bluuebunny/crossref_metadata_2025 huggingface dataset:
Inference and applications of molecular phylogenies: An introductory guide
Authors: Strimmer* Korbinian , Robertsont David L
Published: November 2023

Molecular phylogenies have a wide range of practical applications in the analysis of DNA sequences and are now an essential tool in areas ranging from population genetics to genomics to virology. The use of modem computers has fostered the development of sophisticated methodologies, and subsequently a large number of programs have become available. In this chapter we give an introductory overview of the most important methods of inferring phylogenetic trees from nucleotide or amino acid sequence data, emphasizing concept rather than mathematical detail (Box 1). We discuss simple guidelines for choosing a method appropriate for a data set. Advanced issues in molecular phylogenetics are briefly introduced, along with suggestions for further reading. The versatility of molecular phylogenetics is also highlighted and we present a range of practical problems where evolutionary trees have formed a key component of the analysis. Finally, we provide an overview of phylogenetic software and corresponding Internet resources (Box 2).
Laboratory websites: How to disseminate information, make friends, and influence people
Authors: Lu Chao , Woodgett James R
Published: November 2023

The Internet and World Wide Web were born of the need for scientists to communicate and collaborate. In its early DARPAnet days, the network provided teams of physics and computer scientists with a way to efficiently exchange data and commentary. While the popularization, commercialization, and hype of recent years have exploded the use of this network of networks to virtually anyone with a web-enabled device, its relevance to scientists remains as strong as ever. Scientists and students are less willing to physically visit a library to search for information that can be done more easily and faster at home or in the laboratory. There were about 3 million Internet servers worldwide in 1999 hosting about 8 million pages of web content (1). Of those, about 6% focused on scientific and educational content, with the remainder largely being commercial/corporate. The number has increased three-fold per year since then and shows little sign of slowing.
GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development
Authors: Heo Geun , Lee Song‐Hee , Kim Ji‐Dam , Lee Gyu‐Hyun , Sim Jae‐Min , Zhou Dongjie , Guo Jing , Cui Xiang‐Shun
Published: November 2023

Glucose‐regulated protein 78 (GRP78) binds to and stabilizes melanocortin 4 receptor (MC4R), which activates protein kinase A (PKA) by regulating G proteins. GRP78 is primarily used as a marker for endoplasmic reticulum stress; however, its other functions have not been well studied. Therefore, in this study, we aimed to investigate the function of GRP78 during porcine embryonic development. The developmental quality of porcine embryos, expression of cell cycle proteins, and function of mitochondria were evaluated by inhibiting the function of GRP78. Porcine oocytes were activated to undergo parthenogenesis, and blastocysts were obtained after 7 days of in vitro culture. GRP78 function was inhibited by adding 20 μM HA15 to the in vitro culture medium. The inhibition in GRP78 function led to a decrease in G proteins release, which subsequently downregulated the cyclic adenosine monophosphate (cAMP)/PKA pathway. Ultimately, inhibition of GRP78 function induced the inhibition of CDK1 and cyclin B expression and disruption of the cell cycle. In addition, inhibition of GRP78 function regulated DRP1 and SIRT1 expression, resulting in mitochondrial dysfunction. This study provides new insights into the role of GRP78 in porcine embryonic development, particularly its involvement in the regulation of the MC4R pathway and downstream cAMP/PKA signaling. The results suggest that the inhibition of GRP78 function in porcine embryos by HA15 treatment may have negative effects on embryo quality and development. This study also demonstrated that GRP78 plays a crucial role in the functioning of MC4R, which releases the G protein during porcine embryonic development.
Invasive Multimodality Neuromonitoring to Manage Cerebral Edema in Pediatric Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease
Authors: Fainberg Nina A. , Silver Maya R. , Arena John D. , Landzberg Elizabeth I. , Banwell Brenda , Gambrah-Lyles Claudia , Kirschen Matthew P. , Madsen Peter J. , McLendon Loren , Narula Sona , Tucker Alexander M. , Huh Jimmy W. , Kienzle Martha F.
Published: November 2023

Background:

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disorder of the CNS with a variety of clinical manifestations, including cerebral edema.

Case Summary:

A 7-year-old boy presented with headaches, nausea, and somnolence. He was found to have cerebral edema that progressed to brainstem herniation. Invasive multimodality neuromonitoring was initiated to guide management of intracranial hypertension and cerebral hypoxia while he received empiric therapies for neuroinflammation. Workup revealed serum myelin oligodendrocyte glycoprotein antibodies. He survived with a favorable neurologic outcome.

