bluuebunny/crossref_metadata_2025 huggingface dataset:
Intraductal papillary neoplasms of the bile duct: a European retrospective multicenter observational study (EUR-IPNB study)
Authors: Lluís Núria , Serradilla-Martín Mario , Achalandabaso Mar , Jehaes François , Dasari Bobby V.M. , Mambrilla-Herrero Sara , Sparrelid Ernesto , Balakrishnan Anita , Hoogwater Frederik J.H. , Amaral Maria J. , Andersson Bodil , Berrevoet Frederik , Doussot Alexandre , López-López Víctor , Alsammani Mohammedsuror , Detry Olivier , Domingo-del Pozo Carlos , Machairas Nikolaos , Pekli Damján , Alcázar-López Cándido F. , Asbun Horacio , Björnsson Bergthor , Christophides Thalis , Díez-Caballero Alberto , Francart David , Noel Colin B. , Sousa-Silva Donzília , Toledo-Martínez Enrique , Tzimas George N. , Yaqub Sheraz , Cauchy François , Prieto-Calvo Mikel , D’Souza Melroy A. , Spiers Harry V.M. , van den Heuvel Marius C. , Charco Ramón , Lesurtel Mickaël , Ramia José M.
Published: March 2023

Background/Purpose:

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers.

Methods:

A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien–Dindo grade at least III complications, readmission, or mortality within 90 postoperative days.

Results:

A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55–72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50–82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 (P=0.016), intrahepatic versus extrahepatic tumor (P=0.027), single versus multiple tumors (P=0.007), those who underwent hepatic versus pancreatic resection (P=0.017), or achieved versus failed TO (P=0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11–15.94; P=0.03) was an independent prognostic factor of poor overall survival.

Conclusions:

Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.
Comparison of the perioperative outcomes of laparoscopic and open retroperitoneal lymph node dissection for low-stage (stage I/II) testicular germ cell tumors: a systematic review and meta-analysis
Authors: Ge Si , Gan Lijian , Meng Chunyang , Li Kangsen , Wang Zuoping , Zeng Zhiqiang , Zheng Lei , Li Yunxiang
Published: March 2023

Objective:

Comparison of the perioperative outcomes of laparoscopic retroperitoneal lymph node dissection (L-RPLND) and open retroperitoneal lymph node dissection (O-RPLND) for low-stage (stage I/II) testicular germ cell tumors.

Methods:

The authors performed a systematic review and cumulative meta-analysis of the primary outcomes of interest according to PRISMA criteria, and the quality assessment of the included studies followed the AMSTAR guidelines. Four databases were searched, including Embase, PubMed, the Cochrane Library, and Web of Science. The search period was from the creation of each database to October 2022. The statistical analysis software uses Stata17.

Results:

There were nine studies involving 579 patients. Compared with O-RPLND, L-RPLND was associated with shorter length of stay [weighted mean difference (WMD)=−3.99, 95% CI: −4.80 to −3.19, P<0.05], less estimated blood loss (WMD=−0.95, 95% CI: −1.35 to −0.54, P<0.05), shorter time to oral intake after surgery (WMD=−0.77, 95% CI: −1.50 to −0.03, P<0.05), and lower overall complications (odds ratio=0.58, 95% CI: 0.38–0.87, P<0.05). Subgroup analysis found that the complication rate of Clavien–Dindo grade II was lower in L-RPLND (odds ratio=0.24, 95% CI: 0.11–0.55, P<0.05). Interestingly, there was no statistically significant difference between the two groups in terms of operation time, lymph node yields, and recurrence rate during follow-up.

Conclusion:

L-RPLND is superior to O-RPLND and is worthy of clinical promotion.
The association between frontal QRS-T angle and reverse dipper status in newly diagnosed hypertensive patients
Authors: Karakayali Muammer , Artac Inanç , Omar Timor , Rencuzogullari İbrahim , Karabag Yavuz , Cinar Tufan , Altunova Mehmet , Hamideyin Serif
Published: March 2023

The frontal QRS-T angle (fQRS-T angle) in ECG is a new measure of myocardial repolarization, in which a higher fQRS-T angle is linked with worse cardiac outcomes. Reverse dipper hypertension is also linked to poor cardiac outcomes. The purpose of this study was to investigate the association between the fQRS-T angle and reverse dipper status in individuals newly diagnosed with hypertension who did not have left ventricular hypertrophy (LVH). The investigation recruited 171 hypertensive individuals without LVH who underwent 24-h ambulatory blood pressure monitoring (ABPM). On the basis of the findings of 24-h ABPM, the study population was categorized into the following three groups: patients with dipper hypertension, non-dipper hypertension, and reverse dipper hypertension. LVH was defined by echocardiography. The fQRS-T angle was measured using the 12-lead ECG. The fQRS-T angle in individuals with reverse dipper hypertension was substantially greater than in patients with and without dipper hypertension (51° ± 28° vs. 28° ± 22° vs. 39° ± 25°, respectively, P < 0.001). The fQRS-T angle (odds ratio: 1.040, 95% confidence interval: 1.016–1.066; P = 0.001) was independently associated with reverse dipper hypertension according to multivariate analysis. In receiver operating characteristic curve analysis, the fQRS-T angle to predict reverse dipper hypertension was 33.5° with 76% sensitivity and 71% specificity. This study showed that an increased fQRS-T angle was associated with reverse dipper hypertension in newly diagnosed hypertensive patients without LVH.
Examining Nurses' Perception of Shift Work and Evaluating Supportive Interventions
Authors: Konkol Megan , George Elisabeth L. , Scott Paul W. , Imes Christopher C.
Published: March 2023

Background:

Health care requires a delicate equilibrium of nurse health safety and patient safety outcomes. Shift work can disrupt this balance, resulting in poor outcomes for staff and patients.

