bluuebunny/crossref_metadata_2025 huggingface dataset:
Hot climate, hot koalas: the role of weather, behaviour and disease on thermoregulation
Authors: Mella Valentina S A , Cooper Christine E , Karr Madeline , Krockenberger Andrew , Madani George , Webb Elliot B , Krockenberger Mark B
Published: May 2024

Thermoregulation is critical for endotherms living in hot, dry conditions, and maintaining optimal core body temperature (Tb) in a changing climate is an increasingly challenging task for mammals. Koalas (Phascolarctos cinereus) have evolved physiological and behavioural strategies to maintain homeostasis and regulate their Tb but are thought to be vulnerable to prolonged heat. We investigated how weather, behaviour and disease influence Tb for wild, free-living koalas during summer in north-west New South Wales. We matched Tb with daily behavioural observations in an ageing population where chlamydial disease is prevalent. Each individual koala had similar Tb rhythms (average Tb = 36.4 ± 0.05°C), but male koalas had higher Tb amplitude and more pronounced daily rhythm than females. Disease disrupted the 24-hr circadian pattern of Tb. Koala Tb increased with ambient temperature (Ta). On the hottest day of the study (maximum Ta = 40.8°C), we recorded the highest (Tb = 40.8°C) but also the lowest (Tb = 32.4°C) Tb ever documented for wild koalas, suggesting that they are more heterothermic than previously recognized. This requires individuals to predict days of extreme Ta from overnight and early morning conditions, adjusting Tb regulation accordingly, and it has never been reported before for koalas. The large diel amplitude and low minimum Tb observed suggest that koalas at our study site are energetically and nutritionally compromised, likely due to their age. Behaviour (i.e. tree hugging and drinking water) was not effective in moderating Tb. These results indicate that Ta and koala Tb are strongly interconnected and reinforce the importance of climate projections for predicting the future persistence of koalas throughout their current distribution. Global climate models forecast that dry, hot weather will continue to escalate and drought events will increase in frequency, duration and severity. This is likely to push koalas and other arboreal folivores towards their thermal limit.
Maternal diet influences fecundity in a freshwater turtle undergoing population decline
Authors: Petrov Kristen , Van Dyke James U , Georges Arthur , Keitel Claudia , Spencer Ricky-John
Published: May 2024

Food availability determines the amount of energy animals can acquire and allocate to reproduction and other necessary functions. Female animals that are food limited thus experience reduced energy available for reproduction. When this occurs, females may reduce frequency of reproductive events or the number or size of offspring per reproductive bout. We assessed how maternal diet affects reproductive output in adult female Murray River short-necked turtles, Emydura macquarii, from four wetlands in Victoria. We previously found that turtle diets differ in the composition of plants and animals between our study wetlands. In this study, we tested whether differences in turtle diet composition (i.e. plants and animals) at these wetlands were associated with differences in clutch mass, individual egg mass, bulk egg composition and hatching success. We found total clutch mass increased with maternal body size at each site. At sites where filamentous green algae were scarce and E. macquarii were carnivorous, females produced smaller clutches relative to body size compared to females from sites where algae were abundant, and turtles were more herbivorous. Individual egg mass, bulk egg composition and hatching success did not differ across wetlands. Isotopic analysis revealed significant positive relationships between the carbon and nitrogen isotopes (δ13C, δ15N) of the eggs and those of the mothers, indicating that mothers allocated ratios of carbon and nitrogen isotopes to their eggs similar to those present in their tissues. Our study suggests that at sites where females are more carnivorous due to a relative absence of algae, females produce smaller clutches, but other aspects of their reproduction are not significantly impacted. The reduction in clutch size associated with differences in the availability of dietary plants and animals may have long-term consequences for E. macquarii and other freshwater turtle species that are experiencing population declines.
Consumption of pollen contaminated with field-realistic concentrations of fungicide causes sublethal effects in
Bombus impatiens (Hymenoptera: Apidae) microcolonies
Authors: Runnion Emily N , Strange James P , Sivakoff Frances S
Published: May 2024

Bumble bees are declining across the globe. The causes of this decline have been attributed to a variety of stressors, including pesticides. Fungicides are a type of pesticide that has been understudied in the context of bumble bee health. As a result, fungicides are often applied to flowering plants without consideration of pollinator exposure. Recent work demonstrates that fungicides have sublethal effects in bumble bees, but little is known about how much fungicide it takes to cause these sublethal effects. To address this gap in the literature, we fed microcolonies of the common eastern bumble bee (Bombus impatiens CressonHymenoptera: ApidaeHymenoptera: ApidaeHymenoptera: ApidaeHymenoptera: Apidae) pollen contaminated with a range of fungicide concentrations. We chose these concentrations based on the range of fungicide concentrations in pollen and nectar that were reported in the literature. Results revealed that later-stage pupae and newly emerged males are potentially sensitive to fungicide exposure, showing smaller size and reduced fat reserves at intermediate levels of contamination. Compared to the control, intermediated levels of fungicide-contaminated pollen led to increased pupal mortality and delayed male emergence. Contrary to expectations, higher fungicide levels did not exhibit a linear relationship with negative impacts, suggesting nuanced effects. Because body size and emergence timing are important aspects of bumble bee reproductive behavior, results have implications for mating success, potentially disrupting colony development.
Genetic assessment of efficacy and safety profiles of coagulation cascade proteins identifies Factors II and XI as actionable anticoagulant targets
Authors: Gagnon Eloi , Girard Arnaud , Bourgault Jérôme , Abner Erik , Gill Dipender , Thériault Sébastien , Vohl Marie-Claude , Tchernof André , Esko Tõnu , Mathieu Patrick , Arsenault Benoit J
Published: May 2024

Aims

Anticoagulants are routinely used by millions of patients worldwide to prevent blood clots. Yet, problems with anticoagulant therapy remain, including a persistent and cumulative bleeding risk in patients undergoing prolonged anticoagulation. New safer anticoagulant targets are needed.