Conclusion:

We describe a child who presented with cerebral edema and was ultimately diagnosed with MOGAD. Much of his management was guided using data from invasive multimodality neuromonitoring. Invasive multimodality neuromonitoring may have utility in managing life-threatening cerebral edema due to neuroinflammation.
Central Sleep Apnea in Patients With Coronary Heart Disease Taking P2Y12 Inhibitors
Authors: Tzeng William S. , Klein Christian F. , Roth Robert H. , Cho Yeilim , Munagala Rohit , Bonner Heather , Mazimba Sula , Khayat Rami , Healy William , Lobo Jennifer M. , Kapur Vishesh K. , Kwon Younghoon
Published: November 2023

Central sleep apnea (CSA) is common in patients with heart failure. Recent studies link ticagrelor use with CSA. We aimed to evaluate CSA prevalence in patients with coronary heart disease (CHD) and whether ticagrelor use is associated with CSA. We reviewed consecutive patients with CHD who underwent a polysomnography (PSG) test over a 5-year period from 3 sleep centers. We sampled patients who were on ticagrelor or clopidogrel during a PSG test at a 1:4 ticagrelor:clopidogrel ratio. Patients with an active opioid prescription during PSG test were excluded. Age, left ventricle (LV) dysfunction, and P2Y12 inhibitor use were included in a multivariate logistic regression. A total of 135 patients were included with 26 on ticagrelor and 109 on clopidogrel (age 64.1 ± 11.4, 32% male). High CSA burden (12%) and strict CSA (4.4%) were more common in patients on ticagrelor than in those on clopidogrel (27% vs. 8.3% and 10.0% vs. 1.8%). Ticagrelor use (vs. clopidogrel) was associated with high CSA burden (OR 3.53, 95% CI 1.04–12.9, P = 0.039) and trended toward significance for strict CSA (OR 6.32, 95% CI 1.03–51.4, P = 0.052) when adjusting for age and LV dysfunction. In an additional analysis also adjusting for history of atrial fibrillation, ticagrelor use and strict CSA became significantly associated (OR 10.0, 95% CI 1.32–117, P = 0.035). CSA was uncommon in patients with CHD undergoing sleep studies. Ticagrelor use (vs. clopidogrel) was associated with high CSA burden and trended toward significance for strict CSA.
Customized miniflap for a nondissected flap island during femtosecond laser–assisted laser in situ keratomileusis
Authors: Hassouna Abdallah K. , Wahba Sherine S. , Hermina Marian S. , Samy Sameh N.
Published: November 2023

Three cases of a rare complication that occurred during femtosecond laser–assisted laser in situ keratomileusis are reported. An anterior chamber gas bubble escaped between the cornea and the cone through the canal, which lead to a nondissected island. A new technique, a customized miniflap that could be applied in the same session to treat the nondissected island is described. The results were promising because the flaps were lifted easily with no complications, confirmed by the postoperative visual acuity, the regularity index, and anterior segment optical coherence tomography.
Two cases of diabetic zonular cataracts
Authors: Bronner Aaron , Guzek James P. , Leng Jason
Published: November 2023

Osmotic changes to the lens are known to occur with dramatic variations in blood sugar. Most often, these changes result in refractive changes, but not opacification within the substance of the lens. We present 2 cases with a shared history of dramatic sudden reductions in blood sugar following previously uncontrolled diabetes mellitus and peculiar zonular ridges in the perinuclear zone of their lenses. This unusual cataract might be the result of the rapid blood sugar reduction. To our knowledge, this form of cataract has not been reported previously.
Phosphorylated-S6 Expression in Sturge-Weber Syndrome Brain Tissue
Authors: McCann Meghan , Cho Andrew , Pardo Carlos A. , Phung Thuy , Hammill Adrienne , Comi Anne M.
Published: November 2023

Background:

Sturge-Weber Syndrome (SWS) is a rare neurovascular disorder associated with port-wine birthmarks, glaucoma, and abnormal leptomeningeal blood vessels. It is most commonly caused by a R183Q somatic mutation in GNAQ predicted to result in impaired deactivation of the protein Gαq, and downstream pathways such as the Ras-Raf-MEK-ERK and mTOR pathways. The GNAQ mutation is reportedly enriched in endothelial cells.

Methods:

Using a phosphorylated-S6 (p-S6) antibody, a marker for mTOR pathway activity, we analyzed p-S6 protein expression in human brain tissue samples from SWS subjects and epilepsy controls.

Results:

SWS brain tissue was more likely to have leptomeningeal endothelial p-S6 antibody staining, compared with epilepsy controls, while the percentage of samples with p-S6 staining in perivascular cells and cortex were not significantly different.

Conclusions:

Leptomeningeal endothelial mTOR activity may contribute to abnormal endothelial cell morphology and function. This finding implicates mTOR as a potential treatment target for Sturge-Weber Syndrome.
Detection of NRAS Mutation in Kaposiform Lymphangiomatosis Using Cell-free DNA from Plasma
Authors: Lynch Fiona , Dvorakova Veronika , Irvine Alan D.
Published: November 2023

Kaposiform lymphangiomatosis is a rare lymphatic anomaly that occurs in children and is associated with life-threatening complications. The somatic mutation NRAS Q61R (c.182A>G) has been identified in lesional tissue samples of patients with kaposiform lymphangiomatosis, and can be used to differentiate this condition from other complex lymphatic anomalies and to guide treatment. Tissue sampling in this lymphatic anomaly is inherently risky due to its involvement of thoracic and abdominal organs and associated coagulopathy. Analysis of cell-free DNA isolated from blood plasma presents a promising noninvasive diagnostic strategy. Here, we describe the use of this approach using a commercial assay.
High-Frequency Gain and Maximum Output Effects on Speech Recognition in Bone-Conduction Hearing Devices: Blinded Study
Authors: Sassi Tyuana Sandim da Silveira , Bucuvic Erika Cristina , Castiquini Eliane Aparecida Techi , Chaves Juliana Nogueira , Kimura Marcia , Buzo Byanka Cagnacci , Lourençone Luiz Fernando Manzoni
Published: November 2023

Introduction

Bone-conduction hearing device (BCHD) uses natural sound transmission through bone and soft tissue, directly to the cochlea, via an external processor that captures and processes sound, which is converted into mechanical vibrations. Key parameters, as maximum power output (MPO) and broader frequency range (FR), must be considered when indicating a BCHD because they can be decisive for speech recognition, especially under listening challenge conditions.

