bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and effectiveness of ustekinumab in elderly Crohn’s disease patients
Authors: Fiske Joseph , Liu Eleanor , Limdi Jimmy K. , Conley Thomas E. , Townsend Tristan , Davies Mike , Brockwell Robert , Baig Daniyal , Abdelbadiee Sherif , Uney Anastasia , Liaros Angela , Gaba Waqas , Smith Philip J. , Flanagan Paul K. , Subramanian Sreedhar
Published: September 2022

Objective

Anti-tumour necrosis factor (TNF) agents are associated with increased infection risk among elderly IBD patients, but little is known about non anti-TNF biologics in this cohort. We examined the safety and effectiveness of ustekinumab in elderly Crohn’s patients.

Methods

This retrospective multi-centre cohort study included Crohn’s patients ≥60-years old who commenced ustekinumab. We recorded Harvey-Bradshaw index (HBI), concomitant steroid therapy, treatment persistence and new infections or malignancies. Primary outcome was serious infections requiring hospitalisation.

Results

Seventy patients were included, with median age of 68 years. 43 (61.4%) had prior anti-TNF exposure, and 15 (21.4%) vedolizumab. Median treatment duration was 12 months, totalling 84 patient-years. Nine serious infections were reported, incidence 106.7/1000 patient-years. Systemic steroids were associated with increased risk of serious infections [odds ratio (OR) 7.83, 95% confidence interval (CI): 1.44–44.32, P = 0.02]. There were 27 “non-serious” infections; 321.4/1000 patient-years. Charlson co-morbidity index (OR 1.49, 95% CI: 1.05–2.12, P = 0.03) and steroid exposure (OR 44.10, 95% CI: 1.75–1112.10, P = 0.02) increased non-serious infection risk (P < 0.05). Mean HBI improved from 8.13 to 4.64 at 6 months and 4.10 at last follow up (P < 0.0001). 12-month treatment persistence was 55.7% (N = 39); 34 (48.6%) were steroid-free.

Conclusion

Ustekinumab was safe and effective in a cohort of elderly Crohn’s disease patients. Infections were mostly mild, not resulting in therapy discontinuation. Serious infection risk was comparable to previously reported rates with anti-TNF agents. Steroid exposure was associated with an increased serious infection risk.
Comparison of liver function test- and inflammation-based prognostic scores for coronavirus disease 2019: a single center study
Authors: Cholongitas Evangelos , Bali Triada , Georgakopoulou Vasiliki E , Kamiliou Aikaterini , Vergos Ioannis , Makrodimitri Sotiria , Samara Stamatia , Triantafylou Maria , Basoulis Dimitrios , Eliadi Irene , Karamanakos Georgios , Sipsas Nikolaos V. , Samarkos Michael
Published: September 2022

Background

Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed.

Methods

1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded.

Results

One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3–72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034–1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 >2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P < 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index >36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002–1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004–1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006–1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR >12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024).

Conclusions

FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.
Role of mast cells in eosinophilic esophagitis
Authors: Janarthanam Rethavathi , Bolton Scott M. , Wechsler Joshua B.
Published: September 2022

Purpose of review

This review will present what is known from recent research on the involvement of mast cells in eosinophilic esophagitis and identify questions requiring further investigation.

Recent findings

In the adults and children with eosinophilic esophagitis, there is increasing evidence that mastocytosis can persist, despite resolution of eosinophilia and is associated with persistent mucosal abnormalities and symptoms. Despite, treatment mast cells have an activated transcriptome. Mast cells likely contribute to epithelial barrier dysfunction, smooth muscle hypertrophy and contraction, and subepithelial fibrosis. Targeting mast cells alone is not effective at improving the tissue damage.

Mast cells appear to play a key role in eosinophilic esophagitis and serve as a biomarker of mucosal healing in conjunction with eosinophils. Excessive mast cell activation likely contributes to tissue damage in eosinophilic esophagitis and need to be considered as a target of therapy along with eosinophils.
Immunologic effects of red blood cell and platelet transfusions in neonates
Authors: Davenport Patricia , Sola-Visner Martha
Published: September 2022

Purpose of Review

Premature neonates are frequently transfused red blood cells (RBCs) or platelets to raise hemoglobin or platelet counts. However, these transfusions may have unintended effects on the immune system. This review will summarize the newest discoveries on the immunologic effects of RBC and platelet transfusions in neonates, and their potential impact on neonatal outcomes.

Recent Findings

Neonatal RBC transfusions are associated with increases in plasma pro-inflammatory cytokines, but recent findings suggest sex-specific differential responses. At least one cytokine (monocyte chemoattractant protein-1) rises in females receiving RBC transfusions, but not in males. These inflammatory responses correlate with poorer neurodevelopmental outcomes in heavily transfused female infants, while preterm male infants seem to be more sensitive to severe anemia. Platelet transfusions in preterm neonates are associated with increased neonatal mortality and morbidity. The underlying mechanisms are unknown, but likely related to the immune/inflammatory effects of transfused platelets. Adult platelets are different from neonatal platelets, with the potential to be more pro-inflammatory. Early preclinical data suggest that platelet transfusions alter the neonatal systemic inflammatory response and enhance immune cell migration.