Methods and results

To prioritize anticoagulant targets with the strongest efficacy [venous thromboembolism (VTE) prevention] and safety (low bleeding risk) profiles, we performed two-sample Mendelian randomization and genetic colocalization. We leveraged three large-scale plasma protein data sets (deCODE as discovery data set and Fenland and Atherosclerosis Risk in Communities as replication data sets] and one liver gene expression data set (Institut Universitaire de Cardiologie et de Pneumologie de Québec bariatric biobank) to evaluate evidence for a causal effect of 26 coagulation cascade proteins on VTE from a new genome-wide association meta-analysis of 44 232 VTE cases and 847 152 controls, stroke subtypes, bleeding outcomes, and parental lifespan as an overall measure of efficacy/safety ratio. A 1 SD genetically predicted reduction in F2 blood levels was associated with lower risk of VTE [odds ratio (OR) = 0.44, 95% confidence interval (CI) = 0.38–0.51, P = 2.6e−28] and cardioembolic stroke risk (OR = 0.55, 95% CI = 0.39–0.76, P = 4.2e−04) but not with bleeding (OR = 1.13, 95% CI = 0.93–1.36, P = 2.2e−01). Genetically predicted F11 reduction was associated with lower risk of VTE (OR = 0.61, 95% CI = 0.58–0.64, P = 4.1e−85) and cardioembolic stroke (OR = 0.77, 95% CI = 0.69–0.86, P = 4.1e−06) but not with bleeding (OR = 1.01, 95% CI = 0.95–1.08, P = 7.5e−01). These Mendelian randomization associations were concordant across the three blood protein data sets and the hepatic gene expression data set as well as colocalization analyses.

Conclusion

These results provide strong genetic evidence that F2 and F11 may represent safe and efficacious therapeutic targets to prevent VTE and cardioembolic strokes without substantially increasing bleeding risk.
Association between socioeconomic position and discontinuation of pharmacotherapy for heart failure after cardiac resynchronization therapy
Authors: Frausing Maria Hee Jung Park , Witt Christoffer Tobias , Bakos István , Horváth-Puhó Erzsébet , Løgstrup Brian Bridal , Eiskjær Hans , Nielsen Jens Cosedis , Mols Rikke Elmose
Published: May 2024

Aims

Pharmacological therapy remains a cornerstone in heart failure (HF) treatment despite the implantation of a cardiac resynchronization therapy (CRT) device. The aim of this study was to investigate the association between (i) drug discontinuation and (ii) long-term adherence to HF pharmacotherapy after CRT implantation and socioeconomic position and multimorbidity.

Methods and results

We conducted a registry-based cohort study including all patients who underwent a first-time CRT implantation at Aarhus University Hospital from 2000 to 2017. Heart failure pharmacotherapy included beta-blockers (BBs), renin–angiotensin system inhibitors [angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB)], and mineralocorticoid receptor antagonists (MRAs). Patients were identified using the Danish Pacemaker and International Classification for Disease Registry, and information about medication and comorbidities was obtained through linkage to the Danish health registries. We identified 2007 patients, of whom 1880 (94%) were eligible for inclusion. The cumulative incidence of drug discontinuation at 10 years was 6% [95% confidence interval (CI) 5–8%] for BB, 10% (95% CI 9–12%) for ACEI/ARB, and 24% (95% CI 20–27%) for MRAs. Living alone was associated with higher BB discontinuation rates [hazard ratio (HR) 1.83, 95% CI 1.20–2.79], whereas patients with multimorbidity were more likely to discontinue ACEI/ARB (HR 1.92, 95% CI 1.33–2.80) and MRA therapy (HR 1.51, 95% CI 1.10–2.09). Income and educational level did not influence drug discontinuation rates, and similar adherence patterns were observed across all strata of socioeconomic position and multimorbidity.