Objectives

Compare hearing performance and speech recognition in noise of two sound processors (SPs), with different features of MPO and FR, among BCHD users.

Materials and Methods

This single-blinded, comparative, observational study evaluated 21 individuals Baha 4 system users with conductive or mixed hearing impairment. The free-field audiometry and speech recognition results were blindly collected under the following conditions: unaided, with Baha 5, and with Baha 6 Max SP.

Results

In free-field audiometry, significant differences were observed between the SP at 0.25, 3, 4, 6, and 8 kHz, with Baha 6 Max outperforming Baha 5. The Baha 6 Max provided significantly better speech recognition than Baha 5 under all the speech in noise conditions evaluated. Separating the transcutaneous from the percutaneous users, Baha 6 Max Attract SP provided the best results and significantly lowered the free-field thresholds than Baha 5 Attract. The Baha 6 Max also significantly improved speech recognition in noise, among both Attract and Connect users.

Conclusion

The present study revealed that the greater MPO and broader FR of the Baha 6 Max device helped increase high-frequency gain and improved speech recognition in BCHD-experimented users.
Negative Beliefs About Suicide Disclosure
Authors: Bell Kerri-Anne , O'Loughlin Caitlin M. , Piccirillo Marilyn L. , Ammerman Brooke A.
Published: November 2023

This study examined the differences in negative beliefs about disclosing suicidal thoughts and behaviors (STBs) between US Veterans and non-Veterans, and between Veterans who are and are not enrolled in Veterans Health Administration (VHA) care. Participants included 495 adults with a history of suicide ideation who completed an online self-report questionnaire inquiring about history of STBs, STB disclosure, and beliefs about STB disclosures. Group differences in STB disclosure beliefs were analyzed. Results showed that Veterans (vs. non-Veterans) more strongly believed that STB disclosure would result in firearm confiscation. VHA-enrolled (vs. non-VHA enrolled) Veterans reported stronger beliefs that STB disclosures result in involuntary hospitalization. Among VHA-enrolled Veterans, stronger beliefs regarding providers' interest regarding true STB experiences and others' comfort with STB disclosures were associated with lower STB disclosure likelihood. Findings highlight that educating Veterans on the benefits of STB disclosure and limiting misinformation regarding its consequences is paramount, specifically through improved suicide-related communication within the VHA and stigma reduction campaigns.
Systematic Review and Meta-Analysis of Effects of Nurse-Led Intervention for People With Dementia
Authors: Huang Kuei Hsiang , Saragih Ita Daryanti , Suarilah Ira , Son Nguyen Thi , Lee Bih-O
Published: November 2023

Background

Nurses’ primary role in clinical settings for persons living with dementia is to lessen the strain of dementia on daily life, monitor comorbidities, and manage medications. However, no comprehensive literature review has investigated the effectiveness of nurse-led interventions for persons living with dementia.

Objective

The purpose of this study was to evaluate randomized controlled trials on the efficacy of nurse-led dementia interventions and provide an extended range of outcomes related to cognitive function, depression, and quality of life.

Methods

A comprehensive literature search of six databases was conducted from database inception to August 10, 2022. Methodologies were evaluated, followed by a pooled analysis using random effects models to explain the effects of nurse-led dementia interventions on patients.

Results

Nurse-led interventions were more effective than standard care in alleviating depression and improving quality of life. However, they did not enhance cognitive performance.

Discussion

Nurse-led interventions for dementia alleviate depression and improve quality of life. However, because of lack of randomized controlled trials, the analysis found less effectiveness in improving cognitive function. Therefore, further trials are needed to corroborate these findings.
Diagnostic Performance of Thyroid Nodule Risk Stratification Systems
Authors: Yucel Serap , Balci Isa Gokturk , Tomak Leman
Published: November 2023

The purpose of this study was to compare the diagnostic performance of 4 different ultrasound-based risk scoring systems for thyroid nodules (TNs). This study consecutively included 256 patients (mean age: 43.98 ± 12.94 years, min–max: 18–89 years; 225 females, 31 males) with 266 TNs. Each nodule was evaluated and classified according to the American Thyroid Association (ATA), American College of Radiology (ACR), European Thyroid Association, and Korean Thyroid Imaging Reporting and Data System (ACR-TIRADS, EU-TIRADS, and K-TIRADS, respectively) before performing ultrasound-guided fine-needle aspiration biopsy. Pathological results were reported according to the Bethesda system. Outcomes of the 4 classification systems were compared with respect to Bethesda results. Twenty-eight (10.5%) nodules had malignant cytology results. Diagnostic performances of the scoring systems were comparable with similar area under the curve values according to the reference standards of category 5 of each scoring system. The sensitivity and specificity values of these guidelines were as follows: ACR-TIRADS, 60.7% and 95.4%; EU-TIRADS, 71.4% and 93.3%; ATA-2015, 71.4% and 93.3%; and K-TIRADS, 67.9% and 93.3%. The biopsy rate of malignant nodules was 57.1% for K-TIRADS and ATA, whereas this value was 46.4% for ACR and EU-TIRADS. ACR-TIRADS had the lowest unnecessary biopsy rate (141 of 238 benign nodules, 46%). The diagnostic performance of 4 risk stratification systems appears to be comparable, as shown by similar sensitivity, specificity, and area under the curve values. However, the ACR-TIRADS had slightly higher accuracy and necessitated fewer unnecessary biopsies for benign nodules.
The Right Ventricular Fetal Tricuspid Annular Plane Systolic Excursion Index Is a New Index for Evaluating Fetal Cardiac Function of Gestational Hypertension
Authors: He Shao-Zheng , Lai Fang-Ping , Zeng Piao-Yi , Zhang Shi-Jie , Lyu Guo-Rong
Published: November 2023

