bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics Associated With Survival in Surgically Nonresected Pancreatic Adenocarcinoma in the Military Health System
Authors: Eaglehouse Yvonne L. , Darmon Sarah , Gage Michele M. , Shriver Craig D. , Zhu Kangmin
Published: October 2023

Objectives:

Pancreatic cancer is often diagnosed at advanced stages with high-case fatality. Many tumors are not surgically resectable. We aimed to identify features associated with survival in patients with surgically nonresected pancreatic cancer in the Military Health System.

Methods:

We used the Military Cancer Epidemiology database to identify the Department of Defense beneficiaries aged 18 and older diagnosed with a primary pancreatic adenocarcinoma between January 1998 and December 2014 who did not receive oncologic surgery as treatment. We used Cox Proportional Hazard regression with stepwise procedures to select the sociodemographic and clinical characteristics related to 2-year overall survival, expressed as adjusted hazard ratios (aHR) and 95% CIs.

Results:

Among 1148 patients with surgically nonresected pancreatic cancer, sex, race-ethnicity, marital status, and socioeconomic indicators were not selected in association with survival. A higher comorbidity count (aHR 1.30, 95% CI: 1.06-1.59 for 5 vs. 0), jaundice at diagnosis (aHR 1.57, 95% CI: 1.33-1.85 vs. no), tumor grade G3 or G4 (aHR 1.32, 95% CI: 1.05-1.67 vs. G1/G2), tumor location in pancreas tail (aHR 1.49, 95% CI: 1.22-1.83 vs. head) or body (aHR 1.30, 95% CI: 1.04-1.62 vs. head), and metastases were associated with survival. Patients receiving chemotherapy (aHR 0.66, 95% CI: 0.57-0.76) had better survival compared with no treatment.

Conclusions:

In a comprehensive health system, sociodemographic characteristics were not related to survival in surgically nonresected pancreatic cancer. This implicates access to care in reducing survival disparities in advanced pancreatic cancer and emphasizes the importance of treating patients based on clinical features.
Vascularized Fibular Epiphyseal Transfer for Pediatric Limb Salvage: Review of Applications and Outcomes
Authors: Lee Christine J. , Tiourin Ekaterina , Khoshab Nima , Leis Amber R. , Nassif Nader A. , Misaghi Amir , Vyas Raj M.
Published: October 2023

Vascularized fibular epiphyseal transfer (VFET) offers a functional advantage in pediatric limb salvage due to the preservation of growth potential and an articular surface for remodeling. This review summarizes the available evidence on the clinical characteristics and outcomes of pediatric reconstruction applying VFET at different recipient sites and with varying techniques. VFET was used to reconstruct the proximal humerus, distal radius or ulna, proximal femur, distal fibula, calcaneus, and mandible. Although most often harvested on the anterior tibial artery, VFET has also been performed using the peroneal artery, the inferior lateral genicular artery, and a dual pedicle. Recipient site flap inset most often involved fixation with plates and/or screws as well as soft tissue reconstruction using a retained slip of biceps femoris tendon. Outcomes included limb growth, range of motion, and strength. The most common reported complications were bone flap fracture and peroneal nerve palsy. The anterior tibial artery was the most applied pedicle with reliable limb growth, but with the added risk of postoperative peroneal palsy. Bone flap fracture most often occurred at the proximal humerus and femur recipient sites. Plate fixation and the combined use of allograft had lower instances of bone flap fracture. This review highlights how the anticipated dynamic growth and remodeling this free flap offers in the long term must be weighed against its complexity and potential complications.
Multiscale integrative analyses unveil immune-related diagnostic signature for the progression of MASLD
Authors: Bai Jing , Zhu Lun , Mi Wanqi , Gao Zhengzheng , Ouyang Minyue , Sheng Wanlu , Song Lin , Bao Lidao , Ma Yuheng , Xu Yingqi
Published: October 2023

Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease prevalent worldwide, with an increasing incidence associated with obesity, diabetes, and metabolic syndrome. The progression of MASLD to metabolic dysfunction–associated steatohepatitis (MASH) poses a pressing health concern, highlighting the significance of accurately identifying MASLD and its progression to MASH as a primary challenge in the field. In this study, a systematic integration of 66 immune cell types was conducted. Comprehensive analyses were performed on bulk, single-cell RNA-Seq, and clinical data to investigate the immune cell types implicated in MASLD progression thoroughly. Multiple approaches, including immune infiltration, gene expression trend analysis, weighted gene coexpression network analysis, and 4 machine learning algorithms, were used to examine the dynamic changes in genes and immune cells during MASLD progression. C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 have been identified as potential diagnostic biomarkers for MASLD progression. Furthermore, cell communication analysis at the single-cell level revealed that the involvement of C-X-C motif chemokine receptor 4 and dedicator of cytokinesis 8 in MASLD progression is mediated through their influence on T cells. Overall, our study identified vital immune cells and a 2-gene diagnostic signature for the progression of MASLD, providing a new perspective on the diagnosis and immune-related molecular mechanisms of MASLD. These findings have important implications for developing innovative diagnostic tools and therapies for MASLD.
Effects of Reiki on the Perception of Quality of Life Determined by the Questionnaire WHOQOL-BREF
Authors: Pereira Elisabete , Valente Caroline , Kretzschmar Morgana , Titton Calderari Mirele , Mendes de Cordova Caio Maurício
Published: October 2023

