bluuebunny/crossref_metadata_2025 huggingface dataset:
PharmVar Tutorial on CYP2D6 Structural Variation Testing and Recommendations on Reporting
Authors: Turner Amy J. , Nofziger Charity , Ramey Bronwyn E. , Ly Reynold C. , Bousman Chad A. , Agúndez José A. G. , Sangkuhl Katrin , Whirl‐Carrillo Michelle , Vanoni Simone , Dunnenberger Henry M. , Ruaño Gualberto , Kennedy Martin A. , Phillips Michael S. , Hachad Houda , Klein Teri E. , Moyer Ann M. , Gaedigk Andrea
Published: September 2023

The Pharmacogene Variation Consortium (PharmVar) provides nomenclature for the highly polymorphic human CYP2D6 gene locus and a comprehensive summary of structural variation. CYP2D6 contributes to the metabolism of numerous drugs and, thus, genetic variation in its gene impacts drug efficacy and safety. To accurately predict a patient's CYP2D6 phenotype, testing must include structural variants including gene deletions, duplications, hybrid genes, and combinations thereof. This tutorial offers a comprehensive overview of CYP2D6 structural variation, terms, and definitions, a review of methods suitable for their detection and characterization, and practical examples to address the lack of standards to describe CYP2D6 structural variants or any other pharmacogene. This PharmVar tutorial offers practical guidance on how to detect the many, often complex, structural variants, as well as recommends terms and definitions for clinical and research reporting. Uniform reporting is not only essential for electronic health record‐keeping but also for accurate translation of a patient's genotype into phenotype which is typically utilized to guide drug therapy.
New SAMHSA strategic plan focuses on preventing suicides
Authors: Knopf Alison
Published: September 2023

The 2023–2026 Strategic Plan for the Substance Abuse and Mental Health Services Administration (SAMHSA) focuses reducing suicides. There is a stress on mental health, especially among the workforce, and a general reference to “behavioral” health care, which of course includes both mental health and addiction. The plan also includes a focus on reducing opioid overdoses.
Emotion dysregulation can help predict severity of other disorders
Authors: Knopf Alison
Published: September 2023

Emotion dysregulation is a useful trait which runs across disorders, researchers have found. A study of two large samples of toddlers (1,544 children ages 1.5 to 5 years old) and school‐aged children (7,259 6–18‐year‐olds) found that equal levels of total emotion dysregulation were found across different disorders. The presence of emotion dysregulation predicted lower quality of life and a longer treatment duration, in addition to clinical diagnosis. The diagnoses of the children were internalizing, externalizing, and neurodevelopmental. In particular, the children had attention‐deficit hyperactivity disorder, autism spectrum disorder, oppositional defiant disorder/conduct disorder, and anxiety and mood disorders. Emotion dysregulation was measured by the CBCL‐Emotion Dysregulation Index, quality of life by the Kidscreen‐27, and treatment duration by electronic health records. The researchers concluded that emotion dysregulation is a clinically useful trait which can predict severity of impairment and treatment duration. Importantly, it is composed of shared features across disorders. Children and adolescents can easily be overwhelmed by emotions, but in children with mental disorders this is even more pronounced. Most definitions of emotion dysregulation include symptoms of heightened reactivity and quickness to anger, anxiety, or depression. Being able to regulate emotions means better mental and physical health, social relationships, academic performance, and work functioning. Emotion dysregulation itself, regardless of disorder, should, perhaps, be treated. More youth have emotion dysregulation than any other mental disorder. The study was conducted in the Netherlands. [Bierens, M., Hartman, C. A., Klip, H., et al. (2023, July 20). Emotion dysregulation as cross‐disorder trait in child psychiatry predicting quality of life and required treatment duration. Front Psychiatry, 14, 1101226. http://doi.org/10.3389/fpsyt.2023.1101226.]
Phylogenetic and biogeographic history of brook lampreys (Lampetra: Petromyzontidae) in the river basins of the Adriatic Sea based on DNA barcode data
Authors: Rüber Lukas , Gandolfi Andrea , Foresti Danilo , Paltrinieri Luca , Splendiani Andrea , Seehausen Ole
Published: September 2023

The Adriatic brook lamprey, Lampetra zanandreai Vladykov 1955, was described from northeastern Italy. Its distribution is thought to include left tributaries of the River Po and the river basins of the Adriatic Sea from the River Po to the River Isonzo/Soča in Italy, Switzerland and Slovenia. It also shows a geographically isolated distribution in the Potenza River on the Adriatic slope in Central Italy. Lampetra from the Neretva River system in Croatia and Bosnia and Herzegovina and the Morača River system in Montenegro that were previously identified as L. zanandreai were recently described as a new species Lampetra soljani Tutman, Freyhof, Dulčić, Glamuzina & Geiger 2017 based on morphological data and a genetic distance between the two species of roughly 2.5% in the DNA barcoding gene cytochrome oxidase I (COI). Since DNA barcodes for L. zanandreai are only available for one population from the upper Po River in northwestern Italy, we generated additional COI nucleotide sequence data of this species from Switzerland, northeastern and central Italy comprising near topotypic material and obtained GenBank sequences of the species from Slovenia to better assess the evolutionary history of the two brook lamprey species in the river basins of the Adriatic Sea. Our data show a low sequence divergence of <1% between L. zanandreai from Switzerland, northeastern and central Italy and Slovenia and the Balkan species L. soljani. However, members of the population previously identified as ‘L. zanandreai’ from northwest Italy are genetically highly divergent from those of L. zanandreai and likely belong to an undescribed species, L. sp. ‘upper Po’. The presence of a unique and highly divergent brook lamprey lineage in the upper Po River suggests that L. zanandreai and Lampetra sp. ‘upper Po’ may have evolved in separate paleo drainages during the formation of the modern Po Valley subsequent to marine inundations in the Pliocene.
Progressive enrichment in 18O and 2H in xylem water along sap flow paths in Fagus sylvatica trees
Authors: Montemagno Alessandro , Keim Richard F. , López‐Días Veneranda , Bense Victor , Teuling Adriaan J. , Hissler Christophe
Published: September 2023