RBC and platelet transfusions alter neonatal immune and inflammatory responses. Their pro-inflammatory effects might worsen neonatal disease or affect neurodevelopmental outcomes.
N6-methyladenosine in hematological malignancies: a concise review
Authors: Wang Wan-Jie , Xu Ting-Ting , Bao Jing
Published: September 2022

Purpose of review

Hematological malignancies are a kind of systemic cancers mostly related to abnormal differentiation of blood stem cells. Because of the poor prognosis, chemotherapy resistance and common recurrence, new mechanisms and treatment therapies are looking forward to be discovered.

Recent findings

Over the years, epigenetic abnormalities have been known to act a key part in occurrence and development of hematological tumors. In the internal modifications on long noncoding eukaryotic mRNA, there is a common type called N6-methyladenosine that can change the expression of target genes and participate in the translation, degradation and splicing of mRNA. M6A is related to a wealth of cancers, such as HNRNPA2B1's elevation in multiple myeloma, METTLE3's elevation in acute myeloid leukemia and lung cancer. Immune cells, playing a significant role in hematological cancers, can also be regulated by m6A.

In the review, we summarized the recent progress on hematological malignancies associating with m6A and immune cells, which may offer a new road for the treatment of them.
Offering Support and Staying Inspired
Authors: Begley Robyn
Published: September 2022

This year, Maureen Swick, PhD, MSN, RN, NEA-BC, received the American Organization for Nursing Leadership (AONL) prestigious Lifetime Achievement Award, which honors an AONL member recognized by the nursing community as a significant leader in the nursing profession who has served AONL in an important leadership capacity. Swick served as chair of the AONL Board of Directors and AONL CEO/American Hospital Association chief nursing officer. She has held executive leadership roles at several health systems and now is enterprise senior vice president of nursing and pharmacy at Atrium Health, Charlotte, North Carolina. This is an abridged version of an interview conducted by AONL CEO Robyn Begley, DNP, RN, NEA-BC, FAAN, at the AONL annual conference in San Antonio in April 2022. Dr Swick also responded to questions from the audience.
Not So Sweet
Authors: Smith Amber L. , Quatrara Beth , Miller Kimberly , Novicoff Wendy , Calabrese Nicholas
Published: September 2022

Clearly identifying patients with prediabetes and diabetes prior to surgery allows the clinical team to target interventions and reduce the risks of complications. Yet, protocols for preoperative diabetes screening vary. The purpose of this article is to present an evidence-based practice project examining the implementation of preoperative diabetes screening in an elective total joint patient population. The American Diabetes Association (ADA) Risk Test was used to assess diabetes risk and guide further testing. A total of 121 patients were screened. Of the sample, 55 were undiagnosed and at risk for diabetes according to the instrument. Twelve patients (21.8%) who screened at risk also revealed elevated fasting blood glucose levels. These patients were identified as potentially having prediabetes. The findings of this project support adoption of the ADA Risk Test in the preoperative setting, emphasize the feasibility of its integration in order to obtain valuable patient information, and assist with optimizing patients for surgery.
The Accuracy of In-State Prescription Monitoring Program Database and Electronic Medical Records Compared to Urine Toxicology Screening in Total Joint Arthroplasty Preoperative Evaluation
Authors: Curry Emily , Niu Ruijia , Burapachaisri Aonnicha , Mauricio Paolo , McAlpine Kenneth , Smith Eric L.
Published: September 2022

Preoperative narcotic use is associated with poor postoperative pain management and worse outcomes after total joint arthroplasty (TJA). Therefore, identifying controlled substance use preoperatively is necessary. Electronic medical records (EMRs), prescription monitoring programs (PMP), or urine toxicology screening (UTS) are most commonly used. This study aims to compare the accuracy of EMR and PMP versus UTS to determine whether UTS should be implemented as standard of care in TJA preoperative assessment. Preoperative UTS was performed for primary or revision TJA from November 1, 2018, to March 31, 2019. Patient demographics, medical history, prescription history, and UTS results were retrospectively recorded. Prescription monitoring program and EMR were queried for prescription history in the past 2 years. The accuracy of EMR and PMP compared with UTS was calculated. Multivariable logistic regression analysis was performed to identify patient predictors associated with UTS+. Thirty of 148 patients had UTS+. Positive urine toxicology screening was more common in patients younger than 58 years, White race, and undergoing revision surgery. Electronic medical record and PMP documentation had the highest sensitivity (73.3%), specificity (92.4%), positive predictive value (71.0%), and negative predictive value (93.2%). Patients with higher odds of UTS+ include current/former smokers, those with a history of alcohol abuse, drug abuse, hepatitis C diagnosis, and mental illness. For patients without any risk factors for having a UTS+, the use of EMR and PMP may be sufficient to evaluate for controlled substance use; however, UTS should be considered in patients who present with one of the risk factors for UTS+.
Hot Air Balloon Fatalities in New Mexico
Authors: Gallego Daniel F. , Zuluaga Ruiz Maria E. , Bodor Garon , Lathrop Sarah , Proe Lori
Published: September 2022

Introduction

Albuquerque New Mexico is the “hot air balloon capital of the world,” with balloons flying throughout the year and during the Albuquerque International Balloon Fiesta. The medical literature regarding morbidity and mortality in hot air balloon accidents is relatively scarce.