Reiki is a philosophy and healing technique that directs the use of vital energy (ki) for energy rebalance, as well as healing, in a holistic sense, of physical, emotional, mental, and spiritual processes. The practice is part of the integrative and complementary practices recognized by the World Health Organization. This study aimed to evaluate the Reiki effects on people's life quality perception, by using the World Health Organization Quality of Life-BREF (WHOQOL-BREF). We analyzed the answers of 144 individuals, and the data were categorized in quartiles according to the number of Reiki sessions attended. The results of each question and dimension of the questionnaire were analyzed by Student's t test (individual questions) and analysis of variance (dimensions). We observed significant improvement in the perception of physical pain, need for medical treatment, meaning of life, physical environment, availability of money, availability of information, locomotion, work capacity, access to health, place of residence, and transportation facilities. Reiki sessions have improved people's quality of life perception in many aspects, proving its therapeutic efficacy in a broader approach to health promotion.
The Influencing Factors of Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Sepsis: Analysis from a Large Database
Authors: Zhao Qing , Ma Yubao , Xiao Jianguo , Liu Hui
Published: October 2023

The neutrophil-to-lymphocyte ratio (NLR) is an important predictive prognostic tool. However, its accuracy for predicting sepsis remains debatable. This study aimed to evaluate the factors influencing the ability of NLR to predict sepsis. Adult patients with sepsis or septic shock from the eICU database were enrolled in this study. Results showed that there was a significant difference in NLR between the survival and nonsurvival groups (median [lower quartile–upper quartile], 15.27 [7.92–26.28] vs. 17.97 [8.94–31.85], P = 0.008). Area under the curve (AUC) of NLR on the sixth day was the highest. AUC of NLR was significantly higher in the Simplified Acute Physiological Score (SAPS) 3 ≤52 group than that in the SAPS3 > 52 group (0.78 ± 0.05 vs. 0.69 ± 0.03, P = 0.007). AUC of NLR in the nonshock group was significantly higher than that in the shock group (0.72 ± 0.04 vs. 0.65 ± 0.05, P < 0.01). The ability of NLR as a prognosis predictor of sepsis was influenced by admission time, SAPS3, and shock.
Difference of Clinical Characteristics in Patients with Omicron and Delta Variants of SARS-CoV-2 in Beijing, China
Authors: Tian Di , Pan Yang , Ge Ziruo , Kong Xiangjing , Zhang Yao , Zhang Qing , Wang Aibin , Yang Peng , Chen Zhihai
Published: October 2023

Background

Delta and Omicron are two main variants that have been prevalent since 2021. However, the Omicron variant of severe acute respiratory syndrome coronavirus 2 shows a less severe clinical presentation and high transmissibility. Therefore, we carried out this retrospective study to evaluate Omicron severity compared with the Delta variant and further comprehend the differences in clinical characteristics in patients with the Omicron variant.

Methods

We extracted clinical data and compared clinical severity, symptoms, vaccination status, laboratory parameters, viral shedding time, and computed tomography (CT) imaging between the two groups of patients, which included 109 COVID-19 cases with the Delta variant and 183 cases with the Omicron variant, from January 19 to April 1, 2022, in Beijing Ditan Hospital. In addition, the Beijing Center for Disease Prevention and Control conducted whole-genome sequencing.

Results

We obtained 94 strains of variants of concern/Delta and 110 strains of variants of concern/Omicron. For the 110 Omicron strains, three were assigned as BA.1.1, 53 as BA.2, and 54 as BA.2.2. Among patients with the Delta variant, 54% (59/109) were moderate, which was significantly higher than that of patients with the Omicron variant (7% (12/183), P < 0.001). The number of patients with mild symptoms in the Omicron group was significantly higher than in the Delta group (80% vs. 35%, P < 0.001). Compared with the Omicron group, patients with underlying diseases or obesity, 60 years or older, or unvaccinated in the Delta group had more severe disease, and there was a significant difference between the two groups. The viral shedding time in the Omicron group was shorter than in the Delta group ((11.9 ± 5.9) vs. (14.0 ± 5.8) days, P = 0.003). Among the 183 patients in the Omicron group, 104 (57%) had dry or sore throat symptoms, more than those in the Delta group (34% (37/109); P < 0.001). In the Delta group, patients in the moderate group had more fever and cough symptoms than those in the mild group. The remission time of CT imaging in the Omicron group was shorter than in the Delta group ((9.0 ± 5.2) vs. (13.2 ± 4.2) days, P = 0.018).

