bluuebunny/crossref_metadata_2025 huggingface dataset:
Can We Predict Dissociative Experiences Based on Inner Speech in Nonclinical Population by Mediating Role of Sleep Disturbance?
Authors: Nooripour Roghieh , Mazloomzadeh Mohammadreza , Shirkhani Milad , Ghanbari Nikzad , Var Tabassom Saeid Par , Hosseini Seyed Ruhollah
Published: February 2022

Dissociative experiences include various experiences and behaviors that can cause people to feel disturbed and disconnected from reality. Individuals with dissociative experiences may exhibit various symptoms, particularly in their inner speech. The present study examined how we can predict dissociative experiences based on inner speech in nonclinical populations by mediating the role of sleep disturbance. In this cross-sectional study, data were collected from university students aged 18 to 40 years (N = 400). They were asked to complete online self-report questionnaires: Varieties of the Inner Speech Questionnaire, Dissociative Experiences Scale, and Pittsburgh Sleep Quality Index. Results showed that there was a relationship between dissociative experiences and sleep disturbance (r = 0.29, p < 0.001), dialogic inner speech (r = 0.39, p < 0.001), condensed inner speech (r = 0.31, p < 0.001), other people's inner speech (r = 0.46, p < 0.001), evaluative/motivational inner speech (r = 0.28, p < 0.001), and total inner speech score (r = 0.48, p < 0.001). Thus, the current study showed a significant relationship among inner speech, dissociative experiences, and sleep disturbances. Inner speech was found to predict dissociative experiences by mediating sleep disturbances in the nonclinical population. Individuals with strong dissociative experiences had high scores for inner speech and sleep disturbance. The present study highlights a new area of research and its relationship to inner speech and dissociation. Future studies could further explore this new area to validate the findings reported here and support the authors' theoretical interpretation.
Incidental Pathologic Findings in Young Men with Gynecomastia
Authors: Maroney Jenna C. , Dannheim Katelyn , Hollowell Monica L. , Labow Brian I. , Rogers-Vizena Carolyn R.
Published: February 2022

Background:

Pathologic examination of young adult gynecomastia tissue is controversial given the low incidence of breast carcinoma in this population. The authors examined the pathologic findings in a large cohort of adolescents with gynecomastia to evaluate the need for routine tissue analysis in this population.

Methods:

A retrospective review of men who underwent unilateral or bilateral mastectomy for gynecomastia at a single institution between February of 2007 and November of 2019 identified demographics, medical history, surgical characteristics, and pathologic findings. Descriptive statistics were performed.

Results:

A total of 268 male patients were included. Mean age was 16.6 years. Mean body mass index was 27.8 kg/m2, and 42.5 percent of the sample was obese. The majority (83.2 percent) underwent bilateral subcutaneous mastectomy. There were no abnormal histopathologic findings in 95.1 percent. Among the 13 patients with abnormalities, eight (3 percent) had nonproliferative changes, two (0.8 percent) had proliferative changes without atypia, two (0.8 percent) had atypical ductal hyperplasia, and one (0.4 percent) had both bilateral atypical ductal hyperplasia and unilateral ductal carcinoma in situ. No patients had invasive carcinoma. The three patients with atypical ductal hyperplasia and/or ductal carcinoma in situ were obese but had no other breast cancer or gynecomastia risk factors.

Conclusions:

Findings conferring potentially increased risk of developing breast cancer were identified in three male adolescents (1.2 percent). Incidence of these findings is similar between male adolescents and similarly aged female adolescents undergoing breast reduction surgery. Although worrisome pathology results are rare, too little is known about the natural history of atypical proliferation and ductal carcinoma in situ in young men to recommend against routine analysis.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, IV.
Aromatase Inhibitor–Induced Carpal Tunnel Syndrome and Stenosing Tenosynovitis: A Systematic Review
Authors: Chung Karen Y. , Ho George , Novak Christine B. , Baltzer Heather L.
Published: February 2022

Background:

Although aromatase inhibitors are the first-line treatment in postmenopausal women with hormone receptor–positive breast cancer, there is increasing evidence that they can induce carpal tunnel syndrome and stenosing tenosynovitis. This systematic review summarizes the risk factors, incidence, and management for patients with aromatase inhibitor–induced carpal tunnel syndrome and stenosing tenosynovitis compared to tamoxifen or placebo.

Methods:

A Preferred Reporting Items for Systematic Reviews and Meta-Analyses–guided systematic review of PubMed/MEDLINE, Ovid Embase, and the Cochrane Central Register of Controlled Trials was conducted (to March 19, 2020), supplemented with Google Scholar, Plastic and Reconstructive Surgery, and The Journal of Hand Surgery. Two reviewers independently completed the primary and secondary screens and the quality appraisal.

Results:

This study reviewed 577 abstracts and included 19 studies. Risk factors for aromatase inhibitor–induced carpal tunnel syndrome or stenosing tenosynovitis included hormone replacement therapy before trial entry, history of musculoskeletal symptoms, age younger than 60 years, prior chemotherapy, and body mass index greater than 25 kg/m2. The incidence can be increased up to 10 times compared to tamoxifen. Patient discontinuation of aromatase inhibitor treatment because of carpal tunnel syndrome and stenosing tenosynovitis was reported. Nonsurgical management led to complete resolution of carpal tunnel syndrome symptoms in up to 67 percent of cases. Although most aromatase inhibitor–induced stenosing tenosynovitis original studies were low quality, all recommended surgical release for symptom resolution.