Methods

A series of fatal, hot air balloon accidents were identified by querying and analyzing the databases of the Office of the Medical Investigator in New Mexico from 1972 to 2021.

Results

Twenty-one lethal cases from 11 hot air balloon accidents were evaluated. Fifty-seven percent of decedents were male, the age range was 29 to 74 years, and all the decedents were White. Causes of death were certified as multiple injuries (52.4%), blunt trauma (42.9%), and electrocution (4.76%). The manner of death was accidental in all cases. Most common autopsy findings were rib fractures (100%), pelvic fractures (81.8%), and subarachnoid hemorrhage (72.7%). October was the month with the most accidents (63.63%), the most common cause was the pilot's failure to maintain clearance from obstacles (14.3%), and the most frequent collision was with power lines (63.6%).

Conclusions

Hot air balloon fatalities are rare, and the patterns of injury resemble those seen in free falls from significant heights with extensive blunt trauma.
Evaluation of “Real-Time” Fatal Drug Overdose Surveillance by King County Medical Examiner's Office, Seattle, Washington
Authors: Harruff Richard , Simpson Celia M. , Gifford Amy L. , Yarid Nicole , Barbour William L. , Heidere Catherine
Published: September 2022

To address the challenges in monitoring the continuously accelerating drug overdose epidemic, the King County Medical Examiner's Office in Seattle, Washington, instituted a “real-time” fatal drug overdose surveillance project, depending on scene investigations, autopsy findings, and in-house testing of blood, urine, and drug evidence collected from death scenes. Validation of the project's rapid death certification methodology from 2019 through 2021 was performed at the following 3 levels: blood testing, urine testing, and death certification, and for the following 4 drugs: fentanyl, opiate, methamphetamine, and cocaine. For blood testing, sensitivity ranged from 90% to 99%, and specificity ranged from 86% to 97%. For urine testing, sensitivity ranged from 91% to 92%, and specificity ranged from 87% to 97%. The positive predictive value for cocaine was poor for both blood testing (57%) and urine testing (72%). Of 1034 deaths, 807 were certified as overdose by rapid methodology, and 803 (99.5%) were confirmed by formal toxicology results. Manners of death were changed from accident to natural in 3 of 1034 cases (0.29%). Results of this study indicate that the rapid overdose surveillance methodology described in this study offers benefits to families and provides useful, timely information for responding law enforcement and public health agencies.
PD-L1 Expression in Triple-negative Breast Cancer—a Comparative Study of 3 Different Antibodies
Authors: Vlajnic Tatjana , Baur Fabienne , Soysal Savas D. , Weber Walter P. , Piscuoglio Salvatore , Muenst Simone
Published: September 2022

Background:

Assessment of programmed death protein-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) has entered daily practice to identify patients eligible for treatment with immune checkpoint inhibitors. However, different antibodies and different cut-offs for PD-L1 positivity are used, and the interchangeability of these methods is not clear. The aim of our study was to analyze whether different PD-L1 antibodies can be used interchangeably to identify TNBC patients as PD-L1 positive.

Methods:

A tissue microarray encompassing 147 TNBC cases was immunohistochemically analyzed using 3 different antibodies against PD-L1: SP142, SP263, and E1L3N. PD-L1 positivity was determined as ≥1% of positive tumor-associated immune cells. The staining patterns of the 3 antibodies were compared and correlated with clinicopathological data.

Results:

A total of 84 cases were evaluable for PD-L1 analysis with all 3 antibodies. PD-L1 was positive in 50/84 patients (59.5%) with SP263, in 44/84 (52.4%) with E1L3N, and in 29/84 (34.5%) with SP142. There was no statistical difference between the performance of SP263 and E1L3N, but both antibodies stained significantly more cases than the SP142 antibody.