Conclusions

Patients with Delta variants are more likely to have pneumonia, mainly with fever and cough symptoms, while patients with the Omicron variant are mostly mild, with more prominent dry or sore throat symptoms. In addition, patients with the Omicron variant have a short viral shedding time and rapid absorption of pneumonia.
Cleveland Clinic Continuous-Flow Total Artificial Heart: Progress Report and Technology Update
Authors: Kuroda Taiyo , Miyagi Chihiro , Polakowski Anthony R. , Flick Christine R. , Kuban Barry D. , Fukamachi Kiyotaka , Karimov Jamshid H.
Published: October 2023

Cleveland Clinic’s continuous-flow total artificial heart (CFTAH) is being developed at our institution and has demonstrated system reliability and optimal performance. Based on the results from recent chronic in vivo experiments, CFTAH has been revised, especially to improve biocompatibility. The purpose of this article is to report our progress in developing CFTAH. To improve biocompatibility, the right impeller, the pump housing, and the motor were reviewed for design revision. Updated design features were based on computational fluid dynamics analysis and observations from in vitro and in vivo studies. A new version of CFTAH was created, manufactured, and tested. All hemodynamic and pump-related parameters were observed and found to be within the intended ranges, and the new CFTAH yielded acceptable biocompatibility. Cleveland Clinic’s continuous-flow total artificial heart has demonstrated reliable performance, and has shown satisfactory progress in its development.
“I did not expect the doctor to treat a ghost”: a systematic review of published reports regarding chronic postamputation pain in British First World War veterans
Authors: Dixon Smith Sarah , Aldington Dominic , Hay George , Kumar Alexander , Le Feuvre Peter , Moore Andrew , Soliman Nadia , Wever Kimberley E. , Rice Andrew S.C.
Published: October 2023

Limb trauma remains the most prevalent survivable major combat injury. In the First World War, more than 700,000 British soldiers received limb wounds and more than 41,000 underwent an amputation, creating one of the largest amputee cohorts in history. Postamputation pain affects up to 85% of military amputees, suggesting that up to 33,000 British First World War veterans potentially reported postamputation pain. This qualitative systematic review explores the professional medical conversation around clinical management of chronic postamputation pain in this patient cohort, its development over the 20th century, and how this information was disseminated among medical professionals. We searched The Lancet and British Medical Journal archives (1914–1985) for reports referring to postamputation pain, its prevalence, mechanisms, descriptors, or clinical management. Participants were First World War veterans with a limb amputation, excluding civilians and veterans of all other conflicts. The search identified 9809 potentially relevant texts, of which 101 met the inclusion criteria. Reports emerged as early as 1914 and the discussion continued over the next 4 decades. Unexpected findings included early advocacy of multidisciplinary pain management, concerns over addiction, and the effect of chronic pain on mental health emerging decades earlier than previously thought. Chronic postamputation pain is still a significant issue for military rehabilitation. Similarities between injury patterns in the First World War and recent Iraq and Afghanistan conflicts mean that these historical aspects remain relevant to today's military personnel, clinicians, researchers, and policymakers.
The Utility of Methylphenidate for Fatigue in Long-Term Neurological Conditions: A Meta-analytical Review
Authors: Hagan Alexander James , Kumar Ram
Published: October 2023

Objective

Fatigue is a chronic and debilitating symptom of many long-term neurological conditions (LTNCs). Although methylphenidate provides some promise in alleviating fatigue in other clinical groups, little work has explored its potential utility within LTNCs. The current systematic review and meta-analysis evaluates the utility of methylphenidate for symptoms of fatigue in LTNCs.

Methods

Five databases (PsycINFO, MEDLINE, Embase, Scopus, and Cochrane Library) were searched for relevant articles from their inception to February 2022. A purpose-developed evaluation tool was used to assess each study's research quality (QuEST:F).

Results

Of the 1698 articles identified, 11 articles were included within this review (n = 370). Meta-analytical findings reported an overall significant benefit of methylphenidate for symptoms of fatigue across a mixed neurological sample (g = −0.44; 95% confidence interval, −0.77 to −0.11). Subgroup analyses identified a significantly greater benefit (P < 0.001) of methylphenidate for fatigue in LTNCs with static pathogenic trajectories (eg, traumatic brain injury) (number needed to treat = 2.5) compared with progressive conditions (eg, multiple sclerosis) (number needed to treat = 40.2).

Conclusions

Methylphenidate may pose an effective intervention for the treatment of fatigue in a number of LTNCs. Nonetheless, given the quality of the current evidence base, there exists a clear need for further robust assessment of the utility of methylphenidate—with a focus on subgroup-specific variability.
Involvement of Plasma Melatonin in Medication-Overuse Headache: A Cross-Sectional Study
Authors: Tao Huimin , Wan Qi , Sun Mei , Cai Kefu , Song Yan , He Mingqing , Shen Jiabing
Published: October 2023

Objectives

Patients with medication-overuse headache (MOH) are often complicated with anxiety, depression, and sleep disorders and are associated with dependence behavior and substance abuse. Melatonin has physiological properties including analgesia, regulation of circadian rhythms, soporific, and antidepressant and affects drug preference and addiction. This study aimed to investigate the role of melatonin in MOH compared with episodic migraine (EM) and healthy controls and to verify the relationship between plasma melatonin levels and psychiatric symptoms.

Methods

Thirty patients affected by MOH, 30 patients with EM, and 30 matched healthy controls were enrolled. All subjects completed a detailed headache questionnaire and scales including the Hospital Anxiety and Depression Scale (HADS), the Pittsburgh Sleep Quality Index, the Leeds Dependence Questionnaire. Melatonin levels in plasma samples were measured by enzyme immunoassay method.