Isotopic signatures of xylem water in different tree compartments such as roots, boles and branches, differ due to physiological and physical processes occurring inside trees. Accordingly, we hypothesised that the extent of such differences among the isotopic signatures of tree compartments is coherent with the distance travelled by the water inside trees and to its residence time. To test this, we compared the O–H isotopic composition of xylem water collected using an in‐situ water extraction method from roots, boles and branches of Fagus sylvatica trees growing on three geomorphological units of the Weierbach experimental catchment, Luxembourg. There was progressive 18O and 2H enrichment in xylem waters along the root–branch flow path for all the studied trees. Three explanations could be considered for this progressive enrichment: internal fractionation by xylem–phloem water exchange, chemical reactions of metabolic pathways and variable ages of water retained in the xylem, reflecting historical variation in isotopic composition of uptake water. Support for the hypothesis of isotopic fractionation linked to xylem–phloem water exchange and chemical reactions is that enrichment was generally consistent with the distance travelled by the water and to its residence time inside the trees. However, the relative enrichment of 2H and 18O was not consistent along the flow path, with Δ2H/Δ18O ~7.5 from the soil into the roots and bole and ~4.7–6.5 for pathways that included smaller branches. This contrast suggests different processes controlling above‐ground isotopic enrichment. In particular, the slope of ~7.5 in the lower tree is also consistent with variation in tree water uptake varying along the local meteoric water line, with water in the roots being closer to the composition of rainfall close to the time of sampling and water in the bole being closer to the composition of rainfall from the previous summer. The timing of root and bole sampling in early spring, just before leaf‐out, means sap flow was very slow and makes it plausible that varying‐age water was present in the tree at that time. We also compared the O–H isotopic composition of those samples with the ones of the potential water sources to identify the origin of the water uptaken. The latter varied during the 3 years of sampling, with a preferential uptake from near‐surface waters. Our results suggest multiple biochemical, physiological and physical processes may play fundamental roles in the isotopic composition of xylem water within trees.
Effect of blood pressure index on clinical outcomes in patients with heart failure and chronic kidney disease
Authors: Yuan Ying , Liu Menghui , Zhang Shaozhao , Lin Yifen , Huang Yiquan , Zhou Huimin , Xu Xingfeng , Zhuang Xiaodong , Liao Xinxue
Published: September 2023

Aims

This study aimed to assess the effect of blood pressure (BP) index, in terms of level and variability, on the progression of cardiovascular and renal diseases in patients with both heart failure (HF) and chronic kidney disease (CKD).

Methods and results

The study involved patients with HF and CKD from the database of the Chronic Renal Insufficiency Cohort (CRIC) study. The study endpoint includes the following: (i) primary endpoint, including cardiovascular disease (CVD) events, renal events, and all‐cause death; (ii) CVD events; (iii) renal events; and (iv) all‐cause death. Among 3939 participants in the CRIC study, a total of 382 patients were included. The duration of the follow‐up was 6.3 ± 2.7 years, the age was 60.2 ± 8.9 years, and 57.6% were male. BP index included 20 indicators in relation to BP level and variability, 4 of which were analysed including baseline systolic BP (SBP), standard deviation of SBP, coefficient of variation of diastolic BP (DBP CV), and average real variability of pulse pressure. In the Cox regression analysis after adjustment, baseline SBP was significant for the risk of primary endpoint [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.03–1.44, P = 0.02] and renal events (HR 1.54, 95% CI 1.22–1.95, P < 0.001), and DBP CV was significant for the risk of primary endpoint (HR 1.03, 95% CI 1.01–1.06, P = 0.02) and CVD events (HR 1.04, 95% CI 1.02–1.07, P < 0.01). The result of the forest plot depicted that baseline SBP had a linear association with the risk of CVD and renal events (P = 0.04 and 0.001, respectively) and DBP CV with CVD events (P = 0.02). As the restricted cubic spline models displayed, DBP CV featured a J‐ or L‐curved association with the primary endpoint, renal events, and all‐cause death (P for nonlinearity = 0.01, <0.001, and 0.01, respectively).

Conclusions

The baseline SBP and DBP CV may remain significant for clinical outcomes in patients with both HF and CKD. The increase in baseline SBP is associated with a higher risk of primary endpoint, CVD events, and renal events, and the increase in DBP CV with a higher risk of CVD events. Concerning nonlinear association, DBP CV features a J‐ or L‐curved relationship with the primary endpoint, renal events, and all‐cause death, with a higher risk at both low and high values.