Conclusions:

Our results show that the 3 PD-L1 antibodies identify different TNBC patient subgroups as PD-L1 positive and, therefore cannot be used interchangeably. Additional studies are needed to further investigate the use and impact of different PD-L1 antibody clones for predictive selection of TNBC patients for treatment with immune checkpoint inhibitors.
Modern Low-Field MRI of the Musculoskeletal System
Authors: Khodarahmi Iman , Keerthivasan Mahesh B. , Brinkmann Inge M. , Grodzki David , Fritz Jan
Published: September 2022

Magnetic resonance imaging (MRI) provides essential information for diagnosing and treating musculoskeletal disorders. Although most musculoskeletal MRI examinations are performed at 1.5 and 3.0 T, modern low-field MRI systems offer new opportunities for affordable MRI worldwide. In 2021, a 0.55 T modern low-field, whole-body MRI system with an 80-cm-wide bore was introduced for clinical use in the United States and Europe. Compared with current higher-field-strength MRI systems, the 0.55 T MRI system has a lower total ownership cost, including purchase price, installation, and maintenance. Although signal-to-noise ratios scale with field strength, modern signal transmission and receiver chains improve signal yield compared with older low-field magnetic resonance scanner generations. Advanced radiofrequency coils permit short echo spacing and overall compacter echo trains than previously possible. Deep learning–based advanced image reconstruction algorithms provide substantial improvements in perceived signal-to-noise ratios, contrast, and spatial resolution. Musculoskeletal tissue contrast evolutions behave differently at 0.55 T, which requires careful consideration when designing pulse sequences. Similar to other field strengths, parallel imaging and simultaneous multislice acquisition techniques are vital for efficient musculoskeletal MRI acquisitions. Pliable receiver coils with a more cost-effective design offer a path to more affordable surface coils and improve image quality. Whereas fat suppression is inherently more challenging at lower field strengths, chemical shift selective fat suppression is reliable and homogeneous with modern low-field MRI technology. Dixon-based gradient echo pulse sequences provide efficient and reliable multicontrast options, including postcontrast MRI. Metal artifact reduction MRI benefits substantially from the lower field strength, including slice encoding for metal artifact correction for effective metal artifact reduction of high-susceptibility metallic implants. Wide-bore scanner designs offer exciting opportunities for interventional MRI. This review provides an overview of the economical aspects, signal and image quality considerations, technological components and coils, musculoskeletal tissue relaxation times, and image contrast of modern low-field MRI and discusses the mainstream and new applications, challenges, and opportunities of musculoskeletal MRI.
Synthetic Contrasts in Musculoskeletal MRI
Authors: Hilbert Tom , Omoumi Patrick , Raudner Marcus , Kober Tobias
Published: September 2022

This review summarizes the existing techniques and methods used to generate synthetic contrasts from magnetic resonance imaging data focusing on musculoskeletal magnetic resonance imaging. To that end, the different approaches were categorized into 3 different methodological groups: mathematical image transformation, physics-based, and data-driven approaches. Each group is characterized, followed by examples and a brief overview of their clinical validation, if present. Finally, we will discuss the advantages, disadvantages, and caveats of synthetic contrasts, focusing on the preservation of image information, validation, and aspects of the clinical workflow.
Blood Perfusion Characteristics of Renal Cell Carcinoma in the Process of Tumor Growth: Monitored With Multiple Sonographic Modalities
Authors: Li Cui-Xian , Lu Qing , Li Cong , Wang Wen-Ping , Huang Bei-Jian
Published: September 2022

Tumor angiogenesis is an essential factor for tumor growth and antiangiogenic therapy. To simulate the blood perfusion characteristics of human renal cell carcinoma (RCC) longitudinally in the process of tumor growth, multimodal ultrasound examination was performed on 40 orthotopic xenograft RCC mouse models. According to tumor maximum diameter (d), tumor growth progress was divided into 3 steps: d ≤ 5 mm, 5 mm < d ≤ 10 mm, and d > 10 mm. Color Doppler flow imaging (CDFI), superb microvascular imaging (SMI), and contrast-enhanced ultrasound were administered to monitor tumor perfusion characteristics. The abundance of tumor vascularity on CDFI and SMI was divided into grades 0 to III in ascending order, and their distribution range was categorized into types I to IV. As a result, heterogeneous echogenicity and irregular shape were more common in tumors d > 10 mm than those d < 10 mm (P < 0.001 for both). Tumor perfusion grade and type on both CDFI and SMI made statistic difference among different growth steps, with higher ratio of hypervascular characteristic in bigger ones (all P < 0.05). Tumor in the same growth step had a higher perfusion grade on SMI than that on CDFI (P < 0.001). On contrast-enhanced ultrasound, heterogeneous enhancement was more common in those >10 mm (P < 0.001). It can be concluded that the blood perfusion characteristics of RCC keep on changing during its growth process. In addition, SMI is more sensitive in evaluating tumor perfusion than CDFI.
Influence of Vitamin D Consumption on Bone Mineral Density Among Saudi Women in Jeddah Not Taking Supplements
Authors: Hakim Noor A. , Hussein Khulood S.
Published: September 2022

This cross-sectional study of 341 women in Jeddah, Saudi Arabia, compared a 1-point-in-time vitamin D intake measurement assessed by the Semiquantitative Food Frequency Questionnaire with bone mineral density (BMD) at the lumbar spine and femur in pre- and post-menopausal women. Premenopausal women had significantly higher BMD at the lumbar spine and femur compared with postmenopausal women (P < .01). A significant positive association was seen between dietary vitamin D intake (95.5 ± 81.54 IU/day) and femur BMD at the trochanter (P < .05). Vitamin D intake of Saudi women is inadequate, suggesting the need for public health measures to promote improved nutrition in women and support an expansion of fortification programs.
The Use of the RELiZORB Immobilized Lipase Cartridge in Enterally-Fed Children With Cystic Fibrosis
Authors: Baghae Pour Parasto , Gregg Shannon , Coakley Kathryn E. , Caffey L. Francine , Cohen Deborah , Myers Orrin B. , Gonzales-Pacheco Diana
Published: September 2022