Conclusion

In patients with CRTs, drug discontinuation rates were low, and adherence to HF pharmacotherapy was comparable regardless of socioeconomic position. Living alone and multimorbidity were associated with the discontinuation of specific HF drugs.
Effect of genotyping density on the detection of runs of homozygosity and heterozygosity in cattle
Authors: Falchi Laura , Cesarani Alberto , Criscione Andrea , Hidalgo Jorge , Garcia Andre , Mastrangelo Salvatore , Macciotta Nicolò Pietro Paolo
Published: May 2024

Runs of homozygosity (ROHom) are contiguous stretches of homozygous regions of the genome. In contrast, runs of heterozygosity (ROHet) are heterozygosity-rich regions. The detection of these two types of genomic regions (ROHom and ROHet) is influenced by the parameters involved in their identification and the number of available single-nucleotide polymorphisms (SNPs). The present study aimed to test the effect of chip density in detecting ROHom and ROHet in the Italian Simmental cattle breed. A sample of 897 animals were genotyped at low density (50k SNP; 397 individuals), medium density (140k SNP; 348 individuals), or high density (800k SNP; 152 individuals). The number of ROHom and ROHet per animal (nROHom and nROHet, respectively) and their average length were calculated. ROHom or ROHet shared by more than one animal and the number of times a particular SNP was inside a run were also computed (SNPROHom and SNPROHet). As the chip density increased, the nROHom increased, whereas their average length decreased. In contrast, the nROHet decreased and the average length increased as the chip density increased. The most repeated ROHom harbored no genes, whereas in the most repeated ROHet four genes (SNRPN, SNURF, UBE3A, and ATP10A) previously associated with reproductive traits were found. Across the 3 datasets, 31 SNP, located on Bos taurus autosome (BTA) 6, and 37 SNP (located on BTA21) exceeded the 99th percentile in the distribution of the SNPROHom and SNPROHet, respectively. The genomic region on BTA6 mapped the SLIT2, PACRGL, and KCNIP4 genes, whereas 19 and 18 genes were mapped on BTA16 and BTA21, respectively. Interestingly, most of genes found through the ROHet analysis were previously reported to be related to health, reproduction, and fitness traits. The results of the present study confirm that the detection of ROHom is more reliable when the chip density increases, whereas the ROHet trend seems to be the opposite. Genes and quantitative trait loci (QTL) mapped in the highlighted regions confirm that ROHet can be due to balancing selection, thus related to fitness traits, health, and reproduction, whereas ROHom are mainly involved in production traits. The results of the present study strengthened the usefulness of these parameters in analyzing the genomes of livestock and their biological meaning.
Assessing seromuscular layer and serosa removal on intestinal permeability measurements in weaned piglet everted sac segments
Authors: Noorman Lonneke , van der Hee Bart , Gilbert Myrthe S , de Vries Sonja , van der Hoek Sylvia , Gerrits Walter J J
Published: May 2024

The integrity of the intestinal barrier is crucial for regulating the passage of pathogens and toxins, while facilitating nutrient absorption. The everted gut sac technique, an ex-vivo technique, can be used to study interventions on barrier function. This cost-effective approach utilizes relatively large gut segments to study specific intestinal regions. Typically, intact (non-stripped) intestinal segments are used, but their use may underestimate permeability due to the medial positioning of blood vessels relative to the seromuscular layer and serosa. However, removing these layers risks physical damage, resulting in an overestimation of intestinal permeability. Therefore, we investigated the impact of stripping jejunal segments on permeability to fluorescein isothiocyanate-dextran (FITC, 4 kDa) and tetramethylrhodamine isothiocyanate-dextran (TRITC, 40 kDa), and on the absorption of glucose, lysine, and methionine in jejunal segments from 80 piglets at 8 d postweaning. Piglets were subjected to either high or low sanitary housing conditions and diets provoking intestinal protein fermentation or not, expected to influence intestinal permeability. Stripping of the seromuscular layer and serosa increased the passage of 4 kDa FITC-dextran (stripped vs. non-stripped; 1.1 vs. 0.9 pmol/cm2/min, P < 0.001), glucose (40.0 vs. 19.1 pmol/cm2/min, P < 0.001), lysine (2.5 vs. 2.0 nmol/cm2/min, P < 0.001), and methionine (4.1 vs. 2.7 pmol/cm2/min, P < 0.001). As permeability increased, the differences in methionine passage between stripped and non-stripped intestinal segments also increased (slope = 1.30, P = 0.009). The coefficients of variation were comparable between stripped and non-stripped intestines (over all treatments, stripped vs. non-stripped 38% vs. 40%). Stripping, by isolating mucosal processes without introducing additional variation, is thus recommended for studies on intestinal permeability or absorption.
A Prospective Analysis of Screen-Detected Cancers Recalled and Not Recalled by Artificial Intelligence
Authors: Smith Samantha J , Bradley Sally Anne , Walker-Stabeler Katie , Siafakas Michael
Published: May 2024

Objective

The use of artificial intelligence has potential in assisting many aspects of imaging interpretation. We undertook a prospective service evaluation from March to October 2022 of Mammography Intelligent Assessment (MIA) operating “silently” within our Breast Screening Service, with a view to establishing its performance in the local population and setting. This evaluation addressed the performance of standalone MIA vs conventional double human reading of mammograms.

Methods

MIA analyzed 8779 screening events over an 8-month period. The MIA outcome did not influence the decisions made on the clinical pathway. Cases were reviewed approximately 6 weeks after the screen reading decision when human reading and/or MIA indicated a recall.

Results

There were 146 women with positive concordance between human reading and MIA (human reader and MIA recalled) in whom 58 breast cancers were detected. There were 270 women with negative discordance (MIA no recall, human reader recall) for whom 19 breast cancers and 1 breast lymphoma were detected, with 1 cancer being an incidental finding at assessment. Six hundred and four women had positive discordance (MIA recall, human reader no recall) in whom 2 breast cancers were detected at review. The breast cancers demonstrated a wide spectrum of mammographic features, sites, sizes, and pathologies, with no statistically significant difference in features between the negative discordant and positive concordant cases.