Problem:

Limited evidence exists on nurses' perceptions of shift work, fatigue countermeasures use, and interest in risk-mitigating interventions.

Methods:

An online survey of nurses was conducted. Survey questions assessed perceptions of shift work, use of fatigue countermeasures, and potential interventions.

Results:

The participants perceived multiple differences between day and night shifts when asked about their ability to complete both work- and life-oriented tasks. Use of fatigue countermeasures was more common while working night shift. Potential interventions included the use of blackout curtains, an on-site exercise facility, consulting a nutritionist, and block scheduling.

Conclusions:

Health care leaders should consider nurses' perceptions and interests when incorporating initiatives to mitigate the negative effects of shift work.
Congenital Portosystemic Shunts: Variable Clinical Presentations Requiring a Tailored Endovascular or Surgical Approach
Authors: Robinson Eduardo Bent , Jordan Gregory , Katz Danielle , Sundaram Shikha S. , Boster Julia , Brigham Dania , Ladd Patricia , Chan Christine M. , Shay Rebecca L. , Ochmanek Emily , Annam Aparna
Published: March 2023

Congenital portosystemic shunts (CPSS) are rare developmental anomalies resulting in diversion of portal flow to the systemic circulation. These shunts allow intestinal blood to reach the systemic circulation directly, and if persistent or large, may lead to long-term complications. CPSS can have a variety of clinical presentations that depend on the substrate that is bypassing hepatic metabolism or the degree of hypoperfusion of the liver. Many intrahepatic shunts spontaneously close by 1 year of age, but extrahepatic and persistent intrahepatic shunts require intervention by a single session or staged closure with a multidisciplinary approach. Early detection and appropriate management are important for a good prognosis. The aim of this case series is to describe the varied clinical presentations, treatment approaches, and outcomes of 5 children with CPSS at our institution. Management of these patients should involve a multidisciplinary team, including interventional radiology, surgery, hepatology, and other medical services as the patient’s clinical presentation warrants. Regardless of clinical presentation, if a CPSS persists past 1–2 years of age, closure is recommended.
Beliefs in Regulating Negative Emotions and Vagally Mediated Heart Rate Variability: Does Sex Make a Difference?
Authors: Alessandri Guido , Filosa Lorenzo , Eisenberg Nancy , Ottaviani Cristina
Published: March 2023

Objective

This ecological study explored the association between regulatory emotional self-efficacy beliefs in managing negative emotions (RESE-NE) and heart rate variability (HRV), a measure of parasympathetic modulation of the heart that has been positively associated with a better ability to flexibly adjust to a changing environment and regulate emotions.

Method

To test these associations, we used data from 161 adults working in relational professions (about 40% men; mean [standard deviation] age = 40.45 [14.17] years) whose HRV was assessed continuously for 24 hours.

Results

Individuals high in RESE-NE showed increased HRV levels (β = −0.05, p = .011). However, this effect was moderated by biological sex (β = −0.18, p = .0001) such that RESE-NE positively and significantly predicted HRV for men (β = 0.18, p < .0001) but not for women (β = −0.001, p = .989).

Conclusions

All in all, our study provides initial empirical support for the theoretical expectation derived from social cognitive theory that RESE-NE is positively correlated with a physiological indicator of adaptability to the environmental demands. This was true only for men, likely because of sex differences in physiological stress reactivity and regulation.
Opportunistic Screening for Atrial Fibrillation on Routine Chest Computed Tomography
Authors: Parker William A. , Vigneault Davis M. , Yang Issac , Bratt Alex , Marquardt Alizee C. , Sharifi Husham , Guo Haiwei Henry
Published: March 2023

Purpose:

Quantitative biomarkers from chest computed tomography (CT) can facilitate the incidental detection of important diseases. Atrial fibrillation (AFib) substantially increases the risk for comorbid conditions including stroke. This study investigated the relationship between AFib status and left atrial enlargement (LAE) on CT.

Materials and Methods:

A total of 500 consecutive patients who had undergone nongated chest CTs were included, and left atrium maximal axial cross-sectional area (LA-MACSA), left atrium anterior-posterior dimension (LA-AP), and vertebral body cross-sectional area (VB-Area) were measured. Height, weight, age, sex, and diagnosis of AFib were obtained from the medical record. Parametric statistical analyses and receiver operating characteristic curves were performed. Machine learning classifiers were run with clinical risk factors and LA measurements to predict patients with AFib.