Conclusions:

This study provides current knowledge of the associated risk factors, management options, and quality of literature for aromatase inhibitor–induced carpal tunnel syndrome and stenosing tenosynovitis. Early recognition can prevent self-discontinuation of an aromatase inhibitor and long-term sequelae of poorly treated carpal tunnel syndrome and stenosing tenosynovitis.
Surgical and Nonsurgical Factors Associated with Salvaging Exposed Vertical Expandable Prosthetic Titanium Rib Hardware
Authors: Kalmar Christopher L. , Zapatero Zachary D. , Lott Carina , Kosyk Mychajlo S. , Cahill Patrick J. , Swanson Jordan W. , Anari Jason B. , Taylor Jesse A.
Published: February 2022

Background:

Vertical expandable prosthetic titanium rib (VEPTR) devices were designed to treat childhood scoliosis and thoracic insufficiency syndrome. Although they have drastically reduced patient mortality, they present a profound subcutaneous hardware burden. The authors examined the surgical and nonsurgical factors associated with salvage of VEPTR hardware exposures.

Methods:

Between 2014 and 2020, a prospective institutional database was queried for patients with VEPTR hardware complications who required soft-tissue reconstruction. Hardware salvage was considered successful if reconstruction allowed the hardware to be retained until the next VEPTR expansion.

Results:

Fifty-eight patients required VEPTR hardware salvage. Hardware complications were successfully salvaged in 62.1 percent of patients at 60.0 percent of operative sites. Neuromuscular scoliosis (p = 0.041) and nonambulatory status (p = 0.018) were factors associated with VEPTR hardware salvage failure, whereas congenital scoliosis was associated with successful hardware salvage (p = 0.012) and preventing need for immediate hardware removal (p = 0.049). Exposed hardware, as compared to threatened exposure, was more likely to require immediate removal (p = 0.045) and result in unsuccessful hardware salvage (p = 0.015).

Conclusions:

Local and regional muscle flaps were able to prevent VEPTR hardware removal in the majority of patients, even in the setting of infection, immobility, incontinence, and multiple systemic comorbidities. Patients with neuromuscular scoliosis and nonambulatory status were at increased risk for failure, whereas those with incontinence and low body mass index trended toward increased risk of failure. Threatened exposure was associated with higher rates of salvage than exposed hardware, and thus earlier referral to plastic surgeons for soft-tissue salvage may be advised.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Hybrid Prepectoral Direct-to-Implant and Autologous Fat Graft Simultaneously in Immediate Breast Reconstruction: A Single Surgeon’s Experience with 25 Breasts in 15 Consecutive Cases
Authors: Gronovich Yoav , Winder Gilad , Maisel-Lotan Adi , Lysy Ido , Sela Elad , Spiegel Gilad , Carmon Moshe , Hadar Tal , Elami Anat , Eizenman Nirit , Binenboym Rami
Published: February 2022

Background:

The direct-to-implant method depends on the quality of the mastectomy flaps and can be used only when the flaps are adequately perfused. Even though the method was designed to be a definitive reconstruction procedure, it has been associated with an increased likelihood that additional operative revision will be required in order to achieve the expected final cosmetic outcome. The authors describe a hybrid prepectoral direct-to-implant method that combines autologous fat grafting in the superior medial pole with immediate reconstruction.

Methods:

In this prospective study, 15 patients (25 reconstructed breasts) underwent simultaneous hybrid prepectoral direct-to-implant reconstruction together with autologous fat grafting performed by a single senior plastic surgeon (Y.G).

Results:

The mean quantity of autologous fat grafted in the superior medial aspect of the breast was 59.4 ± 12.8 cc. The mean total volume of the hybrid reconstructed breast, including implant and autologous fat graft, was 497.2 ± 89.1 cc. Satisfying final outcomes were achieved in all cases. There were no major complications, although minor complications were observed.

Conclusions:

The authors’ hybrid approach allows the surgeon to achieve a more satisfying outcome with regard to the cleavage area. It results in a better natural appearance, an improved contour, and reduced upper pole rippling and deflation, with a lower likelihood that an additional operative revision will be required to achieve the desired final aesthetic outcome. The authors believe that their hybrid approach should be implemented as an integral part of the direct-to-implant prepectoral reconstruction procedure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
The Business of Employed Plastic Surgery: Creating Your Seat at the Table
Authors: Ellsworth Warren A. , Gratzon Andrew C. , Friedman Jeffrey D.
Published: February 2022

Background:

While the landscape of medicine changes, hospital employment continues to gain popularity in surgical specialties. The number of plastic surgeons entering an employed relationship has also grown, offering new opportunities and challenges alike. The authors studied the profitability of plastic surgery to the hospital and the necessity of the specialty to hospital administration through financial net revenue, contribution margin, and payer mix, to help plastic surgeons realize and capitalize on their importance and contribution to the hospital system.

Methods:

Facility net revenue and contribution margin from Houston Methodist West Hospital were evaluated. Average net revenue and contribution margin for inpatient and outpatient cases for plastic surgery, orthopedic surgery, and all combined surgical specialties were studied for the 2018 and 2019 fiscal years.