Conclusion

Of 79 breast cancers identified by human readers, 18 were not identified by MIA, and these had no specific features or site to suggest a systematic error for MIA analysis of 2D screening mammograms.
Tips for Addressing Screening Concerns: “Harms of Screening”
Authors: Choe Angela I , Kaya Aumann Emel , Kasales Claudia , Chetlen Alison , Sivarajah Rebecca
Published: May 2024

Early detection decreases deaths from breast cancer. Yet, there are conflicting recommendations about screening mammography by major professional medical organizations, including the age and frequency with which women should be screened. The controversy over breast cancer screening is centered on 3 main points: the impact on mortality, overdiagnosis, and false positive results. Some studies claim that adverse psychological effects such as anxiety or distress are caused by screening mammography. The purpose of this article is to address negative breast cancer screening concerns including overdiagnosis and overtreatment, effect on mortality, false positive results, mammography-related anxiety, and fear of radiation.
Induction of the antiviral factors APOBEC3A and RSAD2 upon CCL2 neutralization in primary human macrophages involves NF-κB, JAK/STAT, and gp130 signaling
Authors: Covino Daniela Angela , Farina Iole , Catapano Laura , Sozzi Silvia , Spadaro Francesca , Cecchetti Serena , Purificato Cristina , Gauzzi Maria Cristina , Fantuzzi Laura
Published: May 2024

The CCL2/CC chemokine receptor 2 axis plays key roles in the pathogenesis of HIV-1 infection. We previously reported that exposure of monocyte-derived macrophages to CCL2 neutralizing antibody (αCCL2 Ab) restricted HIV-1 replication at postentry steps of the viral life cycle. This effect was associated with induction of transcripts coding for innate antiviral proteins, including APOBEC3A and RSAD2. This study aimed at identifying the signaling pathways involved in induction of these factors by CCL2 blocking in monocyte-derived macrophages. Through a combination of pharmacologic inhibition, quantitative reverse transcription polymerase chain reaction, Western blotting, and confocal laser-scanning microscopy, we demonstrated that CCL2 neutralization activates the canonical NF-κB and JAK/STAT pathways, as assessed by time-dependent phosphorylation of IκB, STAT1, and STAT3 and p65 nuclear translocation. Furthermore, pharmacologic inhibition of IκB kinase and JAKs strongly reduced APOBEC3A and RSAD2 transcript accumulation elicited by αCCL2 Ab treatment. Interestingly, exposure of monocyte-derived macrophages to αCCL2 Ab resulted in induction of IL-6 family cytokines, and interference with glycoprotein 130, the common signal-transducing receptor subunit shared by these cytokines, inhibited APOBEC3A and RSAD2 upregulation triggered by CCL2 neutralization. These results provide novel insights into the signal transduction pathways underlying the activation of innate responses triggered by CCL2 neutralization in macrophages. Since this response was found to be associated with protective antiviral effects, the new findings may help design innovative therapeutic approaches targeting CCL2 to strengthen host innate immunity.
Short and Long Run Effects of Leniency Programs on Cartel Stability and Prosecution
Authors: Borrell Joan-Ramon , García Carmen , Jiménez Juan Luis , Ordóñez-de-Haro José Manuel
Published: May 2024

This study investigates the effects of leniency programs on cartel duration, cartel fines, and the length of investigations, providing empirical insights that contribute to the ongoing debate regarding their theoretical and empirical implications. The introduction of leniency programs in two different jurisdictions (EU and Spain) at different times and the exogeneity of the introduction date enable us to identify their impact using difference-in-differences estimations. We empirically show that leniency programs, by destabilizing existing cartels, allow for the detection of the longer-lasting ones in the short run. In the long run, our results suggest that destabilization effects prevail, and leniency programs discourage the creation of new cartels. Specifically, our findings indicate that the duration of detected cartels almost doubles in the short run and nearly halves in the long run. Finally, our study reveals that the introduction of leniency programs results in a significant increase in the average fines per cartel case, both before and after taking into account the fine reductions resulting from these programs. This suggests that leniency programs contribute to stronger sanctions against cartels, enhancing their general deterrent effect. However, our findings also indicate that leniency programs lengthen the average duration of cartel investigations, which may hinder the ability of competition authorities to proactively pursue other cases.
An Analysis of Political Identity Development in State Forest Advisory Groups
Authors: Mallory Gavriela , Crandall Mindy S , Hajjar Reem , Leahy Jessica
Published: May 2024

Purposive stakeholder involvement in public lands management has grown in the United States in recent decades. These collaborative efforts can serve land managers by increasing available resources, fostering creativity, and augmenting public buy-in to processes and outcomes. Whereas such advantages seem to reflect the benefit of democratic norms, few studies have assessed the democratic legitimacy of collaborative natural resource planning initiatives. Additionally, although collaboration on federal lands has been studied extensively, little is documented about stakeholder engagement in state lands management. Through a comparative case study of state forest advisory groups in New York’s High Peaks Region and Oregon’s Elliott State Forest, this article assesses the democratic norm of political identity development by investigating how participants characterize their impacts. Results indicate that participants consistently influenced group processes and outcomes and changed personally through the work of deliberation. However, these impacts were mediated by inclusion and power dynamics at multiple scales.

