bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-perspective view on visibility in EU design law
Authors: Brancusi Lavinia
Published: March 2024

In EU design law, the parameter of visibility must multitask. This article aims to discuss its meaning and legal consequences against the current and amended legal provisions for designs. As the legal notion of a design is the ‘appearance of a product’, visibility has been woven into design features’ requirement of perceptibility to the eye. Visibility also aids in the identification of the object of protection for a registered design through the registration documentation and, analogically, the identification of an unregistered design through proofs of disclosure. By this token, design features visibly displayed by the representation/disclosure of a design determine the comparison between the overall impression of a design and another design/product for the purposes of invalidity or enforcement. The Court of Justice of the European Union (CJEU) has also recently framed visibility in the perspective of evidentiary issues of technical functionality. Visibility represents a prerequisite for the assessment of novelty and/or individual character of a design of a component part of a complex product. This article looks into the CJEU’s guidance concerning the protection of parts of products, including the interpretation of the criterion of visibility during normal use that applies to component parts.
Species composition of Culicoides (Diptera: Ceratopogonidae) in the Ridge and Valley region of Tennessee, USA
Authors: Doub Emily E , Vigil Stacey L , Thompson Alec T , Korns Avery L , Yabsley Michael J , Ruder Mark G , Cleveland Christopher A
Published: March 2024

Biting midges in the genus Culicoides Latreille (Diptera: Ceratopogonidae) are known to transmit many pathogens of veterinary and medical concern. Although much work has been done globally and in certain regions of North America, Culicoides spp. research in rural Appalachia is limited. To begin characterizing the distribution and community structure of Culicoides spp. in Appalachia, we surveyed 2 distinct sites in the Ridge and Valley ecoregion of northeastern Tennessee, USA, from April 2021–September 2021. Culicoides spp. were sampled using 2 methods: Centers for Disease Control ultraviolet LED light traps and potential larval habitat substrate collection (coupled with water chemistry values). Site 1 was dominated by natural features, and Site 2 was a beef cattle operation. During 96 trap nights, a total of 1,568 Culicoides were collected, representing 24 species. Site 1 yielded the highest diversity, with 24 species, while Site 2 yielded 12 species. Overall, the most abundant species in light traps were C. stellifer Coquillett (44%), C. bergi Cochrane (18%), C. haematopotus Malloch (12%), and C. debilipalpis Lutz (11%). From substrate sampling, 8 species were identified. Culicoides haematopotus was the most abundant and was collected during each sampling period. Water chemistry values taken at the time of substrate collection were not significantly related to which Culicoides spp. emerged from a given substrate. Our results indicate a diverse community of Culicoides spp. in our study area, however, further work is needed to identify Culicoides species composition across a variety of landscapes in Appalachia and inform research on vector presence and associated vector disease dynamics.
Video-assisted thoracic surgery for an endobronchial ancient schwannoma obstructing the left main bronchus
Authors: Kang Jiyeon , Kim Yeon Soo , Kim Ji-Ye
Published: March 2024

A schwannoma is a tumor that arises from the Schwann cells of the peripheral nerves. Primary pulmonary schwannomas are extremely rare, although they can occur anywhere in the body. Symptoms of endobronchial schwannoma vary depending upon the extent of bronchi blockage by the tumor. Schwannoma is a benign tumor. However, there is a risk of recurrence if a lesion that has developed extraluminal growth is incompletely resected. Here, a 76-year-old female patient presented with dyspnea and cough. An endobronchial tumor was identified originating from the left lower lobe bronchus and had collapsed the left lower lobe and grown to block most of the left main bronchus. Video-assisted thoracic surgery was performed to resect the left lower lobe. The tumor was diagnosed as an ancient schwannoma.
Estimation of a Population Total Under Nonresponse Using Follow-up
Authors: Stefan Marius , Hidiroglou Michael A
Published: March 2024

In this article, we propose methods to minimize bias due to unit nonresponse. We consider a two-phase sampling design where the second phase is a probability subsample of nonrespondents from the first phase. In this context, we propose three weighting procedures to estimate the total when not all units in the subsample respond. The weighting is based on the response homogeneity group (RHG) model. Given the RHG model, theoretical results on bias and variance estimation are obtained for all estimators. In a simulation study, we evaluate the empirical properties of the three estimators as well as of estimators based on two commonly used procedures to handle unit nonresponse in single-phase sampling design. These two procedures include: (i) nonresponse calibration weighting, also known as the one-step approach, and (ii) nonresponse probability weighting followed by calibration, also known as the two-step approach. Our results indicate that when there is significant deviation from the assumed RHG model, the nonresponse follow-up estimators perform better in terms of bias and coverage.
The impact of the cruise ship Coral Princess on COVID-19 transmission in regional Western Australia in 2022
Authors: Quigley Ashley L , Kunasekaran Mohana , Stone Haley , Honeyman Damian , Notaras Adriana , Lim Samsung , MacIntyre Raina
Published: March 2024

Increased COVID-19 community transmission in regional areas with high Aboriginal populations, limited health infrastructure and low vaccination rates could result in clusters of transmission with increased deaths rates. Pilbara, a regional community with a high Aboriginal population, showed a 34.8% increase in COVID-19 cases in the 4-week post-cruise-ship docking.
Text Message-Based Cessation Intervention for People Who Smoked or Used Smokeless Tobacco in India: A Feasibility Randomized Controlled Trial
Authors: Nadkarni Abhijit , Gaikwad Leena , Sequeira Miriam , D’souza Joseline , Lopes Megan , Haldankar Rajanish , Murthy Pratima , Velleman Richard , Bhatia Urvita , Naughton Felix
Published: March 2024

Introduction

Despite the high burden of tobacco use in India, users do not have access to adequate help. This pilot trial aimed to evaluate the feasibility and acceptability of a text messaging intervention for tobacco cessation, generate preliminary estimates of its impact, and fine-tune procedures for a definitive trial.

