bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-life stress induces persistent astrocyte dysfunction associated with fear generalisation
Authors: Guayasamin Mathias , Depaauw-Holt Lewis R. , Adedipe Ifeoluwa I. , Ghenissa Ossama , Vaugeois Juliette , Duquenne Manon , Rogers Benjamin , Latraverse-Arquilla Jade , Peyrard Sarah , Bosson Anthony , Murphy-Royal Ciaran 
Published: December 2022

Early-life stress can have lifelong consequences, enhancing stress susceptibility and resulting in behavioural and cognitive deficits. While the effects of early-life stress on neuronal function have been well-described, we still know very little about the contribution of non-neuronal brain cells. Investigating the complex interactions between distinct brain cell types is critical to fully understand how cellular changes manifest as behavioural deficits following early-life stress. Here, using male and female mice we report that early-life stress induces anxiety-like behaviour and fear generalisation in an amygdala-dependent learning and memory task. These behavioural changes were associated with impaired synaptic plasticity, increased neural excitability, and astrocyte hypofunction. Genetic perturbation of amygdala astrocyte function by either reducing astrocyte calcium activity or reducing astrocyte network function was sufficient to replicate cellular, synaptic, and fear memory generalisation associated with early-life stress. Our data reveal a role of astrocytes in tuning emotionally salient memory and provide mechanistic links between early-life stress, astrocyte hypofunction, and behavioural deficits.Summary Figure
A high-throughput cytotoxicity screening platform revealsagr-independent mutations in bacteraemia-associatedStaphylococcus aureusthat promote intracellular persistence
Authors: Hachani Abderrahman , Giulieri Stefano G. , Guérillot Romain , Walsh Calum J. , Herisse Marion , Soe Ye Mon , Baines Sarah L. , Thomas David R. , Cheung Shane , Hayes Ashleigh S. , Cho Hyun-Jung , Newton Hayley J. , Pidot Sacha , Massey Ruth C. , Howden Benjamin P. , Stinear Timothy P. 
Published: December 2022

AbstractStaphylococcus aureusinfections are associated with high mortality rates. Often considered an extracellular pathogen,S. aureuscan persist and replicate within host cells, evading immune responses and causing host cell death. Classical methods for assessingS. aureuscytotoxicity are limited by testing culture supernatants and endpoint measurements that do not capture the phenotypic diversity of intracellular bacteria. Using a well-established epithelial cell line model, we have developed a platform calledInToxSa(IntracellularToxicity ofS. aureus) to quantify intracellula cytotoxicS. aureusphenotypes. Studying a panel of 387S. aureusbacteraemia isolates, and combined with comparative, statistical and functional genomics, our platform identified mutations inS. aureusclinical isolates that reduced bacterial cytotoxicity and promoted intracellular persistence. In addition to numerous convergent mutations in the Agr quorum sensing system, our approach detected mutations in other loci that also impacted cytotoxicity and intracellular persistence. We discovered that clinical mutations inausA,encoding the aureusimine non-ribosomal peptide synthetase, reducedS. aureuscytotoxicity and increased intracellular persistence.InToxSais a versatile, high-throughput cell-based phenomics platform and we showcase its utility by identifying clinically relevantS. aureuspathoadaptive mutations that promote intracellular residency.
Development of a protocol for soil transmitted helminths DNA extraction from feces by combining commercially available solutions
Authors: Devyatov AA , Davydova EE , Luparev AR , Karseka SA , Shuryaeva AK , Zagainova AV , Shipulin GA 
Published: December 2022