Results:

The authors demonstrated net increase per year for both outpatient and inpatient revenue in favor of plastic surgery versus orthopedics and combined surgical specialties. Plastic surgery contributed higher facility net revenue when compared to orthopedics, contributing 20 percent more per outpatient case and 86 percent more per inpatient case. A higher contribution margin for each year was realized for inpatient cases versus orthopedics and combined surgical specialties, increasing by 8 percent and 53 percent and 61 percent and 86 percent, respectively.

Conclusions:

A surgeon’s ability to present objective financial data and develop leadership roles within the hospital system can lead to a favorable outcome for both physician and hospital. An objective dialogue with hospital administration is critical and offers an avenue to negotiate the development of your practice.
Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis
Authors: Verhoeff Kevin , Raffael Kendra , Connell Matthew , Kung Janice Y. , Strickland Matt , Parker Arabesque , Anantha Ram V.
Published: February 2022

BACKGROUND

Trauma patients have simultaneously high venous thromboembolism (VTE) and bleeding risk. Optimal chemoprophylaxis regimens remain unclear. This study aims to answer three questions for trauma patients. Is there any association between anti-Xa and VTE? Does dose adjustment improve prophylactic anti-Xa rates? Does dose adjustment improve anti-Xa adequacy and VTE compared with standard dosing?

METHODS

Systematic search of MEDLINE, Embase, Scopus, and Web of Science occurred in May 2021. Two author reviews included trauma studies that evaluated low molecular weight heparin chemoprophylaxis, reported anti-Xa level, and evaluated more than one outcome. Data were dually extracted and estimated effects were calculated using RevMan 5.4 applying the Mantel-Haenszel method. Analysis 1 compared patients with peak anti-Xa of 0.2 IU/mL or greater or trough 0.1 IU/mL or greater to those with lower anti-Xa using VTE as the primary outcome. Analysis 2 reported the effect of dose adjustment on anti-Xa. Analysis 3 compared standard dosing to dose adjustment with the primary outcome being anti-Xa adequacy; secondary outcomes were VTE, pulmonary embolism, and bleeding complications.

RESULTS

There were 3,401 studies evaluated with 24 being included (19 retrospective studies, 5 prospective studies). In analysis 1, achieving adequate anti-Xa was associated with reduced odds of VTE (4.0% to 3.1%; odds ratio [OR], 0.52; p = 0.03). Analysis 2 demonstrated that 768 (75.3%) patients achieved prophylactic anti-Xa with adjustment protocols. Analysis 3 suggested that dose-adjusted chemoprophylaxis achieves prophylactic anti-Xa more frequently (OR, 4.05; p = 0.007) but without VTE (OR, 0.72; p = 0.15) or pulmonary embolism (OR, 0.48; p = 0.10) differences. In subgroup analysis, anti-Xa dose adjustment also suggested no VTE reduction (OR, 0.68; p = 0.08).

CONCLUSION

Patients with higher anti-Xa levels are less likely to experience VTE, and anti-Xa guided chemoprophylaxis increases anti-Xa adequacy. However, dose adjustment, including anti-Xa guided dosing, may not reduce VTE.

LEVEL OF EVIDENCE

Systematic Review Meta-Analysis, Level IV.
Effectiveness of Atomoxetine (Strattera) for the Treatment of Poststroke Aphasia Combined With Cognitive Impairment
Authors: Park Jong Mi , Choi Soojin , Kim Yong Wook
Published: February 2022

Objective

In this study, we aimed for the first time to evaluate the effectiveness of atomoxetine (Strattera) in the treatment of cognitive impairment and aphasia after stroke in a large sample.

Methods

We reviewed the data of 106 patients with poststroke aphasia and cognitive impairment (atomoxetine treatment group = 55 patients vs control group = 51 patients), including scores of the Korean version of the Mini-Mental State Examination (K-MMSE) and the Korean version of the Western Aphasia Battery. Wilcoxon signed-rank tests were used to compare the initial and follow-up K-MMSE and Korean version of the Western Aphasia Battery scores. Mann-Whitney U tests were used to compare the degree of improvement in K-MMSE and Aphasia Quotient (AQ) scores between the atomoxetine and control groups.

Results

Baseline characteristics including age, years of education, and scores of the initial Functional Independence Measure, Korean version of the Modified Barthel Index, Hamilton Depression Rating Scale, K-MMSE, and AQ did not differ significantly between the 2 groups. Follow-up K-MMSE and AQ scores were significantly better than the initial scores in both the treatment and control groups. However, improvements in K-MMSE scores were significantly greater in the treatment group than in the control group. In addition, the atomoxetine group had significantly higher AQ scores than the control group, especially for auditory verbal comprehension and naming.

Conclusions

Atomoxetine has been shown to significantly improve cognitive function and language in patients with poststroke aphasia. It is also the first study to report improvement in auditory comprehension and naming by administration of atomoxetine.
Metronidazole-Induced Toxic Neuropathy With the “Boomerang” Sign
Authors: Ghosh Ritwik , Chatterjee Subhankar , Dubey Mahua Jana , Dubey Souvik , Benito-León Julián
Published: February 2022

Background

Metronidazole has been used to treat a broad range of infections over the decades, and its safety profile has been presumably well studied. However, neurological severe adverse events after prescription and nonprescription use of metronidazole is well recognized but underdiagnosed.