Aims and Methods

Parallel two-arm single blind individually randomized controlled pilot trial with nested qualitative study. Participants included adult current tobacco users (smoked and smokeless). Eligible and consenting participants were randomized to receive either (1) text messaging intervention (ToQuit) which covered specific content areas such as psychoeducation about consequences of tobacco use and benefits of quitting and tobacco avoidance strategies or (2) information about tobacco cessation helplines such as the helpline number and the languages in which tobacco cessation support was available (control). Feasibility data included screening and consent rates, treatment dropouts, and outcome ascertainment. The primary abstinence outcome was self-reported abstinence from tobacco in the past seven days at 3 months post-randomization. In-depth interviews were conducted with a subsample of participants primarily to collect acceptability data. The primary abstinence analysis used a chi-squared test and logistic regression (complete case), and qualitative data was analyzed using thematic analysis.

Results

Ninety-eight participants were randomized into the two trial arms; 77 (79%) completed outcome evaluation. No between-arm differences in abstinence were found though findings favored the intervention (7-day abstinence: ToQuit 23%, control 19%; adjusted odds ratio 1.23, 95% confidence interval 0.38, 3.97). Participants appreciated the language, comprehensibility, and relevance of the messages; and reported overall satisfaction with and positive impact from the intervention on their lives.

Conclusions

The findings indicate the acceptability and feasibility of ToQuit and if found effective, it could be a potentially scalable first-line response to tobacco use in low-resource settings.

Implications

Our pilot randomized control trial provides sufficient findings supporting the acceptability and feasibility of an intervention for tobacco cessation which is suitable for a context which has a shortage of healthcare workers and for individuals who use smoked or smokeless tobacco. This is critical on a background of limited contextually relevant interventions for a problem with a high burden in low- and middle-income countries such as India.
The Moment of Patient Safety: Iatrogenic Injury, Clinical Error and Cultures of Healthcare in the NHS
Authors: Sirrs Christopher
Published: March 2024

This article explores the ‘the moment of patient safety’—the period around 2000 when patient safety became a key policy concern of the British National Health Service (NHS), and other healthcare systems. While harm caused by medical care (iatrogenic injury) had long been acknowledged by clinicians and scientists, from 2000 a new systemic language of patient safety emerged in the NHS that promoted novel managerial and regulatory approaches to patient harm. This language reflected the state’s increasing role in regulating healthcare, as well as the erosion of medical autonomy and the rise of new forms of bureaucratic management. Acknowledging a transnational, intellectual context behind the rise of policy interest in patient safety—for example, the application of insights from the industrial safety sciences—this article examines the role played by domestic cultural factors, such as medical negligence litigation and healthcare scandals, in helping to define the new language in Britain.
The effect of ectomycorrhizal fungal exposure on nursery-raised Pinus sylvestris seedlings: plant transpiration under short-term drought, root morphology and plant biomass
Authors: De Quesada Gonzalo , Xu Jie , Salmon Yann , Lintunen Anna , Poque Sylvain , Himanen Kristiina , Heinonsalo Jussi
Published: March 2024

Drought is a major environmental stressor that limits seedling growth. Several studies have found that some ectomycorrhizal fungi may increase the drought tolerance of nursery-raised seedlings. However, the precise role that different ectomycorrhizal fungi species play in drought tolerance remains unclear. We evaluated the transpiration rate of Pinus sylvestris seedlings under drought stress in greenhouse conditions by exposing seedlings to 10 ectomycorrhizal fungi species, with different functional traits (exploration type and hydrophobicity), and to 3 natural soil inoculums. We measured the transpiration and water potential of the seedlings during a 10-day drought period and a 14-day recovery period. We then analyzed their root morphology, stem, needle, root biomass and needle chlorophyll fluorescence. We showed that exposing seedlings to ectomycorrhizal fungi or soil inoculum had a positive effect on their transpiration rate during the driest period and through the recovery phase, leading to 2- to 3-fold higher transpiration rates compared with the nonexposed control seedlings. Seedlings exposed to medium-distance ectomycorrhizal fungi performed better than other exploration types under drought conditions, but ectomycorrhizal fungi hydrophobicity did not seem to affect the seedlings response to drought. No significant differences were observed in biomass accumulation and root morphology between the seedlings exposed to different ectomycorrhizal fungi species and the control. Our results highlight the positive and species-specific effect of ectomycorrhizal fungi exposure on drought tolerance in nursery-raised Scots pine seedlings. The studied ectomycorrhizal fungi functional traits may not be sufficient to predict the seedling response to drought stress, thus physiological studies across multiple species are needed to draw the correct conclusion. Our findings have potential practical implications for enhancing seedling drought tolerance in nursery plant production.
Spongospora subterranea f. sp. subterranea Affects Plant Susceptibility to Subsequent Pathogen Infections Under Controlled-Environment Conditions
Authors: Ozturk Ibrahim Kutay , Buchholz Elizabeth , Bentley Ally , Halterman Dennis , Rioux Renee
Published: March 2024