Trial registration: https://www.clinicaltrials.gov; unique identifier: NCT00304148.
Equatorial Perturbation Driven Reaction Bifurcation in Non‐Heme Iron Complexes for Chlorite Oxidation
Authors: Sahoo Limashree , Satpathy Jagnyesh Kumar , Yadav Rolly , de Visser Sam P. , Sastri Chivukula V.
Published: September 2023

Chlorine oxyanions have various applications, such as bleaching and oxidizers in rocket fuels. However, their high solubility in water and long environmental lifetimes have led to ecological concerns, especially regarding drinking water quality. This study focuses on the conversion of chlorite to chlorine dioxide, which is of significant interest as it exhibits superior antimicrobial activity and generates less harmful byproducts for water treatment. Two nonheme iron(II) complexes capable of producing chlorine dioxide from chlorite at room temperature and pH 5.0 are presented. These complexes oxidize chlorite through high‐valent iron (IV)‐oxo intermediates formed in‐situ. The study establishes second‐order rate constants for chlorite oxidation and investigates the effects and mechanisms involved by substituting a methyl group in the secondary coordination sphere of the FeIV(O)(N4Py) system. By employing kinetic analysis and spectroscopic investigations, the crucial elements for the reaction mechanism in chlorite oxidation are identified. These findings pave the way for future advancements in this field.
Multiplexity of human brain oscillations as a personal brain signature
Authors: Dimitriadis Stavros I. , Routley B. , Linden David E. J. , Singh Krish D.
Published: September 2023

Human individuality is likely underpinned by the constitution of functional brain networks that ensure consistency of each person's cognitive and behavioral profile. These functional networks should, in principle, be detectable by noninvasive neurophysiology. We use a method that enables the detection of dominant frequencies of the interaction between every pair of brain areas at every temporal segment of the recording period, the dominant coupling modes (DoCM). We apply this method to brain oscillations, measured with magnetoencephalography (MEG) at rest in two independent datasets, and show that the spatiotemporal evolution of DoCMs constitutes an individualized brain fingerprint. Based on this successful fingerprinting we suggest that DoCMs are important targets for the investigation of neural correlates of individual psychological parameters and can provide mechanistic insight into the underlying neurophysiological processes, as well as their disturbance in brain diseases.
Health and labor market effects of an unanticipated rise in retirement age. Evidence from the 2012 Italian pension reform
Authors: Serrano‐Alarcón Manuel , Ardito Chiara , Leombruni Roberto , Kentikelenis Alexander , d’Errico Angelo , Odone Anna , Costa Giuseppe , Stuckler David ,   IWGRH
Published: September 2023

As retirement ages increase around the world, not all workers may be equally able to extend their working lives. In this article, we examine the health and labor market effects of an Italian pension reform that suddenly increased the normal retirement age up to 7 years for women and up to 2 years for men. To do this, we use linked labor and healthcare administrative data, jointly with survey data and difference‐in‐difference methods. Our results show that the reform was effective in postponing retirement among both genders, as pension claiming dropped substantially for older workers. However, there were also side effects as the reform significantly pushed previously employed men and women into unemployment and disability pension. Among women only, the reform also increased sick leave and hospitalizations related to mental health and injuries. These effects were driven by women with previously low health status, suggesting that undifferentiated and abrupt increases in pension age might harm more vulnerable workers. Coherently with the milder tightening of retirement age experienced by men, labor market responses were smaller in size, and they did not suffer any significant health effects.
Shallow groundwater temperature patterns revealed through a regional monitoring well network
Authors: Smith Kathryn A. , O'Sullivan Antóin M. , Kennedy Gavin , Benz Susanne A. , Somers Lauren D. , Kurylyk Barret L.
Published: September 2023

Groundwater temperature is a critical control on groundwater quality, geothermal system efficiency and ecosystem dynamics in receiving surface waters. Despite the known importance of groundwater temperature, there is a lack of dedicated aquifer thermal monitoring across spatial and temporal scales. Pressure transducers and other sensors installed in groundwater monitoring well networks often record temperature as a secondary function, but these comprehensive groundwater temperature data sets are seldom analysed. In this study, we analysed seasonal, interannual and spatial patterns of shallow groundwater temperatures from a regional groundwater monitoring network in Nova Scotia, Canada and compared these subsurface temperature data to air temperature data from nearby climate stations using linear regressions and Fourier analysis. The results showed that seasonal groundwater temperatures were damped (with seasonal amplitudes 3.6%–42% of air temperature amplitudes) and lagged (phase shifted 43–145 days) compared to air temperature, with notable year‐to‐year variations in both damping and lagging. Results also highlighted the role of snowpack thickness on the lowest mean monthly groundwater temperatures. Given potential impacts of climate change, land cover change, urbanization and geothermal energy development on groundwater temperatures, we encourage water authorities and regulators to begin or enhance aquifer thermal monitoring and provide guidance for capitalizing on existing monitoring well infrastructure to track temperature dynamics and changes.
Mesenchymal stem/stromal cell‐based cell‐free therapy for the treatment of acute lung injury
Authors: Cui Enhai , Lv Lu , Chen Wenyan , Chen Na , Pan Ruolang
Published: September 2023

