bluuebunny/crossref_metadata_2025 huggingface dataset:
Le suivi de l’extrême prématuré après le congé des soins intensifs néonatals
Authors: Hendson Leonora , Church Paige T , Banihani Rudaina
Published: October 2022

La survie des extrêmes prématurés (moins de 28 semaines d’âge gestationnel) s’est améliorée au fil du temps. Bon nombre s’en sortent bien et ont une bonne qualité de vie. Ils demeurent toutefois vulnérables à des problèmes de santé, y compris des difficultés neurosensorielles et neurodéveloppementales, que les médecins de première ligne, les pédiatres et les cliniques spécialisées doivent surveiller. Le présent document de principes passe en revue les conséquences médicales et neurodéveloppementales potentielles pour les extrêmes prématurés dans les deux ans suivant leur congé et fournit des stratégies de counseling, de dépistage précoce et d’intervention. Parce qu’ils sont tous liés à l’extrême prématurité, la dysplasie bronchopulmonaire ou les troubles respiratoires, les problèmes d’alimentation et de croissance, le développement neurosensoriel (vision et audition), la paralysie cérébrale et le trouble du spectre de l’autisme doivent faire rapidement l’objet d’une évaluation. Pour évaluer la croissance et le développement, il faut corriger l’âge chronologique en fonction de l’âge gestationnel jusqu’à 36 mois de vie. Par ailleurs, l’attention au bien-être émotionnel des parents et des proches fait partie intégrante des soins de qualité de l’extrême prématuré.
La négligence en matière de soins médicaux : travailler auprès des enfants, des adolescents et des familles
Authors: Ward Michelle G K , Baird Burke
Published: October 2022

Les soins de santé sont un droit fondamental pour tous les enfants. Lorsque les besoins de santé de l’enfant ne sont pas respectés, quelle qu’en soit la raison, les professionnels de la santé doivent réfléchir aux obstacles en cause et aux processus nécessaires pour trouver des solutions. Des obstacles sociaux, économiques ou autres peuvent empêcher les parents d’accéder aux soins pour leur enfant. Il arrive que les avis, les priorités ou les valeurs des professionnels de la santé de l’enfant divergent de ceux des parents, ce qui compromet les soins à l’enfant. Dans certains cas, l’abstention des personnes qui s’occupent de l’enfant à assurer les soins nécessaires peut être considérée comme de la négligence en matière de soins médicaux. Des habiletés et des connaissances particulières peuvent aider les professionnels de la santé à éviter de telles situations et à collaborer avec efficacité avec la famille lorsque ces situations se produisent. Le présent document de principes offre une approche que peuvent utiliser les professionnels de la santé pour promouvoir l’intérêt supérieur, le bien-être et la sécurité des enfants ou des adolescents vulnérables à la négligence en matière de soins médicaux.
What Drives the Size and Value Factors?
Authors: Li Jiacui
Published: October 2022

I find that approximately 30% of price fluctuations in the Fama-French size and value factors are nonfundamental price pressures driven by correlated fund flows, which generate price movements that revert over time. Is this really demand-based price pressure? I show that the price effects happen exclusively in periods when mutual funds place trades, a fact that is difficult to explain using traditional mechanisms such as unobserved investor preference changes. The estimated price elasticity is also consistent with other studies. Overall, my findings show that a sizable fraction of size and value factor movements do not represent economic risk. (JEL G10, G12, G23, G40)
Open Editors: A dataset of scholarly journals’ editorial board positions
Authors: Nishikawa-Pacher Andreas , Heck Tamara , Schoch Kerstin
Published: October 2022

Editormetrics analyses the role of editors of academic journals and their impact on the scientific publication system. Such analyses would best rely on open, structured, and machine-readable data about editors and editorial boards, which still remains rare. To address this shortcoming, the project Open Editors collects data about academic journal editors on a large scale and structures them into a single dataset. It does so by scraping the websites of 7,352 journals from 26 publishers (including predatory ones), thereby structuring publicly available information (names, affiliations, editorial roles, ORCID etc.) about 594,580 researchers. The dataset shows that journals and publishers are immensely heterogeneous in terms of editorial board sizes, regional diversity, and editorial role labels. All codes and data are made available at Zenodo, while the result is browsable at a dedicated website (https://openeditors.ooir.org). This dataset carries implications for both practical purposes of research evaluation and for meta-scientific investigations into the landscape of scholarly publications, and allows for critical inquiries regarding the representation of diversity and inclusivity across academia.
Can behavior change techniques be delivered via short text messages?
Authors: Doğru Onur Cem , Webb Thomas L , Norman Paul
Published: October 2022

Despite significant advancements in behavioral science it is unclear whether behavior change techniques (or BCTs) can be delivered to large numbers of people in a cost-effective and reliable way. The current study investigated whether it is possible to reliably deliver BCTs using short text messages. Short text messages were designed to deliver each of the 93 BCTs specified in the BCT taxonomy v1. Following initial coding and refinement by the team, a Delphi study with a panel of 15 experts coded which BCT each short text message was designed to deliver and also rated whether they were likely to be understood by recipients and easily converted to target different behaviors. After two iterations, the experts correctly assigned 66 of the 93 messages to the BCT that they were designed to deliver and indicated that these messages were likely to be easy to apply to a range of behaviors and understood by recipients. Experts were not able to identify which BCT 27 of the messages were designed to deliver and it was notable that some clusters of BCTs (e.g., “Goals and planning”) were easier to deliver via short text messages than other clusters (e.g., “Scheduled consequences”). The findings suggest that short text messages can be a reliable way to deliver many, but not all, BCTs. The implications of the current study are discussed with respect to the delivery of specific BCTs and clusters of the taxonomy, as well as the need to test the acceptability of interventions delivered via short messages and the impact of messages on behavior.
Assessment of potential in vitro toxicity of Cissus sicyoides L. and Wedelia paludosa DC. leaves water extracts
Authors: Ponath Amanda Schu , Volz Débora Rech , Suyenaga Edna Sayuri , Ziulkoski Ana Luíza , Perassolo Magda Susana
Published: October 2022