Spongospora subterranea f. sp. subterranea (Sss) is a soilborne potato pathogen responsible for causing powdery scab on tubers and galls on roots, reducing root water uptake through colonizing root hairs, and vectoring of Potato mop-top virus (PMTV). However, effects of Sss on overall plant susceptibilities against subsequent infections of potato pathogens above ground have not been previously reported. This study aimed to investigate the effects of Sss on root and tuber disease expression, yield, and susceptibilities to subsequent late blight and white mold infections across six potato varieties. Sss-infected Silverton plants had 28.3% less total tuber yield and 29% fewer tubers compared to noninfected Silverton plants. We did not find a correlation across the varieties between root colonization and root gall formation. Sss-infected Silverton plants were more susceptible to hemibiotrophic late blight and less susceptible to necrotrophic white mold. Sss infection also increased susceptibilities of Goldrush and Atlantic plants to white mold. We also evaluated prevalence of asymptomatic Sss infections across the six varieties. Between 50 and 92% of the asymptomatic tubers tested positive for Sss DNA, depending on the variety. Further research is required to understand the possibility and extent of these asymptomatic infections to the spread of Sss in the field. These findings highlight the complexity of Sss-host interactions and give precedence that the lack of disease expression does not necessarily indicate resistance of a variety to Sss.
Peptide derived from RAGE efficiently improves oocyte development through attenuating oxidative stress in oocytes of mice with polycystic ovary syndrome
Authors: Hou Xiaojing , Ling Zhonghui , Guo Yaping , Su Yan , Wang Hanbin , Li Hang , Lu Yuxia , Chen Xiaojiao , Ji Chenbo , Shen Rong
Published: March 2024

Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in reproductive‐aged women that frequently leads to infertility due to poor oocyte quality. In this study, we identified a new active peptide (advanced glycation end products receptors RAGE344‐355) from PCOS follicular fluid using mass spectrometry. We found that supplementing PCOS‐like mouse oocytes with RAGE344‐355 attenuated both meiotic defects and oxidative stress levels, ultimately preventing developmental defects. Additionally, our results suggest that RAGE344‐355 may interact with eEF1a1 to mitigate oxidative meiotic defects in PCOS‐like mouse oocytes. These findings highlight the potential for further clinical development of RAGE344‐355 as a potent supplement and therapeutic option for women with PCOS. This research addresses an important clinical problem and offers promising opportunities for improving oocyte quality in PCOS patients.
Genetic causal relationship between gut microbiota and cutaneous melanoma: a two-sample Mendelian randomization study
Authors: Wang Peizhou , Liu Tun , Zhang Qingguo , Luo Pan
Published: March 2024

Currently, numerous studies suggest a potential association between the gut microbiota and the progression of melanoma. Hence, our objective was to examine the genetic impact of the gut microbiota on melanoma through the utilization of the Mendelian randomization (MR) approach. This research employed Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae as exposure variables and cutaneous melanoma (CM) as the outcome in a two-sample MR analysis. In this MR research, the primary analytical approach was the random-effects inverse-variance weighting (IVW) model. Complementary methods included weighted median, MR Egger, and basic and weighted models. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual SNP. The random-effects IVW outcomes indicated that Streptococcus, Bacteroides, Lachnospiraceae and Proteobacteria had no causal relationship with CM, with odds ratios of 1.001 [95% confidence interval (CI) = 0.998–1.004, P = 0.444], 0.999 (95% CI = 0.996–1.002, P = 0.692), 1.001 (95% CI = 0.998–1.003, P = 0.306), and 0.999 (95% CI = 0.997–1.002, P = 0.998), respectively. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. Our research determined that Bacteroides, Streptococcus, Proteobacteria, and Lachnospiraceae do not induce CM at the genetic level. However, we cannot dismiss the possibility that these four gut microbiotas might influence CM through other mechanisms.
LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials
Authors: Cox Sue Ellen , Kaufman-Janette Joely , Cohen Joel L. , Gold Michael , Joseph John , Nestor Mark S. , Rzany Berthold , Taylor Susan , Zhou Jihao , Cecerle Michael , Pueraro Elena , Irvine Ryan , Dayan Steven
Published: March 2024

BACKGROUND

Hyperfunctional glabellar frown lines can transmit facial miscues that adversely affect emotional communication, increase perceptions of age, and diminish self-esteem.

OBJECTIVE

To evaluate the efficacy of letibotulinumtoxinA in mitigating the negative psychological impact associated with moderate to severe glabellar lines and to assess subject satisfaction with treatment outcome in the BLESS phase 3 clinical trials.

MATERIALS AND METHODS

Baseline and posttreatment assessments were made using validated subject-administered instruments: Modified Skindex-16 Glabellar Line Quality of Life (GL-QoL) Scale, Facial Assessment and Cosmetic Evaluation Questionnaire (FACE-Q) Appraisal of Lines Between Eyebrows Scale, FACE-Q Age Appraisal Visual Analog Scale, and FACE-Q Satisfaction with Outcome Scale. An integrated analysis using pooled BLESS data was conducted on these secondary end points.