Results:

Eighty-five patients with a diagnosis of AFib were identified. Mean LA-MACSA and LA-AP were significantly larger in patients with AFib than in patients without AFib (28.63 vs. 20.53 cm2, P<0.000001; 4.34 vs. 3.5 cm, P<0.000001, respectively), both with area under the curves (AUCs) of 0.73. Multivariable logistic regression analysis including age, sex, and VB-Area with LA-MACSA improved the AUC for predicting AFib (AUC=0.77). An LA-MACSA threshold of 30 cm2 demonstrated high specificity for AFib diagnosis at 92% and sensitivity of 48%, and LA-AP threshold at 4.5 cm demonstrated 90% specificity and 42% sensitivity. A Bayesian machine learning model using age, sex, height, body surface area, and LA-MACSA predicted AFib with an AUC of 0.743.

Conclusions:

LA-MACSA or LA-AP can be rapidly measured from routine chest CT, and when >30 cm2 and >4.5 cm, respectively, are specific indicators to predict patients at increased risk for AFib.
Reliability and Validity Evaluation of the Chin Augmentation With Medpor Using FACE-Q Scales Effectiveness
Authors: Zang Tianying , Liu Bingyang , Tang Xiaojun , Yin Lin
Published: March 2023

Background:

Chin augmentation (CA) is important treatment modality for microgenia. The use of implantable alloplastic biomaterials in CA grows in popularity, and there is no verifiable documentation of patients’ satisfaction about CA with Medpor (CAWM) exists in the literature, this study examined effectiveness of CAWM by analyzing patient satisfaction.

Methods:

Patients had undergone CAWM were followed up postoperatively. Occurrence of complications was collected, patients’ satisfactions with chin shape and surgical decision were analyzed using FACE-Q scales, the reliability of operation was studied through analyzing the statistics, and the influences of sex and follow-up time on satisfaction were compared.

Results:

One hundred ten patients who had undergone CAWM received FACE-Q scales and 64 valid questionnaires were collected. 61 (95.3%) showed high satisfaction with chin shape after CAWM (Cronbach α coefficients were all above 0.8), the median values of satisfaction of chin shape and decision making were 85 (67, 100) and 100 (75,100), respectively. The median chin satisfactions of females and males were 87 (67, 100), 79 (61,100). The median chin satisfactions of patients had surgery before 2 years ago and within 2 years were 81 (67, 100), 87 (64,100), respectively. During the follow-up, among 110, 1 (0.91%) developed graft-related infection and 1 (0.91%) developed an allergic reaction, 1 (0.91%) underwent prosthesis removal because dissatisfaction with chin shape.

Conclusions:

Chin augmentation with prothesis is a safe and efficacious way to improve microgenia. Medpor is the desired implant material with less infection, displacement and bone absorption, which is worthy of promotion and further study in CA surgery.
Comparing outcomes of ultra-low-cost hearing aids to programmable, refurbished hearing aids for adults with high frequency hearing loss in Malawi: A feasibility study
Authors: Parmar Bhavisha , Phiri Mwanaisha , Jailos Louis , Kachapila Regina , Seleb Ben , Mulwafu Wakisa , Manchaiah Vinay , Bhamla M. Saad
Published: March 2023

Introduction

Access to ear and hearing health services are limited or non-existent in low-income countries, with less than 10% of the global production of hearing aids is distributed to this population. The aim of this feasibility study was to compare the outcomes of an ultra-low-cost hearing aid (LoCHAid) to programmable, refurbished hearing aids for adults with high-frequency hearing loss, in Blantyre, Malawi.

Methods

Sixteen adults with high frequency hearing loss, and no prior experience of hearing aids, took part in this study, nine were fitted with the LoCHAid and seven were fitted with refurbished, programmable hearing aids, for a one-month trial. Five standardized hearing qualities questionnaires were used to compare outcomes pre and post device fitting and between devices. Questionnaire scales were analysed using general linear models and inductive thematic analysis was used to evaluate qualitative data.

Results

Overall, there was no significant difference found between LoCHAid and refurbished hearing aids, and the two device types each showed a similar degree of improvement after fitting. Qualitative data identified two key themes: Sound Quality and User experience.

Conclusion

The results from this feasibility study are encouraging, but a comprehensive, larger clinical study is needed to draw firm conclusions about the LoCHAid’s performance. This study has identified key improvement indicators required to enhance sound quality and user experience of the LoCHAid.
An Opportunity to Standardize and Enhance Intelligent Virtual Assistant-Delivered Layperson Cardiopulmonary Resuscitation Instructions
Authors: Murk William , Goralnick Eric , Brownstein John S. , Landman Adam B.
Published: March 2023

Importance

Intelligent virtual assistants (IVAs) are ubiquitous and hold the potential to provide bystander cardiopulmonary resuscitation (CPR) instructions during an emergency.

Objective

To evaluate the quality of CPR instructions provided by IVAs.

Design

We evaluated the appropriateness of responses of four IVAs (Amazon Alexa, Apple Siri, Google Assistant, and Microsoft Cortana) to eight CPR-related questions. We also evaluated text-based responses provided by OpenAI ChatGPT, a recently developed artificial intelligence large language model.

Results

Out of 32 responses provided by IVAs, only 19 (59%) were related to CPR, 9 (28%) suggested calling emergency services, and 4 (12%) provided verbal CPR instructions. All responses provided by ChatGPT were related to CPR and suggested calling emergency services. Among responses related to CPR, the answers provided varied significantly in the utility of information provided.