Acute lung injury (ALI) is a severe medical condition that causes inflammation and fluid buildup in the lung, resulting in respiratory distress. Moreover, ALI often occurs as a complication of other medical conditions or injuries, including the coronavirus disease of 2019. Mesenchymal stem/stromal cells (MSCs) are being studied extensively for their therapeutic potential in various diseases, including ALI. The results of recent studies suggest that the beneficial effects of MSCs may not be primarily due to the replacement of damaged cells but rather the release of extracellular vesicles (EVs) and other soluble factors through a paracrine mechanism. Furthermore, EVs derived from MSCs preserve the therapeutic action of the parent MSCs and this approach avoids the safety issues associated with live cell therapy. Thus, MSC‐based cell‐free therapy may be the focus of future clinical treatments.
Construction of rank 4 self‐dual association schemes inducing three partial geometric designs
Authors: Hanaki Akihide
Published: September 2023

Xu characterized rank 4 self‐dual association schemes inducing three partial geometric designs by their character tables. We construct such association schemes as Schur rings over Abelian 2‐groups.
How do women talk about self‐funded breast cancer genetic testing?: Small stories and stance‐taking strategies
Authors: Bechaz Alan , Sexton Adrienne , Gill Gulvir , Karidakis Maria
Published: September 2023

Genetic testing for breast cancer genes is an experience which is inextricably linked with health communication practices and the broader social context in which it occurs. Linguistic approaches can provide perspective on how women seeking self‐funded BRCA1/2 gene testing represent their experiences, knowledge, roles, choices and emotions through the way they talk. A discursive constructionist epistemology and narrative theoretical framework informed the applied linguistics methodology. Analysis of ‘small stories’ and stance‐taking was performed on eight transcripts of audio‐recorded telephone interviews with women at low to moderate risk of carrying BRCA1/2 pathogenic variants who self‐funded genetic testing. We found a high prevalence of ‘small stories’ including accounts of events, hypotheticals, habitual narratives, and stories which combined multiple genres. Stance‐taking was a means by which participants constructed personal identities in the conversational context, such as that of a responsible person. Via stance‐taking strategies, participants also actively negotiated the conversational agenda, for example expressing different degrees of alignment with the interviewer's orientation towards emotions. This study provides a basis for recognizing linguistic markers in genetic counseling interactions about genetic testing for breast cancer genes. Enhanced awareness of client language choice, and the ways in which small stories and stance can signify the client's evaluation of experience and choices, alignment with the genetic counselor's questions/statements, and investment in the conversation, has potential to improve the therapeutic interaction.
Disability training for genetic counseling students: The advocates' perspective
Authors: Winchester Dena , Karger Lisa , Wasserman David , Naik Hetanshi
Published: September 2023

The genetics and disability communities have had a complicated relationship that is rooted in the history of the eugenics movement. Disability scholars claim that in order for healthcare professionals to provide optimal services to disabled patients, disability education must be implemented into healthcare training programs. No studies have explored the perspectives of disability advocates regarding the implementation and use of disability training in genetic counseling. This exploratory study recruited 13 advocates with lived experience of disability and genetic counseling exposure to participate in a semi‐structured interview to share their recommendations for disability education opportunities in genetic counseling training programs and their perceived benefits of increased student exposure to disability. All advocates received genetic counseling themselves and four advocates reported working with genetic counselors in the advocacy setting. Advocates recounted their experiences working with genetic counselors, identifying qualities they deemed critical for effective counseling. All the advocates expressed interest in participating in experiential opportunities, with few concerns noted. The most frequently discussed recommendations for disability training included inviting advocates to speak in classrooms, and having students shadow disabled individuals. Advocates noted barriers to consider when implementing such educational opportunities, such as accessibility issues. Potential benefits of implementing disability education for students included providing students with a broader scope of knowledge and a deeper understanding of disability and resources available to the disability community. This novel study found that advocates are interested in participating in genetic counseling education, with recommendations on preferred experiential learning. By increasing a genetic counseling student's exposure to a disability, they may develop a comprehensive understanding of life with a disability, which may improve genetic counseling services to those with newly diagnosed disabilities.
Conducting inclusive research in genetics for transgender, gender‐diverse, and sex‐diverse individuals: Case analyses and recommendations from a clinical genomics study
Authors: Bland Harris T. , Gilmore Marian J. , Andujar Justin , Martin Makenna A. , Celaya‐Cobbs Natasha , Edwards Clasherrol , Gerhart Meredith , Hooker Gillian W. , Kraft Stephanie A. , Marshall Dana R. , Orlando Lori A. , Paul Natalie A. , Pratap Siddharth , Rosenbloom S. Trent , Wiesner Georgia L. , Mittendorf Kathleen F.
Published: September 2023