RESULTS

Among enrolled and treated subjects (N = 1,272), 85.5% had moderate to severe psychological impact at baseline. LetibotulinumtoxinA subjects experienced significant improvements compared with placebo on all measures. Mean improvement to Week 4 for the Modified Skindex-16 GL-QoL Scale overall score was −33.84 for letibotulinumtoxinA subjects compared with −1.37 for placebo subjects (p < .001). Attenuation of psychological burden was highly correlated with improvement in glabellar line severity (p < .0001).

CONCLUSION

LetibotulinumtoxinA significantly improved the psychosocial burden associated with glabellar lines across all trials. Treated subjects experienced improved quality of life, younger perceived age, and satisfaction with treatment outcome.
Systematic review of neurokinin-3 receptor antagonists for the management of vasomotor symptoms of menopause
Authors: Cieri-Hutcherson Nicole E. , Marji Elaine K. , Hutcherson Timothy C.
Published: March 2024

Importance

Vasomotor symptoms (VMS) affect many postmenopausal persons and impact sleep and quality of life.

Objective

This systematic review examines the literature describing the safety and efficacy of neurokinin-3 receptor antagonists approved and in development for postmenopausal persons with VMS.

Evidence Review

A search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts was conducted using the search terms and permutations of neurokinin-3 receptor antagonist, elinzanetant, fezolinetant, and osanetant. Inclusion criteria of reporting on efficacy or safety of fezolinetant, elinzanetant, or osanetant; studies in participants identifying as female; full record in English; and primary literature were applied. Abstract-only records were excluded. Extracted data were synthesized to allow comparison of reported study characteristics, efficacy outcomes, and safety events. Eligible records were evaluated for risk of bias via the Cochrane Risk of Bias 2 tool for randomized studies and the Grading of Recommendations Assessment, Development and Evaluation system was used. This study was neither funded nor registered.

Findings

The search returned 191 records; 186 were screened after deduplication. Inclusion criteria were met by six randomized controlled trials (RCT), four reported on fezolinetant, and two reported on elinzanetant. One record was a post hoc analysis of a fezolinetant RCT. An additional study was identified outside the database search. Three fezolinetant RCT demonstrated a reduction in VMS frequency/severity, improvement in Menopause-Specific Quality of Life scores, and improvement in sleep quality at weeks 4 and 12 compared with placebo without serious adverse events. The two RCT on elinzanetant also showed improvements in VMS frequency and severity. All eight records evaluated safety through treatment-emergent adverse events; the most common adverse events were COVID-19, headache, somnolence, and gastrointestinal. Each record evaluated had a low risk of bias. There is a strong certainty of evidence as per the Grading of Recommendations Assessment, Development and Evaluation system.

Conclusions and Relevance

Because of the high-quality evidence supporting the efficacy of fezolinetant and elinzanetant, these agents may be an effective option with mild adverse events for women seeking nonhormone treatment of VMS.
Reflections on the Multicenter Randomized Trial of Treatment for Mild Gestational Diabetes
Authors: Landon Mark B.
Published: March 2024

After the 2006 hyperglycemia and adverse pregnancy outcomes study, which confirmed the relationship between maternal glycemia and pregnancy outcomes, the debate remained on whether treatment benefited gestational diabetes mellitus (GDM). Nonetheless, practitioners continued to universally screen for and treat women identified as GDM. To assess the benefits and harms of screening and treatment of GDM, the National Institute of Child Health and Human Development Maternal and Fetal Medicine Unit Network designed and conducted a well-designed randomized controlled trial in women with mild GDM. The trial established that treatment of GDM resulted in a significant reduction in several important perinatal and maternal outcomes.
Evaluation of prone vs supine positioning in fresh rhegmatogenous retinal detachment treated with pars plana vitrectomy and gas
Authors: Agarwalla Anushka , Chawla Rohan , Azad Shorya Vardhan , Venkatesh Pradeep , Vohra Rajpal , Kumar Vinod
Published: March 2024

Purpose:

To compare Supine versus Prone positioning in fresh rhegmatogenous retinal detachments (RRDs) treated with vitrectomy and gas tamponade.

Methods:

This was a prospective randomized controlled trial of 72 eyes with fresh RRD who underwent 25-gauge vitrectomy. 37 eyes were allotted supine position and 35 were allotted prone position. Cases were evaluated for single surgery reattachment rates, best corrected visual acuity (BCVA), intraocular pressure (IOP), cataract formation and any complications. The patients were followed up for a period of 3 months.

Results:

Both groups had similar demographics, and no significant difference was found between the two groups in terms of extent of retinal detachment, position and number of breaks. The anatomical success after single surgery was 97.3% in Supine group and 94.3% in Prone group (p=0.609). The BCVA at the end of 3 months was 0.44 ± 0.27 in Supine group and 0.35 ± 0.27 in Prone group (p=0.119) with a significant increase in BCVA preoperatively from 0.11 ± 0.22 and 0.13 ± 0.22 in Supine and Prone group respectively (p=<0.001). The IOP in the two groups was comparable at each follow up. The rates of cataract formation were also similar in the two groups - 60% and 53.8% in Supine and Prone group respectively(p=1.00). Complications such as spikes in IOP, epiretinal membrane formation, cystoid macular oedema etc were similar in both groups.