The right ventricular fetal tricuspid annular plane systolic excursion index (FTI) can be used to evaluate right ventricular systolic function. The purpose of this study was to establish the reference range of the FTI in normal fetuses and evaluate its diagnostic value in hypertensive disorders during pregnancy. In this prospective observational study, the right ventricular FTI was measured in 208 normal single-gestation fetuses between 20 and 40 weeks. With the increase in gestational age, the right ventricular FTI did not significantly fluctuate. With the increase in the severity of HDCP, the right ventricular FTI decreased gradually. Compared with the normal group, the low right ventricular FTI group had a higher incidence of premature delivery and emergency delivery due to continuous abnormal fetal heart monitoring, but there were no significant differences in low birth weight, new born Apgar score less than 7 in 5 minutes, or admission to the neonatal intensive care unit. The FTI of the right ventricle of normal fetuses is relatively constant at different gestational weeks. The right ventricular FTI can be used to evaluate fetal cardiac function changes in pregnant women with HDCP.
Association of High Body Mass Index With Postoperative Complications After Chest Masculinization Surgery
Authors: Hassan Bashar , Schuster Calvin R. , Ascha Mona , Del Corral Gabriel , Fischer Beverly , Liang Fan
Published: November 2023

Purpose

Body mass index (BMI) requirements for transgender and nonbinary patients undergoing chest masculinization surgery (CMS) are not standardized and based on small sample sizes. This is the largest and first national retrospective study to determine the association between BMI and postoperative complications.

Methods

The National Surgical Quality Improvement Program 2012–2020 was queried for CMS patients. The primary outcome was incidence of at least one complication within 30 days. Secondary outcomes were incidence of major and minor complications. Body mass index (in kilograms per square meter) was categorized as category 0 (<30), 1 (30–34.9), 2 (35–39.9), 3 (40–44.9), 4 (45–49.9), and 5 (≥50). Logistic regression was used to evaluate the association between BMI and outcomes.

Results

Of 2317 patients, median BMI was 27.4 kg/m2 (interquartile range, 23.4–32.2 kg/m2). Body mass index range was 15.6 to 64.9 kg/m2. While increasing BMI was significantly associated with greater odds of at least one complication, no patients experienced severe morbidity, regardless of BMI. Patients with BMI ≥50 kg/m2 had an adjusted odds ratio [aOR, 95% confidence interval (CI)] of 3.63 (1.02–12.85) and 36.62 (2.96–>100) greater odds of at least one complication and urinary tract infection compared with nonobese patients, respectively. Patients with BMI ≥35 kg/m2 had an adjusted odds ratio (95% CI) of 5.06 (1.5–17.04) and 5.13 (1.89–13.95) greater odds of readmission and surgical site infection compared with nonobese patients, respectively.

Conclusions

Chest masculinization surgery in higher BMI patients is associated with greater odds of unplanned readmission. Given the low risk for severe complications in higher BMI individuals, we recommend re-evaluation of BMI cutoffs for CMS patients.
Evolving Trends in Kidney Transplant Outcomes Among Older Adults: A Comparative Analysis Before and During the COVID-19 Pandemic
Authors: Li Yiting , Menon Gayathri , Wu Wenbo , Musunuru Amrusha , Chen Yusi , Quint Evelien E. , Clark-Cutaia Maya N. , Zeiser Laura B. , Segev Dorry L. , McAdams-DeMarco Mara A.
Published: November 2023

Background.

Advancements in medical technology, healthcare delivery, and organ allocation resulted in improved patient/graft survival for older (age ≥65) kidney transplant (KT) recipients. However, the recent trends in these post-KT outcomes are uncertain in light of the mounting burden of cardiovascular disease, changing kidney allocation policies, heterogeneity in candidates’ risk profile, and the coronavirus disease 2019 pandemic. Thus, we examined secular trends in post-KT outcomes among older and younger KT recipients over the last 3 decades.

Methods.

We identified 73 078 older and 378 800 younger adult (aged 18–64) recipients using Scientific Registry of Transplant Recipients (1990–2022). KTs were grouped into 6 prepandemic eras and 1 postpandemic-onset era. Kaplan-Meier and Cox proportional hazards models were used to examine temporal trends in post-KT mortality and death-censored graft failure.

Results.