Conclusions and Relevance

These results highlight the need for the technology industry to partner with the medical community to improve and standardize bystander CPR instruction provided by IVAs.

Key points

Question

What is the quality of cardiopulmonary resuscitation (CPR) instruction provided by intelligent virtual assistants (IVAs) including Amazon Alexa, Apple Siri, Google Assistant, and Microsoft Cortana?

Findings

When asked questions related to CPR, IVAs frequently did not provide relevant information. Moreover, even when the information provided was relevant, actual CPR instruction was not given in most cases.

Meaning

These results highlight the need to standardize bystander CPR instruction provided by IVAs.
Prediction of MCI-to-AD progression with atrophy-weighted standard uptake value ratios of18F-Florbetapir PET
Authors: Fang Yu-Hua Dean , Perucho Jose U. , Chiu Sheng-Chieh , Lin Yun-Chi , McConathy Jonathan E.
Published: March 2023

Accurate prediction of MCI-to-AD progression is an important yet challenging task. We introduce a new quantitative parameter: the atrophy-weighted standard uptake value ratio (awSUVR), defined as the PET SUVR divided by the hippocampal volume measured with MR, and evaluate whether it may provide better prediction of the MCI-to-AD progression. Materials and Methods: We used ADNI data to evaluate the prediction performances of the awSUVR against SUVR. 571, 363 and 252 18-F-Florbetaipir scans were selected based on criteria of conversion at the third, fifth and seventh year after the PET scans, respectively. Corresponding MR scans were segmented with Freesurfer and applied on PET for SUVR and awSUVR computation. We also searched for the optimal combination of target and reference regions. In addition to evaluating the overall prediction performances, we also evaluated the prediction for APOE4 carriers and non-carriers. For the scans with false predictions, we used 18-F-Flortaucipir scans to investigate the potential source of error. Results: awSUVR provides more accurate prediction than the SUVR in all three progression criteria. The 5-year prediction accuracy/sensitivity/specificity is 90/81/93% for awSUVR and 86/81/88% for SUV. awSUVR also yields good 3- and 7-year prediction accuracy/sensitivity/specificity of 91/57/96 and 92/89/93, respectively. APOE4 carriers generally are slightly more difficult to predict for the progression. False negative prediction is found to either due to a near-cutoff mis-classification or potentially non-AD dementia pathology. False positive prediction is mainly due to the slightly delayed progression than the expected progression time. Conclusion: We demonstrated with ADNI data that 18-F-Florbetapir SUVR weighted with hippocampus volume may provide good prediction power with over 90% accuracy in MCI-to-AD progression.
Regular deworming and seasonality are potential challenges but also offer opportunities for hookworm elimination
Authors: Lamptey Amanda NL , Larbi Irene A , Owusu Donkor Irene Ofei , Sumboh Jeffrey G , Ashong Yvonne , Osabutey Dickson , Cappello Michael , Adu-Gyasi Dennis , Konadu Dennis Gyasi , Asante Kwaku Poku , Koram Kwadwo A , Wilson Michael D
Published: March 2023

The global health community has targeted the elimination of neglected tropical diseases (NTDs) including soil-transmitted helminthiasis by 2030. The elimination strategy has not changed from that of control using regular mass drug administration (MDA) with albendazole, WASH and education. Already doubts have been expressed about this achievement, principally because drugs do not interrupt transmission. We report here the findings of a cohort study aimed to identify host modifiable and environmental factors associated with hookworm infection and reinfection in rural communities in Kintampo North Municipality, Ghana. Faecal samples of 564 consented participants were screened for intestinal parasites at baseline, 9 months and 24 months using the Kato-Katz method. At each time point, positive cases were treated with a single dose of albendazole (400 mg) and their samples were again screened 10-14 days post-treatment to record treatment failures. The hookworm prevalence at the three-time points was 16.7%, 9.22% and 5.3% respectively, whilst treatment failure rates were 17.25%, 29.03% and 40.9% respectively. The intensities of hookworm infection (in eggs per gram) at the time points were 138.3, 40.5 and 135, which showed a likely association with wet and dry seasons. We posit that the very low intensity of hookworm infections in humans during the dry season offers a window of opportunity for any intervention that could drastically reduce the community worm burden before the rainy season.
How long is the long COVID? a retrospective analysis of football players in two major European Championships
Authors: Miccinilli Sandra , Bravi Marco , Conti Giorgio , Bressi Federica , Sterzi Silvia , Santacaterina Fabio , Ciccozzi Massimo
Published: March 2023

Objectives

the goal of this study was to investigate the correlation between SARS-CoV-2 infection and muscle injuries among a large sample of professional soccer players.

Methods

A retrospective cohort study was conducted on professional soccer players from the Serie A and LaLiga leagues during the 2019-2020 and 2020-2021 football seasons. The players were divided into two groups based on whether they contracted the Sars-CoV-2 infection (C+) or not (C-) during the 2020/2021 season. Data collection was conducted using the Transfermarkt24 site.