Medicinal plants have been employed as an alternative method to treat diabetes. One is Cissus sicyoides, a plant from the Amazon region (Northern Brazil), which is morphologically similar to Wedelia paludosa, a plant easily found in Southern Brazil. Thus, this study aimed to assess the potential toxicity of C. sicyoides and W. paludosa’s leaves water extracts. Through phytochemical screening, phenolic compounds and alkaloids were observed in both species and coumarins only W. paludosa’s aqueous extract. Phenolic compounds were quantified in both extracts and C. sicyoides presented 1.36 ± 0.04 mg/pyrogalic acid equivalent (PAE), whereas W. paludosa presented 3.27 ± 0.07 mg/PAE. Total antioxidant power was measured by the ferric reduction assay. Cissus sicyoides exhibited total antioxidant activity of 748.0 ± 104.5 μM and W. paludosa, 1971.5 ± 141.0 μM. Cissus sicyoides showed an inhibition rate for the alpha-glucosidases enzyme assay of 55.2 ± 1.7% and W. paludosa, 85.8 ± 9.7%. The formation of reactive oxygen species was evaluated by the DCFH-DA method, its formation being higher in W. paludosa’s water extracts than in C. sicyoides. Cell viability was evaluated by the Sulforhodamine B and MTT assays. Wedelia paludosa’s extracts’ exposure presented a cell viability close to positive control starting from 2 mg/mL to 30 mg/mL, whereas C. sicyoides demonstrated statistical significant low viability at the highest concentration when compared with the negative control. Moreover, cell death mechanism was investigated, having W. paludosa’s extract indicated death by necrosis. The results suggest low toxicity for C. sicyoides’ extract and high toxicity for W. paludosa’s extract.
The Quest to Identify a New Virus Disease of Sunflower from Nebraska
Authors: Harveson R. M. , Al Rwahnih M. , Tian T. , Karasev A. , Gulya T. J. , Bradshaw J. D.
Published: October 2022

Between 2010 and 2018, sunflower plants exhibiting virus-like symptoms, including stunting, mottling, and chlorotic ringspots on leaves, were observed from commercial fields and research plots from four sites within three distinct counties of western Nebraska (Box Butte, Kimball, and Scotts Bluff). Near identical symptoms from field samples were reproduced on seedlings mechanically in the greenhouse on multiple occasions, confirming the presence of a sap-transmissible virus from each site. Symptomatic greenhouse-inoculated plants from the 2010 and 2011 Box Butte samples tested negative for sunflower mosaic virus (SuMV), sunflower chlorotic mottle virus (SuCMoV), and all potyviruses in general by ELISA and RT-PCR. Similar viral-like symptoms were later observed on plants in a commercial sunflower field in Kimball County in 2014, and again from volunteers in research plots in Scotts Bluff County in 2018. Samples from both of these years were again successfully reproduced on seedlings in the greenhouse as before following mechanical transmissions. Symptom expression for all years began 12 to 14 days after inoculation as mild yellow spots followed by the formation of chlorotic ringspots from the mottled pattern. The culture from 2014 tested negatively for three groups of nepoviruses via RT-PCR, ruling this group out. However, transmission electron microscopy assays of greenhouse-infected plants from both 2014 and 2018 revealed the presence of distinct, polyhedral virus particles. With the use of high throughput sequencing and RT-PCR, it was confirmed that the infections from both years were caused by a new virus in the tombusvirus genus and was proposed to be called Sunflower ring spot mottle virus (SuRSMV). Although the major objective of this project was to identify the causal agent of the disease, it became evident that the diagnostic journey itself, with all the barriers encountered on the 10-year trek, was actually more important and impactful than identification.
Muscle injury induces a transient senescence‐like state that is required for myofiber growth during muscle regeneration
Authors: Young Laura V. , Wakelin Griffen , Cameron Alasdair W. R. , Springer Stevan A. , Ross Joel P. , Wolters Grant , Murphy J. Patrick , Arsenault Michel G. , Ng Sean , Collao Nicolás , De Lisio Michael , Ljubicic Vladimir , Johnston Adam P. W.
Published: October 2022