Results

The levels of plasma melatonin were significantly different among 3 groups of subjects (MOH, 7.74 [5.40–9.89]; EM, 9.79 [8.23–10.62]; Control, 10.16 [8.60–17.57]; H = 13.433; P = 0.001). Significantly lower levels of melatonin were found in MOH patients compared with healthy controls (P = 0.001). The level of plasma melatonin inversely correlated with the scores of HADS-Anxiety (r = −0.318, P = 0.002), HADS-Depression (r = −0.368, P < 0.001), Pittsburgh Sleep Quality Index (r = −0.303, P = 0.004), and Leeds Dependence Questionnaire (r = −0.312, P = 0.003).

Conclusions

This study innovatively detects the plasma melatonin levels in MOH patients and explores the association between melatonin levels and psychiatric symptoms. Melatonin may be potential complementary therapy in the treatment of MOH considering its comprehensive role in multiple aspects of MOH.
A 5-structured visits multidisciplinary clinical care approach to optimize the care of patients with type 2 diabetes: a pilot study
Authors: Allam Magdy Mohamed , Younan Mariam , Abdelhamid Mohamed , Khan Muhammad , Elshafee Mohamed , Nada Aml Mohamed
Published: October 2023

Introduction

Multidisciplinary coordinated care has been associated with improvement of diabetes care.

Aim and methods

This is a retrospective cohort analysis aimed to assess the effect of application of the five-structured visits Multi-disciplinary Clinical Care Approach (FMCA) on each of T2DM control, complications and comorbidities. The patients’ records were assessed for one year of regular diabetes care followed with a year after implementation of FMCA for patients attending the diabetes clinic at Zulekha hospital. The patients were divided according to HbA1c (cutoff 7%) at the end of the FMCA year of follow-up into a group of controlled and another group of uncontrolled diabetes designated CDM and UCDM, respectively.

Results

49% of patients were males and the mean age was 44.22 years. HbA1c levels, LDL and urinary albumin/creatinine ratio (UACR) showed a marked decrease among the patients after implementation of FMCA (P = 0.02, P = 0.04, P = 0.003, respectively). Compared with an increase in the atherosclerotic cardiovascular risk score (ASCVD) during the regular period, exposure to FMCA significantly decreased the cardiovascular risk score (0.17%, 11.41%, P = 0.001, P = 0.001, respectively). A self-management score was significantly higher in CDM patients. After a multivariate regression analysis of factors affecting DM control, we detected that baseline HbA1c, UACR, self-management score and hospital admission rate were the most important factors to predict diabetes control.

Conclusion

The implementation of FMCA has shown a significant improvement in clinical and humanistic aspects of individuals with T2DM with a better outcome, more control and less complications.
Bifidobacterium longum subsp. iuvenis subsp. nov., a novel subspecies isolated from the faeces of weaning infants
Authors: Modesto Monica , Ngom-Bru Catherine , Scarafile Donatella , Bruttin Anne , Pruvost Solenn , Sarker Shafiqul Alam , Ahmed Tahmeed , Sakwinska Olga , Mattarelli Paola , Duboux Stéphane
Published: October 2023

The species

Bifidobacterium longum

currently comprises four subspecies:

B. longum

subsp.

longum

,

B. longum

subsp.

infantis

,

B. longum

subsp.

suis

and

B. longum

subsp.

suillum

. Recently, several studies on

B. longum

suggested the presence of a separate clade containing four strains isolated from infants and one from rhesus macaque. These strains shared a phylogenetic similarity to

B. longum

subsp.

suis

DSM 20210T and

B. longum

subsp.

suillum

JCM1995T [average nucleotide identity (ANI) of 98.1 %) while showed an ANI of 96.5 % with both

B. longum

subsp.

infantis

and

B. longum

subsp.

longum

. The current work describes five novel additional

B. longum

strains isolated from Bangladeshi weaning infants and demonstrates their common phylogenetic origin with those of the previously proposed separated clade. Based on polyphasic taxonomic approach comprising loci multilocus sequence analysis and whole genome multilocus sequence typing, all ten examined strains have been confirmed as a distinct lineage within the species

B. longum

with

B. longum

subsp.

suis

and

B. longum

subsp.

suillum

as closest subspecies. Interestingly, these strains are present in weaning infants and primates as opposed to their closest relatives which have been typically isolated from pig and calves. These strains, similarly to

B. longum

subsp.

infantis

, show a common capacity to metabolize the human milk oligosaccharide 3-fucosyllactose. Moreover, they harbour a riboflavin synthesis operon, which differentiate them from their closest subspecies,

B. longum

subsp.

suis

and

B. longum

subsp.

suillum

. Based on the consistent results from genotypical, ecological and phenotypical analyses, a novel subspecies with the name

Bifidobacterium longum

subsp. iuvenis, with type strain NCC 5000T (=LMG 32752T=CCOS 2034T), is proposed.
Abrogation and Homeostatic Restoration of IgE Responses by a Universal IgE Allergy CTL Vaccine—The Three Signal Self/Non-Self/Self (S/NS/S) Model
Authors: Chen Swey-Shen , Zhang Hailan
Published: October 2023