Conclusion:

Rates of retinal reattachment were comparable in both groups, showing that supine position is equally safe and effective for adequate tamponade.
Frequency of Hematologic and Nonhematologic Conditions in Pediatric Patients with Vascular Anomalies: A Pediatric Health Information System Database Study
Authors: Lucas Bryony , Malay Sindhoosha , Pateva Irina
Published: March 2024

Background:

Vascular anomalies (VA) are a heterogeneous group of diseases which include vascular malformations and vascular tumors. In the pediatric population, there is a sparsity of data on the frequency of associated hematologic and nonhematologic conditions as well as overall outcomes for patients.

Objectives:

The objective of this study was to determine the rate of certain concurrent hematologic and nonhematologic conditions in patients with VA who underwent procedures and compare those to patients who did not undergo procedures. To examine the rates of intensive care unit admissions and discharge mortality in patients who had a vascular anomaly.

Methods:

This is a multicenter retrospective cohort study using data from the Pediatric Health Information System. The database was queried for children 0–18 years old with a diagnosis of a VA who had inpatient encounters between January 2016 and September 2021.

Results:

The most common hematologic conditions were thrombocytopenia, iron deficiency anemia, and venous thrombosis. The most common nonhematologic condition was electrolyte imbalances. Intensive care unit admissions were highest among patients with other congenital malformations of the peripheral vascular system, cerebral cavernous malformations, and sporadic arteriovenous malformations. Discharge mortality was highest in patients with lymphatic malformations and primary lymphedema.

Conclusions:

This is the largest database study of pediatric patients with VA and their concurrent medical conditions and outcomes to date. While our study could not prove associations, we hope that our results will serve as a foundation for more extensive research regarding the impact of these identified conditions and outcomes and contribute to improved management of patients with VA.
Duodenal Duplication Cyst Masquerading as Metastatic Nonseminomatous Germ Cell Tumor
Authors: Faber Lauren S. , Hodges Hannah , Hashemi-Sadraei Neda , Alba Frances M.
Published: March 2024

Testicular cancer can result in retroperitoneal metastatic disease, requiring further intervention with chemotherapy and/or surgical resection. We present the case of a large retroperitoneal mass concerning for metastasis resulting in the identification of a duodenal duplication cyst rather than metastatic disease.
Combining Spleen Diameter and the Baveno VI Criteria Assessed by 2-Dimensional Shear Wave Elastography to Rule Out High-Risk Varices
Authors: Zhang Zhilin , Zhou Huihui , Duan Kunlong , Chen Feifei , Zhang Jun , Sang Lin , Zhu Xiansheng , Yu Ming
Published: March 2024

Patients with compensated advanced chronic liver disease (cACLD) can safely spared screening esophagogastroduodenoscopy (EGD) when they meet the Baveno VI criteria as assessed by transient elastography. Recently, the cutoff values of the Baveno VI criteria assessed by 2-dimensional shear wave elastography (2D-SWE) were proposed. We aimed to validate it to rule out high-risk varices (HRVs) in cACLD patients; combine spleen diameter (SPD) with the Baveno VI criteria and assess whether it can spare more screening EGD. A total of 173 cACLD patients with successful liver stiffness (LS) measurements and EGD examinations were included. We analyzed the risk factors that predicted HRVs and compared the performances of different models for ruling out HRVs. The platelet count, LS, and SPD were independent predictors of HRVs. The AUCs of platelet count, LS, spleen stiffness and SPD for diagnosing HRVs were 0.797, 0.757, 0.834, and 0.804, respectively. The Baveno VI criteria assessed by 2D-SWE spared 25.4% of EGD screenings and missed 2.4% of the HRV patients. Combining SPD ≤11.1 cm with the Baveno VI criteria could spare more EGD screenings than just applying the Baveno VI criteria (45.1% vs 25.4%, P < 0.001), and missed 4.9% of the HRV patients. The Baveno VI criteria assessed by 2D-SWE could be safely applied in cACLD patients to rule out HRV patients. The combined model Baveno VI/SPD could safely and significantly increase the rate of spared EGD.
A Patient With Minimally Conscious Syndrome Due to Cerebrovascular Accident Whose Symptoms Resolved With Zolpidem
Authors: Smack Caleb , Johnson Katherine , Meester Noah , Shelton Leah , Singh Namrata
Published: March 2024

Objective

In this report, we discuss the case of a patient with minimally conscious state (MCS) whose clinical condition significantly improved after Zolpidem therapy. We aim to provide supportive evidence for inclusion of zolpidem trials in patients with MCS.

Methods

Our team used electronic medical records, direct patient care experiences, and literature review to obtain information for this case report.

Results

Twice daily zolpidem therapy led to significant clinical improvement in our patient with MCS. In addition, this improvement was maintained throughout an increasingly arduous medical course.