Cellular senescence is the irreversible arrest of normally dividing cells and is driven by the cell cycle inhibitors Cdkn2a, Cdkn1a, and Trp53. Senescent cells are implicated in chronic diseases and tissue repair through their increased secretion of pro‐inflammatory factors known as the senescence‐associated secretory phenotype (SASP). Here, we use spatial transcriptomics and single‐cell RNA sequencing (scRNAseq) to demonstrate that cells displaying senescent characteristics are “transiently” present within regenerating skeletal muscle and within the muscles of D2‐mdx mice, a model of Muscular Dystrophy. Following injury, multiple cell types including macrophages and fibrog–adipogenic progenitors (FAPs) upregulate senescent features such as senescence pathway genes, SASP factors, and senescence‐associated beta‐gal (SA‐β‐gal) activity. Importantly, when these cells were removed with ABT‐263, a senolytic compound, satellite cells are reduced, and muscle fibers were impaired in growth and myonuclear accretion. These results highlight that an “acute” senescent phenotype facilitates regeneration similar to skin and neonatal myocardium.
Impact of the COVID-19 Pandemic on Liver Cancer Staging at a Multidisciplinary Liver Cancer Clinic
Authors: Li Daniel , Jia Angela Y. , Zorzi Jane , Griffith Paige , Kim Amy K. , Dao Doan , Anders Robert A. , Georgiades Christos , Liddell Robert P. , Hong Kelvin , Azad Nilofer S. , Ho Won Jin , Baretti Marina , Christenson Eric , Baghdadi Azarakhsh , Kamel Ihab R. , Meyer Jeffrey , Ghabi Elie , Burkhart Richard A. , Lafaro Kelly , He Jin , Shubert Chris , Yarchoan Mark
Published: October 2022

Objectives:

To compare liver cancer resectability rates before and during the COVID-19 pandemic.

Background:

Liver cancers usually present with nonspecific symptoms or are diagnosed through screening programs for at-risk patients, and early detection can improve patient outcomes. In 2020, the COVID-19 pandemic upended medical care across all specialties, but whether the pandemic was associated with delays in liver cancer diagnosis is not known.

Methods:

We performed a retrospective review of all patients evaluated at the Johns Hopkins Multidisciplinary Liver Cancer Clinic from January 2019 to June 2021 with a new diagnosis of suspected or confirmed hepatocellular carcinoma (HCC) or biliary tract cancer (BTC).

Results:

There were 456 liver cancer patients (258 HCC and 198 BTC). From January 2019 to March 2020 (pre-pandemic), the surgical resectability rate was 20%. The subsequent 6 months (early pandemic), the resectability rate decreased to 11%. Afterward from October 2020 to June 2021 (late pandemic), the resectability rate increased to 27%. The resectability rate early pandemic was significantly lower than that for pre-pandemic and later pandemic combined (11% lower; 95% confidence interval [CI], 2%–20%). There was no significant difference in resectability rates pre-pandemic and later pandemic (7% difference; 95% CI, –3% to 16%). In subgroup analyses, the early pandemic was associated with a larger impact in BTC resectability rates than HCC resectability rates. Time from BTC symptom onset until Multidisciplinary Liver Clinic evaluation increased by over 6 weeks early pandemic versus pre-pandemic (Hazard Ratio, 0.63; 95% CI, 0.44–0.91).

Conclusions:

During the early COVID-19 pandemic, we observed a drop in the percentage of patients presenting with curable liver cancers. This may reflect delays in liver cancer diagnosis and contribute to excess mortality related to the COVID-19 pandemic.
Risk Factors of Flexor Tendon Rupture After ORIF of Distal Radius Fracture
Authors: Kwon Young Woo , Choi In Cheul , Kim Myongwhan , Nam Jae Jun , Park Jong Woong
Published: October 2022

Objectives:

To analyze the risk factors associated with postoperative flexor tendon rupture, after a volar plate fixation of distal radius fractures.

Design:

Retrospective observational case–control study.

Setting:

Tertiary Care University Hospital in the Republic of Korea (2009–2020).

Patients:

Sixteen referred patients were treated for flexor tendon rupture, following previously performed volar plating of distal radius fractures at other institutions. 16 patients were randomly selected from our database as controls, and were matched based on the Soong grade of the case group.

Intervention:

Not applicable.

Main Outcome Measurements:

Radial tilt and radial height were measured on anteroposterior radiographs. The volar tilt, tear drop angle, carpal translation, and Soong grade were measured in a lateral view.

Results:

Quantitative measurements of the volar tilt, carpal translation, and tear drop angle were positively correlated with the flexor tendon rupture. The mean volar tilt and tear drop angle in the tendon rupture group were significantly smaller than those in the control group. The mean carpal translation in the tendon rupture group was significantly greater than that in the control group.

Conclusions:

This study demonstrated that volar tilt, carpal translation, and tear drop angle are significant risk factors for flexor tendon rupture, especially for plates placed at Soong grade 1 or 2. We suggest that the potential for tendon rupture because of incomplete reduction of the distal radius fracture along with implant prominence volar to the watershed line aggravates flexor tendon irritation at the distal edge of the plate because of distorted flexor tendon paths.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Posterior Cervical Fusion for Fracture Is Not the Same as Fusion for Degenerative Cervical Spine Disease
Authors: Malik Azeem Tariq , Yu Elizabeth , Kim Jeffery , Khan Safdar N.
Published: October 2022

Study Design/Setting:

Retrospective.

Objective:

To understand differences in 30-day outcomes between patients undergoing posterior cervical fusion (PCF) for fracture versus degenerative cervical spine disease.

Summary of Background Data:

Current bundled payment models for cervical fusions, such as the Bundled Payments for Care Improvement revolve around the use of diagnosis-related groups to categorize patients for reimbursement purposes. Though a PCF performed for a fracture may have a different postoperative course of care as compared with a fusion being done for degenerative cervical spine pathology, the current DRG system does not differentiate payments based on the indication/cause of surgery.