Natural IgE cytotoxic peptides (nECPs), which are derived from the constant domain of the heavy chain of human IgE producing B cells via endoplasmic reticulum (ER) stress, are decorated onto MHC class 1a molecules (MHCIa) as unique biomarkers for CTL (cytotoxic T lymphocyte)-mediated immune surveillance. Human IgE exhibits only one isotype and lacks polymorphisms; IgE is pivotal in mediating diverse, allergen-specific allergies. Therefore, by disrupting self-IgE tolerance via costimulation, the cytotoxic T lymphocytes (CTLs) induced by nECPs can serve as universal allergy vaccines (UAVs) in humans to dampen IgE production mediated by diverse allergen-specific IgE- secreting B cells and plasma cells expressing surface nECP-MHCIa as targets. The study herein has enabled the identification of nECPs produced through the correspondence principle1, 2. Furthermore, nECP-tetramer-specific CTLs were found to be converted into CD4 Tregs that restored IgE competence via the homeostatic principle, mediated by SREBP-1c suppressed DCs. Thus, nECPs showed causal efficacy and safety as UAVs for treating type I hypersensitivity IgE-mediated allergies. The applied vaccination concept presented provides the foundation to unify, integrate through a singular class of tetramer-specific TCR clonotypes. The three signal model is proposed on the mechanisms underlying central tolerance, breaking tolerance and regaining peripheral tolerance via homeostasis concerning nECP as an efficacious and safe UAV to treat type I IgE-mediated hypersensitivity.

One Sentence Summary

Human IgE self-peptides are identified as universal allergy vaccines that inhibit IgE synthesis while allowing homeostatic IgE recovery.

Graphic abstract text

Three cell S/NS/S model of Universal Allergy Vaccines (UAV): Natural IgE peptides (nECPs) presented by enabler DCs break central IgE tolerance (Self), leading to CTLs that inhibit IgE production (Non-self). Generative DCs converted by the metabolic milieu transform the pre-existing nECP-specific CTLs into nECP-specific Tregs leading to homeostatic recovery of IgE competence (S).
CD1d-dependent neuroinflammation impairs tissue repair and functional recovery following a spinal cord injury
Authors: Wu Xiangbing , Liu Jianyun , Li Wei , Khan Mohammad Faizan , Dai Heqiao , Tian Jeremy , Priya Raj , Tian Daniel J. , Wu Wei , Yaacoub Alan , Gu Jun , Syed Fahim , Yu Christopher H. , Gao Xiang , Yu Qigui , Xu Xiao-Ming , Brutkiewicz Randy R.
Published: October 2023

Tissue damage resulting from a spinal cord injury (SCI) is primarily driven by a robust neuroimmune/neuroinflammatory response. This intricate process is mainly governed by a multitude of cytokines and cell surface proteins in the central nervous system (CNS). However, the critical components of the neuroimmune/neuroinflammatory response during SCI are still not well-defined. In this study, we investigated the impact of CD1d, an MHC class I-like molecule mostly known for presenting lipid antigens to natural killer T (NKT) cells and regulating immune/inflammatory responses, on neuroimmune/neuroinflammatory responses induced by SCI. We observed an increased expression of CD1d on various cell types within the spinal cord, including microglia/macrophages, oligodendrocytes (ODCs), and endothelial cells (DCs), but not on neurons or astrocytes post-SCI. In comparison to wildtype (WT) mice, a T10 contusive SCI in CD1d knockout (CD1dKO orCd1d-/-) mice resulted in markedly reduced proinflammatory cytokine release, microglia/macrophage activation and proliferation. Following SCI, the levels of inflammatory cytokines and activation/proliferation of microglia/macrophages were dramatically reduced, while anti-inflammatory cytokines such as IL-4 and growth factors like VEGF were substantially increased in the spinal cord tissues of CD1dKO mice when compared to WT mice. In the post-acute phase of SCI (day 7 post-SCI), CD1dKO mice had a significantly higher frequency of tissue-repairing macrophages, but not other types of immune cells, in the injured spinal cord tissues compared to WT mice. Moreover, CD1d-deficiency protected spinal cord neuronal cells and tissue, promoting functional recovery after a SCI. However, the neuroinflammation in WT mouse spinal cords was independent of the canonical CD1d/NKT cell axis. Finally, treatment of injured mice with a CD1d-specific monoclonal antibody significantly enhanced neuroprotection and improved functional recovery. Therefore, CD1d promotes the proinflammatory response following a SCI and represents a potential therapeutic target for spinal cord repair.