Study Implications: Collaborative forest planning initiatives may benefit land managers by increasing available resources, promoting creativity, and developing public buy-in to processes and outcomes. Such benefits depend on impactful stakeholder participation; if collaborative initiatives only empower the historically powerful, advantages may be limited. This study uses participants’ perceived impacts in forest planning efforts as a partial proxy for the quality of collaboration. We demonstrate that participant perceptions of their impacts are shaped by inclusion, influence, process structure, conversational quality, and the duration of collaborative institutions. By attending to these factors, land managers can bolster the advantages of collaborative planning efforts.
Response of vegetation phenology to climate factors in the source region of the Yangtze and Yellow Rivers
Authors: Jiang Qingqing , Yuan Zhe , Yin Jun , Yao Mingze , Qin Tianling , Lü Xizhi , Wu Guangdong
Published: May 2024

Exploring the impact of climate factors on vegetation phenology is crucial to understanding climate–vegetation interactions as well as carbon and water cycles in ecosystems in the context of climate change. In this article, we extracted the vegetation phenology data from 2002 to 2021 based on the dynamic threshold method in the source region of the Yangtze and Yellow Rivers. Trend and correlation analyses were used to investigate the relationship between vegetation phenology and temperature, precipitation and their spatial evolution characteristics. The results showed that: (i) From 2002 to 2021, the multi-year average start of growing season (SOS), end of growing season (EOS) and length of growing season (LOS) for plants were concentrated in May, October and 4–6 months, with a trend of 4.9 days (earlier), 1.5 days (later), 6.3 days/10 a (longer), respectively. (ii) For every 100 m increase in elevation, SOS, EOS and LOS were correspondingly delayed by 1.8 days, advanced by 0.8 days and shortened by 2.6 days, respectively. (iii) The impacts of temperature and precipitation on vegetation phenology varied at different stages of vegetation growth. Influencing factors of spring phenology experienced a shift from temperature to precipitation, while autumn phenology experienced precipitation followed by temperature. (iv) The climate factors in the previous period significantly affected the vegetation phenology in the study area and the spatial variability was obvious. Specifically, the temperature in April significantly affected the spring phenology and precipitation in August widely affected the autumn phenology.
Case report: a case report of neoadjuvant mFOLFIRINOX leading to a partial pathologic response in pancreatic adenosquamous carcinoma
Authors: Vivekanandan Deepak Dev , Singh Hardeep , Royall Nelson Andrew
Published: May 2024

A female in her 60s with vague abdominal symptoms was found to have a pancreatic mass in her CT scan. A core needle biopsy done endoscopically demonstrated a poorly differentiated adenocarcinoma. The patient completed nine cycles of neoadjuvant systemic mFOLFIRINOX. Repeat staging demonstrated a partial radiographic response. She underwent an open pylorus-preserving pancreatoduodenectomy with segmental superior mesenteric vein resection with primary reconstruction (ISGPS Type 3). The final pathology demonstrated a poorly differentiated adenosquamous carcinoma, R1 margin status. The case report demonstrates the effect of mFOLFIRINOX on pancreatic adenosquamous (PASC) carcinoma with a review of the microscopic pictures following the neoadjuvant therapy. It can be postulated that glandular component being the major component in a PASC has a good response to mFOLFIRINOX like that seen in pancreatic ductal adenocarcinoma with some presumed effect on the squamous component as well. From the above case report, we are proposing that mFOLFIRINOX can be an effective chemotherapy regime in the management of PASC.
Evaluating the efficacy and clinical outcomes of minimally invasive laser interstitial thermal therapy in the treatment of recurrent glioblastoma multiforme: meta-analysis protocol
Authors: Alare Kehinde , Adetunji Busayo , Jagunmolu Habiblah , Kayode Ayomide , Omoniyo Taiwo , Afolabi Samson , Tajudeen Qudus , Ogungbemi Bridget , Fagbenro Ayomide , Aderinto Nicholas
Published: May 2024

Laser interstitial thermal therapy (LITT) is a neurosurgical technique that has become increasingly popular in recent years due to its minimally invasive nature and ability to reduce the size of brain tumors. Advances in technology, such as magnetic resonance imaging thermometry and better laser probe design, have made LITT procedures more feasible and safe. Many studies have been conducted on using LITT to treat various conditions like tumors and epilepsy, but the specific uses for LITT are still evolving. In this article, we explain the basic principles of LITT, the process of performing the procedure, and both established and emerging applications for it. The effectiveness of LITT in treating recurrent glioblastoma (rGBM) is not yet established. This study aimed to systematically review and analyze existing literature to determine the outcomes of patients with rGBM who undergo LITT.
Hydrogen recombination continua in stellar flares
Authors: Heinzel P
Published: May 2024