A person's phenotypic sex (i.e., endogenous expression of primary, secondary, and endocrinological sex characteristics) can impact crucial aspects of genetic assessment and resulting clinical care recommendations. In studies with genetics components, it is critical to collect phenotypic sex, information about current organ/tissue inventory and hormonal milieu, and gender identity. If researchers do not carefully construct data models, transgender, gender diverse, and sex diverse (TGSD) individuals may be given inappropriate care recommendations and/or be subjected to misgendering, inflicting medical and psychosocial harms. The recognized need for an inclusive care experience should not be limited to clinical practice but should extend to the research setting, where researchers must build an inclusive experience for TGSD participants. Here, we review three TGSD participants in the Family History and Cancer Risk Study (FOREST) to critically evaluate sex‐ and gender‐related survey measures and associated data models in a study seeking to identify patients at risk for hereditary cancer syndromes. Furthermore, we leverage these participants' responses to sex‐ and gender identity‐related questions in FOREST to inform needed changes to the FOREST data model and to make recommendations for TGSD‐inclusive genetics research design, data models, and processes.
Phosphorylcholine esterase is critical for Dolichos biflorus and Helix pomatia agglutinin binding to pneumococcal teichoic acid
Authors: Zhou Meng‐Lan , Frost Michael R. , Xu Ying‐Chun , Nahm Moon H.
Published: September 2023

Streptococcus pneumoniae (the pneumococcus) has wall teichoic acid (WTA) and lipoteichoic acid (LTA) expressing the Forssman antigen (FA). Two lectins, Dolichos biflorus agglutinin (DBA) and Helix pomatia agglutinin (HPA), are known to bind FA. To determine the molecular structure targeted by these two lectins, different pneumococcal strains were studied for DBA/HPA binding with flow cytometry and fluorescence microscopy. Genetic experiments were used to further examine the lectins’ molecular target. Twelve strains were positive for DBA binding, whereas three were negative. Super‐resolution microscopy showed that DBA stained only the subcapsular area of pneumococci. The three DBA nonbinders showed no phosphorylcholine esterase (Pce) activity in vitro, whereas 10 DBA binders displayed Pce activity (the remaining two strains were DBA binders with no Pce activity in vitro). The pcegene sequence for 10 representative strains revealed two functional pce alleles, the previously recognized “allele A” and a newly discovered “allele B” (with 12 additional nucleotides). Isolates with allele B showed no Pce activity in vitro but did bind to DBA, indicating allele B Pce is functional in vivo. Genetic transfer experiments confirmed that either allele is sufficient (and necessary) for DBA binding. The three DBA nonbinders had various mutations that affected Pce function. Observations with HPA were identical to those with DBA. We show that DBA and HPA bind only to the WTA/LTA of pneumococcal isolates with a functional Pce enzyme. A newly discovered Pce variant (allele B) is functional in vivo but nonfunctional when assayed in vitro.
Electrochemical communication in biofilm of bacterial community
Authors: Manna Sounik , Ghanty Chandan , Baindara Piyush , Barik Tarun KR. , Mandal Santi M.
Published: September 2023

Electrochemical communication during biofilm formation has recently been identified. Bacteria within biofilm‐adopt different strategies for electrochemical communication such as direct contact via membrane‐bound molecules, diffusive electron transfer via soluble redox‐active molecules, and ion channel‐mediated long‐range electrochemical signaling. Long‐range electrical signals are important to communicate with distant members within the biofilm, which function through spatially propagating waves of potassium ion (K+) that depolarizes neighboring cells. During propagation, these waves coordinate between the metabolic states of interior and peripheral cells of the biofilm. The understanding of electrochemical communication within the biofilm may provide new strategies to control biofilm‐mediated drug resistance. Here, we summarized the different mechanisms of electrochemical communication among bacterial populations and suggested its possible role in the development of high level of antibiotic resistance. Thus, electrochemical signaling opens a new avenue concerning the electrophysiology of bacterial biofilm and may help to control the biofilm‐mediated infection by developing future antimicrobials.
Socioeconomic disparities in patients with small bowel neuroendocrine tumors
Authors: DiPeri Timothy P. , Manguso Nicholas , Gong Jun , Atkins Katelyn M. , Hendifar Andrew E. , Gangi Alexandra
Published: September 2023

Background and Objectives

Demographic and socioeconomic disparities affect cancer specific outcomes in numerous malignancies, but the impact of these for patients with small bowel neuroendocrine tumors (SBNETs) is not well understood. The primary objective was to investigate the impact of demographic and socioeconomic factors on overall survival (OS) for patients with SBNETs.

Methods

We performed a retrospective cohort study utilizing the National Cancer Database to assess patients diagnosed with SBNET between 2004 and 2015. Patients were stratified by demographics, socioeconomic factors, insurance status, and place of living.

Results

The 5‐year OS for the entire cohort was 78.5%. The 5‐year survival was worse in patients with lower income (p < 0.0001), lower education (p < 0.0001), not in proximity to a metro area (p = 0.0004), and treatment at a community cancer center (p < 0.0001). Adjusting for age and sex, factors associated with worse OS were lower income (<$38 000) (hazard ratio [HR]: 1.16, 95% confidence interval [CI]: 1.04−1.28), lower education (>20% no HSD) (HR: 1.14, 95% CI: 1.02−1.26), no insurance (HR: 1.66, 95% CI: 1.33−2.06), and not living in proximity to a metro area (HR: 1.27, 95% CI: 1.10−1.47).