Significance Statement

The cell surface molecule, CD1d, is known to be recognized by cells of the immune system. To our knowledge, this is the first observation that the CD1d molecule significantly contributes to neuroinflammation following a spinal cord injury (SCI) in a manner independent of the CD1d/NKT cell axis. This is important, because this work reveals CD1d as a potential therapeutic target following an acute SCI for which there are currently no effective treatments.
Homogenization of taxonomic, phylogenetic, and functional characteristics of bumble bee communities at regional scales in anthropogenic landscapes
Authors: Perry Kayla I , Gratton Claudio , Tai Taylor , Strange James P
Published: October 2023

Biotic homogenization has been documented following extensive anthropogenic landscape change such as urbanization and agriculture, but diverse native communities also have been reported in these ecosystems. Understanding the influence of landscape-level characteristics on processes of community assembly can inform how human-dominated landscapes shape the structure and composition of local communities, including important pollinators such as bumble bees (Bombusspp.). The objective of this study was to investigate multi-scale patterns of taxonomic, phylogenetic, and functional beta- diversity of bumble bees in greenspaces along an urban-agricultural gradient to understand landscape- scale constraints on processes of community assembly. Bumble bees were collected in greenspaces along an urban-agricultural gradient in Madison, WI, USA. Patterns of biotic homogenization were investigated using measures of beta-diversity and null models relative to a regional bumble bee species pool in a 100 km area surrounding the city. Nine of the expected 13 species from the regional pool were collected in greenspaces in urban and agricultural landscapes. At the regional scale, we found evidence of taxonomic, phylogenetic, and functional homogenization among bumble bee communities in urban and agricultural landscapes, with species that were smaller in size, had shorter wings, were less hairy, but had larger eyes and longer setae on the corbicula (pollen-carrying hind legs) being more common than expected based on null models. When we evaluated filtering from the anthropogenic species pools (i.e., urban and agricultural) to local greenspaces, we found nuanced differences among land cover types, wherein agricultural landscapes supported higher beta-diversity of bumble bee communities than expected while urban landscapes continued to show signals of homogenization. Overall, anthropogenic landscapes acted as a strong filter for bumble bees, broadly selecting for a subset of functionally similar and phylogenetically related species that resulted in homogenization of communities within the region. Our findings support a landscape-level approach to biodiversity conservation that promotes diversifying landscapes to support diverse pollinator populations.

OPEN RESEARCH STATEMENT

Data and novel code associated with this submission are provided in an external repository to be evaluated during the peer review process and are available athttps://github.com/kiperry/WI_Bumble_Bees. If this paper is accepted for publication, data and code will be permanently archived within a linked Zenodo repository.
Immediate and Long-Term Electrophysiological Biomarkers of Antidepressant Behavioral Effects After Subanesthetic Ketamine and Medial Prefrontal Cortex Deep Brain Stimulation Treatment
Authors: Bergosh Matthew , Medvidovic Sasha , Zepeda Nancy , Crown Lindsey , Ipe Jennifer , Debattista Lauren , Romero Luis , Amjadi Eimon , Lam Tian , Hakopian Erik , Choi Wooseong , Wu Kevin , Lo Yu Tung Jack , Lee Darrin Jason
Published: October 2023

1

Ketamine and medial prefrontal cortex (mPFC) deep brain stimulation (DBS) are emerging depression treatments, however their mechanisms and efficacy biomarkers have not been established. This study investigates immediate and long-term mPFC electrophysiological correlates of their antidepressant effects, and explores the effects of combinatorial treatment. Local field potential electrodes were implanted into the mPFC of male Sprague Dawley rats, then corticosterone was administered for 21 days, except in the control group (n = 8). In the last week of depression induction, the remaining groups received mPFC DBS (n = 8), ketamine (n = 9), both (n = 9), or neither (n = 8). All groups then performed a behavioral assay. We found that DBS treatment immediately suppressed relative low gamma power and improved cognition in the long-term, which correlated with rescued apathy-like behavior in the Groom Test (GT). In contrast, ketamine treatment suppressed sample entropy in the long-term, which correlated with its immediate decrease in sample entropy as well as rescued GT behavior. In the combinatorial group these changes were inhibited, which correlated with a failure to fully rescue GT behavior. Despair-like behavior in the Forced Swim Test was rescued by all three treatments, which correlated with increased relative high frequency oscillation (HFO) power immediately after ketamine and combinatorial treatment. Our findings support the utility of low gamma and HFO power, sample entropy, and cognitive tests in the search for mechanisms and biomarkers of depression and novel treatments.

2

Significance Statement

There is growing interest in psychedelic pharmacological agents, such as ketamine, and direct neurostimulation techniques, like deep brain stimulation, as treatments for depression. However, their mechanisms are poorly understood, particularly those underlying their sustained benefits. Our study addresses this by correlating behavioral rescue with immediate and long-term changes in the function of the medial prefrontal cortex. These antidepressant correlates may represent therapeutically relevant functional changes, and therefore also have potential as biomarkers. Clinically, such biomarkers enable predicting and monitoring of treatment efficacy, and thereby contribute to the personalization of care. In research, utilizing these translatable biomarkers enhances the etiological validity of disease models, and enables the development of more targeted, next-generation treatment strategies.
Negative Binomial Mixture Model for Identification of Noise in Antigen-Specificity Predictions by LIBRA-seq
Authors: Wasdin Perry T. , Abu-Shmais Alexandra A. , Irvin Michael W. , Vukovich Matthew J. , Georgiev Ivelin S.
Published: October 2023

Structured Abstract

Motivation

LIBRA-seq (linking B cell receptor to antigen specificity by sequencing) provides a powerful tool for interrogating the antigen-specific B cell compartment and identifying antibodies against antigen targets of interest. Identification of noise in LIBRA-seq antigen count data is critical for improving antigen binding predictions for downstream applications including antibody discovery and machine learning technologies.