Methods:

The 2012-2017 American College of Surgeons–National Surgical Quality Improvement Program was queried using Current Procedural Terminology code 22600 to identify patients receiving elective PCFs. Multivariate analyses were used to compare rates of 30-day severe adverse events, minor adverse events, readmissions, length of stay, and nonhome discharges between the 2 groups.

Results:

A total 2546 (91.4%) PCFs were performed for degenerative cervical spine pathology and 240 (8.6%) for fracture. After adjustment for differences in baseline clinical characteristics, patients undergoing a PCF for a fracture versus degenerative pathology had higher odds of severe adverse events [18.8% vs. 10.6%, odds ratio (OR): 1.65 (95% CI, 1.10–2.46); P=0.015], prolonged length of stay >3 days [54.2% vs. 40.5%, OR: 1.93 (95% CI, 1.44–2.59); P<0.001], and nonhome discharges [34.2% vs. 27.6%, OR: 1.54 (95% CI, 1.10–2.17); P=0.012].

Conclusions:

Patients undergoing PCFs for fracture have significant higher rates of postoperative adverse events and greater resource utilization as compared with individuals undergoing elective PCF for degenerative spine pathology. The study calls into question the need of risk adjustment of bundled prices based on indication/cause of the surgery to prevent the creation of a financial disincentive when taking care/performing surgery in spinal trauma patients.
Oral Immunotherapy and Risk of Eosinophilic Esophagitis in Children
Authors: Morales‐Cabeza Cristina , Infante Sonsoles , Cabrera‐Freitag Paula , Fuentes‐Aparicio Victoria , Zubeldia José Manuel , Álvarez‐Perea Alberto
Published: October 2022

Objectives:

Oral immunotherapy (OIT) is an effective treatment for children with persistent food allergy, and has concerns about its safety, including eosinophilic esophagitis (EoE). The aim of this study was to evaluate the prevalence of EoE in a large cohort of children who underwent OIT in our center, and to determine if there were any clinical, endoscopic, or histologic differences depending on the food employed for the OIT.

Methods:

A retrospective study was performed over a 15‐year period (2005–2020). Children who underwent cow’s milk (CM), egg, and/or peanut OIT and developed EoE were included.

Results:

Six hundred and seven OIT were carried out (277 CM‐OIT, 322 egg‐OIT, and 8 peanut‐OIT). Seventeen patients (2.8%) had a confirmed histologic diagnosis of EoE with a higher prevalence for patients who underwent CM‐OIT (3.9%) than egg‐OIT (2.2%). Symptoms suggestive of EoE and a confirmed diagnosis occurred at median times of 25 and 36 months, respectively, after the build‐up phase of the OIT was completed. Choking, abdominal pain, and dysphagia were the most frequent symptoms and lamina propria fibrosis was observed in 41.2% of patients. No significant differences in clinical symptoms, endoscopic, or histologic findings between patients under CM or egg‐OIT were found. One‐third of patients reported mild symptoms suggestive of EoE before the OIT.

Conclusions:

EoE appears to be a rare but important adverse event that can occur even years after OIT. Validated questionnaires to screen EoE before the OIT and in the follow‐up of these patients may be the main tool for an early diagnosis.
Impact of Pediatric Dental Resident Availability in the Pediatric Emergency Department
Authors: Fleagle Jenelle , Xiao Wendi , Cottam Michael , Lorch Margarita S.
Published: October 2022

Objective

The purpose of this study is to describe the impact of Delaware's first pediatric dental residency program on treatment of patients presenting to the pediatric emergency department (PED).

Methods

Charts were reviewed for patients presenting to the PED with a dental chief complaint over a 9-month period with a comparison period. Chief complaint, diagnosis, treatment interventions, disposition, and demographic information were included. χ2, Fisher exact, and Student t tests with a P value less than 0.05 were regarded as significant.

Results

A total of 432 patients met inclusion criteria; 197 before dental residency commencement and 235 after residency commencement. Dental consultation significantly increased (56% vs 7%, P < 0.01) between the study periods. There were no statistically significant differences in sex, race, insurance type, admissions, or proportion of presentations of trauma or infection between the study periods. Dental residents provided in-person evaluation for 40% of patients. The proportion of patients receiving dental intervention increased significantly postresidency period (57% vs 47%, P = 0.04). Pediatric emergency department extractions and splints both occurred in a significantly larger portion of patients after the start of the residency program (17% vs 1% and 5% vs 0%, P < 0.01). A higher proportion of patients with dental complaints received procedural sedation in the PED after residency (13% vs 2%, P < 0.01).

Conclusions

Pediatric dental resident availability in the PED significantly increased dental consultation and intervention. A significantly higher percentage of PED patients received definitive treatment at point of service without requiring referral to another facility.
Simultaneous Mandibular Anterior Segmental Osteotomy and Genioplasty: A Novel Technique
Authors: Fadel Reda , Nicot Romain , Schlund Matthias , Ferri Joël
Published: October 2022

The current standard approach to treat class II malocclusion is orthodontic preparation followed by a mandibular advancement through bilateral sagittal split osteotomy associated or not with a genioplasty. However, when a malocclusion with an important incisors’ axis deviation is associated with a chin malposition, an alternative technique can be considered: simultaneous mandibular anterior segmental osteotomy and genioplasty. This technique is performed without a bony bridge between osteotomies. Care must be taken not to wound the lingual mucosa. If preserved, this technique is safe. The result is stable and predictable.
The Relationship Between Health Literacy and Outcomes Before and After Kidney Transplantation
Authors: Lorenz Elizabeth C. , Petterson Tanya M. , Schinstock Carrie A. , Johnson Bradley K. , Kukla Aleksandra , Kremers Walter K. , Sanchez William , Yost Kathleen J.
Published: October 2022

Background.