Conclusions

Minimally conscious state is a disorder with limited proven therapeutic options. Zolpidem administration has demonstrated immense benefit in a select population of patients, including ours. Given the potential for great improvement with limited downside, zolpidem trial presents an intriguing treatment option. Further clarification of prognostic features to stratify responders and nonresponders to therapy is needed.
Asymmetry in synaptic connectivity balances redundancy and reachability in theC. elegansconnectome
Authors: Birari Varun Sanjay , Rabinowitch Ithai
Published: March 2024

The brain is overall bilaterally symmetrical, but exhibits also considerable asymmetry. While symmetry may endow neural networks with robustness and resilience, asymmetry may enable parallel information processing and functional specialization. How is this functional tradeoff between symmetrical and asymmetrical brain architecture balanced? To address this, we focused on theC. elegansconnectome, which comprises 99 classes of bilaterally symmetrical neuron pairs. We found symmetry in the number of synaptic partners between neuron class members, but pronounced asymmetry in the identity of these synapses. We developed graph theoretical metrics for evaluating Redundancy, the selective reinforcement of specific neural paths by multiple alternative synaptic connections, and Reachability, the extent of synaptic connectivity of each neuron class. We found Redundancy and Reachability to be stochastically tunable by the level of network asymmetry, driving theC. elegansconnectome to favor Redundancy over Reachability. These results elucidate fundamental relations between lateralized neural connectivity and function.
The Zinc Finger proteinSlZFP2 is essential for tomato fruit locular tissue morphogenesis
Authors: Hoang Gabriel , Joana Jorly , Constantinescu Dario , Martin Pascal G P , Gadin Stéphanie , Mauxion Jean-Philippe , Brès Cécile , Garcia Virginie , Gonzalez Nathalie , Rothan Christophe , Bertin Nadia , Fernandez-Lochu Lucie , Lemaire-Chamley Martine
Published: March 2024

In tomato (Solanum lycopersicum L.) fruit, the locular tissue (LT) is a unique jelly-like tissue that differentiates from the central axis of the fruit after ovule fertilization. LT is essential for seed development and dispersal by preventing early germination and initiating fruit ripening. In this work, we studied a “gel-less” mutant and identified the underlying mutation in the coding sequence of the C2H2 zinc finger transcription factor (TF)SlZFP2. Histological, cytological and molecular characterization from knockout-CRISPR/Cas9 lines for this gene revealed the strong and early impact ofzfp2mutation on cell cycle and endocycle in LT. Additionally, model-based analysis of cellular data revealed that cell cycle was the main altered process, explaining thezfp2mutant phenotype. Further laser capture microdissection coupled with RNA-Seq analysis of young LT highlighted global expression changes between WT andzfp2mutant and led to a preliminary list of potential direct targets of theSlZFP2 TF. This multifaceted approach not only uncovered a new role forSlZFP2 TF as an essential regulator of LT morphogenesis, but also provides a foundation for future works aimed at deciphering the intricate regulatory networks governing fruit tissue development in tomato.

One sentence summary

Alteration of cell division and endoreduplication in agel-lessmutant reveals the role of the transcription factorSlZFP2 in tomato locular tissue morphogenesis
Putative Looping Factor ZNF143/ZFP143 is an Essential Transcriptional Regulator with No Looping Function
Authors: Narducci Domenic N. , Hansen Anders S.
Published: March 2024

Interactions between distal loci, including those involving enhancers and promoters, are a central mechanism of gene regulation in mammals, yet the protein regulators of these interactions remain largely undetermined. The zinc finger transcription factor ZNF143/ZFP143 has been strongly implicated as a regulator of chromatin interactions, functioning either with or without CTCF. However, ZNF143/ZFP143’s role in this process and its function, either with or without CTCF, are not well understood. Here, we tagged both CTCF and ZNF143/ZFP143 with dual-purpose degron/imaging tags to combinatorially assess their looping function and effect on each other. We find that ZNF143/ZFP143 possesses no general looping function in mouse and human cells, and that it largely functions independently of CTCF. Instead, ZNF143/ZFP143 is an essential and highly conserved transcription factor possessing an extremely stable chromatin residence time (>20 min) that regulates an important subset of mitochondrial and ribosomal genes.
The P600 during sentence reading predicts behavioral and neural markers of recognition memory
Authors: Contier Friederike , Höger Melissa , Rabovsky Milena
Published: March 2024

The P600 ERP component is elicited by a wide range of anomalies and ambiguities during sentence comprehension and remains important for neurocognitive models of language processing. It has been proposed that the P600 is a more domain-general component, signaling phasic norepinephrine release from the locus coeruleus in response to salient stimuli that require attention and behavioral adaptation. Since such norepinephrine release promotes explicit memory formation, we here investigated whether the P600 during sentence reading (encoding) is thus predictive of such explicit memory formation using a subsequent old/new word recognition task. Indeed, the P600 amplitude during our encoding task was related to behavioral recognition effects in the memory task on a trial-by-trial basis, though only for one type of violation. Recognition performance was better for semantically, but not syntactically violated words that had previously elicited a larger P600. However, the P600 to both types of violations during encoding was positively related to a more subtle, neural marker of recognition, namely the amplitude of the recollection ERP component in response to old words. In sum, we find that the P600 predicts later recognition memory both on the behavioral and neural level. Such explicit memory effects further link the late positivity to norepinephrine activity, suggesting a more domain-general nature of the component. The connection between the P600 and later recognition indicates that the neurocognitive processes that deal with salient and anomalous aspects in the linguistic input in the moment will also be involved in keeping this event available for later recognition.
The acute effects of cocoa flavanols on cognitive control and response inhibition: A randomised crossover trial
Authors: Altınok Ahmet , Moruzzi Monica , Akyürek Elkan G.
Published: March 2024