An increasing interest in stellar flares stimulated various modelling approaches in order to analyse the observed flare fluxes. A particular interest was focused on photometric data obtained from Kepler and TESS satellites which detected thousands of flares on cool dwarf stars, including extremely energetic superflares. Radiation-hydrodynamical simulations, together with a rather rare broad-band spectroscopy, indicate much larger densities in the superflare chromospheres as compared to solar flares. Formation of hydrogen recombination continua under such different densities ranging from 1013 to 1015 cm−3 or more is governed by physics of optically thin to largely thick plasmas, the continuum optical thickness being within the range of four orders of magnitude. Various authors presented simple approximate methods to analyse the photometric data from Kepler or TESS under such diverse regimes of physical conditions. In this letter, we summarize the general physical approach and compute the hydrogen recombination spectra under the above range of electron densities. We show the theoretical contrast with respect to quiet-star continuum for two characteristic stars of G and dMe type. Based on that we distinguish three regimes of the continuum formation and discuss the applicability of various simple approaches.
Multiomic analyses reveal key sectors of jasmonate-mediated defense responses in rice
Authors: Chen Yumeng , Jin Gaochen , Liu Mengyu , Wang Lanlan , Lou Yonggen , Baldwin Ian , Li Ran
Published: May 2024

The phytohormone jasmonate (JA) plays a central role in plant defenses against biotic stressors. However, our knowledge of the JA signaling pathway in rice (Oryza sativa) remains incomplete. Here, we integrated multiomic data from three tissues to characterize the functional modules involved in organizing JA-responsive genes. In the core regulatory sector, MYC2 transcription factor transcriptional cascades are conserved in different species but with distinct regulators (e.g. bHLH6 in rice), in which genes are early expressed across all tissues. In the feedback sector, MYC2 also regulates the expression of JA repressor and catabolic genes, providing negative feedback that truncates the duration of JA responses. For example, the MYC2-regulated NAC (NAM, ATAF1/2, and CUC2) transcription factor genes NAC1, NAC3, and NAC4 encode proteins that repress JA signaling and herbivore resistance. In the tissue-specific sector, many late-expressed genes are associated with the biosynthesis of specialized metabolites that mediate particular defensive functions. For example, the terpene synthase gene TPS35 is specifically induced in the leaf sheath and TPS35 functions in defense against oviposition by brown planthoppers and the attraction of this herbivore's natural enemies. Thus, by characterizing core, tissue-specific, and feedback sectors of JA-elicited defense responses, this work provides a valuable resource for future discoveries of key JA components in this important crop.
Antisense transcription from stress-responsive transcription factors fine-tunes the cold response in Arabidopsis
Authors: Meena Shiv Kumar , Quevedo Marti , Nardeli Sarah Muniz , Verez Clément , Bhat Susheel Sagar , Zacharaki Vasiliki , Kindgren Peter
Published: May 2024

Transcription of antisense long noncoding RNAs (lncRNAs) occurs pervasively across eukaryotic genomes. Only a few antisense lncRNAs have been characterized and shown to control biological processes, albeit with idiosyncratic regulatory mechanisms. Thus, we largely lack knowledge about the general role of antisense transcription in eukaryotic organisms. Here, we characterized genes with antisense transcription initiating close to the poly(A) signal of genes (PAS genes) in Arabidopsis (Arabidopsis thaliana). We compared plant native elongation transcript sequencing (plaNET-seq) with RNA sequencing during short-term cold exposure and detected massive differences between the response in active transcription and steady-state levels of PAS gene-derived mRNAs. The cold-induced expression of transcription factors B-BOX DOMAIN PROTEIN28 (BBX28) and C2H2-TYPE ZINC FINGER FAMILY PROTEIN5 (ZAT5) was detected by plaNET-seq, while their steady-state level was only slightly altered due to high mRNA turnover. Knockdown of BBX28 and ZAT5 or of their respective antisense transcripts severely compromised plant freezing tolerance. Decreased antisense transcript expression levels resulted in a reduced cold response of BBX28 and ZAT5, revealing a positive regulatory role of both antisense transcripts. This study expands the known repertoire of noncoding transcripts. It highlights that native transcription approaches can complement steady-state RNA techniques to identify biologically relevant players in stress responses.
COI1 F-box proteins regulate DELLA protein levels, growth, and photosynthetic efficiency in maize
Authors: Feiz Leila , Shyu Christine , Wu Shan , Ahern Kevin R , Gull Iram , Rong Ying , Artymowicz Caroline J , Piñeros Miguel A , Fei Zhangjun , Brutnell Thomas P , Jander Georg
Published: May 2024

The F-box protein Coronatine Insensitive (COI) is a receptor for the jasmonic acid signaling pathway in plants. To investigate the functions of the 6 maize (Zea mays) COI proteins (COI1a, COI1b, COI1c, COI1d, COI2a, and COI2b), we generated single, double, and quadruple loss-of-function mutants. The pollen of the coi2a coi2b double mutant was inviable. The coi1 quadruple mutant (coi1-4x) exhibited shorter internodes, decreased photosynthesis, leaf discoloration, microelement deficiencies, and accumulation of DWARF8 and/or DWARF9, 2 DELLA family proteins that repress the gibberellic acid (GA) signaling pathway. Coexpression of COI and DELLA in Nicotiana benthamiana showed that the COI proteins trigger proteasome-dependent DELLA degradation. Many genes that are downregulated in the coi1-4x mutant are GA-inducible. In addition, most of the proteins encoded by the downregulated genes are predicted to be bundle sheath- or mesophyll-enriched, including those encoding C4-specific photosynthetic enzymes. Heterologous expression of maize Coi genes in N. benthamiana showed that COI2a is nucleus-localized and interacts with maize jasmonate zinc-finger inflorescence meristem domain (JAZ) proteins, the canonical COI repressor partners. However, maize COI1a and COI1c showed only partial nuclear localization and reduced binding efficiency to the tested JAZ proteins. Together, these results show the divergent functions of the 6 COI proteins in regulating maize growth and defense pathways.
Older age and risk for delayed abdominal pain care in the emergency department
Authors: Bloom Ben , Fritz Christie L. , Gupta Shivani , Pott Jason , Skene Imogen , Astin-Chamberlain Raine , Ali Mohammad , Thomas Sarah A. , Thomas Stephen H.
Published: May 2024