From 1990 to 2022, a 19-fold increase in the proportion of older KT recipients was observed compared to a 2-fold increase in younger adults despite a slight decline in the absolute number of older recipients in 2020. The mortality risk for older recipients between 2015 and March 14, 2020, was 39% (adjusted hazard ratio [aHR] = 0.61, 95% confidence interval [CI], 0.50-0.75) lower compared to 1990–1994, whereas that for younger adults was 47% lower (aHR = 0.53, 95% CI, 0.48-0.59). However, mortality risk during the pandemic was 25% lower (aHR = 0.75, 95% CI, 0.61-0.93) in older adults and 37% lower in younger adults (aHR = 0.63, 95% CI, 0.56-0.70) relative to 1990–1994. For both populations, the risk of graft failure declined over time and was unaffected during the pandemic relative to the preceding period.

Conclusions.

The steady improvements in 5-y mortality and graft survival were disrupted during the pandemic, particularly among older adults. Specifically, mortality among older adults reflected rates seen 20 y prior.
Solibacillus daqui sp. nov., isolated from high-temperature Daqu
Authors: Liang Yuan , Shi Wei , Wu Lin-Huan , Zhang Xiao-Juan , Chai Li-Juan , Liu Guang-Qian , Zheng Lei , Wang Song-Tao , Zhang Su-Yi , Chen Fu-Wei , Shen Cai-Hong , Xu Zheng-Hong , Lu Zhen-Ming
Published: November 2023

A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterial strain, designated ZS111008T, was isolated from high-temperature Daqu, a starter for production of Chinese Jiang-flavour Baijiu, and was characterized by polyphasic taxonomy. This novel isolate grew in the presence of 0–5 % (w/v) NaCl, at pH 6.0–9.0 and 25–45 °C; optimum growth was observed with 1 % (w/v) NaCl, at pH 8.0 and 30 °C. A comparative analysis of the 16S rRNA gene sequence (1461 bp) of strain ZS111008T showed highest similarity to

Solibacillus silvestris

DSM12223T (96.7%), followed by

Solibacillus cecembensis

PN5T (96.6%) and

Solibacillus isronensis

AMCK01000046 (96.5%). The DNA G+C content of strain ZS111008T was 37.21 mol%. The respiratory quinone was identified as menaquinone-7 and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unknown phospholipid. Lys was detected as the diagnostic diamino acid in the cell wall. Based on morphological characteristics, chemotaxonomic characteristics and physiological properties, strain ZS111008T represents a novel species of the genus

Solibacillus

, for which the name Solibacillus daqui sp. nov. is proposed. The type strain for this proposed species is ZS111008T (=CGMCC 1.19455T=JCM 35214T).
Functional expression of a Mo-dependent formate dehydrogenase inEscherichia coliunder aerobic conditions
Authors: Schulz Marion , Berger Anne , Dubois Ivan , Delmas Valérie , Cadillon Mélodie , Bouzon Madeleine , Döring Volker
Published: November 2023

Background

Oxygen tolerant complex metal-dependent formate dehydrogenases hold potential for biotechnological applications.

Principle Findings

In this work, we report the functional expression of the complex, molybdenum-dependent soluble formate dehydrogenase encoded by thefdsGBACDoperon fromCupriavidus necator(CnFDH) inEscherichia coli.Expression of the operon from plasmids or from a copy integrated in the chromosome enabled growth of an energy-auxotrophic selection strain on formate as sole energy source under aerobic conditions. Growth could be accelerated in turbidostat, leading to a drop of the generation time of 1 hour. While no mutation was found in the operon of evolved isolates, genome sequencing revealed non-synonymous point mutations in the genefocAcoding for a bidirectional formate transporter carried in all isolates sequenced. Reverting the mutations led to a drop in the growth rate demonstrating thefocAmutation as principle target of continuous culture adaptation.

Significance

A member of the oxygen-tolerant subclass of complex FDH showed stable formate oxidation activity when expressed in the heterologous hostE. coli, a model organism of biotechnology. The integration of the operon in the chromosome offers the possibility of structure/function studies and activity enhancements throughin vivomutagenesis, which can also be applied to CO2reduction in appropriate selection hosts.
A polydiolcitrate-MoS2composite for 3D printing Radio-opaque, Bioresorbable Vascular Scaffolds
Authors: Szydlowska Beata M. , Ding Yonghui , Moore Connor , Cai Zizhen , Torres-Castanedo Carlos G. , Jones Evan , Hersam Mark C. , Sun Cheng , Ameer Guillermo A.
Published: November 2023

Implantable polymeric biodegradable devices, such as biodegradable vascular stents or scaffolds, cannot be fully visualized using standard X-ray-based techniques, compromising their performance due to malposition after deployment. To address this challenge, we describe composites of methacrylated poly(1,12 dodecamethylene citrate) (mPDC) and MoS2 nanosheets to fabricate novel X-ray visible radiopaque and photocurable liquid polymer-ceramic composite (mPDC-MoS2). The composite was used as an ink with micro continuous liquid interface production (μCLIP) to fabricate bioresorbable vascular scaffolds (BVS). Prints exhibited excellent crimping and expansion mechanics without strut failures and, importantly, required X-ray visibility in air and muscle tissue. Notably, MoS2nanosheets displayed physical degradation over time in a PBS environment, indicating the potential for producing bioresorbable devices. mPDC-MoS2is a promising bioresorbable X-ray-visible composite material suitable for 3D printing medical devices, particularly vascular scaffolds or stents, that require non-invasive X-ray-based monitoring techniques for implantation and evaluation. This innovative composite system holds significant promise for the development of biocompatible and highly visible medical implants, potentially enhancing patient outcomes and reducing medical complications.