ABSTRACTBackgroundOne of the main challenges for the mass introduction of molecular diagnostics of soil-transmitted helminths (STHs) into clinical practice is the lack of a generally recognized effective method for isolating parasitic DNA from fecal samples. In the present study, we assessed the effect of various pretreatment procedures on the efficiency of removing PCR inhibitors and extractingToxocara canisDNA from feces.Methodology and main resultsIn the first part of the work, we evaluated the effectiveness of four destructive methods (bead beating, the action of temperature-dependent enzymes, freeze-heat cycles, and incubation in a lysis buffer of a commercial kit) on the integrity of Toxocara eggs using microscopy and the efficiency of DNA extraction using PCR. Our results showed that Toxocara eggs were most effectively destroyed using the bead beating procedure, while the effect of enzymes and freeze-heat cycles did not lead to significant destruction of the eggs or the release of Toxocara DNA. In the second part of the work, we evaluated the effect of prewashes with 0.1% Tween-20 solution and the use of commercial concentrators on DNA extraction from fecal samples contaminated withT. caniseggs. We have shown that the use of commercial concentrators in combination with sample washing can significantly increase the DNA yield and reduce PCR inhibition.ConclusionsA bead beating procedure for 30 minutes at a shaking frequency of 50 Hz was sufficient to completely destroy theToxocara caniseggs. Helminth DNA isolation protocols that do not include a bead beating step are not preferred. The use of a commercial concentrator followed by washing with a 0.1% Tween-20 solution can significantly increase the yield of STHs DNA and reduce PCR inhibition.AUTHOR SUMMARYDNA-based techniques are increasingly being used for the diagnosis of intestinal helminth infections in both clinical and research laboratories. However, extracting DNA from intestinal worm eggs in feces remains a challenge because the very tough eggshell protects their DNA. In addition, feces contain inhibitors that can interfere with test results, and these must be removed during DNA extraction. In the present study, we assessed the effect of different STHs egg destruction methods, as well as concentration and washing procedures for fecal samples, on the PCR test results. We have shown that bead beating is the most effective and sufficient method for the complete destruction of helminth eggs. In addition, we have shown that parasite concentrators significantly increase the sensitivity of the PCR-based test.
To snooze, schmooze, peruse, booze, or learn new views: a rejected Christmas Issue research study
Authors: Wallach Joshua D. , Ross Joseph S. 
Published: December 2022

AbstractObjectiveTo evaluate the frequency of snoozing, schmoozing, perusing, and boozing among attendees at an international conference.DesignSurvey and field studySettingThe 9thInternational Congress on Peer Review and Scientific Publication in Chicago, Illinois (the conference).Participants53 attendees (perhaps just enough to be scientific).Main outcome measuresSelf-reported conference behavior including frequency of falling asleep (snoozing), interacting with other attendees (schmoozing), and multi-tasking (perusing) during presentations, as well as drinking (boozing) at the conference.Results53 attendees completed the survey, which represents a 100% response rate among the attendees who decided to complete the survey. Most of the respondents reported that they preferred in-person conferences before (47/53, 89%) and since (43/53, 81%) the COVID-19 pandemic. 49 (49/53, 92%) reported that multi-day, in-person conferences are still a good use of time. Although 49 (49/53, 92%) reported learning something new (new views), nearly half (24/49, 49%) stated that they could have learned this information from a book or journal article, as opposed to traveling to a conference. Two respondents (2/51, 4%) admitted to snoozing and 43 (84%) to perusing (e.g., emailing, working, and using Twitter) during presentations on the first day of the conference (we suspect that all 5 respondents who claimed that their sleep schedule was “none of our business” also snoozed regularly). The rate of boozing (up to 3 alcoholic beverages) on the first night of the conference was alarming (39/52, 75%), with an additional 10% unable to recall the total number of drinks consumed.ConclusionsFormal, presentation-based conferences may no longer be needed, as attendees appear to be overly preoccupied with snoozing, schmoozing, perusing, and boozing.What is already known on this topic-Scientific conferences have functioned as both professional and social events, allowing attendees to learn about the newest research findings while they schmooze, and sometimes booze, with their colleagues.-Since the COVID-19 pandemic, the research community has grown increasingly accustomed to the benefits of attending conferences from behind their computers.-Little is known about the behaviors and preferences of attendees following the COVID-19 conference hiatus.What this study adds-Almost all respondents reported that multi-day, in-person conferences were still a good use of time and that they had learned something new (even though over half admitted that they could have learned this information from a book or journal article, as opposed to traveling to a conference)-Conference attendees rarely snoozed but frequently perused (email, work, and Twitter) during presentations; over three-quarters boozed on the first night of the conference.-Formal, presentation-based conferences may no longer be needed, as attendees appear to be overly preoccupied with snoozing, schmoozing, perusing, and boozing.
Emergency Department average wait time before admission, average time till sent home, and average number of violations for different hospitals types in Tennessee: Date Analysis of Medicare Data
Authors: Brahmbhatt Viraj 
Published: December 2022