Background and importance

Suboptimal acute pain care has been previously reported to be associated with demographic characteristics.

Objectives

The aim of this study was to assess a healthcare system’s multi-facility database of emergency attendances for abdominal pain, to assess for an association between demographics (age, sex, and ethnicity) and two endpoints: time delay to initial analgesia (primary endpoint) and selection of an opioid as the initial analgesic (secondary endpoint).

Design, setting, and participants

This retrospective observational study assessed four consecutive months’ visits by adults (≥18 years) with a chief complaint of abdominal pain, in a UK National Health Service Trust’s emergency department (ED). Data collected included demographics, pain scores, and analgesia variables.

Outcome measures and analysis

Categorical data were described with proportions and binomial exact 95% confidence intervals (CIs). Continuous data were described using median (with 95% CIs) and interquartile range (IQR). Multivariable associations between demographics and endpoints were executed with quantile median regression (National Health Service primary endpoint) and logistic regression (secondary endpoint).

Main results

In 4231 patients, 1457 (34.4%) receiving analgesia had a median time to initial analgesia of 110 min (95% CI, 104–120, IQR, 55–229). The univariate assessment identified only one demographic variable, age decade (P= 0.0001), associated with the time to initial analgesia. Association between age and time to initial analgesia persisted in multivariable analysis adjusting for initial pain score, facility type, and time of presentation; for each decade increase the time to initial analgesia was linearly prolonged by 6.9 min (95% CI, 1.9–11.9;P= 0.007). In univariable assessment, time to initial analgesia was not associated with either detailed ethnicity (14 categories,P= 0.109) or four-category ethnicity (P= 0.138); in multivariable analysis ethnicity remained non-significant as either 14-category (all ethnicities’P≥ 0.085) or four-category (allP≥ 0.138). No demographic or operational variables were associated with the secondary endpoint; opioid initial choice was associated only with pain score (P= 0.003).

Conclusion

In a consecutive series of patients with abdominal pain, advancing age was the only demographic variable associated with prolonged time to initial analgesia. Older patients were found to have a linearly increasing, age-dependent risk for prolonged wait for pain care.
Comprehensive treatment of gallbladder cancer: a case report
Authors: Cui Zhaoyang , Le Yi , Liu Hu , Feng Linjing , Zhang Shaogeng
Published: May 2024

Introduction and importance:

Gallbladder cancer is an extremely aggressive digestive system tumor. It is difficult to treat as early symptoms are insidious, and patients are usually diagnosed in advanced stages. The authors’ case highlights the need for effective treatment strategies and underscores the critical role of an individualized approach in the management of complicated gallbladder cancer.

Case presentation:

The authors report a patient admitted to the hospital with back pain and discomfort who was diagnosed with advanced gallbladder cancer. The patient received two cycles of chemotherapy with gemcitabine and cisplatin (GC), but the response was unsatisfactory. The authors changed the treatment regimen to gemcitabine and oxaliplatin (GEMOX) combined with targeted therapy (lenvatinib) and immunotherapy (toripalimab), and achieved significant therapeutic effect. Subsequently, the patient underwent "extended right hemihepatectomy, cholecystectomy, lymph node dissection of the hepatoduodenal ligament " and continued to receive combined therapy after surgery, and no tumor recurrence has been observed so far.

Clinical discussion:

The authors delve into the challenges faced during treatment, exploring the subtle impact of modified regimens and the strategic integration of surgery and combination therapy. The focus of this study is on the intricate synergy between GEMOX, lenvatinib and teraplizumab, providing a holistic view of treatment effects and new insights into the clinical decision-making process.

Conclusions:

This case emphasizes the success of precision medicine in the treatment of advanced gallbladder cancer. The adjustment of strategy can not only improve the therapeutic effect but also promote the success of surgical intervention. This case provides a valuable lesson in the holistic management of gallbladder cancer patients and prompts further reflection on the nuances of individualized therapeutic approaches in cancer treatment.
Awareness of consanguineous marriage burden and willingness towards premarital genetic testing in Sudan: a national cross-sectional study
Authors: Elmugadam Fatima M. , Ahmed Haythem , KARAMELGHANI MOHAMMED , Ali Almigdad , Ali Israa , Ahmed Almegdad , Salman Mohammed , Mohamed Wadah , Ahmed Elhami A. , Abbasher Hussien Mohamed Ahmed Khabab , Mustafa Ahmed Ghassan E. , Elsayed Liena , Musa Ahmed
Published: May 2024

Background:

Despite the widespread practice of consanguinity in Sudan, there is a lack of exploration into the community’s awareness of its health implications on offspring and their overall attitude towards consanguineous unions.