Case Presentation

We report the case of a 48-year-old Indian man who presented with unremitting symptoms of peripheral neuropathy along with a silent callosal lesion in the splenium (“boomerang” sign). Because he had visited 3 neurologists previously, there were many targeted and nontargeted investigations, which failed to reach an etiological diagnosis and hence to provide relief. The patient was questioned about a potential neurotoxin exposure, and at this point, he said that he was taking metronidazole for a long time, without any supervision, as an over-the-counter remedy for self-diagnosed “chronic amebiasis.” On stopping metronidazole, he recovered gradually. In the sixth month of follow-up, brain magnetic resonance imaging showed disappearance of the callosal lesion and significant improvement in the nerve conduction studies.

Conclusions

Clinicians should keep metronidazole toxicity in mind while dealing with a case of cytotoxic lesion of the corpus callosum with splenium involvement and peripheral neuropathy.
Mechanisms of Entry Into the Central Nervous System by Neuroinvasive Pathogens
Authors: Valizadeh Navid , Rudmann Emily A. , Solomon Isaac H. , Mukerji Shibani S.
Published: February 2022

Background:

The literature on neurological manifestations, cerebrospinal fluid analyses, and autopsies in patients with COVID-19 continues to grow. The proposed mechanisms for neurological disease in patients with COVID-19 include indirect processes such as inflammation, microvascular injury, and hypoxic-ischemic damage. An alternate hypothesis suggests direct viral entry of SARS-CoV-2 into the brain and cerebrospinal fluid, given varying reports regarding isolation of viral components from these anatomical sites.

Evidence Acquisition:

PubMed, Google Scholar databases, and neuroanatomical textbooks were manually searched and reviewed.

Results:

We provide clinical concepts regarding the mechanisms of viral pathogen invasion in the central nervous system (CNS); advances in our mechanistic understanding of CNS invasion in well-known neurotropic pathogens can aid in understanding how viruses evolve strategies to enter brain parenchyma. We also present the structural components of CNS compartments that influence viral entry, focusing on hematogenous and transneuronal spread, and discuss this evidence as it relates to our understanding of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).

Conclusions:

Although there is a paucity of data supporting direct viral entry of SARS-CoV-2 in humans, increasing our knowledge of the structural components of CNS compartments that block viral entry and pathways exploited by pathogens is fundamental to preparing clinicians and researchers for what to expect when a novel emerging virus with neurological symptoms establishes infection in the CNS, and how to design therapeutics to mitigate such an infection.
Biocompatible, photo-responsive layer-by-layer polymer nanocapsules with an oil core:
in vitro
and
in vivo
study
Authors: Di Cicco Chiara , Vecchione Raffaele , Quagliariello Vincenzo , Busato Alice , Tufano Immacolata , Bedini Emiliano , Gerosa Marco , Sbarbati Andrea , Boschi Federico , Marzola Pasquina , Maurea Nicola , Netti Paolo A.
Published: February 2022

In cancer therapy, stimulus-responsive drug delivery systems are of particular interest for reducing side effects in healthy tissues and improving drug selectivity in the tumoral ones. Here, a strategy for the preparation of a photo-responsive cross-linked trilayer deposited onto an oil-in-water nanoemulsion via a layer-by-layer technique is reported. The system is made of completely biocompatible materials such as soybean oil, egg lecithin and glycol chitosan, with heparin as the polymeric shell. The oil core is pre-loaded with curcumin as a model lipophilic active molecule with anti-tumoral properties. The trilayer cross-linkage is performed via a photoinitiator-free thiol-ene ‘click’ reaction. In particular, the system is implemented with an
o
-nitrobenzyl group functionalized with a thiol moiety which can perform both the thiol-ene ‘click’ reaction and the cleavage meant for controlled drug release at two different wavelengths, respectively. So the preparation and characterization of a photo-responsive natural nanocarrier (PNC) that is stable under physiological conditions owing to the thiol-ene cross-linkage are reported. PNC performance has been assessed
in vitro
on melanoma cells as well as
in vivo
on xenograft tumour-induced mice.
Cation-doping strategies for tuning of zirconia acid–base properties
Authors: Delarmelina Maicon , Catlow C. Richard A.
Published: February 2022

The role of Y-, Ca- and Ce-doping of cubic zirconia (c-ZrO
2
) (111) surface on its acidity, basicity and the interplay between surface acid–base pairs is investigated by computational methods. The most stable surface structures for this investigation were initially determined based on previous studies of Y-doped c-ZrO
2
(111) and by a detailed exploration of the most stable configuration for Ca-doped c-ZrO
2
(111) and Ce-doped c-ZrO
2
(111). Next, surface mapping by basic probe molecules (NH
3
and pyridine) revealed a general reduction of the acidity of the surface sites, although a few exceptions were observed for zirconium ions at next nearest neighbour (NNN) positions to the oxygen vacancy and at the nearest neighbour (NN) position to the dopants. Adsorption of CO
2
over basic sites revealed a cooperative interplay between acid–base groups. In this case, the overall effect observed was the decrease of the calculated adsorption energies when compared with the pristine surface. Moreover, spontaneous formation of
η
3
-CO
2
systems from initial
η
2
-CO
2
configurations indicates a decrease in the required energy for forming oxygen vacancies in the doped ZrO
2
systems at NNN positions or further away from the existing vacancy site.
The topological origin of the Peierls–Nabarro barrier
Authors: Hocking Brook J. , Ansell Helen S. , Kamien Randall D. , Machon Thomas
Published: February 2022