Limited health literacy (HL) is associated with decreased kidney function and death in patients with chronic kidney disease. Less is known about the impact of HL on kidney transplant (KT) outcomes. The aim of this study was to examine the relationship between HL and KT outcomes, including rates of waitlisting, healthcare utilization, acute rejection, renal allograft function, renal allograft failure, and death.

Methods.

We performed a retrospective review of HL data previously collected at our center. HL was assessed in a convenience sample of consecutive, English-speaking patients age ≥18 y who were evaluated for KT at Mayo Clinic in Minnesota between June 2015 and March 2017 as part of a practice improvement feasibility project (n = 690). HL was assessed using the 4-item Brief Health Literacy Screening Tool modified for the outpatient KT evaluation process. The 4 items assess confidence completing forms, reading comprehension, and oral literacy.

Results.

Overall, 30.4% of patients had limited or marginal HL. Patients with limited or marginal HL were less likely than those with adequate HL to be waitlisted for KT (hazard ratio = 0.62 and 0.69, respectively), even after adjusting for age, marital status, body mass index, Charlson comorbidity index, or dialysis dependency. Patient HL was not associated with post-KT healthcare utilization, acute rejection, or renal allograft function. Patients with limited or marginal HL appeared to experience a higher risk of renal allograft failure and post-KT death, but the number of events was small, and the relationship was statistically significant only for marginal HL.

Conclusions.

Inadequate HL is common in KT candidates and independently associated with decreased waitlisting for KT. We observed no statistically significant relationship between HL and posttransplant outcomes in our cohort. Further efforts to improve communication in patients with inadequate HL may improve access to KT.
Noradrenergic input from nucleus of the solitary tract regulates parabrachial activity in mice
Authors: Ji Yadong , Onwukwe Chimdiya , Smith Jesse , Laub Hanna , Posa Luca , Keller Asaf , Masri Radi , Cramer Nathan
Published: October 2022

The parabrachial complex (PB) is critically involved in aversive processes, and chronic pain is associated with amplified activity of PB neurons in rodent models of neuropathic pain. Here we demonstrate that catecholaminergic input from the caudal nucleus of the solitary tract (cNTScat)—a stress responsive region that integrates intero- and exteroceptive signals—causes amplification of PB activity and their sensory afferents. We used a virally mediated expression of a norepinephrine (NE) sensor, NE2h, fiber photometry, and extracellular recordings in anesthetized mice to show that noxious mechanical and thermal stimuli activate cNTS neurons. These stimuli also produce prolonged NE transients in PB that far outlast the noxious stimuli. Similar NE transients can be evoked by focal electrical stimulation of cNTS, a region that contains the noradrenergic A2 cell group that projects densely upon PB. In vitro, optical stimulation of cNTScatterminals depolarized PB neurons and caused a prolonged increase the frequency of excitatory synaptic activity. A dual opsin approach showed that sensory afferents from the caudal spinal trigeminal nucleus are potentiated by cNTScatterminal activation. This potentiation was coupled with a decrease in the paired pulse ratio, consistent with an cNTScat- mediated increase in the probability of release at SpVc synapses. Together, these data suggest that A2 neurons of the cNTS generate long lasting NE transients in PB which increase excitability and potentiate responses of PB neurons to sensory inputs. These reveal a mechanism through which stressors from multiple modalities may potentiate the aversiveness of nociceptive stimuli.

Significance Statement

Increased excitability of the parabrachial nucleus (PB), a key integrative hub for aversive stimuli, is linked to amplified pain behaviors. We show that prolonged norepinephrine (NE) transients in PB following noxious stimulation in mice. These NE transients potentiate sensory input to PB and arise, at least in part, from catecholaminergic projections from the caudal nucleus of the solitary tract (cNTScat). We propose that activity this cNTScatto PB pathway may potentiate the aversiveness of pain.
Cortical thickness, gray matter volume and cognitive performance: a cross-sectional study of the moderating effects of age on their inter-relationships
Authors: de Chastelaine Marianne , Srokova Sabina , Hou Mingzhu , Kidwai Amber , Kafafi Seham S. , Racenstein Melanie L , Rugg Michael D
Published: October 2022

In a sample comprising younger, middle-aged and older cognitively healthy adults (N = 375), we examined associations between mean cortical thickness, gray matter volume (GMV) and performance in four cognitive domains - memory, speed, fluency and crystallized intelligence. In almost all cases, the associations were moderated significantly by age, with the strongest associations in the older age group. An exception to this pattern was identified in a younger adult sub-group aged less than 23 yrs, when a negative association between cognitive performance and cortical thickness was identified. Other than for speed, all associations between structural metrics and performance in specific cognitive domains were fully mediated by mean cognitive ability. Cortical thickness and GMV explained unique fractions of the variance in mean cognitive ability, speed and fluency. In no case, however, did the amount of variance jointly explained by the two metrics exceed 7% of the total variance. These findings suggest that cortical thickness and GMV are distinct correlates of domain-general cognitive ability, that the strength and, for cortical thickness, the direction of these associations is moderated by age, and that these structural metrics offer only limited insights into the determinants of individual differences in cognitive performance across the adult lifespan.
Adsorption Race Between Activated Carbon and Lactase for Intermolecular Interaction with Lactose
Authors: Zümrütdal Emin , Kuşvuran Erdal , Kökbaş Umut , Çürük Mine , Mertoğlu Tuba Şimşek , Dağ Büşra , Kılınççeker Güray
Published: October 2022

Background

Disturbing dyspeptic complaints may be seen in the use of milk and dairy products in people with lactose intolerance. Lactose-free milk and dairy products are produced for people with these complaints. The widespread use of activated carbon for dyspeptic complaints can also be used for adsorbing lactose.