AbstractThe Emergency Department is a key facet of modern healthcare facilities and is responsible for bringing in a lot of patient volume. This healthcare asset is prone to a lot of shortcomings, primarily long waiting times. Though, patients primarily go to the emergency department in emergency scenarios, they still have a choice on which hospital they choose to attend. As such, it may be important for patients to be informed on the expected wait times at hospitals. Though the wait times vary each day, it may be important to know the average expected wait times, time till sent home, and number of violations by hospital type. Using the hospital data published by Medicare, the hospitals were grouped into 3 categories (Not for profit, For profit, and Academic) and data analysis was conducted and Analysis of Variance (ANOVA)was used to determine if the results were statistically significant. The analysis revealed that Academic hospital emergency departments had the highest time before admission, highest time until admission, and highest number of violations. The ANOVA revealed that the difference observed was significant in both time until admission (p-value=.0867) and number of violations (p-value = .011). The results of the study suggest that patients should consider attending a for-profit hospital emergency department if waiting time is a major concern. Analysis of the number of violations (indicative of poor care quality) suggested that for-profit hospitals do not have worse care quality and patients should not be worried about compromised quality care for the shorter wait time.
High Density Domain-Focused CRISPR Screens Reveal Novel Epigenetic Regulators ofHOX/MEISActivation in Acute Myeloid Leukemia
Authors: Barbosa Karina , Deshpande Anagha , Perales Marlenne , Xiang Ping , Murad Rabi , Minkina Anna , Robertson Neil , Schischlik Fiorella , Lei Xue , Sun Younguk , Brown Adam , Amend Diana , Jeremias Irmela , Doench John G. , Humphries R. Keith , Ruppin Eytan , Shendure Jay , Mali Prashant , Adams Peter D , Deshpande Aniruddha J. 
Published: December 2022

ABSTRACTAberrant expression of stem-cell-associated genes is a common feature in acute myeloid leukemia (AML) and is linked to leukemic self-renewal and therapy resistance. Using AF10-rearranged leukemia as a prototypical example displaying a recurrent “stemness” network activated in AML, we screened for chromatin regulators that sustain aberrant activation of these networks. We deployed a CRISPR-Cas9 screen with a bespoke domain-focused library and identified several novel chromatin-modifying complexes as regulators of the TALE domain transcription factor MEIS1, a key leukemia stem cell (LSC)-associated gene. CRISPR droplet sequencing revealed that many of these MEIS1 regulators coordinately controlled the transcription of several AML oncogenes. In particular, we identified a novel role for the Tudor-domain containing chromatin reader protein SGF29 in the transcription of key AML oncogenes. Furthermore, SGF29 deletion impaired leukemogenesis in models representative of multiple AML subtypes. Our studies reveal a novel role for SGF29 as a non-oncogenic dependency in AML and identify the SGF29 Tudor domain as an attractive target for drug discovery.
A genome-wide screen in macrophages identifies PTEN as required for myeloid restriction ofListeria monocytogenesinfection
Authors: Glover Rochelle C. , Schwardt Nicole H. , Leano Shania-Kate E. , Sanchez Madison E. , Thomason Maureen K. , Olive Andrew J. , Reniere Michelle L. 
Published: December 2022