Crystals and other condensed matter systems described by density waves often exhibit dislocations. Here we show, by considering the topology of the ground state manifolds (GSMs) of such systems, that dislocations in the density phase field always split into disclinations, and that the disclinations themselves are constrained to sit at particular phase values in the GSM. This constraint on the location of the disclinations results in an energy barrier to dislocation glide. Consequently, the topology of the GSM alone gives rise to a Peierls–Nabarro barrier.
Ecosystem engineer morphological traits and taxon identity shape biodiversity across the euphotic–mesophotic transition
Authors: Voerman Sofie E. , Marsh Beauregard C. , Bahia Ricardo G. , Pereira-Filho Guilherme H. , Yee Thomas W. , Becker Ana Clara F. , Amado-Filho Gilberto M. , Ruseckas Arvydas , Turnbull Graham A. , Samuel Ifor D. W. , Burdett Heidi L.
Published: February 2022

The euphotic–mesophotic transition is characterized by dramatic changes in environmental conditions, which can significantly alter the functioning of ecosystem engineers and the structure of their associated communities. However, the drivers of biodiversity change across the euphotic–mesophotic transition remain unclear. Here, we investigated the mechanisms affecting the biodiversity-supporting potential of free-living red coralline algae—globally important habitat creators—towards mesophotic depths. Across a 73 m depth gradient, we observed a general decline in macrofaunal biodiversity (fauna abundance, taxon richness and alpha diversity), but an increase in beta-diversity (i.e. variation between assemblages) at the deepest site (86 m depth, where light levels were less than 1% surface irradiance). We identified a gradient in abundance decline rather than distinct ecological shifts, driven by a complex interaction between declining light availability, declining size of the coralline algal host individuals and a changing host taxonomy. However, despite abundance declines, high between-assemblage variability at deeper depths allowed biodiversity-supporting potential to be maintained, highlighting their importance as coastal refugia.
Postnatal expression of
IGF2
is the norm in amniote vertebrates
Authors: Beatty Abby , Rubin Alexander M. , Wada Haruka , Heidinger Britt , Hood Wendy R. , Schwartz Tonia S.
Published: February 2022

The insulin and insulin-like signalling (IIS) network plays an important role in mediating several life-history traits, including growth, reproduction and senescence. Although insulin-like growth factors (IGFs) 1 and 2 are both key hormones in the vertebrate IIS network, research on IGF2 in juveniles and adults has been largely neglected because early biomedical research on rodents found negligible IGF2 postnatal expression. Here, we challenge this assumption and ask to what degree IGF2 is expressed during postnatal life across amniotes by quantifying the relative gene expression of
IGF1
and
IGF2
using publicly available RNAseq data for 82 amniote species and quantitative polymerase chain reaction on liver cDNA at embryonic, juvenile and adult stages for two lizard, bird and mouse species. We found that (i)
IGF2
is expressed postnatally across amniote species and life stages—often at a higher relative expression than
IGF1
, contradicting rodent models; (ii) the lack of rodent postnatal
IGF2
expression is due to phylogenetic placement, not inbreeding or artificial selection; and (iii) adult
IGF2
expression is sex-biased in some species. Our results demonstrate that
IGF2
expression is typical for amniotes throughout life, suggesting that a comprehensive understanding of the mechanisms mediating variation in life-history traits will require studies that measure both IGFs.
Emergence of kinship structures and descent systems: multi-level evolutionary simulation and empirical data analysis
Authors: Itao Kenji , Kaneko Kunihiko
Published: February 2022

In many indigenous societies, people are categorized into several cultural groups, or clans, within which they believe they share ancestors. Clan attributions provide certain rules for marriage and descent. Such rules between clans constitute kinship structures. Anthropologists have revealed several kinship structures. Here, we propose an agent-based model of indigenous societies to reveal the evolution of kinship structures. In the model, several societies compete. Societies themselves comprise multiple families with parameters for cultural traits and mate preferences. These values determine with whom each family cooperates and competes, and they are transmitted to a new generation with mutation. The growth rate of each family is determined by the number of cooperators and competitors. Through this multi-level evolution, family traits and preferences diverge to form clusters that can be regarded as clans. Subsequently, kinship structures emerge, including dual organization and generalized or restricted exchange, as well as patrilineal, matrilineal and double descent systems. These structures emerge depending on the necessity of cooperation and the strength of mating competition. Their dependence is also estimated analytically. Finally, statistical analysis using the Standard Cross-Cultural Sample, a global ethnographic database, empirically verified the theoretical results. Such collaboration between theoretical and empirical approaches will unveil universal features in anthropology.
An Analysis Between Trump’s Presidency and Health-Seeking Behaviors of African Americans in the United States
Authors: Animasahun Adeola A. , Nunez Ashley M. , Jean Rachelle F.
Published: February 2022

Background

Slavery legally ended over 150 years ago, yet African Americans are still oppressed. The lingering effects of systemic and institutional racism are still present in all walks of life, especially in healthcare. As a result, Black patients have historically been less likely to seek preventative care and subsequently, reported lower health outcomes compared to their white counterparts. The election of Donald Trump in 2016 forced a shift in that narrative. This study aimed to investigate whether there was any correlation between changing racial preferences fueled by Trump’s racist rhetoric and the health-seeking behaviors of Black patients. Through this, we explored if the number of Black patients that reported not having a primary care physician has changed, and how online search history trends researching Black physicians have also changed.