Methods

For this purpose, the binding energy of lactase to lactose was studied in silico, lactose adsorption enthalpic changes of activated carbon were calculated by HPLC, plain and activated carbon yoghurt was produced and glucose+galactose and lactose levels were determined in yoghurts. The effects of these yogurts on serum glucose levels were compared in mice.

Results

In silico studies, the affinity of lactase with lactose was found to be -7.12 kcal/mol. It was determined by HPLC that activated carbon adsorbed lactose with an energy of -1,785 kcal/mol, and glucose+galactose levels and lactose ratios were lower in yogurt with added activated carbon. It was determined that there was no change in serum glucose levels in the 45th and 90th minutes following fasting in the mice fed with activated carbon yogurt compared to the mice fed plain yogurt.

Conclusion

Yogurt with activated carbon can be an alternative diet for individuals with lactose intolerance, by converting lactose to lactase in the presence of lactase and adsorbing lactose in the absence of lactose.
Imaging crossing fibers in mouse, pig, monkey, and human brain using small-angle X-ray scattering
Authors: Georgiadis Marios , Menzel Miriam , Reuter Jan A , Born Donald , Kovacevich Sophie , Alvarez Dario , Gao Zirui , Guizar-Sicairos Manuel , Weiss Thomas M , Axer Markus , Rajkovic Ivan , Zeineh Michael M
Published: October 2022

Myelinated axons (nerve fibers) efficiently transmit signals throughout the brain via action potentials. Multiple methods that are sensitive to axon orientations, from microscopy to magnetic resonance imaging, aim to reconstruct the brain’s structural connectome. As billions of nerve fibers traverse the brain with various possible geometries at each point, resolving fiber crossings is necessary to generate accurate structural connectivity maps. However, doing so with specificity is a challenging task because signals originating from oriented fibers can be influenced by brain (micro)structures unrelated to myelinated axons.

X-ray scattering can specifically probe myelinated axons due to the periodicity of the myelin sheath, which yields distinct peaks in the scattering pattern. Here, we show that small-angle X-ray scattering (SAXS) can be used to detect myelinated, axon-specific fiber crossings. We first demonstrate the capability using strips of human corpus callosum to create artificial double- and triple-crossing fiber geometries, and we then apply the method in mouse, pig, vervet monkey, and human brains. Given its specificity, capability of 3-dimensional sampling and high resolution, SAXS can serve as a ground truth for validating MRI as well as microscopy-based methods.

Statement of Significance

To study how the nerve fibers in our brain are interconnected, scientists need to visualize their trajectories, which often cross one another. Here, we show the unique capacity of small-angle X-ray scattering (SAXS) to study these fiber crossings without use of labelling, taking advantage of SAXS’s specificity to myelin - the insulating sheath that is wrapped around nerve fibers. We use SAXS to detect double and triple crossing fibers and unveil intricate crossings in mouse, pig, vervet monkey, and human brains. This non-destructive method can uncover complex fiber trajectories and validate other less specific imaging methods (e.g., MRI or microscopy), towards accurate mapping of neuronal connectivity in the animal and human brain.

Graphical Abstract
Integrative CUT&Tag/RNA-Seq analysis of histone variant macroH2A1-dependent orchestration of human iPSCs reprogramming
Authors: Liorni Niccolò , Napoli Alessandro , Castellana Stefano , Giallongo Sebastiano , Řeháková Daniela , Lo Re Oriana , Koutná Irena , Mazza Tommaso , Vinciguerra Manlio
Published: October 2022

Human-induced pluripotent stem cells (iPSCs) can be derived from adult stem cells by forced expression of defined transcription factors. This paves the way for autologous iPSC-derived therapies, which, however, are not yet considered safe. Moreover, reprogramming of somatic cells into iPSCs is an inefficient process, in the range of 0.1%–1%. The epigenetic mechanisms implicated in iPSCs reprogramming are not well understood. The substitution of canonical histone H2A with macroH2A1 histone variant exon-spliced isoforms (macroH2A1.1 and macroH2A1.2) appears as an emerging regulator of iPSCs identity. In particular, we have previously shown that overexpression of macroH2A1.1 led to a more efficient iPSCs reprogramming, by not fully defined mechanisms. Cleavage under targets and tagmentation (CUT&Tag) is a recent methodology used for robust epigenomic profiling of a limited amount of cells. Here, we performed the first integrative CUT&Tag/RNA-Seq analysis of the histone variant macroH2A1-dependent orchestration of iPSCs reprogramming using human umbilical vein endothelial cells (HUVEC) during their reprogramming into iPSC over-expressing tagged macroH2A1.1 or macroH2A1.2. Our results demonstrate a higher and more widespread genome occupancy and a greater number of differentially expressed genes orchestrated by macroH2A1.1 in HUVEC undergoing reprogramming as compared to macroH2A1.2, which involved pervasive functions related to the three embryonic germ layers and increased overlap with CTCF, FOS, GATA2, and POLR2A transcription factor binding sites. In particular, all predicted macroH2A1.1 activating pathways were related to ectoderm/neural processes. As macroH2A1 isoforms have been previously associated with pathologies of the nervous system, our findings may provide relevant molecular insights for modeling neurodegenerative diseases using iPSCs.
Targeting plasma membrane and mitochondrial instability in breast cancer cells and breast epithelial to mesenchymal transition-model cells by adamantyl diaza-crown ether ZG613
Authors: Ester Katja , Mioč Marija , Spurny Pavel , Bonhenry Daniel , Marjanović Marko , Uzelac Lidija , Gabrilo Jelena , Šumanovac Tatjana , Schreibmayer Wolfgang , Majerski Kata , Minofar Babak , Ludwig Jost , Kralj Marijeta
Published: October 2022