Results

In this study, we present a method for denoising LIBRA-seq data by clustering antigen counts into signal and noise components with a negative binomial mixture model. This approach leverages the VRC01 negative control cells included in a recent LIBRA-seq study(Abu-Shmaiset al.) to provide a data-driven means for identification of technical noise. We apply this method to a dataset of nine donors representing separate LIBRA-seq experiments and show that our approach provides improved predictions for in vitro antibody-antigen binding when compared to the standard scoring method used in LIBRA-seq, despite variance in data size and noise structure across samples. This development will improve the ability of LIBRA-seq to identify antigen-specific B cells and contribute to providing more reliable datasets for future machine learning based approaches to predicting antibody-antigen binding as the corpus of LIBRA-seq data continues to grow.

Availability and Implementation

Jupyter notebooks detailing model fitting and figure generation in Python are available athttps://github.com/perrywasdin/mixture_model_denoising.

Contact

Email:Ivelin.Georgiev@Vanderbilt.edu

Supplementary Information

Supplementary figures are provided in the attached PDF.
Conscious and unconscious perception of errors in auditory feedback during vocalization: Behavioral functions and event-related potential correlates
Authors: Suchý Daniel , Behroozmand Roozbeh , Railo Henry
Published: October 2023

During vocalization, errors in the auditory feedback are processed rapidly and automatically, suggesting that feedback control of vocalization operates unconsciously. Humans are also able to consciously detect errors in their auditory feedback during vocalization, but the question whether consciousness modulates speech feedback control remains little studied. To address this question, we concurrently measured behavioral vocal responses and electroencephalography (EEG) in 30 participants while their online auditory feedback was altered using individually calibrated threshold-level pitch-shift perturbations (i.e., errors). Following each vocalization trial, participants rated if they consciously detected pitch errors in their auditory feedback. We analyzed the data on a trial-by-trial basis to test if vocal responses to pitch perturbations are modulated by conscious perception. Our results revealed that even on trials where participants reported not noticing the perturbation at all, a vocal compensation to the altered auditory feedback was generated. Conscious error detection was associated with increased magnitude of vocal responses roughly 500-700 ms after the altered feedback compared to the unconscious trials. Conscious detection of the altered feedback correlated with early (Auditory awareness negativity) and late (Late positivity) neural activity responses as indexed by the modulation of event-related potentials (ERPs). Source localization of ERP responses suggested that conscious error detection was attributed to increased neural activity within the temporal, frontal and parietal cortical networks known to be involved in speech motor control. These findings emphasize the importance of investigating the role of higher-level conscious processing mechanisms in regulating speech feedback control, and their effect on the underlying neural and behavioral functions.
Resting-state is not enough: alpha and mu rhythms change shape across development, but lack diagnostic sensitivity
Authors: Bender Andrew , Voytek Bradley , Schaworonkow Natalie
Published: October 2023

In the human brain, the alpha rhythm in occipital cortex and the mu rhythm in sensorimotor cortex are among the most prominent rhythms, with both rhythms functionally implicated in gating modality-specific information. Separation of these rhythms is non-trivial due to the spatial mixing of these oscillations in sensor space. Using a computationally efficient processing pipeline, we show that alpha and mu rhythms can be separated from electroencephalography recordings performed on nearly 3000 children aged 5–18. Using the extracted time series for each rhythm, we characterized the waveform shape on a cycle-by-cycle basis and examined whether and how the waveform shape differs across development and in attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Alpha and mu rhythms both exhibit nonsinusoidal waveform shape that changes significantly across development. We found no differences in the resting-state features of these alpha-band rhythms for either ADHD or ASD in comparison to typically developing participants. While waveform shape is ignored by traditional Fourier spectral analyses, these nonsinusoidal properties may be informative for building more constrained generative models for different types of alpha-band rhythms. Our results highlight the difficulties in identifying targeted biomarkers for ADHD and ASD from resting-state alpha-band rhythms.
Recommendations For a Standardized Approach to Histopathologic Evaluation of Synovial Membrane in Murine Models of Experimental Osteoarthritis
Authors: Obeidat Alia M , Kim Sung Yeon , Burt Kevin G , Hu Baofeng , Li Jun , Ishihara Shingo , Xiao Rui , Miller Rachel E , Little Christopher , Malfait Anne-Marie , Scanzello Carla R
Published: October 2023

Background

Synovial pathology has been linked to osteoarthritis (OA) pain in patients. Microscopic grading systems for synovial changes in human OA have been described, but a standardized approach for murine models of OA is needed. We sought to develop a reproducible approach and set of minimum recommendations for synovial histopathology in mouse models of OA.

Methods

Coronal and sagittal sections from male mouse knee joints subjected to destabilization of medial meniscus (DMM) or partial meniscectomy (PMX) were collected as part of other studies. Stains included Hematoxylin and Eosin (H&E), Toluidine Blue (T- Blue) and Safranin O/Fast Green (Saf-O). Four blinded readers graded pathological features (hyperplasia, cellularity, and fibrosis) at specific anatomic locations in the medial and lateral compartments. Inter-reader reliability of each feature was determined.