AbstractListeria monocytogenes(Lm) is an intracellular foodborne pathogen which causes the severe disease listeriosis in immunocompromised individuals. Macrophages play a dual role duringLminfection by both promoting dissemination ofLmfrom the gastrointestinal tract and limiting bacterial growth upon immune activation. Despite the relevance of macrophages toLminfection, the mechanisms underlying phagocytosis ofLmby macrophages are not well understood. To identify host factors important forLminfection of macrophages, we performed an unbiased CRISPR/Cas9 screen which revealed pathways that are specific to phagocytosis ofLmand those that are required for internalization of bacteria generally. Specifically, we discovered the tumor suppressor PTEN promotes macrophage phagocytosis ofLmandL. ivanovii, but not other Gram-positive bacteria. Additionally, we found that PTEN enhances phagocytosis ofLmvia its lipid phosphatase activity by promoting adherence to macrophages. Using conditional knockout mice lackingPtenin myeloid cells, we show that PTEN-dependent phagocytosis is important for host protection during oralLminfection. Overall, this study provides a comprehensive identification of macrophage factors involved in regulatingLmuptake and characterizes the function of one factor, PTEN, duringLminfectionin vitroandin vivo. Importantly, these results demonstrate a role for opsonin-independent phagocytosis inLmpathogenesis and suggest that macrophages play a primarily protective role during foodborne listeriosis.Author SummaryListeria monocytogenes(Lm) is a bacterial pathogen that causes the foodborne illness listeriosis primarily in immunocompromised, elderly, and pregnant individuals. Listeriosis is one of the deadliest bacterial infections known, with a mortality rate of ~30% even when treated with antibiotics. The high mortality rate of listeriosis is due to inefficient restriction ofLmby the immune system, and subsequent spread of bacteria beyond the gastrointestinal tract to internal organs such as the liver and brain. Macrophages are important for immune clearance ofLmbut are also hypothesized to promote dissemination of intracellularLm; thus, studies ofLm-macrophage interactions are critical for understanding the balance between bacterial growth and restriction by these phagocytes. We performed a forward genetic screen in macrophages and discovered that the tumor suppressor PTEN promotes phagocytosis ofLmby enhancing adherence to macrophages. These results demonstrate a novel function of macrophage PTEN, which canonically acts as a repressor of phagocytosis. In addition, we found that PTEN protects mice from severe disease and lowers bacterial burdens following oral inoculation ofLm. Our results demonstrate for the first time that macrophage phagocytosis is an important immune defense against invasiveLmduring the foodborne route of infection.
TREX1 restricts CRISPR-Cas9 genome editing in human cells
Authors: Karasu Mehmet E. , Toufektchan Eléonore , Maciejowski John , Corn Jacob E. 
Published: December 2022

AbstractCRISPR-Cas mediated homology-directed repair (HDR) can flexibly introduce desired mutations at targeted sites in a genome. But achieving high HDR efficiencies is a major hurdle in many cellular contexts. Moreover, cells from patients with mutations in DNA repair factors can exhibit low CRISPR-Cas-mediated HDR, complicating genome editing as a potential treatment. We used genome-wide screening in Fanconi anemia (FA) patient lymphoblastic cell lines to uncover suppressors of CRISPR-Cas mediated HDR. Surprisingly, we found that a single exonuclease calledTREX1is an important determinant of HDR efficiency when single-stranded templates are used as a repair template.TREX1expression acts as a biomarker for CRISPR-Cas mediated HDR, such that cell lines expressing high levels ofTREX1have poor HDR that can be rescued byTREX1removal. CRISPR-Cas mediated HDR can also be rescued by using single-stranded DNA templates that are chemically protected in a manner consistent with TREX1’s exonucleolytic activity. Overall, our data provide a mechanistic explanation for why some cells are easier to edit than others and suggest a route to increase CRISPR-Cas mediated HDR inTREX-expressing context.
Novel synergies and isolate specificities in the drug interactions landscape ofMycobacterium abscessus
Authors: Van Nhi , Degefu Yonatan N. , Leus Pathricia A. , Larkins-Ford Jonah , Klickstein Jacob , Maurer Florian P. , Stone David , Poonawala Husain , Thorpe Cheleste M. , Smith Trever C. , Aldridge Bree B. 
Published: December 2022