Conclusions

Patient demographics and socioeconomic factors play an important role in survival of patients with SBNETs, specifically proximity to a metro area, median income, education level, and type of treatment center. Strategies to improve access to care must be considered in this at‐risk population.
Fluorescent Guided Sentinel Lymph Mapping of the Oral Cavity with Fluorescent‐Labeled Tilmanocept
Authors: Guo Theresa , Jang Sophie S. , Ogawa Ryotaro , Davis Morgan , Ashworth Edward , Barback Christopher V. , Hall David J. , Vera David R.
Published: September 2023

Objective

With the shift toward utilization of sentinel lymph node biopsy (SLNB) in oral cavity cancer, improved techniques for intraoperative sentinel node identification are needed. This study investigates the feasibility of fluorescently labeled tilmanoscept in SLNB in an oral cancer rabbit model.

Methods

An animal study was designed using 21 healthy male New Zealand rabbits. Gallium‐68‐labeled tilmanocept labeled with IRDye800CW was injected submucosally into the buccal mucosa (n = 6) or lateral tongue (n = 7) followed by PET imaging. One hour after injection, SLNB was performed using fluorescence imaging followed by a bilateral neck dissection and sampling of non‐nodal surrounding tissue. All tissues were measured for radioactivity and fluorescence. In addition, eight rabbits were injected with delayed SLNB performed 48 h after injection.

Results

Buccal injections all had ipsilateral SLN drainage and tongue injections exhibited 18.2% contralateral drainage. An average of 1.9 ± 1.0 SLN (range 1–5) were identified. In addition, an average of 16.9 ± 3.3 non‐sentinel lymph nodes were removed per animal. SLNs had an average of 0.69 ± 0.60 percent‐of‐injected dose (%ID) compared with non‐sentinel nodes with 0.012 ± 0.025 %ID and surrounding tissue with 0.0067 ± 0.015 %ID. There was 98.0% agreement between sentinel lymph nodes identified using fluorescence compared to radioactivity with Cohen's kappa coefficient of 0.879. In 48‐h delayed SLNB, results were consistent with 97.8% agreement with radioactivity and Cohen's Kappa coefficient of 0.884. Fluorescence identified additional lymph nodes that were not identified by radioactivity, and with one false negative.

Conclusion

Fluorescent‐labeled Tc‐99 m‐tilmanocept represents a highly accurate adjunct to enhance SLNB for oral cavity cancer.

Level of Evidence

N/A Laryngoscope, 134:1299–1307, 2024
Decision‐Making in the Treatment of Idiopathic Subglottic Stenosis: A Survey of Laryngologists
Authors: Razura Diego E. , Bensoussan Yael , Lui Christopher G. , Johns Michael M. , Reder Lindsay , Gelbard Alexander , O'Dell Karla
Published: September 2023

Objective

Idiopathic subglottic stenosis (iSGS) is a rare condition involving the subglottic larynx and upper trachea, commonly affecting Caucasian females between 30 and 50 years of age. Despite its homogeneous presentation, clinical management for iSGS is yet to be standardized, leading to variability in outcomes between predominant interventions. In recognition of the heterogenicity in iSGS treatment and the need to improve patient outcomes, this study aimed to survey laryngologists to understand the factors influencing clinical decision‐making and the incorporation of new treatment modalities for iSGS.

Methods

An online survey was sent to 145 academic laryngologists. The survey assessed respondents' professional backgrounds, experience treating iSGS, treatment algorithms, and how various patient factors affect management.

Results

Of the 87 (60%) laryngologists who responded to the survey, the most common clinical assessments were tracheoscopy/bronchoscopy (96.8%) and pulmonary function tests (43.6%). Endoscopic dilation (ED) was the most common primary treatment offered (97.5%): 28.7% of surveyed laryngologists offer SISI as a primary treatment, and 74.7% perform SISI as a planned postoperative treatment. The most common SISI protocol was repeated injections every 4–6 weeks for a series of 1–3 total injections. Notably, 9.2% perform the Maddern procedure. Routine algorithms of care involving surgery were most often based on prior experience and prior patient outcomes (75.9%) and conversations with colleagues (64.4%). Only 31% report using the same protocol learned during their fellowship training.

Conclusion

This survey highlights significant variation in the management of patients with iSGS. Understanding the factors that influence decision‐making may lead to potential standardization in heterogeneous treatment approaches and may improve clinical outcomes.

Level of Evidence

5 Laryngoscope, 134:865–872, 2024
Multimodel simulations revealed strong spatial heterogeneity in temperature‐, photoperiod‐ and moisture‐driven modes of autumn phenology in Northern Hemisphere grasslands (25° N–55° N)
Authors: Li Yating , Ren Shilong
Published: September 2023

Autumn phenology plays a critical role in regulating growing season length and matter and energy exchanges in terrestrial ecosystems. The climate‐driven mechanism of the grassland autumn phenology process and its spatial distribution patterns at the hemispheric scale are, however, still poorly understood. In this study, we employed 17 existing and modified models to simulate the satellite‐derived end‐of‐season (EOS) over northern mid‐latitude grasslands (25° N–55° N), aiming to determine how grassland autumn phenology responds to individual and combined changes in low temperature, photoperiod, and water supply. The results showed that the prediction accuracy of EOS based on models driven by daily minimum temperature is slightly superior to that of the counterparts forced by daily average temperature. The model modified with water content as a regulatory factor of leaf senescence rate determined by low temperature and photoperiod performed best (root‐mean‐square error, 10.4 days; correlation coefficient, 0.38) on average. The autumn phenology process in 68.4% of grassland areas was better simulated by the models that incorporated water conditions. Spatially, optimal models jointly forced by low temperature, photoperiod, and water supply occupied 61.4% of the North American grasslands, 58.5% of the Central‐West Asian grasslands, and 42.1% of the Mongolian grasslands. Grasslands on the Tibetan Plateau were primarily forced by the associated effects of low temperature and photoperiod. Further analysis revealed that low temperature‐photoperiod driven models and low temperature‐photoperiod‐moisture driven models were mostly distributed in relatively hotter and wetter grasslands, while optimal models forced solely by low temperature were largely concentrated in those grassland areas with cooler and drier autumn. Overall, this study highlights the complex patterns and spatial heterogeneity of environmental control on autumn phenology in the Northern Hemisphere grasslands, which could shed light on global grassland development investigation.
Factors influencing maternal death surveillance and review implementation in Dodoma City, Tanzania. A qualitative case study
Authors: Rumbeli Nelson M. , August Furaha , Silvestri Valeria , Sirili Nathanael
Published: September 2023