The adamantane derived diaza-crown ether ZG613 was assessed as a potential breast cancer cells and breast epithelial to mesenchymal transition (EMT)-model cells targeting agent. We postulated that ZG613 activity relies on its plasma/mitochondria membrane disruption ability based on adamantane hydrophobicity and/or crown ether related ionophoric properties. We performed molecular dynamics (MD) simulations and next generation sequencing, followed by in vitro study of cell death, membrane perturbations and ionophoric ability, as well as in vivo study of effects on the tumour growth. MD simulation and RNA sequencing pointed toward physical disruption of plasma membrane by ZG613, corroborated by measured increase in membrane permeability leading to cell death. Measurements of ion fluxes confirmed ZG613 inability to transport Na+ and K+, as predicted by MD simulation. EMT-model cells exhibit changes in mitochondrial morphology and ATP levels, successfully targeted by ZG613. ZG613 caused mild retardation of tumour growth in vivo. In conclusion, ZG613 kills breast cancer cells and breast EMT-model cells by physical disruption of plasma membrane and impairments of mitochondrial functions. Breast EMT cells represent good potential targets within the breast tumour, due to their plasma membrane and mitochondrial instability.
Host-plant adaptation as a driver of incipient speciation in the fall armyworm (Spodoptera frugiperda)
Authors: Fiteni Estelle , Durand Karine , Gimenez Sylvie , Meagher Robert L. , Legeai Fabrice , Kergoat Gael J. , Nègre Nicolas , d’Alençon Emmanuelle , Nam Kiwoong
Published: October 2022

Background

Divergent selection on host-plants is one of the main evolutionary forces driving ecological speciation in phytophagous insects. The ecological speciation might be challenging in the presence of gene flow and assortative mating because the direction of divergence is not necessarily the same between ecological selection (through host-plant adaptation) and assortative mating. The fall armyworm (FAW), a major lepidopteran pest species, is composed of two sympatric strains, corn and rice strains, named after two of their preferred host-plants. These two strains have been hypothesized to undergo incipient speciation, based on (i) several lines of evidence encompassing both pre- and post-zygotic reproductive isolation, and (ii) the presence of a substantial level of genetic differentiation. Even though the status of these two strains has been established a long time ago, it is still yet to be found whether these two strains indeed exhibit a marked level of genetic differentiation from a large number of genomic loci. Here, we analyzed whole genome sequences from 56 FAW individuals either collected from pasture grasses (a part of the favored host range of the rice strain) or corn to assess the role of host-plant adaptation in incipient speciation.

Results

Principal component analysis of whole genome data shows that the pattern of divergence in the fall armyworm is predominantly explained by the genetic differentiation associated with host-plants. The level of genetic differentiation between corn and rice strains is particularly marked in the Z chromosome. We identified one autosomal locus and two Z chromosome loci targeted by selective sweeps specific to rice strain and corn strain, respectively. The autosomal locus has both increased DXYand FSTwhile the Z chromosome loci had decreased DXYand increased FST.

Conclusion

These results show that the FAW population structure is dominated by the genetic differentiation between corn and rice strains. This differentiation involves divergent selection targeting at least three loci, which include a locus potentially causing reproductive isolation. Taken together, these results suggest the evolutionary scenario that host-plant speciation is a driver of incipient speciation in the fall armyworm.
Protein Language Model Predicts Mutation Pathogenicity and Clinical Prognosis
Authors: Liu Xiangling , Yang Xinyu , Ouyang Linkun , Guo Guibing , Su Jin , Xi Ruibin , Yuan Ke , Yuan Fajie
Published: October 2022

Accurately predicting the effects of mutations in cancer has the potential to improve existing treatments and identify novel therapeutic targets. In this paper, we evidence for the first time that the large-scale pre-trained protein language models (PPLMs) are zero-shot predictors for twoclinicallyrelevant tasks: identifying diseasecausing mutations and predicting patient survival rate. Then we benchmark a series of state-of-the-art (SOTA) PPLMs on 2279 protein variants across 20 cancer-related genes. Our empirical results show that the PPLMs outperform the SOTA baseline, EVE [1], trained on multiple sequence alignment (MSA) data. We also demonstrate that the evolutionary index score, generated from the PPLM’s softmax layer, is good indicator for both mutation pathogenicity and patient survival rate. Our paper has taken a key step toward the clinical utility of large-scale PPLMs.
Whole-brain multivariate hemodynamic deconvolution for multi-echo fMRI with stability selection
Authors: Uruñuela Eneko , Gonzalez-Castillo Javier , Zheng Charles , Bandettini Peter , Caballero-Gaudes César
Published: October 2022