ABSTRACTMycobacterium abscessusinfections are difficult to treat and are often considered untreatable without tissue resection. Due to the intrinsic drug-resistant nature of the bacteria, combination therapy of three or more antibiotics is recommended. A major challenge in treatingM. abscessusinfections is the absence of a universal combination therapy with satisfying clinical success rates, leaving clinicians to treat infections using antibiotic lacking efficacy data. We systematically measured drug combinations inM. abscessusto establish a resource of drug interaction data and identify patterns of synergy to help design optimized combination therapies. We measured approximately 230 pairwise drug interactions among 22 antibiotics and identified 71 synergistic pairs, 54 antagonistic pairs, and four potentiator-antibiotics not previously reported. We found that commonly used drug combinations in the clinic, such as azithromycin and amikacin, are antagonistic in lab reference strain ATCC19977, whereas novel combinations, such as azithromycin and rifampicin, are synergistic. Another challenge in developing universally effective multidrug therapies forM. abscessusis the significant variation in drug response between isolates. We measured drug interactions in a focused set of 36 drug pairs across a small panel of clinical isolates with rough and smooth morphotypes. We observed highly strain-dependent drug interactions that cannot be predicted from single-drug susceptibility profiles or known drug mechanisms of action. Our study demonstrates the immense potential to identify synergistic drug combinations in the vast drug combination space and emphasizes the importance of strain-specific combination measurements for designing improved therapeutic interventions.
The impact of corporate attributes on voluntary HR disclosure practices: a study of Indian corporate sector
Authors: Aggarwal Kirti 
Published: December 2022

PurposeThe objective of the present study is to examine the impact of corporate characteristics on human resource disclosures in Indian corporate sector.Design/methodology/approachThe study investigates the annual reports of 336 Indian listed companies of NSE-500 Index. The data are collected for the latest time period which contains eight years (FY 2012–13 to 2019–2020). The data of independent variables (company characteristics) have collected from annual reports and CMIE ProwessIQ Database of the Indian listed companies. The data of human resource dissclosure index (HRDI) is collected form annual reports using content analysis approach. For analysis purpose, descriptive statistics, Pearson's correlation matrix, Two-way Least Square Dummy Variable (LSDV) regression model have been used.FindingsThe outcomes show that net sales, market capitalisation, ROTA, return on equity, quick ratio, PAR have significant positive and age, profit after tax, current ratio have significant negative effect on HRDI. On the contrary, debt-equity ratio, earnings per share, type of auditor, listing status have insignificant positive and net fixed assets, promoter's holding have insignificant negative effect on HR disclosures of the selected Indian listed companies.Originality/valueThe HRDI constructed in the present study helps the Institute of Chartered Accountants of India (ICAI) and other regulatory bodies to make some standards regarding voluntary HR disclosure practices in Indian corporate sector.
Consumer engagement with self-driving cars: a theory of planned behavior-informed perspective
Authors: Hollebeek Linda D. , Menidjel Choukri , Itani Omar S. , Clark Moira K. , Sigurdsson Valdimar 
Published: December 2022

PurposeThis study investigates the mediating role of consumer engagement (CE) in the relationship between perceived behavioral control (PBC) and purchase intent and the moderating role of perceived safety in the relationship between PBC and CE in the self-driving car (SDC) context.Design/methodology/approachTo test the model, a sample of 368 consumers was deployed using partial least-squares structural equation modeling (PLS-SEM).FindingsThe findings reveal that consumers' SDC engagement mediates the relationship between PBC and their intent to purchase an SDC. Consumer-perceived SDC safety also moderates the association of PBC/engagement.Originality/valueWhile prior research has examined consumer-based drivers of SDC adoption, understanding of consumers' SDC engagement-related dynamics and outcomes lags behind. Addressing this gap, we propose and test a model that explores consumers' SDC engagement vis-à-vis its drivers (perceived SDC safety/behavioral control) and outcomes (SDC purchase intent).