Results

In the 2019-2020 both championships showed non-significant differences in the average number of muscular injuries between the C+ group and the C- group (Serie A: p=0.194; 95%CI: - 0.044 to 0.215, LaLiga p=0.915; 95%CI: -0.123 to 0.137). In the 2020-2021 the C+ group had a significantly higher number of muscular injuries compared to the C- group in both championships (Serie A: p<0.001; 95%CI 0.731 to 1.038; LaLiga: p<0.001; 95%CI: 0.773 to 1.054). Multiple linear regression analysis confirmed that belonging to C+ in the season 2020/2021 was the variable that most strongly influenced the probability of having a muscle injury in both championships. Survival analysis revealed a hazard ratio of 3.73 (95%CI 3.018 to 4.628) and of 5.14 (95% CI 3.200 to 8.254) for Serie A and LaLiga respectively.

Conclusions

This retrospective cohort study revealed a significant association between SARS-CoV-2 infection and increased risk of muscle injury, emphasizing the importance of carefully considering the infection in the decision-making process for determining athletes’ readiness to return to sport.
Switching of RNA splicing regulators in immature neuroblasts: a key step in adult neurogenesis
Authors: Bernou Corentin , Mouthon Marc-André , Daynac Mathieu , Kortulewski Thierry , Demaille Benjamin , Barroca Vilma , Couillard-Despres Sébastien , Dechamps Nathalie , Ménard Véronique , Bellenger Léa , Antoniewski Christophe , Chicheportiche Alexandra , Boussin François D.
Published: March 2023

The lateral wall of the subventricular zone harbors neural stem cells (NSC, B cells) which generate proliferating transient-amplifying progenitors (TAP, C cells) that ultimately give rise to neuroblasts (NB, A cells). Molecular profiling at the single cell level struggles to distinguish these different cell types. Here, we combined transcriptome analyses of FACS-sorted cells and single-cell RNAseq to demonstrate the existence of an abundant, clonogenic and multipotent population of immature neuroblasts (iNB cells) at the transition between TAP and migrating NB (mNB). iNB are reversibly engaged in neuronal differentiation. Indeed, they keep molecular features of both undifferentiated progenitors, plasticity and unexpected regenerative properties. Strikingly, they undergo important progressive molecular switches, including changes in the expression of splicing regulators leading to their differentiation in mNB subdividing them into 2 subtypes, iNB1 and iNB2. Due to their plastic properties, iNB could represent a new target for regenerative therapy of brain damage.
Economic and social determinants of health disparities in India: A systematic review of sleep literature
Authors: Zoukal Sofia , Cordova Gabriel Zarate , Etindele Sosso Faustin Armel
Published: March 2023

Among multiple determinants affecting sleep health, there is people socioeconomic status (SES), a multidimensional concept of an individual’s social, economic and ecological position associated to public health inequalities at different levels. No systematic review on the relation between SES and sleep health has been previously conducted in India. Following Prisma protocol, seven articles were selected. Findings revealed that all studies were cross-sectional. The combined number of participants is N=12,746 participants, composed of 81.15% of adults (n=10,343), 10.56% of children (n=1346) and 8.29% of adolescents (n=1057). The smallest sample was N=268 and the larger was N=7017. The socioeconomic determinants the most reported by authors were perceived SES/composite indices, education, income and employment/occupation. The most reported sleep disturbances were obstructive sleep apnea (OSA), insomnia, restless legs syndrome (RLS) and sleep quality. Higher SES (specifically high education and high income) was associated on one hand in adults, with insomnia and a lower risk for OSA; and on the other hand, in adolescents, with poor quality of sleep and shorter sleep duration. Unemployment was significantly associated with insomnia and risk for pediatric OSA (specifically maternal employment). These findings are coherent with the conceptual socioeconomic model of sleep health published by Etindele Sosso et al. and one previous ecological model of sleep published by Grandner et al., both explaining the relationship between SES and sleep disparities. More studies on the subject and more longitudinal research are necessary to support public health programs related to sleep health disparities in India.
An O-GlcNAc transferase pathogenic variant that affects pluripotent stem cell self-renewal
Authors: Omelková Michaela , Fenger Christina Dühring , Murray Marta , Hammer Trine Bjørg , Pravata Veronica M. , Bartual Sergio Galan , Czajewski Ignacy , Bayat Allan , Ferenbach Andrew T. , Stavridis Marios P. , van Aalten Daan M. F.
Published: March 2023

O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential enzyme that modifies proteins with O-GlcNAc. InbornOGTgenetic variants were recently shown to mediate a novel type of Congenital Disorder of Glycosylation (OGT-CDG) which is characterized by X-linked intellectual disability (XLID) and developmental delay. Here, we report an OGTC921Yvariant which co-segregates with XLID and epileptic seizures, and results in loss of catalytic activity. Colonies formed by mouse embryonic stem cells carrying OGTC921Yshow decreased levels of protein O-GlcNAcylation accompanied by decreased levels of Oct4, Sox2 and extracellular alkaline phosphatase (ALP), implying reduced self-renewal capacity. These data establish a link between OGT-CDG and embryonic stem cell self-renewal, providing a foundation for examining the developmental aetiology of this syndrome.