Background

With 295 000 maternal deaths in 2017, 94% in low‐ and middle‐income countries, maternal death is a matter of global public health concern. To address it, Maternal Death Surveillance and Response (MDSR) strategy was introduced in 2013 by the World Health Organization. With a reported maternal mortality ratio of 556:100000 per live births, Tanzania adopted the strategy in 2015. Studies are needed to understand factors influencing the implementation of MDSR in this specific setting.

Aims and Objectives

The study aimed to assess the processes influencing MDSR implementation in Dodoma city council.

Methods

A qualitative case study was conceptualized according to the Consolidated Framework for Implementation Research, focusing on implementation process domain. Members of MDSR committees were enrolled by purposeful sampling in the five health centres in Dodoma where the strategy was fully implemented and functional. In‐depth interviews were conducted with key informants concerning the implementation processes influencing MDSR. Saturation was reached with the 15th respondent. Qualitative inductive content analysis was used to analyse data.

Results

The inclusiveness in participatory planning process, stakeholders’ readiness and accountability and collective learning were acknowledged as factors positively influencing the implementation of MDSR strategy by respondents. The interaction and alignment of influential factors were essential for successful implementation.

Conclusions

MDSR implementation is positively influenced by factors that interact and converge in the building of a learning health system, to increase knowledge through practice and improve practice through knowledge. Further studies are needed to analyse the influence of additional factors at different levels of implementation to fully understand and empower the MDSR implementation network, and to better target the goal of closing the knowledge to practice loop.
Melasma treatment with a 1064 nm, picosecond‐domain laser with a fractionated multibeam lens array
Authors: Bernstein Eric F. , Basilavecchio Lisa D. , Wang Jenny
Published: September 2023

Background and Objectives

Picosecond‐domain lasers have been fitted with fractionated optics for dermal remodeling. This study evaluates the safety and efficacy of a multiwavelength picosecond‐domain laser, using a 1064 nm multibeam lens array, for improving the appearance of melasma.

Study Design/Materials and Methods

Twenty adults with a clinical diagnosis of melasma were enrolled and received 4 monthly 1064‐nm, 450 ps laser treatments delivered with a 10 × 10 fractional array of 150 µm microbeams. Cosmetic units with melasma were treated with fluences ranging from 1.7 to 2.9 mJ/microbeam with a repetition rate of 6 Hz. Treatment effect was evaluation of digital images by dermatologists blinded as to the treatment conditions, comparing baseline and 3‐ and 8‐month post‐treatment images. Modified melasma area and severity index (mMASI) scores were determined by the study investigator based on clinical photography. Subject self‐assessment of treatment effects was also recorded.

Results

Blinded reviewers correctly identified the post‐treatment image in 16 of the 20 image sets (80%). Ratings demonstrated statistically significant (p < 0.001) improvement on an 11‐point scale at both the 3‐ and 8‐month timepoints for a mean improvement of 3.7 point (range −8 to 10) or 37% improvement at the 3‐month follow‐up, and 2.7 (range −8 to 9) or 27% at the 8‐month follow‐up for all subjects. The average mMASI score showed highly significant reduction at both the 3‐ and 8‐month follow‐ups compared to baseline (p < 0.01). Most subjects (90%) were satisfied with the treatment outcome in melasma at both follow‐ups, which is consistent with the treatment outcome and mMASI scores.

Conclusion

The fractionated, picosecond‐domain, 1064 nm laser is safe and effective for improving melasma and should be considered as an adjunct to topical treatment regimens and sun‐protection for management of melasma.
Approximate isomorphism of metric structures
Authors: Hanson James E.
Published: September 2023

We give a formalism for approximate isomorphism in continuous logic simultaneously generalizing those of two papers by Ben Yaacov [2] and by Ben Yaacov, Doucha, Nies, and Tsankov [6], which are largely incompatible. With this we explicitly exhibit Scott sentences for the perturbation systems of the former paper, such as the Banach‐Mazur distance and the Lipschitz distance between metric spaces. Our formalism is simultaneously characterized syntactically by a mild generalization of perturbation systems and semantically by certain elementary classes of two‐sorted structures that witness approximate isomorphism. As an application, we show that the theory of any ‐tree or ultrametric space of finite radius is stable, improving a result of Carlisle and Henson [8].
Synthesis and Conformational Behaviors of Unnatural Peptides Alternating Chiral and Achiral α,α‐Disubstituted α‐Amino Acid Units
Authors: Takeuchi Nanami , Taniguchi Masataka , Kato Yuki , Takata Riko , Osaka Issey , Nakajima Noriyuki , Hamada Masahiro , Koyama Yasuhito
Published: September 2023