Conventionally, analysis of functional MRI (fMRI) data relies on available information about the experimental paradigm to establish hypothesized models of brain activity. However, this information can be inaccurate, incomplete or unavailable in multiple scenarios such as resting-state, naturalistic paradigms or clinical conditions. In these cases, blind estimates of neuronal-related activity can be obtained with paradigm-free analysis methods such as hemodynamic deconvolution. Yet, current formulations of the hemodynamic deconvolution problem have three important limitations: 1) their efficacy strongly depends on the appropriate selection of regularization parameters, 2) being univariate, they do not take advantage of the information present across the brain, and 3) they do not provide any measure of statistical certainty associated with each detected event. Here we propose a novel approach that addresses all these limitations. Specifically, we introduce MvME-SPFM (multivariate multi-echo sparse paradigm free mapping), a novel hemodynamic deconvolution algorithm that operates at the whole brain level and adds spatial information via a mixed-norm regularization term over all voxels. Additionally, MvME-SPFM employs a stability selection procedure that removes the need to select regularization parameters and also lets us obtain an estimate of the true probability of having a neuronal-related BOLD event at each voxel and time-point based on the area under the curve (AUC) of the stability paths. Besides, the formulation is tailored for multi-echo fMRI acquisitions, which allows us to better isolate fluctuations of BOLD origin on the basis of their linear dependence with Echo Time (TE) and to assign physiologically interpretable units (i.e., changes in the apparent transverse relaxation) to the resulting deconvolved events. We demonstrate that this algorithm outperforms existing state-of-the-art deconvolution approaches, and shows higher spatial and temporal agreement with the activation maps and BOLD signals obtained with a standard model-based linear regression approach, even at the level of individual neuronal events. Consequently, the proposed algorithm provides more reliable estimates of neuronal-related activity, here in terms of, for the study of the dynamics of brain activity when no information about the timings of the BOLD events is available. This algorithm will be made publicly available as part of thesploraPython package.
Optogenetic stimulation of septal somatostatin neurons disrupts locomotory behavior and regulates hippocampus cholinergic theta oscillations
Authors: Espinosa Nelson , Caneo Mauricio , Alonso Alejandra , Moran Constanza , Fuentealba Pablo
Published: October 2022

The septal complex regulates both motivated and innate behaviors, chiefly by the action of its diverse population of long-range projection neurons. Among those cells are lateral septum somatostatin neurons which collateral axons profusely innervate cortically-projecting neurons located in the medial septum. Thus, somatostatin cells are ideally positioned at the crossroads of ascending and descending modulatory pathways, likely supporting functional roles in both anatomical directions. Here, we used optogenetic stimulation and extracellular recordings in acutely anesthetized transgenic mice to show that septal somatostatin neurons can disinhibit the cholinergic septo-hippocampal pathway, thus enhancing the amplitude and synchrony of theta oscillations, while depressing sharp wave ripple episodes in the dorsal hippocampus. Nonetheless, photosuppressing septal somatostatin cells hindered goal-directed behavior in a spatial memory task by disrupting task engagement, evidenced in increased immobility, followed by repetitive self-grooming, a hallmark innate behavior. These results suggest that septal somatostatin cells can recruit ascending cholinergic pathways to promote hippocampal theta oscillations, while gating repetitive displacement behaviors mediated by descending subcortical pathways.

Significance Statement

A small population of somatostatin-expressing GABAergic cells in the lateral septum projects deep into subcortical regions, yet on its way it also targets neighboring medial septum neurons that profusely innervate cortical targets. We show here that selective inhibition of septal somatostatin cells exerts significant consequences in both ascending and descending synaptic pathways. Indeed, cortical targets increased the expression of hippocampal theta oscillations, which are relevant for sensorimotor processing, temporal coding, and a marker of anxious behaviour; whereas subcortical targets triggered repetitive self-grooming, an innate displacement behaviour. Our results suggest that septal somatostatin cells are a potential target for the control of altered innate behaviors in translational neuroscience.
Therapeutic depletion of CD8+ T-cells prevents myelin pathology in Globoid Cell Leukodystrophy
Authors: Sutter Pearl A. , Ménoret Antoine , Jellison Evan R. , Nicaise Alexandra M. , Bradbury Allison M. , Vella Anthony T. , Bongarzone Ernesto R. , Crocker Stephen J.
Published: October 2022

Globoid cell leukodystrophy (GLD) or Krabbe’s disease is a fatal genetic demyelinating disease of the central nervous system caused by loss-of-function mutations in the galactosylceramidase (galc) gene. While the metabolic basis for disease is known, the understanding of how this results in neuropathology is not well understood. Herein we report that the rapid and protracted elevation of CD8+ cytotoxic T lymphocytes occurs coincident with clinical disease in a mouse model of GLD. Administration of a function blocking antibody against CD8α effectively prevented disease onset, reduced morbidity and mortality and prevented CNS demyelination in mice. These data indicate that subsequent to the genetic cause of disease, neuropathology is driven by pathogenic CD8+ T cells, thus offering novel therapeutic potential for treatment of GLD.

One-Sentence Summary

CD8 T-cells mediate demyelination and neuroinflammation in a genetic white matter disease.