Summary statement

We show that the C921Y O-GlcNAc transferase variant found in patients with intellectual disability leads to a defect in pluripotent stem cell self-renewal and decreased levels of stem cell markers.
An extra-circadian function for human CLOCK in the neocortex
Authors: Liu Yuxiang , Fontenot Miles R. , Kulkarni Ashwinikumar , Khandelwal Nitin , Park Seon-Hye E. , Douglas Connor , Harper Matthew , Xu Pin , Gupta Nisha , Gibson Jay R. , Takahashi Joseph S. , Konopka Genevieve
Published: March 2023

Core circadian-related proteins such as the transcription factor CLOCK are ubiquitously expressed and important for regulating molecular pathways underlying circadian rhythms. Previous work has suggested that CLOCK has evolved human neocortex-specific gene regulation and therefore may have extra-circadian functions. To test this in vivo, we generated a mouse model that recapitulates human cortical expression of CLOCK. The CLOCK humanized (HU) mice show enhanced cognitive flexibility, which is associated with the alteration in spatiotemporal expression of CLOCK. Cell type specific genomic profiling of HU mice identified upregulated genes related to dendritic growth and spine formation in excitatory neurons. Consistent with this result, we found that excitatory neurons in HU mice have increased complexity of dendritic branching and spine density, as well as a greater frequency of excitatory postsynaptic currents, suggesting an increase in neural connectivity. In contrast, CLOCK knockout in human induced pluripotent stem cell-induced neurons showed reduced complexity of dendrites and lower density of presynaptic puncta. Together, our data demonstrate that CLOCK evolved extra-circadian gains of function via altered spatiotemporal gene expression and these functions may underlie human brain specializations.
Permute-match tests: Detecting significant correlations between time series despite nonstationarity and limited replicates
Authors: Yuan Alex E. , Shou Wenying
Published: March 2023

Researchers in fields from ecology to neuroscience analyze correlations between pairs of time series, often working with nonstationary data, wherein statistical properties change over time. This commonly involves a statistical test to determine whether an observed correlation is stronger than expected under the null hypothesis of independence. Testing for dependence between nonstationary time series with only one experimental replicate is exceedingly challenging. However, with many replicates, a nonparametric trial-swapping permutation test can be employed, comparing within-replicate correlations to between-replicate correlations. Although largely assumption-free, this test is severely limited by the number of replicates because its minimum achievablep-value is 1/n! wherenis the number of replicates. This curtails its applicability to many biomedical studies, wherenis frequently as low as 3, which would render significance thresholds like 0.05 unattainable. To address this, we propose modified permutation tests that can report lowerp-values of 2/nnor 1/nnwhen there is strong evidence of dependence. We prove that the tests guarantee a false positive rate at or below the significance level, as long as replicates come from independent and identical experiments. We demonstrate this approach by confirming the observation that groups of zebrafish swim faster when directionally aligned, using an existing dataset with 3 biological replicates.
Coupling microdroplet-based sample preparation, multiplexed isobaric labeling, and nanoflow peptide fractionation for deep proteome profiling of tissue microenvironment
Authors: Veličković Marija , Fillmore Thomas L. , Attah Kwame , Posso Camilo , Pino James C. , Zhao Rui , Williams Sarah M. , Veličković Dušan , Jacobs Jon M. , Burnum-Johnson Kristin E. , Zhu Ying , Piehowski Paul D.
Published: March 2023

There is increasing interest in developing in-depth proteomic approaches for mapping tissue heterogeneity at a cell-type-specific level to better understand and predict the function of complex biological systems, such as human organs. Existing spatially resolved proteomics technologies cannot provide deep proteome coverages due to limited sensitivity and poor sample recovery. Herein, we seamlessly combined laser capture microdissection with a low-volume sample processing technology that includes a microfluidic device named microPOTS (Microdroplet Processing in One pot for Trace Samples), the multiplexed isobaric labelling, and a nanoflow peptide fractionation approach. The integrated workflow allowed to maximize proteome coverage of laser-isolated tissue samples containing nanogram proteins. We demonstrated the deep spatial proteomics can quantify more than 5,000 unique proteins from a small-sized human pancreatic tissue pixel (∼60,000 µm2) and reveal unique islet microenvironments.
Using Neural Style Transfer to study the evolution of animal signal design: A case study in an ornamented fish
Authors: Héjja-Brichard Yseult , Million Kara , Renoult Julien P , Mendelson Tamra C
Published: March 2023

The sensory drive hypothesis of animal signal evolution describes how animal communication signals and preferences evolve as adaptations to local environments. While classical approaches to testing this hypothesis often focus on preference for one aspect of a signal, deep learning techniques like generative models can create and manipulate stimuli without targeting a specific feature. Here, we used an artificial intelligence technique called neural style transfer to experimentally test preferences for color patterns in a fish. Findings in empirical aesthetics show that humans tend to prefer images with the visual statistics of the environment because the visual system is adapted to process them efficiently, making those images easier to process. Whether this is the case in other species remains to be tested. We therefore manipulated how similar or dissimilar male body patterns were to their habitats using the Neural Style Transfer (NST) algorithm. We predicted that males whose body patterns are more similar to their native habitats will be preferred by conspecifics. Our findings suggest that both males and females are sensitive to habitat congruence in their preferences, but to different extents, requiring additional investigation. Nonetheless, this study demonstrates the potential of artificial intelligence for testing hypotheses about animal communication signals.

