to significantly explain differences in community assembly of abundant and rare taxa, directly affecting the strength of DDRs. While conditionally rare and abundant taxa displayed the strongest DDR due to higher environmental filtering and dispersal limitation, moderate taxa sub‐communities had the weakest DDR due to greater environmental tolerance and dispersal rate. Random forest models indicated that soil pH (9.13%–49.78%) and average annual air temperature (16.59%–46.49%) were the most important predictors of the variation in the bacterial community. This study advances our understanding of the intrinsic links between fundamental ecological processes and microbial biogeographical patterns in paddy soils.