The objective of this retrospective study was to evaluate the impact of the RELiZORB immobilized lipase cartridge with overnight enteral nutrition (EN) on body mass index (BMI) or weight-for-length percentile, stool quality, and gastrointestinal (GI) symptoms in children with cystic fibrosis (CF) and pancreatic insufficiency. Frequency of diarrhea, steatorrhea, and malodorous stools significantly decreased at final visit compared with baseline (P = .008, P = .004, P = .031, respectively). Improved BMI or weight-for-length percentile was observed in 10 out of 16 participants; however, the change was not significant. RELiZORB use decreased frequency of most GI symptoms in pediatric patients with CF on EN.
Enhanced anxiolytic and analgesic effectiveness or a better safety profile of morphine and tramadol combination in cholestatic and addicted mice
Authors: Khakpai Fatemeh , Issazadeh Yasaman , Rezaei Niloofar , Zarrindast Mohammad-Reza
Published: September 2022

The involvement of the opioidergic system on anxiolytic and antinociceptive responses induced by cholestasis was investigated in cholestatic and addicted mice. Elevated plus-maze and tail-flick devices were used to assess anxiety and pain levels, respectively. The data indicated that induction of cholestasis and injection of opioid drugs including morphine and tramadol enhanced %OAT and %OAE but naloxone reduced %OAT and %OAE in the sham-operated and bile duct ligation (BDL) mice. Induction of cholestasis and addiction to morphine and tramadol prolonged tail-flick latency, which was reversed by naloxone. Coadministration of morphine and tramadol enhanced anxiolytic and analgesic effects in the sham-operated and BDL mice. It seems (a) cholestasis and addiction affect anxiety and pain behaviors, (b) μ-opioid receptors play a key role in anxiolytic and analgesic effects induced by cholestasis, and (c) cotreatment with morphine and tramadol augmented the effectiveness of them for induction of anxiolytic and analgesic effects both in cholestatic and addicted mice.
Mechanism of acteoside-activated let-7g-5P attenuating Aβ-induced increased permeability and apoptosis of brain microvascular endothelial cells based on experimental and network pharmacology
Authors: Wu Meijun , Gao Yue , Chen Bin
Published: September 2022

Objectives

Amyloid β-protein (Aβ)-induced apoptosis and oxidative stress of human brain microvascular endothelial cells(BMECs) are contributors to the development of Alzheimer’s disease (AD). Acteoside has shown its therapeutic potential for AD treatment. Therefore, this study investigated the effect of acteoside on Aβ-induced blood–brain barrier damage, oxidative stress and apoptosis as well as to explore the underlying mechanisms through network pharmacology.

Methods

The study used Aβ to induce human BMECs to construct an in-vitro injury model. Following treatment with acteoside, transendothelial electrical resistance (TEER), RT-qPCR and Western blot were used to evaluate the permeability of BMECs. The apoptosis level was detected by TUNEL and Western blot, ROS assay kit was used for the detection of reactive oxygen species (ROS) expression. The let-7g-5p expression level was detected by RT-qPCR. After additional treatment with let-7g-5p inhibitor, corresponding assays were performed again. Finally, network pharmacology was used to verify the mechanism.

Results

Acteoside decreased the permeability, oxidative stress and cell apoptosis of Aβ-stimulated cells. More importantly, acteoside-activated let-7g-5p and additional treatment with let-7g-5p inhibitor abated the effects of acteoside on Aβ-induced permeability, oxidative stress and apoptosis of Aβ-stimulated BMECs. According to network pharmacology, 233 targeted genes of acteoside and 122 potential targets of let-7g-5p were determined by screening several databases, and two targets called Casp-3 and ITGB3 were obtained after taking the intersection.

Conclusion

In conclusion, these results reveal that acteoside-activated let-7g-5p attenuating Aβ-induced increased permeability and apoptosis of human BMECs.
A LITERATURE REVIEW ON COMPLEMENTARY THERAPIES IN AUTISM CHILDREN: A NURSING SCIENCE PHILOSOPHY
Authors: Alfiyanti Dera , Pandin Moses Glorino Rumambo , Rahayuningtyas Imelda Rizky
Published: September 2022

Introduction

Autism is a neurodevelopmental disorder that can cause repetitive behavior, limited activity, and a lack of ability to communicate and socialize. The purpose of this literature review is to identify the effectiveness of Complementary mind-body-spirit therapies, manipulative and body-based therapies, and energy therapies in children with autism.