Methods

This study utilized datasets from the Behavioral Risk Factor Surveillance System (BRFSS) and Google Trends. Pearson’s correlation testing was run to establish any correlation between the number of google searches and positive health-seeking behaviors.

Results

GoogleTrends data does support an increased popularity for the search term “black doctor near me” over the years of 2015-2018, supporting our hypothesis. Multiple logistic regression analysis was performed to determine if race, among other variables, was a significant predictor for our predetermined health indicators. The results showed race was significant in nine out of our eleven health indicators.

Discussion

Despite decades of work to minimize healthcare disparities, this study has demonstrated how much more still needs to be done. It has shown how the intersection of seemingly unrelated issues, such as politics and health, as described in this study, can drastically impact health outcomes. This study highlights the importance of targeted and equitable programming to ensure quality care for all, that can withstand political and social pressures.
High-resolution lung adenocarcinoma expression subtypes identify tumors with dependencies on MET, CDK4, CDK6, and PD-L1
Authors: Roh Whijae , Geffen Yifat , Miller Mendy , Anand Shankara , Kim Jaegil , Heiman David , Gainor Justin F. , Laird Peter W. , Cherniack Andrew D. ,   National Cancer Institute Center for Cancer Genomics Tumor Molecular Pathology (TMP) Analysis Working Group, Getz Gad
Published: February 2022

Lung adenocarcinoma is one of the most common cancer types with various treatment modalities. However, better biomarkers to predict therapeutic response are still needed to improve precision medicine. We utilized a consensus hierarchical clustering approach on 509 LUAD cases from TCGA to identify five robust LUAD expression subtypes. We then integrated genomic (patient and cell line) and proteomic data to help define biomarkers of response to targeted therapies and immunotherapies. This approach defined subtypes with unique proteogenomic and dependency profiles. S4-associated cell lines exhibited specific vulnerability to CDK6 and CDK6-cyclin D3 complex gene, CCND3. S3 was characterized by dependency on CDK4, immune-related expression patterns, and altered MET signaling; experimental validation showed that S3-associated cell lines responded to MET inhibitors, leading to increased PD-L1 expression. We further identified genomic features in S3 and S4 as biomarkers for enabling clinical diagnosis of these subtypes. Overall, our consensus hierarchical clustering approach identified robust tumor expression subtypes, and our subsequent integrative analysis of genomics, proteomics, and CRISPR screening data revealed subtype-specific biology and vulnerabilities. Our lung adenocarcinoma expression subtypes and their biomarkers could help identify patients likely to respond to CDK4/6, MET, or PD-L1 inhibitors, potentially improving patient outcome.

Significance

Through integrative analysis of genomic, proteomic, and drug dependency data, we identified robust lung adenocarcinoma expression subtypes and found subtype-specific biomarkers of response, including CDK4/6, MET, and PD-L1 inhibitors.
Cell-Mediated Immune Response after COVID 19 Vaccination in Patients with Inflammatory Bowel Disease
Authors: Caldera Freddy , Farraye Francis A. , Necela Brian M. , Cogen Davitte , Saha Sumona , Wald Arnold , Daoud Nader D. , Chun Kelly , Grimes Ian , Lutz Megan , Swift Melanie D. , Virk Abinash , Bharucha Adil E. , Patel Tushar C. , Gores Gregory J. , Chumsri Saranya , Hayney Mary S. , Knutson Keith L.
Published: February 2022

Introduction

Most patients with IBD mount an antibody response to mRNA COVID-19 vaccines, but few studies have evaluated the cell mediated immune response (CMIR).

Methods

We performed a prospective study (HERCULES) to evaluate CMIR among patients with IBD and healthy controls (HC) after completion of the primary series of mRNA COVID-19 vaccines.

Results

One hundred 158 patients with IBD and 20 HC were enrolled. The majority (89%) of IBD patients developed a CMIR which was not different than HC (94%, p=0.6667). There was no significant difference (p=0.5488) in CMIR response between those not immunosuppressed (median 255 Spike T cells/million PBMC, IQR 146, 958) and immunosuppressed (median 377, IQR 123, 1440). There was also no correlation between antibody responses and CMIR (p=0.5215)

Discussion

Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.
Hypomethylation of miR-17-92 cluster in lupus T cells and no significant role for genetic factors in the lupus-associated DNA methylation signature
Authors: Coit Patrick , Roopnarinesingh Xiavan , Ortiz-Fernandez Lourdes , Maksimowicz-McKinnon Kathleen , Lewis Emily E. , Merrill Joan T. , McCune W. Joseph , Wren Jonathan D. , Sawalha Amr H.
Published: February 2022

Objectives

Epigenetic dysregulation plays an important role in the pathogenesis of lupus, a systemic autoimmune disease characterized by autoantibody production. Lupus T cells demonstrate aberrant DNA methylation patterns dominated by hypomethylation of interferon-regulated genes. The objective of this study was to identify additional disease-associated DNA methylation changes in naïve CD4+ T cells from an extended cohort of lupus patients and determine the genetic contribution to epigenetic changes characteristic of lupus.