In this pre-registered study, we investigated the effects of acute cocoa flavanol (CF) consumption on cognitive control and response inhibition processes, at two different dosage levels. This study was randomised, placebo-controlled, gender-balanced, double-blind, and utilised a crossover design. Participants consumed three different drinks across three separate sessions: A placebo drink with alkalised cocoa powder, a low dosage (415 mg), and a medium dosage (623 mg) of cocoa flavanols from flavanol-rich cocoa powder. Following the administration of these treatment conditions, participants were tested in the Flanker, Simon, and Go/No-go tasks in a counterbalanced order in each session. We analysed accuracy and response times from incongruent and congruent trials of the Simon and Flanker tasks, and commission errors, omission errors, and response times for the Go/No-go task. In addition to these main measurements, we considered interference and sequence effects, accounting for the influence of previous trials in Simon and Flanker tasks. The acute effects of CF on cognitive control and response inhibition were examined using (Generalised) Linear Mixed Model analysis, which included random intercepts, fixed effects, and random slopes. Analysis results revealed that neither dose of cocoa flavanols consumption acutely improved accuracies, interferences, errors, or response times in these three tasks. Furthermore, neither the gender of participants nor BMI scores predicted their cognitive control and response inhibition functions in addition to the treatment conditions. Our findings suggest that acute consumption of cocoa flavanols does not significantly enhance cognitive control or response inhibition in healthy young adults.
INGEsT: An Open-Source Behavioral Setup for Studying Self-motivated Ingestive Behavior and Learned Operant Behavior
Authors: Zhao Zhe , Xu Binbin , Loomis Cody L. , Anthony Skylar A. , McKie Isaac , Srigiriraju Abhishikta , Bolton McLean , Stern Sarah A.
Published: March 2024

Ingestive behavior is driven by negative internal hunger and thirst states, as well as by positive expected rewards. Although the neural substrates underlying feeding and drinking behaviors have been widely investigated, they have primarily been studied in isolation, even though eating can also trigger thirst, and vice versa. Thus, it is still unclear how the brain encodes body states, recalls the memory of food and water reward outcomes, generates feeding/drinking motivation, and triggers ingestive behavior. Here, we developed an INstrument for Gauging Eating and Thirst (INGEsT), a custom-made behavioral chamber which allows for precise measurement of both feeding and drinking by combining a FED3 food dispenser, lickometers for dispensing liquid, a camera for behavioral tracking, LED light for optogenetics, and calcium imaging miniscope. In addition,in vivocalcium imaging, optogenetics, and video recordings are well synchronized with animal behaviors, e.g., nose pokes, pellet retrieval, and water licking, by using a Bpod microprocessor and timestamping behavioral and imaging data. The INGEsT behavioral chamber enables many types of experiments, including free feeding/drinking, operant behavior to obtain food or water, and food/water choice behavior. Here, we tracked activity of insular cortex and mPFC Htr3a neurons using miniscopes and demonstrate that these neurons encode many aspects of ingestive behavior during operant learning and food/water choice and that their activity can be tuned by internal state. Overall, we have built a platform, consisting of both hardware and software, to precisely monitor innate ingestive, and learned operant, behaviors and to investigate the neural correlates of self-motivated and learned feeding/drinking behaviors.
Sacbrood viruses and select Lake Sinai virus variants dominated Apis mellifera colonies symptomatic for European foulbrood
Authors: Hesketh-Best Poppy J , Fowler Peter D , Odogwu Nkechi M , Milbrath Meghan O , Schroeder Declan C
Published: March 2024

European foulbrood (EFB) is a prevalent disease of the European honey bee (Apis mellifera) in the US, which can lead to colony decline and collapse. The bacterial components of EFB are well studied, but the diversity of viral infections within infected colonies has not been explored. Here we use meta-transcriptomics sequencing of 12 honey bee hives, symptomatic (+) and asymptomatic (-) for EFB to explore viral infection associated with the disease. We identified 41 viral genomes, belonging to two families, with a predominant occurrence of 34 genomes observed in colonies with severe EFB. This is in contrast to fewer, and a complete absence of Dicistroviridae genomes, recovered from healthy colonies (7 genomes). Identified viruses included multiple lineages previously reported in honey bees, namely Lake Sinai virus, Deformed wing virus, Sacbrood virus, Black queen cell virus, and Israeli acute paralysis virus. We observed specific Lake Sinai virus clades associated exclusively with EFB+ or EFB- colonies, in addition to EFB-afflicted colonies that exhibited an increase in relative abundance of sacbrood viruses. Multivariant analyses highlighted that a combination of site and EFB disease status influenced RNA virome composition, while EFB status alone didn't significantly impact it, presenting a challenge for comparisons between colonies kept in different yards. These findings contribute to the understanding of viral dynamics in honey bee colonies compromised by EFB and underscore the need for future investigations to consider viral composition when investigating EFB.
A shifting role of thalamocortical connectivity in the emergence of large-scale functional brain organization during early lifespan
Authors: Park Shinwon , Haak Koen V. , Oldham Stuart , Cho Hanbyul , Byeon Kyoungseob , Park Bo-yong , Thomson Phoebe , Chen Haitao , Gao Wei , Xu Ting , Valk Sofie , Milham Michael P. , Bernhardt Boris , Martino Adriana Di , Hong Seok-Jun
Published: March 2024