Aim:

This study aimed to evaluate the community’s awareness of the possible health adversities of consanguinity on children and assess the effect of knowledge level on the prevailing attitude towards this practice in Sudan.

Methods:

From August to December 2018, data were collected from adults aged 18 years and above in five provinces of Sudan regardless of their marital status. The analysis involved both descriptive and multivariate statistical techniques.

Results:

This study revealed a consanguinity rate of 30.2%. Despite a high awareness level (73.7%) regarding the effects of consanguineous marriage on the health of the offspring, a moderately negative attitude towards this practice (63.9%) was observed.

Conclusion:

The discordance between the high consanguinity rate in the Sudanese population and the moderately negative attitude suggests a potential persistence of this practice in the future. Without the implementation of educational programs and the provision of genetic counselling services to consanguineous couples, the prevalence of consanguinity is likely to endure.
Primary Sjögren’s syndrome without ocular manifestation: a case report
Authors: Mohammad Aya , Btrush Sana , Makhlouf Zeina , Alkasem Abeer , Abdoh Hoda , Kudsi Maysoun
Published: May 2024

Introduction and importance:

Sjögren’s Syndrome is a systemic immune disorder, manifested in dry eyes and mouth. Primary Sjögren’s syndrome without ocular manifestation is seldom mentioned in the literature.

Case presentation:

The authors report a case of a 48-year-old female who complained of dryness of mouth and dysphagia for 6 months. Physical examinations showed dry lips with angular cheilitis, an erythematous tongue, and dry buccal mucosa, with multiple carious teeth. The salivary flow was scanty from the Stenson’s and Wharton’s ducts on both sides. Her ophthalmological examination was normal. Laboratory tests revealed leukopenia, anemia, thrombocytopenia, elevated levels of C-reactive protein and erythrocyte sedimentation rate, a strongly positive antinuclear antibody, anti-SS-A, anti-SS-, and rheumatic factor. Hyperechoic nodules in both parotids were shown by Ultrasonography. Salivary gland biopsy showed lymphocytic infiltration. Diagnosis of primary Sjögren’s syndrome was made. She was treated with Pilocarpine 5 mg for 3 months, Vitamin C, and artificial saliva for oral dryness. She is under continuous follow-up with 50–60% relief, without any systemic complications

Discussion:

Sjögrenʼs Syndrome affects the exocrine glands causing dry mouth and eyes, and can cause systemic symptoms, including fatigue and joint pain. The incidence of ocular involvement among the reported cases is 86.1%, whereas our patient did not have any ocular involvement, and this represents a rare condition. The differential diagnosis included diabetes mellitus, hypothyroidism, chronic virology infection, and some medications that cause dryness, which were very much ruled out. Treatment of sicca symptoms involves artificial tears and medications that stimulate saliva flow while treatment of systemic disease includes corticosteroids, and various DMARDs, Rituximab. this disease has an increased relative risk for the development of B-cell non-Hodgkinʼs lymphoma. Therefore, patients need to be monitored, especially in the presence of risk factors.

Conclusion:

It is very important to diagnose this disorder early, using the various diagnostic criteria.
A Case of Long-Term Survival After Glioblastoma, IDH-Wild Type
Authors: Webb Lauren M. , Neth Bryan J. , Raghunathan Aditya , Greipp Patricia T. , Ida Cristiane M. , Carabenciov Ivan D. , Ruff Michael W.
Published: May 2024

Introduction:

Glioblastoma is a uniformly lethal primary central nervous system neoplasm. Despite the increased understanding of its pathophysiology and treatment advancements, median overall survival for patients with glioblastoma, IDH-wild type remains 14 to 21 months from diagnosis.

Case Report:

We present the case of a 48-year-old female who presented with a focal seizure and was found to have a right frontal lobe mass on the brain magnetic resonance imaging. She underwent gross total resection and received a histological diagnosis of glioblastoma. She received radiotherapy and 6 cycles of carmustine (BCNU). Seventeen months later, she developed left hemiparesis. Imaging was concerning for tumor progression, and she was treated with 1 cycle of mechlorethamine, vincristine (oncovin), procarbazine, and prednisone (MOPP). Subsequent surveillance imaging demonstrated a therapeutic response. Twenty-seven years after her glioblastoma diagnosis, she developed status epilepticus and died from respiratory failure. Neuropathology on autopsy demonstrated extensive treatment-related changes but no evidence of recurrent glioblastoma. Genomic testing performed over 30 years after her original diagnosis revealed a profile diagnostic of glioblastoma, IDH-wild type per 2021 World Health Organization criteria.

Conclusions:

This patient is one of the longest-known survivors of glioblastoma, IDH-wild type, with pathologic confirmation of glioblastoma at the time of her resection and no evidence of residual disease 26 years after her last treatment. She presented with multiple factors associated with long-term glioblastoma survivorship, including female sex, young age, high Karnofsky score, and multimodal therapy. This case shows that long-term survival after glioblastoma diagnosis is possible and likely mediated through a combination of individual, tumor, and treatment factors.