Results

There was acceptable to very good agreement between raters. After DMM, increased hyperplasia and cellularity and a trend towards increased fibrosis were observed 6 weeks after DMM in the medial locations, and persisted up to 16 weeks. In the PMX model, cellularity and hyperplasia were evident in both medial and lateral compartments while fibrotic changes were largely seen on the medial side. Synovial changes were consistent from section to section in the mid-joint area mice. H&E, T-blue, and Saf-O stains resulted in comparable reliability.

Conclusions

To allow for a standard evaluation that can be implemented and compared across labs and studies, we recommend using 3 readers to evaluate a minimum set of 3 pathological features at standardized anatomic areas. Pre-defining areas to be scored, and reliability for each pathologic feature should be considered.
Evolution of novel sensory organs in fish with legs
Authors: Allard Corey AH , Herbert Amy L , Krueger Stephanie P , Liang Qiaoyi , Walsh Brittany L , Rhyne Andrew L , Gourlay Allex N , Seminara Agnese , Baldwin Maude W , Kingsley David M , Bellono Nicholas W
Published: October 2023

How do animals evolve new traits? Sea robins are unusual “walking” fishes that use leg-like appendages to navigate the seafloor. Here, we show that legs arebona fidesense organs that mediate the unique ability to localize and uncover buried prey. We then probe the developmental and physiological basis of these novel sense organs as a striking example of a major trait gain in evolution. We find certain sea robin species have legs with unique end-organs called papillae that mediate enhanced mechanical and chemical sensitivity to enable predatory digging behavior. Papillae exhibit dense innervation from touch-sensitive neurons, noncanonical epithelial taste receptors, and chemical sensitivity that drives predatory digging behavior. Using a combination of developmental analyses, crosses between species with and without papillae, and interspecies comparisons of sea robins from around the world, we demonstrate that papillae represent a key evolutionary innovation associated with behavioral niche expansion on the seafloor. These discoveries provide a conceptual framework for understanding how molecular, cellular, and tissue-scale adaptations integrate to produce novel organismic traits and behavior.
Competing adaptations maintain non-adaptive variation in a wild cricket population
Authors: Rayner Jack G. , Eichenberger Franca , Bainbridge Jessica V. A. , Zhang Shangzhe , Zhang Xiao , Yusuf Leeban H. , Balenger Susan , Gaggiotti Oscar E. , Bailey Nathan W.
Published: October 2023

How emerging adaptive variants interact is an important factor in the evolution of wild populations. However, the opportunity to empirically study this interaction is rare. We recently documented the emergence of an adaptive phenotype ‘curly-wing’ in Hawaiian populations of field crickets (Teleogryllus oceanicus). Curly-wing inhibits males’ ability to sing, protecting them from eavesdropping parasitoid flies (Ormia ochracea). Surprisingly, curly-wing co-occurs with similarly protective silent ‘flatwing’ phenotypes in multiple populations, in which neither phenotype has spread to fixation. These two phenotypes are frequently co-expressed, but since either phenotype sufficiently reduces song amplitude to evade the fly, co-expression confers no additional fitness benefit. Numerous negative fitness consequences are known to accompany flatwing, and we find that curly-wing, too, incurs fitness costs via reduced male courtship success and reduced female longevity. We show through crosses, genomic and mRNA sequencing that curly-wing expression is associated with variation on a single autosome. In parallel analyses of flatwing, our results reinforce previous findings of X-linked single-locus inheritance, with the phenotype likely arising through down-regulation ofdoublesex. By combining insights about the genetic architecture of these alternative phenotypes with simulations and field observations, we show that the co-occurrence of these two adaptations impedes either from fixing, despite extreme fitness benefits. Interestingly, both flatwing and curly-wing are statistically associated with nearby inversions, which are also retained as polymorphisms. This co-occurrence of similar adaptive forms in the same populations might be more common than generally considered, and could be an important force inhibiting adaptive evolution in wild populations.
Information gathering explains decision dynamics during human and monkey reward foraging
Authors: Barack David L , Parodi Felipe , Ludwig Vera , Platt Michael L
Published: October 2023

Foraging in humans and other animals requires a delicate balance between exploitation of current resources and exploration for new ones. The tendency to overharvest—lingering too long in depleting patches—is a routine behavioral deviation from predictions of optimal foraging theories. To characterize the computational mechanisms driving these deviations, we modeled foraging behavior using a virtual patch-leaving task with human participants and validated our findings in an analogous foraging task in two monkeys. Both humans and monkeys overharvested and stayed longer in patches with longer travel times compared to shorter ones. Critically, patch residence times in both species declined over the course of sessions, enhancing reward rates in humans. These decisions were best explained by a logistic transformation that integrated both current rewards and information about declining rewards. This parsimonious model demystifies both the occurrence and dynamics of overharvesting, highlighting the role of information gathering in foraging. Our findings provide insight into computational mechanisms shaped by ubiquitous foraging dilemmas, underscoring how behavioral modeling can reveal underlying motivations of seemingly irrational decisions.