TOC
What is Known, Unknown, and Needed to be Known about Damage Caused by Wild Pigs
Authors: VerCauteren Kurt C. , Pepin Kim M. , Cook Seth M. , McKee Sophie , Pagels Abigail , Kohen Keely J. , Messer Ingrid A. , Glow Michael P. , Snow Nathan P.
Published: November 2023

Damage assessments provide evidence for initiating and evaluating management programs that protect natural resources and human livelihoods against invasive species. Wild pigs (Sus scrofa) cause extensive damage in their native and non-native ranges, but the extent of current damage and efficacy of management of the damage (i.e., population control of wild pigs, exclusion fencing, etc.) remains poorly described. We conducted a systematic review of physical damage caused by wild pigs to summarize what is known and identify knowledge gaps for damage assessment. Wild pig damage assessments have been overwhelmingly qualitative (84% of studies) and measured differently across studies, which prevents the determination of typical damage amounts to a particular resource and comparison across studies. Key priorities going forward are to standardize damage assessments quantitatively and measure population density (or index of such) of wild pigs concurrently with damage assessments to determine the relationship between damage and population levels. We provide a framework for inferring damage in new areas and assessing the benefits of management – to evaluate and optimize landscape-scale management programs. Overall, we recommend future studies strive for: 1) report the amount of damages in a standardized fashion (e.g., area damaged/area surveyed), 2) evaluate and report the amount of damage relative to the density of wild pigs, and 3) when reporting economic costs of damages incurred and management actions, describe the economic valuation method used along with the year of reference for the valuation. Capturing these elements are necessary steps to predict the benefits of management for an area with particular profile of resources and wild pig density, even in areas where damage assessments are not available. Meeting these criteria with allow for more generalizable results that can inform managers across the nearly global distribution of wild pigs
Simplifying bioinformatics data analysis through conversation
Authors: Dong Zhengyuan , Zhou Han , Jiang Yifan , Zhong Victor , Lu Yang Young
Published: November 2023

The rapid advancements in high-throughput sequencing technologies have produced a wealth of omics data, facilitating significant biological insights but presenting immense computational challenges. Traditional bioinformatics tools require substantial programming expertise, limiting accessibility for experimental researchers. Despite efforts to develop user-friendly platforms, the complexity of these tools continues to hinder efficient biological data analysis. In this paper, we introduce BioMANIA– an AI-driven, natural language-oriented bioinformatics pipeline that addresses these challenges by enabling the automatic and codeless execution of biological analyses. BioMANIA leverages large language models (LLMs) to interpret user instructions and execute sophisticated bioinformatics work-flows, integrating API knowledge from existing Python tools. By streamlining the analysis process, BioMANIA simplifies complex omics data exploration and accelerates bioinformatics research. Compared to relying on general-purpose LLMs to conduct analysis from scratch, BioMANIA, informed by domain-specific biological tools, helps mitigate hallucinations and significantly reduces the likelihood of confusion and errors. Through comprehensive benchmarking and application to diverse biological data, ranging from single-cell omics to electronic health records, we demonstrate BioMANIA’s ability to lower technical barriers, enabling more accurate and comprehensive biological discoveries.
dms-viz: Structure-informed visualizations for deep mutational scanning and other mutation-based datasets
Authors: Hannon William W. , Bloom Jesse D.
Published: November 2023

Summary and Purpose

Understanding how mutations impact a protein’s functions is valuable for many types of biological questions. High-throughput techniques such as deep-mutational scanning (DMS) have greatly expanded the number of mutation-function datasets. For instance, DMS has been used to determine how mutations to viral proteins affect antibody escape (Dadonaite et al. 2023), receptor affinity (Starr et al. 2020), and essential functions such as viral genome transcription and replication (Li et al. 2023). With the growth of sequence databases, in some cases the effects of mutations can also be inferred from phylogenies of natural sequences (Bloom and Neher 2023) (Figure 1).

The mutation-based data generated by these approaches is often best understood in the context of a protein’s 3D structure; for instance, to assess questions like how mutations that affect antibody escape relate to the physical antibody binding epitope on the protein. However, current approaches for visualizing mutation data in the context of a protein’s structure are often cumbersome and require multiple steps and softwares. To streamline the visualization of mutation-associated data in the context of a protein structure, we developed a web-based tool,dms-viz. Withdms-viz, users can straightforwardly visualize mutation-based data such as those from DMS experiments in the context of a 3D protein model in an interactive format. Seehttps://dms-viz.github.io/to usedms-viz.
Proteomic evidence of depression-associated astrocytic dysfunction in the human male olfactory bulb
Authors: Rahimian Reza , Perlman Kelly , Fakhfouri Gohar , Mpai Refilwe , Richard Vincent R. , Hercher Christa , Penney Lucy , Davoli Maria Antonietta , Nagy Corina , Zahedi René P. , Borchers Christoph H. , Giros Bruno , Turecki Gustavo , Mechawar Naguib
Published: November 2023