While cortical patterning has been a perennial research topic in neuroscience, the mechanism for its consequence, namely functional specialization at the macro scale, remains an open question in the human brain. Here, we focused on age-dependent changes of resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks across infancy, childhood and young adulthood. We found that the thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically-influenced axonal projection. This initial role of the thalamus, however, seems to change during childhood, by establishing connectivity with the salience network and decoupling externally- and internally-oriented functional processes. Developmental simulation and perturbation analyses corroborated these findings, demonstrating the highest contribution of thalamic connectivity, especially in the later age of youth, in the formation of key characteristics of the mature brain, such as functional gradient and cortical hierarchy. Our study highlights a developmentally shifting role of the thalamus in orchestrating complex brain organization and its potential implications for developmental conditions characterized by compromised internal and external processing.
Distribution-driven disturbance of a molecular community: a theoretical framework
Authors: Ramírez Gustavo A. , Mel Gabriel C.
Published: March 2024

An important and understudied area in microbial ecology concerns the very large number of very rare species within an environment. Study of such species based on non-specific sequencing of environmental samples is practically difficult simply due to their rarity. A previous report demonstrated that pretreating samples with the photoactive dye PMA before subsequent PCR and sequencing can increase sensitivity to rare species. Here we propose a mathematical model based on equilibrium chemical thermodynamics that explains this effect and suggests a simple quantitative experiment.
The gamma-butyrolactone receptors ScbR and AtrA form a quorum sensing switch between coelimycin and actinorhodin synthesis inStreptomyces coelicolorA3(2)
Authors: Bednarz Bartosz , Kotowska Magdalena , Wenecki Mateusz , Derkacz Marta , Jastrzemska Adrianna , Ciekot Jarosław , Pawlik Krzysztof J.
Published: March 2024

Background

Quorum sensing enables gene expression regulation in response to changes in cell population density and controls diverse processes, such as biofilm formation, virulence and antibiotic production, in bacteria. In one of the largest, soil-dominant phylumActinobacteria, cell-to-cell communication occurs through the small, membrane-diffusible signalling molecules gamma-butyrolactones (GBLs). Their actions are exerted through receptor proteins that also act as response regulators in a one-component system manner. With only a few GBL systems characterized, most of them come from the large, antibiotic-producer genusStreptomyces. In the model organismStreptomyces coelicolorA3(2), two GBL receptors, ScbR and SlbR, which are both antibiotic production repressors, have been reported so far.

Results

In this work, we identified a new GBL receptor protein, the conserved and pleiotropic regulator AtrA, which has an activating mode of action. Moreover, we elucidated the precise mechanism by which it controls the production of the antibiotic actinorhodin through the actinorhodin biosynthetic gene cluster activator ActII-orf4. GBL binding to AtrA prevents its binding to the promoter of theactII-orf4gene, thereby disabling its transcription, while at the same time, GBL binding to ScbR causes coelimycin antibiotic synthesis derepression.

Conclusions

The opposite modes of action of ScbR (repressor) and AtrA (activator) have opposite effects upon GBL binding, activating coelimycin and blocking actinorhodin production at the same time. This phenomenon constitutes an elegant regulatory mechanism that ensures that coelimycin and actinorhodin production are mutually exclusive. These findings also suggest that quorum sensing must be taken into account when designing efficient antibiotic production processes and can be manipulated to ensure both better yield and specificity.
DNA replication and polymer chain duplication reshape the genome in space and time
Authors: D’Asaro Dario , Tortora Maxime M. C. , Vaillant Cédric , Arbona Jean-Michel , Jost Daniel
Published: March 2024

In eukaryotes, DNA replication constitutes a complex process whereby multiple origins are stochastically fired, and from which the replication machinery proceeds along chromosomes to achieve the faithful synthesis of two identical copies of the genome during the S-phase of the cell cycle. Experimental evidence show a functional correlation between the dynamics of replication and the spatial organization of the genome inside cell nuclei, suggesting that the process of replicating DNA may impact chromosome folding. However, the theoretical and mechanistic bases of such an hypothesis remain elusive. To address that question, we propose a quantitative, minimal framework that integrates the dynamics of replication along a polymer chain by accounting explicitly for the progression of the replication machinery and the resulting formation of sister chromatids. By systematically characterizing the 3D structural consequences of replication, and of possible interactions between active replication machineries, we show that the formation of transient loops may potentially impact chromosome organization across multiple temporal and spatial scales, from the level of individual origins to that of the global polymer chain. Comparison with available microscopy and chromosome conformation capture data in yeast suggests that a replication-dependent loop extrusion process may be actingin vivo, and may shape chromosomes as loose polymer bottle-brushes during the S-phase. Lastly, we explore the post-replication relative organization of sister chromatids and demonstrate the emergence of catenations and intertwined structures, which are regulated by the density of fired origins.