Method

Literature search method using ProQuest, PubMed, and Science Direct databases with include the keywords Complementary therapy in children with autism or Complementary therapy in children with autism. The search was limited to publication criteria in the 2018-2022 timeframe, full-text articles, and not review articles.

Results

Of the study showe that Complementary therapies are effective in improving development in children with autism consisting of mind-body-spirit therapies (music, yoga, Qur’an Murrotal Audio) effective in improving: communication and social skills also brain connectivity, the concentration, and attention span, and sleep quality, manipulative and body based therapies (physical activity, Tai Chi Chuan, massage) are effective in improving social interaction and communication skills, reducing stereotyped behavior, and preventing the risk of autism, energy therapies (reflexology, hypnotherapy, and healing touch) are effective in reducing the symptoms of autism and constipation and overcome hyperactive behavior.

Conclusion

Complementary mind-body-spirit therapies, manipulative and body-based therapies, and energy therapies are effective in improving the development of children with autism.
Identifying Genes with Location Dependent Noise Variance in Spatial Transcriptomics Data
Authors: Abrar Mohammed Abid , Kaykobad M. , Rahman M. Saifur , Samee Md. Abul Hassan
Published: September 2022

Spatial transcriptomics (ST) holds the promise to identify the existence and extent of spatial variation of gene expression in complex tissues. Such analyses could help identify gene expression signatures that distinguish between healthy and disease samples. Existing tools to detect spatially variable genes assume a constant noise variance across location. This assumption might miss important biological signals when the variance could change across spatial locations, e.g., in the tumor microenvironment. In this paper, we proposeNoVaTeST, a framework to identify genes with location-dependent noise variance in ST data. NoVaTeST can model gene expression as a function of spatial location with a spatially variable noise. We then compare the model to one with constant noise to detect genes that show significant spatial variation in noise. Our results show genes detected by NoVaTeST provide complimentary information to existing tools while providing important biological insights.
Thalamic volume and functional connectivity are associated with nicotine dependence severity and craving
Authors: Lor Cindy Sumaly , Haugg Amelie , Zhang Mengfan , Schneider Letitia M. , Herdener Marcus , Quednow Boris B. , Golestani Narly , Scharnowski Frank
Published: September 2022

Tobacco smoking is associated with deleterious health outcomes. Most smokers want to quit smoking, yet relapse rates are high. Understanding neural differences associated with tobacco use may help generate novel treatment options. Several animal studies have recently highlighted the central role of the thalamus in substance use disorders, but this research focus has been understudied in human smokers. Here, we investigated associations between structural and functional magnetic resonance imaging measures of the thalamus and its subnuclei to distinct smoking characteristics. We acquired anatomical scans of 32 smokers as well as functional resting-state scans before and after a cue-reactivity task. Thalamic functional connectivity was associated with craving and dependence severity, whereas the volume of the thalamus was associated with dependence severity only. Craving, which fluctuates rapidly, was best characterized by differences in brain function, whereas the rather persistent syndrome of dependence severity was associated with both brain structural differences and function. Our study supports the notion that functional versus structural measures tend to be associated with behavioral measures that evolve at faster versus slower temporal scales, respectively. It confirms the importance of the thalamus to understand mechanisms of addiction and highlights it as a potential target for brain-based interventions to support smoking cessation, such as brain stimulation and neurofeedback.
Feasibility Analyses and Experimental Confirmation of Dove Prism Based Dual-fiberscope Rotary Joint
Authors: Liu Yuehan , Park Hyeon-Cheol , Zhang Haolin , Li Xingde
Published: September 2022

Two-photon fluorescence microscopy has enjoyed its wide adoption in neuroscience. Head-mounted miniaturized fiberscopes offered an exciting opportunity for enabling neural imaging in freely-behaving animals with high 3D resolution. Here we propose a dual-fiberscope rotary joint based on a Dove prism, for enabling simultaneous two-photon imaging of two brain regions with two fiberscopes in freely-walking/rotating mice. Analytic proof has confirmed the key properties of a Dove prism. Feasibility analyses and proof-of-concept experimental results have demonstrated the feasibility of such a rotary joint for allowing two fiberscopes to rotate simultaneously while maintaining an excellent single-mode fiber-to-fiber coupling for the excitation femtosecond laser. Fiberscopes with a dual-probe rotary joint offer an exciting opportunity to explore neural network dynamics of multiple interconnected brain regions in freely-walking rotating animals.
AF2-multimer guided high accuracy prediction of typical and atypical ATG8 binding motifs
Authors: Ibrahim Tarhan , Khandare Virendrasinh , Mirkin Federico Gabriel , Tumtas Yasin , Bubeck Doryen , Bozkurt Tolga O.
Published: September 2022