Methods

Genome-wide DNA methylation was assessed in naïve CD4+ T cells isolated from a cohort of 74 lupus patients and 74 age-, sex-, and race-matched healthy controls. We applied a trend deviation analysis approach, comparing methylation data in our cohort to methylation data from over 16,500 samples to characterize lupus-associated DNA methylation patterns. Methylation quantitative trait loci (meQTL) analysis was used to determine genetic contribution to lupus-associated DNA methylation changes.

Results

In addition to the previously reported epigenetic signature in interferon-regulated genes, we observed hypomethylation of the promoter regions of microRNA (miRNA) genes in the miR-17-92 cluster in lupus patients. Members of this miRNA cluster play an important role in regulating T cell proliferation and differentiation. Expression of two miRNAs within this cluster, miR-19b1 and miR-18a, showed a significant positive correlation with disease activity in lupus patients. meQTL were identified by integrating genome-wide DNA methylation profiles with genotyping data in lupus patients and controls. Patient meQTL show overlap with genetic risk loci for lupus. However, less than 1% of differentially methylated CpG sites in lupus patients were associated with an meQTL, suggesting minimal genetic contribution to lupus-associated epigenotypes.

Conclusion

The lupus defining epigenetic signature, characterized by robust hypomethylation of interferon-regulated genes, does not appear to be determined by genetic factors. Hypomethylation of the miR-17-92 cluster that plays an important role in T cell activation is a novel epigenetic locus for lupus.
Prepronociceptin-expressing neurons in the extended amygdala signal darting away from an aversive odor
Authors: Ung Randall L. , Ortiz-Juza Maria M. , Curtis Vincent R. , Alghorazi Rizk A. , Velazquez-Hernandez Geronimo , Ring Ayden , Garcia-Reyes Ruben A. , Stuber Garret D. , Zhou Pengcheng , Kato Hiroyuki K. , Pégard Nicolas C. , Rodriguez-Romaguera Jose
Published: February 2022

Dysregulation in the neural circuitry that encodes physiological arousal responses is thought to contribute to the manifestation of the maladaptive behaviors observed in neuropsychiatric disorders. We previously found that prepronociceptin-expressing neurons in the bed nucleus of the stria terminalis (PnocBNST neurons) modulate rapid changes in physiological arousal upon presentation of motivationally salient stimuli (Rodriguez-Romaguera et al., 2020). However, whether PnocBNST neurons are necessary to regulate behavioral actions to motivationally salient stimuli is still unknown. Here, we investigated the role of PnocBNST neurons in encoding behavioral responses to motivationally salient stimuli using in vivo calcium imaging and optogenetic approaches in freely behaving mice. We find that the bulk activity of PnocBNST neurons increases when mice are near an aversive odor in comparison to a rewarding odor. However, optogenetic inhibition of PnocBNST neurons does not affect the amount of time mice spend near an aversive odor. Further analysis revealed that a subgroup of PnocBNST neurons that correlate with proximity to the aversive odor also correlate to darting away from the same aversive odor. Since these two behaviors are opposite to each other and since we previously found PnocBNST neurons correlate with arousal responses, we believe these results may be due in part to the encoding of arousal responses that occur when mice approach and dart away from aversive stimuli.
Deciphering the tissue-specific regulatory role of intronless genes across cancers
Authors: Aviña-Padilla Katia , Ramírez-Rafael José Antonio , Herrera-Oropeza Gabriel Emilio , Romero Guillermo , Zambada-Moreno Octavio , Gupta Ishaan , Hernández-Rosales Maribel
Published: February 2022

Intronless genes (IGs) or single-exon genes lacking an intron are found across most Eukaryotes. Notably, IGs display a higher transcriptional fidelity as they are not regulated through alternative splicing, suggesting better predictability biomarkers and easier regulation as targets for therapy.Canceris a complex disease that relies on progressive uncontrolled cell division linked with multiple dysfunctional biological processes. Tumor heterogeneity remains the most challenging feature in cancer diagnosis and treatment. Given the clinical relevance of IGs, we aim to identify their unique expression profiles and interactome, that may act as functional signatures across eight different cancers. We identified 940 protein-coding IGs in the human genome, of which about 35% were differentially expressed across the analyzed cancer datasets. Specifically, ∼78% of differentially expressed IGs were undergoing transcriptional reprogramming with elevated expression in tumor cells. Remarkably, in all the studied tumors, a highly conserved induction of a group of deacetylase-histones located in a region of chromosome 6 enriched in nucleosome and chromatin condensation processes. This study highlights that differentially expressed human intronless genes across cancer types are prevalent in epigenetic regulatory roles participating in specific PPI networks for ESCA, GBM, and LUAD tumors. We determine that IGs play a key role in the tumor phenotype at transcriptional and post-transcriptional levels, with important mechanisms such as interactomics rewiring.
Honey bees change the microbiota of pollen
Authors: Prado Alberto , Barret Matthieu , Vaissière Bernard E. , Torres-Cortes Gloria
Published: February 2022

Pollen, as all other plant tissues, harbors different microorganisms. As honey bees (Apis mellifera) collect and pack pollen they add regurgitated nectar to moisten and glue the pollen grains, possibly changing the microbial composition. In this study, we compared the microbiota of cleanBrassica napuspollen with that of bee-worked corbicular pollen. We found that by working pollen, bees increase the bacterial diversity of pollen, by adding honey bee symbionts such asBombella, Frischella, GilliamellaandSnodgrassella, bee pathogens asSpiroplasmaand nectar dwellingLactobacillusto the new pollen microbiota. The bee gut is an important source of inoculum of the corbicular pollen microbiota. We discuss the implications of these findings and propose future research avenues.
Antibacterial effects of propolis and brood comb extracts on the causative agent of European Foulbrood (Melissococcus plutonius) in honey bees (Apis mellifera)
Authors: Murray Stephanie K. , Kurkul Colin M. , Mularo Andrew J. , Hale Vanessa L. , Adams Rachelle M. M. , Johnson Reed M.
Published: February 2022