Highlights

– Neural style transfer was used to test preferences for patterns in a colorful fish

– Results trend in support of the processing bias hypothesis, a component of sensory drive

– This study demonstrates the use of generative AI for animal behavioral studies
EZH2 represses mesenchymal genes and upholds the epithelial state of breast carcinoma cells
Authors: Gallardo Amador , López-Onieva Lourdes , Belmonte-Reche Efres , Fernández-Rengel Iván , Serrano-Prados Andrea , Molina Aldara , Sánchez-Pozo Antonio , Landeira David
Published: March 2023

Emerging studies support that the Polycomb Repressive Complex 2 (PRC2) regulates phenotypic changes of carcinoma cells by modulating their shifts among metastable states within the epithelial and mesenchymal spectrum. This new role of PRC2 in cancer has been recently proposed to stem from the ability of its catalytic subunit EZH2 to bind and modulate the transcription of mesenchymal genes during epithelial-mesenchymal transition (EMT) in lung cancer cells. Here, we asked whether this mechanism is conserved across different types of carcinomas. By combining TGF-β-mediate reversible induction of epithelial to mesenchymal transition and pharmacological inhibition of EZH2 activity we demonstrate that EZH2 represses a large set of mesenchymal genes and favours the residence of breast cancer cells towards the more epithelial spectrum during EMT. In agreement, analysis of human patient samples support that EZH2 is required to efficiently repress mesenchymal genes in breast cancer tumours. Our results indicate that PRC2 operates through similar mechanisms in breast and lung cancer cells. We propose that PRC2-mediated direct transcriptional modulation of the mesenchymal gene expression program is a conserved molecular mechanism underlying cell dissemination across human carcinomas.
Perceptual learning of random acoustic patterns: Impact of temporal regularity and attention
Authors: Ringer Hanna , Schröger Erich , Grimm Sabine
Published: March 2023

Perceptual learning is a powerful mechanism to enhance perceptual abilities and to form robust memory representations of previously unfamiliar sounds. Memory formation through repeated exposure takes place even for random and complex acoustic patterns devoid of semantic content. The current study sought to scrutinise how perceptual learning of random acoustic patterns is shaped by two potential modulators: temporal regularity of pattern repetition and listeners’ attention. To this end, we adapted an established implicit learning paradigm and presented short acoustic sequences that could contain embedded repetitions of a certain sound segment (i.e., pattern) or not. During each experimental block, one repeating pattern recurred across multiple trials, while the other patterns were presented in only one trial. During the presentation of sound sequences that contained either temporally regular or jittered within-trial pattern repetitions, participants’ attention was directed either towards or away from the auditory stimulation. Overall, we found a memory-related modulation of the event-related potential (ERP) and an increase in inter-trial phase coherence for patterns that recurred across multiple trials (compared to non- recurring patterns), accompanied by a performance increase in a (within-trial) repetition detection task when listeners attended the sounds. Remarkably, we show a memory-related ERP effect even for the first pattern occurrence per sequence when participants attended the sounds, but not when they were engaged in a visual distractor task. These findings suggest that learning of unfamiliar sound patterns is robust against temporal irregularity and inattention, but attention facilitates access to established memory representations upon first occurrence within a sequence.
Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23
Authors: Bloch Yehudi , Felix Jan , Merceron Romain , Provost Mathias , Symakani Royan Alipour , De Backer Robin , Lambert Elisabeth , Savvides Savvas N.
Published: March 2023

Cell-surface receptor complexes mediated by pro-inflammatory Interleukin-12 and -23, both validated therapeutic targets, are incompletely understood due to the lack of structural insights into their complete extracellular assemblies. Furthermore, there is a paucity of structural details describing the IL-12:receptor interaction interfaces, in contrast to IL23:receptor complexes. Here we report cryo-EM structures of fully assembled IL-12/IL-23:receptor complexes comprising the complete extracellular segments of the cognate receptors. The structures reveal important commonalities but also surprisingly diverse features. Whereas IL-12 and IL-23 both utilize a conspicuously presented aromatic residue on their α-subunit as a hotspot to interact with the N-terminal Ig-domain of their high affinity receptors, only IL-12 juxtaposes receptor domains proximal to the cell-membrane. Collectively, our findings will enable a cytokine-specific interrogation of IL-12 and IL-23 signaling in physiology and disease.
The FAAH inhibitor URB597 reduces cocaine seeking during conditioned punishment and withdrawal
Authors: Alegre-Zurano Laia , García-Baos Alba , Castro-Zavala Adriana , Martín-Sánchez Ana , Medrano Mireia , Gallego-Landin Ines , Valverde Olga
Published: March 2023