Macroautophagy/autophagy is an intracellular degradation process central to cellular homeostasis and defense against pathogens in eukaryotic cells. Regulation of autophagy relies on hierarchical binding of autophagy cargo receptors and adaptors to ATG8/LC3 protein family members. Interactions with ATG8/LC3 are typically facilitated by a conserved, short linear sequence, referred to as the ATG8/LC3 interacting motif/region (AIM/LIR), present in autophagy adaptors and receptors as well as pathogen virulence factors targeting host autophagy machinery. Since the canonical AIM/LIR sequence can be found in many proteins, identifying functional AIM/LIR motifs has proven challenging. Here we show that protein modelling using Alphafold-Multimer (AF2-multimer) identifies both canonical and atypical AIM/LIR motifs with a high level of accuracy. AF2-multimer can be modified to detect additional functional AIM/LIR motifs by using protein sequences with mutations in primary AIM/LIR residues. By combining protein modelling data from AF2-multimer with phylogenetic analysis of protein sequences and protein-protein interaction assays, we demonstrate that AF2-multimer predicts the physiologically relevant AIM motif in the ATG8-interacting protein 2 (ATI-2) as well as the previously uncharacterized non-canonical AIM motif in ATG3 from potato (Solanum tuberosum). AF2-multimer also identified the AIM/LIR motifs in pathogen-encoded virulence factors that target ATG8 members in their plant and human hosts, revealing that cross-kingdom ATG8-LIR/AIM associations can also be predicted by AF2-multimer. We conclude that the AF2-guided discovery of autophagy adaptors/receptors will substantially accelerate our understanding of the molecular basis of autophagy in all biological kingdoms.
Rapid reductions in population size drive evolutionary divergence in diatoms
Authors: Walworth Nathan G. , Espinoza Josh L. , Argyle Phoebe A. , Hinners Jana , Levine Naomi M. , Doblin Martina A. , Dupont Chris L. , Collins Sinéad
Published: September 2022

Unicellular photosynthetic marine microbes, or phytoplankton, make up the base of marine food webs and drive global nutrient cycles. Despite their key roles in ecology and biogeochemistry, we have a limited understanding of how the basic features of their demographics along with dynamic environments affect trait evolution. A key feature of diatom ecology is frequent extreme reductions in population size, both as part of their bloom-and-bust growth dynamics, and as a result of living within ocean currents. Here, we use experimental evolution to understand which metabolic pathways and functions readily diversify in diatom populations following population bottleneck events. We subjected replicate populations of six genetically distinct diatom strains to population bottlenecks and then subsequently allowed them to evolve as large populations in the absence of environmental change. Phylogenies and global expression of orthologs were generally strain-specific, indicating that vertical (inherited) evolutionary constraints largely determine the occupation of specific locations in the transcriptional landscape (i.e. tran-scape). Following bottlenecks and subsequent evolution as large populations, transcriptional networks of most populations returned to those of the ancestral population. However, at least one replicate population per lineage migrated in the tran-scape, demonstrating that evolutionary changes in gene expression patterns and transcriptional relationships can be driven by population bottlenecks even in the absence of environmental change. Importantly, the orthologs dominating transcriptional diversification resided in common, central metabolic pathways. These data advance our understanding of constraints and patterns of transcriptional relationships underlying trait evolution in microbes that drive global food webs and elemental cycles.
Recombination rate variation shapes genomic variability of phylogeographic structure in a widespread North American songbird (Aves:Certhia americana)
Authors: Manthey Joseph D. , Spellman Garth M.
Published: September 2022

The nonrandom distribution of chromosomal characteristics and functional elements—genomic architecture—impacts the relative strengths and impacts of population genetic processes across the genome. Due to this relationship, genomic architecture has the potential to shape variation in population genetic structure across the genome. Population genetic structure has been shown to vary across the genome in a variety of taxa, but this body of work has largely focused on pairwise population genomic comparisons between closely related taxa. Here, we used whole genome sequencing of seven phylogeographically structured populations of a North American songbird, the Brown Creeper (Certhia americana), to determine the impacts of genomic architecture on phylogeographic structure variation across the genome. Using multiple methods to infer phylogeographic structure—ordination, clustering, and phylogenetic methods— we found that recombination rate variation explained a large proportion of phylogeographic structure variation. Genomic regions with low recombination showed phylogeographic structure consistent with the genome-wide pattern. In regions with high recombination, we found strong phylogeographic structure, but with discordant patterns relative to the genome-wide pattern. In regions with high recombination rate, we found that populations with small effective population sizes evolve relatively more rapidly than larger populations, leading to discordant signatures of phylogeographic structure. These results suggest that the interplay between recombination rate variation and effective population sizes shape the relative impacts of linked selection and genetic drift in different parts of the genome. Overall, the combined interactions of population genetic processes, genomic architecture, and effective population sizes shape patterns of variability in phylogeographic structure across the genome of the Brown Creeper.
The genetic overlap between Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease
Authors: Wightman Douglas P. , Savage Jeanne E. , Tissink Elleke , Romero Cato , Jansen Iris E. , Posthuma Danielle
Published: September 2022