The development of peptidomimetics to modulate the conformational profile of peptides has been extensively studied in the fields of biological and medicinal chemistry. However, large‐scale synthesis of peptidomimetics with both an ordered sequence and a controlled secondary structure is highly challenging. In this paper, the framework of peptidomimetics has been designed to be alternating an achiral α,α‐disubstituted α‐amino acid unit and a chiral α‐methylphenylalanine unit. The polymers are synthesized via invented Ugi reaction‐based polycondensation technique. The chiral higher‐order structures of the alternating peptides are evaluated mainly through circular dichroism (CD) spectroscopy. The UV–Vis and CD spectra of the polymers in three solvents are systematically measured at various temperatures. The anisotropic factors of CD (gCD) values are calculated to know the chiroptical response. The results indicate the characteristic conformational behaviors. In a polar solvent, the hydrogen bonds between the N‐H group of MePhe unit and the C=O of α,α‐diphenylglycine unit outweigh the intraresidue hydrogen bonds in α,α‐diphenylglycine unit, leading to the formation of a prevailing preferred‐handed 310‐helical conformation. On the other hand, in a less polar solvent, the intrachain hydrogen bonds switch to intraresidue hydrogen bonds in α,α‐diphenylglycine unit, which make the polymer adopting a prevailing extended planar C5‐conformation.
Media freedom, information and communication technology infrastructure, and foreign direct investment inflows
Authors: Liu Wenjing , Wang Jiang
Published: September 2023

In an era of globalization, attracting foreign capital inflows remains a significant concern among nations. This paper aims to examine the individual and joint effects of media freedom and information and communication technologies (ICT) infrastructure on foreign direct investment (FDI) inflows. Utilizing a panel dataset of FDI inflows from 144 countries worldwide from 2003 to 2016 for our empirical analysis, we find that media freedom significantly increases FDI inflows. Interestingly, ICT infrastructure plays an essential moderating role in this relationship. When ICT infrastructure is underdeveloped, the expected impact of media freedom may not materialize; however, as the level of ICT infrastructure improves, the positive effect of media freedom becomes increasingly significant. Hence, we argue that a free media and robust ICT infrastructure are complementary in attracting FDI. Our study not only fills a crucial gap in the literature by examining their joint effect but also provides insightful implications for host countries looking to attract foreign investment. This work thus significantly contributes to understanding the complex relationships among media freedom, ICT infrastructure levels, and FDI inflows at the national level.
Pathwise methods for the integration of a stochastic SVIR model
Authors: Muñoz Mario , de la Cruz Hugo , Mora Carlos
Published: September 2023

We propose an approach for the precise numerical integration of a stochastic SVIR model defined by a stochastic differential equation (SDE) with non‐globally Lipschitz continuous coefficients and multiplicative noise. This equation, based on a compartmental epidemic model, describes a continuous vaccination strategy with environmental noise effects. By means of an appropriate invertible continuous transformation, we link the solution to the stochastic SVIR model to the solution of an auxiliary random differential equation (RDE) that has an Ornstein–Uhlenbeck process as the only input parameter of the system. In this way, based on this explicit conjugacy between both equations, new pathwise numerical schemes are constructed for the SVIR model. In particular, we propose an exponential method that outperforms other integrators in the literature and is able to approximate, with high stability, meaningful probabilistic features of the continuous system, including its stationary distribution and ergodicity. A simulation study is presented to illustrate the practical performance of the introduced methods, and a comparative analysis with other integrators commonly used for the simulation of epidemiological models is performed.
An exploration of actigraphy in the context of ketamine and treatment‐resistant depression
Authors: Punturieri Claire , Duncan Wallace C. , Greenstein Dede , Shandler Gavi , Zarate Carlos A. , Evans Jennifer W.
Published: September 2023

Objectives

This study explored the potential of non‐parametric and complexity analysis metrics to detect changes in activity post‐ketamine and their association with depressive symptomatology.

Methods

Individuals with treatment‐resistant depression (TRD: n = 27, 16F, 35.9 ± 10.8 years) and healthy volunteers (HVs: n = 9, 4F, 36.4 ± 9.59 years) had their activity monitored during an inpatient, double‐blind, crossover study where they received an infusion of ketamine or saline placebo. All participants were 18–65 years old, medication‐free, and had a MADRS score ≥20. Non‐parametric metrics averaged over each study day, metrics derived from complexity analysis, and traditionally calculated non‐parametric metrics averaged over two weeks were calculated from the actigraphy time series. A separate analysis was conducted for a subsample (n = 17) to assess the utility of these metrics in a hospital setting.

Results

In HVs, lower intradaily variability was observed within daily rest/activity patterns post‐ketamine versus post‐placebo (F = 5.16(1,15), p = 0.04). No other significant effects of drug or drug‐by‐time or correlations between depressive symptomatology and activity were detected.

Conclusions

Weak associations between non‐parametric variables and ketamine were found but were not consistent across actigraphy measures.

Clinical Trial registration

ClinicalTrials.gov, NCT00088699.