The endocannabinoid system is prominently implicated in the control of cocaine reinforcement due to its relevant role in synaptic plasticity and neurotransmitter modulation in the mesocorticolimbic system. The inhibition of fatty acid amide hydrolase (FAAH), and the resulting increase in anandamide and other N-acylethanolamines, represents a promising strategy for reducing drug seeking. In the present study, we aimed to assess the effects of the FAAH inhibitor URB597 (1 mg/kg) on crucial features of cocaine addictive-like behaviour in mice. Therefore, we tested the effects of URB597 on acquisition of cocaine (0.6 mg/kg/inf) self-administration, compulsive-like cocaine intake and cue-induced drug-seeking behaviour during withdrawal. URB597 reduced cocaine intake under conditioned punishment while having no impact on acquisition. This result was associated to increased cannabinoid receptor 1 gene expression in the ventral striatum and medium spiny neurons activation in the nucleus accumbens shell. Moreover, URB597 reduced cue-induced drug-seeking behaviour during prolonged abstinence and prevented the withdrawal-induced increase in FAAH gene expression in the ventral striatum. In this case, URB597 decreased activation of medium spiny neurons in the nucleus accumbens core. Our findings evidence the prominent role of endocannabinoids in the development of cocaine addictive-like behaviours and support the potential of FAAH inhibition as a therapeutical target for the treatment of cocaine addiction.
Molecular and functional characterization of different BrainSphere models for use in neurotoxicity testing on microelectrode arrays
Authors: Hartmann Julia , Henschel Noah , Bartmann Kristina , Dönmez Arif , Brockerhoff Gabriele , Koch Katharina , Fritsche Ellen
Published: March 2023

The currently accepted methods for neurotoxicity (NT) testing rely on animal studies. However, high costs and low testing throughput hinder their application for large numbers of chemicals. To overcome these limitations,in vitromethods are currently developed which are based on human induced pluripotent stem cells (hiPSC) that allow higher testing throughput at lower costs. We applied six different protocols to generate 3D BrainSphere models for acute NT evaluation. These include three different media for 2D neural induction and two media for subsequent 3D differentiation resulting in self-organized, organotypic neuron/astrocyte microtissues. All induction protocols yielded nearly 100 % nestin-positive hiPSC-derived neural progenitor cells (hiNPCs) yet with different gene expression profiles concerning regional patterning. Moreover, gene expression and immunocytochemistry analyses revealed that the choice of media determines neural differentiation patterns. On the functional level, BrainSpheres exhibited different levels of electrical activity on microelectrode arrays (MEA). Spike sorting allowed BrainSphere functional characterization with the mixed cultures consisting of GABAergic, glutamatergic, dopaminergic, serotonergic, and cholinergic neurons. A test method for acute NT testing, the human multi-neurotransmitter receptor (hMNR) assay, was proposed applying such MEA-based spike sorting. These models are not only promising tools in toxicology but also for drug development and disease modeling.
Evolutionary rescue under demographic and environmental stochasticity
Authors: Xu Kuangyi , Vision Todd J. , Servedio Maria R.
Published: March 2023

Wild populations suffer two types of stochasticity: demographic stochasticity, from sampling error in offspring number, and environmental stochasticity, from temporal variation of the growth rate. By modeling evolution through phenotypic selection following an abrupt environmental change, we investigate how genetic and demographic dynamics, as well as effects of selection intensity after the environmental change and genetic variance on population survival, differ under demographic and environmental stochasticity. We find that the survival probability declines sharply with stronger selection under demographic stochasticity, but declines more continuously under environmental stochasticity. However, the genetic variance that confers the highest survival probability differs little under demographic and environmental stochasticity. Since the influence of demographic stochasticity is stronger when population size is smaller, a slow initial decline of genetic variance which allows quicker evolution and increase of fitness, is important for persistence. In contrast, the influence of environmental stochasticity is density-independent, so higher initial fitness becomes important for survival under strong environmental stochasticity. Combining both types of stochasticity shows that adding even weak environmental stochasticity can exaggerate the effects of different levels of demographic stochasticity on survival probabilities. Our work suggests the importance of explicitly distinguishing and measuring the forms of stochasticity for evolutionary rescue studies.
Hierarchical behavior control by a single class of interneurons
Authors: Huo Jing , Xu Tianqi , Liu Qi , Polat Mahiber , Kumar Sandeep , Zhang Xiaoqian , Leifer Andrew M , Wen Quan
Published: March 2023

Animal behavior is organized into nested temporal patterns that span multiple timescales. This behavior hierarchy is believed to arise from a hierarchical neural architecture: neurons near the top of the hierarchy are involved in planning, selecting, initiating, and maintaining motor programs, whereas those near the bottom of the hierarchy act in concert to produce fine spatiotemporal motor activity. InCaenorhabditis elegans, behavior on a long timescale emerges from ordered and flexible transitions between different behavioral states, such as forward, reversal, and turn. On a short timescale, different parts of the animal body coordinate fast rhythmic bending sequences to produce directional movements. Here, we show that SAA, a class of interneurons that enable cross-communication between dorsal and ventral head motor neurons, play a dual role in shaping behavioral dynamics on different timescales. On a short timescale, SAA regulate and stabilize rhythmic bending activity during forward movements. On a long timescale, the same neurons suppress spontaneous reversals and facilitate reversal termination by inhibiting RIM, an integrating neuron that helps maintain a behavioral state. These results suggest that feedback from a lower-level cell assembly to a higher-level command center is essential for bridging behavioral dynamics at different levels.