Among a long list of parasites and pathogens that threaten the European honey bee (Apis mellifera), European Foulbrood (EFB) has become an urgent apiary disease, as epidemic outbreaks are becoming increasingly common. EFB is a bacterial disease of larval honey bees, caused by a gram-positive, anaerobic bacterium,Melissococcus plutonius. The most effective current treatment for EFB, oxytetracycline hydrochloride, can disrupt the bee microbiome, cause bee mortality and residues may persist in honey harvested for human consumption. In this study, we explore the efficacy of more sustainable bee-derived solutions, including propolis, honey comb and brood comb ethanol extracts. Using a series of dilutions of these extracts, we determined the minimum inhibitory concertation (MIC) of each bee-derived product onM. plutonius, as well as two model bacterial species,Staphylococcus saprophyticus(gram-positive) andEscherichia coli(gram-negative). Overall, we found that propolis extract was most effective at inhibiting growth of gram-positive bacteria, and thatM. plutoniouswas also susceptible to honey comb (MIC = 16.00 mg/mL) and brood comb (MIC = 45.33 mg/mL) extracts, but at much higher concentrations than that of propolis (MIC = 1.14 mg/mL).
Different transcriptional responses by the CRISPRa system in distinct types of heterochromatin in Drosophila melanogaster
Authors: Ortega-Yáñez Andrea , Cruz-Ruiz Samantha , Vázquez Martha , Zurita Mario
Published: February 2022

Transcription factors (TFs) activate gene expression by binding to elements close to promoters or enhancers. Some TFs can bind to heterochromatic regions to initiate gene activation, suggesting that if a TF is able to bind to any type of heterochromatin, it can activate transcription. To investigate this possibility, we used the CRISPRa system based on dCas9-VPR as an artificial TF in Drosophila. dCas9-VPR was targeted to the TAHRE subtelomeric element, an example of constitutive heterochromatin, and to promoters and enhancers of the HOX Ultrabithorax (Ubx) and Sex Combs Reduced (Scr) genes in the context of facultative heterochromatin. dCas9-VPR robustly activated TAHRE transcription, showing that although this element is heterochromatic, dCas9-VPR was sufficient to activate its expression. In the case of HOX gene promoters, although these genes are epigenetically silenced by Polycomb complexes, both were ectopically activated. When the artificial TF was directed to enhancers, we found that the expression pattern was different compared to the effect on the promoters. In the case of the Scr upstream enhancer, dCas9-VPR activated the gene ectopically but with less expressivity; however, ectopic activation also occurred in different cells. In the case of the bxI enhancer located in the third intron of Ubx, the presence of dCas9-VPR is capable of increasing transcription initiation while simultaneously blocking transcription elongation, generating a lack of functional phenotype. Our results show that transcription can be activated in any type of heterochromatin by CRISPRa; nevertheless, its effect on transcription is subject to the intrinsic characteristics of each gene or regulatory element.

Significance

Whether transcription only depends on activating factors binding to chromatin, even though it is found in a silent state as heterochromatin, remains an open question. In this work, we addressed this question using the CRISPRa system via dCas9-VPR as a synthetic transcriptional activator in Drosophila. This activator was directed to a constitutive heterochromatin element and to promoters and enhancers of two HOX genes, which in the tissues where they are not expressed, are present as facultative heterochromatin. In all cases, the CRISPRa system was able to activate transcription, showing that its sole presence is sufficient for this to occur. Although transcription in constitutive heterochromatin was very robust, in the case of promoters and enhancers of HOX genes, the degree of expressivity, penetrance and ectopic effect was different between promoters and enhancers. These results indicate that the presence of a synthetic activator can activate transcription by binding to transcriptional regulatory elements; however, its effect depends on the particular characteristics of each one. These results show how artificial transcription factors can be used to understand transcription regulation at the organismal level.
period Translation as a Core Mechanism Controlling Temperature Compensation in an Animal Circadian Clock
Authors: Itoh Taichi Q. , Yildirim Evrim , Surabhi Satya , Braun Rosemary , Allada Ravi
Published: February 2022

The most enigmatic of the canonical properties of circadian clocks is temperature compensation where circadian period length is stable across a wide temperature range despite the temperature dependence of most biochemical reactions. While the core mechanisms of circadian clocks have been well described, the molecular mechanisms of temperature compensation are poorly understood especially in animals. A major gap is the lack of temperature compensation mutants that do not themselves unambiguously affect the temperature dependence of the encoded protein. Here we show that null alleles of two genes encoding components of a complex important for translation of the core clock component period in circadian pacemaker neurons robustly alter the temperature dependence of circadian behavioral period length. These changes are accompanied by parallel temperature dependent changes in oscillations of the PER protein and are consistent with the model that these translation factors mediate the temperature-dependence of PER translation. Consistent with findings from modeling studies, we find that translation of the key negative feedback factor PER plays an instrumental role in temperature compensation.