The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p<0.05) between depressed cases and controls. Gene ontology and gene enrichment analyses suggested that these proteins are involved in biological processes including the complement and coagulation cascades. Cell type enrichment analysis displayed a significant reduction in several canonical astrocytic proteins in OBs from depressed patients. Furthermore, using RNA-fluorescencein-situhybridization, we observed a decrease in the percentage of ALDH1L1+cells expressing canonical astrocytic markers includingALDOC,NFIA,GJA1 (connexin 43)andSLC1A3 (EAAT1). These results are consistent with previous reports of downregulated astrocytic marker expression in other brain regions in depressed patients. We also conducted a comparative phosphoproteomic analysis of OB samples and found a dysregulation of proteins involved in neuronal and astrocytic functions. To determine whether OB astrocytic abnormalities is specific to humans, we also performed proteomics on the OB of socially defeated male mice, a commonly used model of depression. Cell-type specific analysis revealed that in socially defeated animals, the most striking OB protein alterations were associated with oligodendrocyte- lineage cells rather than with astrocytes, highlighting an important species difference. Overall, this study further highlights cerebral astrocytic abnormalities as a consistent feature of depression in humans.
A Method for Optimizing Imaging Parameters to Record Neuronal and Cellular Activity at Depth with Bioluminescence
Authors: Silvagnoli Alexander D. , Taylor Kaylee A. , Slaviero Ashley N. , Petersen Eric D.
Published: November 2023

Optical imaging of activity has provided valuable insight into brain function and accelerated the field of neuroscience in recent years. Genetically encoded fluorescent activity sensors of calcium, neurotransmitters and voltage have been tools of choice for optical recording of neuronal activity. However, photon scattering and absorbance limits fluorescence imaging to superficial regions forin vivoactivity imaging. This limitation prevents recording of population level activity in lower brain regions of experimental animals without implanted hardware. Single and multiphoton methods find maximal use in the cortex and experience loss of signal at greater depths. Successful efforts have been made to increase the depth of fluorescence imaging using fiber photometry and gradient reflective index lenses. However, these methods are highly invasive, requiring an implant within the brain. Bioluminescence imaging offers a promising alternative to achieve activity imaging in deeper brain regions without hardware implanted within the brain. Bioluminescent reporters can be genetically encoded and produce photons without external excitation. The use of enzymatic photon production also enables prolonged imaging sessions without the risk of photobleaching or phototoxicity. These characteristics render bioluminescence suitable to non-invasive imaging of deep neuronal populations. To facilitate the adoption of bioluminescent activity imaging, we sought to develop a low cost, simplein vitromethod to optimize imaging parameters for determining optimal exposure times and optical hardware configurations to determine what frame rates can be captured with an individual lab’s imaging hardware with sufficient signal-to-noise ratios without the use of animals prior to starting anin vivoexperiment. To achieve this, we developed an assay for modelingin vivooptical conditions with a brain tissue phantom paired with engineered cells that produce bioluminescence. We then used this assay to limit-test the detection depth vs maximum frame rate for bioluminescence imaging at experimentally relevant tissue depths using off the shelf imaging hardware. With this method, we demonstrate an effective means for increasing the utility of bioluminescent tools and lowering the barrier to adoption of bioluminescence activity imaging with bioluminescent sensors.
Nucleolus and centromere TSA-Seq reveals variable localization of heterochromatin in different cell types
Authors: Kumar Pradeep , Gholamalamdari Omid , Zhang Yang , Zhang Liguo , Vertii Anastassiia , van Schaik Tom , Peric-Hupkes Daan , Sasaki Takayo , Gilbert David M. , van Steensel Bas , Ma Jian , Kaufman Paul D. , Belmont Andrew S.
Published: November 2023

Genome differential positioning within interphase nuclei remains poorly explored. We extended and validated TSA-seq to map genomic regions near nucleoli and pericentric heterochromatin in four human cell lines. Our study confirmed that smaller chromosomes localize closer to nucleoli but further deconvolved this by revealing a preference for chromosome arms below 36-46 Mbp in length. We identified two lamina associated domain subsets through their differential nuclear lamina versus nucleolar positioning in different cell lines which showed distinctive patterns of DNA replication timing and gene expression across all cell lines. Unexpectedly, active, nuclear speckle-associated genomic regions were found near typically repressive nuclear compartments, which is attributable to the close proximity of nuclear speckles and nucleoli in some cell types, and association of centromeres with nuclear speckles in hESCs. Our study points to a more complex and variable nuclear genome organization than suggested by current models, as revealed by our TSA-seq methodology.
Altered astrocytic and microglial homeostasis characterizes a decreased proinflammatory state in bipolar disorder
Authors: Amossé Quentin , Tournier Benjamin B. , Badina Aurélien M. , Marchand-Maillet Lilou , Abjean Laurene , Lengacher Sylvain , Fancy Nurun , Smith Amy M. , Leung Yeung-Yeung , Santer Verena , Garibotto Valentina , Owen David R. , Piguet Camille , Ceyzériat Kelly , Tsartsalis Stergios , Millet Philippe
Published: November 2023