Neurodegenerative diseases are a group of disorders characterised by neuronal cell death causing a variety of physical and mental problems. While these disorders can be characterised by their phenotypic presentation within the nervous system, their aetiologies differ to varying degrees. Some disorders, such as Lewy body dementia and Parkinson’s disease, show overlap in the major proteins found in aggregates, and some diseases, like Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease, are influenced by the same non-neuronal cell types (microglia), suggesting partly shared aetiologies. The identification of shared genetic risk factors common to many neurodegenerative diseases may highlight fundamental biological processes involved in neurodegeneration and provide promising targets for treatment and drug repurposing. The majority of genetic evidence for overlap between neurodegenerative diseases has been pairwise, with little genetic evidence for genes or biological processes found across more than two neurodegenerative diseases. In this study, we aimed to identify overlap between the four investigated neurodegenerative disorders (Alzheimer’s disease, amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease) at the variant, gene, genomic locus, gene-set, cell, or tissue level, with specific interest in overlap between three or more diseases. Using local genetic correlation, we found that the TMEM175 locus was a shared locus between amyotrophic lateral sclerosis, Lewy body dementia, and Parkinson’s disease, and the HLA region was shared between Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. We also highlighted genes, genomic loci, gene-sets, cell types, and tissue types which may be important to two or more disorders by analysing the association of variants with a common factor estimated from the four disorders. Our study successfully highlighted genetic loci and tissues associated with two or more neurodegenerative diseases.
Venom protection by broadly neutralizing antibody from a snakebite subject
Authors: Glanville Jacob , Andrade Joel Christian , Bellin Mark , Kim Sangil , Pletnev Sergei , Tsao David , Verardi Raffaello , Bedi Rishi , Liao Sindy , Newland Raymond , Bayless Nicholas L. , Youssef Sawsan , Tully Ena , Zhang Baoshan , Bylund Tatsiana , Kim Sujeong , Liu Tracy , Kwong Peter D.
Published: September 2022

Snake envenomation is a neglected tropical disease, causing >100,000 deaths and 300,000 permanent disabilities in humans annually. Could monoclonal antibody technology provide a solution? Here, we recover Centi-3FTX-D09, a potent broadly neutralizing antivenom antibody from the B-cell memory of a human subject with snake venom exposure. Centi-3FTX-D09 recognized a conserved neutralizing epitope on long 3-finger toxins (3FTXs), a dominant snake neurotoxin. Crystal structures of Centi-3FTX-D09 in complex with 3FTXs from mamba, taipan, krait, and cobra revealed epitope mimicry of the interface between these neurotoxins and their host target, the nicotinic acetylcholine receptor. Centi-3FTX-D09 providedin-vivoprotection against diverse recombinant long 3FTXs,in-vivorescue from whole venom challenge from cobras, black mamba, and king cobra, and, when combined with the phospholipase inhibitor varespladib,in-vivoprotection extending to a majority of tested elapid venoms. Thus, a single antibody can broadly neutralize long neurotoxins and contribute to broad protection from envenomation.
Spatial Heterogeneity of Brain Lipids in SIV-infected Macaques Treated with Antiretroviral Therapy
Authors: White Cory J. , Gausepohl Andrew M. , Wilkins Hannah N. , Eberhard Colten D. , Orsburn Benjamin C. , Williams Dionna W.
Published: September 2022

Human immunodeficiency virus (HIV) infection continues to promote neurocognitive impairment, mood disorders, and brain atrophy even in the modern era of viral suppression. Brain lipids are vulnerable to HIV-associated energetic strain and contribute to HIV-associated neurologic dysfunction due to alterations in lipid breakdown and structural lipid composition. HIV neuropathology is region dependent, yet there has not been comprehensive characterization of the spatial heterogeneity of brain lipids during infection that may impact neurologic function. To address this gap, we evaluated the spatial lipid distribution using matrix laser desorption/ionization imaging mass spectrometry (MALDI-IMS) across four brain regions (parietal cortex, midbrain, thalamus, and temporal cortex), as well as kidney for a peripheral tissue control, in a virally suppressed simian immunodeficiency virus (SIV)-infected rhesus macaque. We assessed lipids indicative of fat breakdown [acylcarnitines (CARs)] and critical structural lipids [phosphatidylcholines (PCs) and phosphatidylethanolamines (PEs)] across fatty acid chain lengths and degrees of unsaturation. CARs with very long-chain, polyunsaturated fatty acids (PUFAs) were more abundant across all brain regions than shorter chain, saturated or monounsaturated species. We observed distinct brain lipid distribution patterns for CARs and PCs. However, no clear expression patterns emerged for PEs. Surprisingly, kidney was nearly devoid of ions corresponding to PUFAs common in brain. PE’s and PC’s with PUFAs had little intensity and less density than other species and, only one CAR species was observed in kidney at high intensity. Overall, our study provides substantial evidence for persistent bioenergetic changes to the brain despite viral suppression, including region-dependent mobilization of CARs for oxidation and disparities in the presence of key phospholipids necessary for maintaining proper brain structure and function. These data indicate that region-specific interventions to restore proper lipid metabolism are essential for treating HIV neurologic disease in the era of antiretroviral therapy.

Graphical Abstract