Multiple lines of evidence point to peripheral immune alterations in bipolar disorder (BD) although the activity of brain immune mechanisms remain largely unexplored. To identify the cell type-specific immune alterations in the BD brain, we performed a proteomic and single nuclear transcriptomic analysis ofpostmortemcingulate cortex samples from BD and control subjects. Our results showed that genes associated to the genetic risk for BD are enriched in microglia and astrocytes. Transcriptomic alterations in microglia point to a reduced proinflammatory phenotype, associated to reduced resistance to oxidative stress and apoptosis, which was confirmed with immunohistochemical quantification of IBA1 density. Astrocytes show transcriptomic evidence of an imbalance of multiple metabolic pathways, extracellular matrix composition and downregulated immune signalling. These alterations are associated toADCY2andNCAN,two GWAS genes upregulated in astrocytes. Finally, cell-cell communication analysis prioritized upregulated SPP1-CD44 signalling to astrocytes as a potential regulator of the transcriptomic alterations in BD. Our results indicate that microglia and astrocytes are characterized by downregulated immune responses associated to a dysfunction of core mechanisms via which these cells contribute to brain homeostasis.
Safety Assessment of Intravenous Injection of Rat Embryonic Proteome Extract forin-vivoRegenerative Therapies
Authors: Darsi Siva Rama Prasad , Kandula Siva Kumar , Bharani Kala Kumar , Pasupalati Anil Kumar , Cheekatla Satyanarayana Swamy , Darsi Sujesh Kumar , Kamireddy Adi Reddy , Barra Ram Reddy , Devarasetti Ashok Kumar , Surampudi Sreedhar , Singireddy Jaya Ram Raddy
Published: November 2023

Back ground

Tissue differentiation and organogenesis are exclusively embryonic-phase activities, and these two activities are strictly under the control of the embryonic proteome, the developing embryo is a prime source of molecules for regenerative therapy. Manyex-vivorudimentary organoid culture studies confirmed the inherent biological function of embryonic factors. Before using embryonic proteins for in vivo therapies, their safety should be confirmed first. Hence, we aimed for anin vivostudy to inject rat embryonic proteome extract (EPE) through the intravenous route and investigate the impact on immunological, biochemical, and hematological parameters in the adult rats.

Methods

In this study, we isolated rat embryonic proteins from the 14th, 16th, and 19thembryonic days by homogenization of embryos and isolated protein extracts through ultra-centrifugation. Six pairs of rats have been taken; six are allotted for control, and six are for the embryonic extract injection. The isolated embryonic protein extract was injected intravenously into the treatment group of rats and the normal saline into the control group. After the injections, blood samples are collected from both the treated and control groups to analyse immunological markers Il6, CRP, biochemical parameters creatinine, urea, sugar, proteins, albumin, globulin, and hematological parameters total leucocyte count, neutrophils, and lymphocyte percentage

Result

After the EPE injection, biochemical parameters, immunological markers, and hematological parameters were analyzed in both control and treated groups. All the above mentioned parameters are within normal limits. Statistical analyses were done using the t-test for unequal variance (p< 0.05). We observed no significant difference between the control and treated groups, soin vivoinjections of embryonic protein extract is safe for the use ofin vivoregenerative therapies.

Conclusion

Despite extensivein vitrostudies confirmed the biological function of embryonic growth factors for organ differentiations and rudimentary organoids, butin vivoclinical applications are not yet started because of immunogenicity, heterogeneity, and tumorigeniety. In our study we injected EPE intravenously and showed that EPE is non-immunogenic, non-heterogeneic, and non-tumorigenic. This study concludes that EPE is safe for in vivo injection, so that further studies can be continued for intra-organ injections for organ regenerative therapy.
Pepid: a Highly Modifiable, Bioinformatics-Oriented Peptide Search Engine
Authors: Zumer Jeremie , Lemieux Sébastien
Published: November 2023

Motivation

Current peptide search engines are optimized for wet-lab workflows, i.e. they operate in an “end-to-end” manner to achieve good identification results, not to be modified or provide algorithmic insight. This makes developing new software methods to solve problems in peptide identification methods difficult, often requiring a full engine rewrite. Recently, many deep learning methods were proposed as solutions to various parts of the peptide identification task, but virtually none of those methods have been implemented in any actual peptide search process. We believe that the lack of a reliable bioinformatics research platform for peptide identification that enables such integrations is slowing down proteomics research as a whole.

Results

We present pepid, a bioinformatics research-oriented peptide search engine. Unlike other search engines, pepid is specifically designed with ease of computational research in mind. Our design is highly flexible and allows easy modifications with little required software development expertise, allowing researchers to focus on analysing and improving peptide identification methods.It also takes recent computational trends into account, such as the recent slew of deep learning publications in proteomics, and features a multi-phased batched operations design that is more appropriate than the spectrum batch “end-to-end” designs of existing search engines for those approaches. We show that pepid is competitive with common engines in terms of both identification rates and runtime, forming a minimum required baseline to enable further identification research.

Availability and Implementation

Pepid is available as open source software under the MIT license athttps://github.com/lemieux-lab/pepid. Other data referenced in the text is 3rd party. The selected yeast proteome can be found on SwissProt with accession ID UP000002311 while the human proteome’s accession ID is UP0000005640. The ProteomeTools spectra can be found in the PRIDE archive under accession D PXD004732 and the One Hour Yeast Proteome can be found at the ChorusProject athttps://chorusproject.org/anonymous/download/experiment/-8823069691100997209andhttps://chorusproject.org/anonymous/download/experiment/449795368199176159.