bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of leg length discrepancy on paraspinal muscles activation using surface electromyography
Authors: Kim Hee Soo , Ha Yuna , Lim Jiwoon , Kim Hyun Jin , Kang Heeyung , Ryu Ju Seok
Published: August 2023

Objective

To assess the effects of leg length discrepancy (LLD) on paraspinal muscle activity and kinematic variables during gait.

Design

Thirty-nine healthy participants aged 5 to 12 years performed the 10-m walk test using the surface electromyography and G-walk sensor for the following conditions: 1) non-LLD condition (LLD 0 cm) and 2) LLD condition with an insole on the right leg at three different heights (LLD 0.5 cm, 1.0 cm, and 1.5 cm). The root mean square (RMS) was normalized using maximal voluntary contraction and reference voluntary contraction methods (RMS_MVC and RMS_ref) and compared between the sides.

Results

The mean RMS_MVC of the 12th thoracic erector spinae (EST12) on the right side was significantly higher at an LLD 0.5 cm and 1 cm. Regarding the 3rd lumbar multifidus (MuL3), the mean RMS_MVC on the right side was significantly higher at an LLD 1.5 cm. The mean RMS_ref exhibited similar patterns. Pelvic obliquity and rotation showed asymmetry at an LLD 1.5 cm compared with an LLD 0 cm.

Conclusions

A small LLD significantly affected the asymmetric hyperactivation of the MuL3 and EST12 muscles during gait. Considering the action of these muscles, asymmetric hyperactivation might result in rotation and bending of the lumbar spine and the bending of the thoracolumbar spine.
Changes in Patterns of Referral for Inpatient Rehabilitation Cancer Patients due to COVID-19: A Retrospective Study
Authors: Gupta Ekta , Ng Amy H. , de Moraes Aline Rozman , Fu Jack B. , Tennison Jegy M , Ahmed Maaheen , Fellman Bryan M. , Bruera Eduardo
Published: August 2023

There is a paucity of literature on the effect of COVID-19 on hospital processes. We hypothesized that COVID-19 was associated with decreased cancer physiatry referrals in 2020. This is a retrospective cohort study of consecutive patients from April- July of 2019 and 2020 admitted at an academic quaternary cancer center. The main outcomes were number of hospital admissions, rate and characteristics of inpatient rehabilitation admissions and change in percentage of physiatry referrals as the primary endpoint. Results showed in 2019, there were 387 referrals from 10,274 inpatient admissions (3.8%; 95% CI: 2.4 - 4.2), compared to 337 referrals from 7,051 admissions in 2020 (4.8%; 95% CI: 4.3 - 5.3, p = 0.001). Hematology services referred more patients than neurosurgery in 2020 (20.4% vs 31.4%; 48.2% vs 26.5%; p = 0.01). Discharge disposition reflected an increased frequency of return to acute care service in 2020 (10.2% vs 21.8%; p = 0.03). In conclusion, there was an increase in the rate of physiatry referrals despite a decrease in hospital admissions. There was an increase in referrals by hematology, likely due to emphasis on safe discharge and the populations hospitalized.
Score to Predict the Occurrence of Pneumothorax After Computed Tomography-guided Percutaneous Transthoracic Lung Biopsy
Authors: Lamfichekh Yassine , Lafay Valentin , Hamam Joffrey , Guillien Alicia , Puyraveau Marc , Behr Julien , Manzoni Philippe , Calame Paul , Dalphin Jean-Charles , Eberst Guillaume , Grillet Franck , Westeel Virginie
Published: August 2023

Purpose:

The main objective of this study was to identify risk factors for post-percutaneous transthoracic lung biopsy (PTLB) pneumothorax and to establish and validate a predictive score for pneumothorax occurrence to identify patients eligible for outpatient care.

Material and Methods:

Patients who underwent PTLB between November 1, 2012 and March 1, 2017 were retrospectively evaluated for clinical and radiologic factors potentially related to pneumothorax occurrence. Multivariate logistic regression was used to identify risk factors, and the model coefficient for each factor was used to compute a score. Then, a validation cohort was prospectively evaluated from March 2018 to October 2019.

Results:

Among the 498 eligible patients in the study cohort, pneumothorax occurred in 124 patients (24.9%) and required drainage in 34 patients (6.8%). Pneumothorax risk factors were chronic obstructive pulmonary disease (OR 95% CI 2.28[1.18–4.43]), several passages through the pleura (OR 95% CI 7.71[1.95–30.48]), an anterior biopsy approach (OR 95% CI 6.36 3.82–10.58]), skin-to-pleura distance ≤30 mm (OR 95% CI 2.25[1.09–6.65]), and aerial effusion >10 mm (OR 95% CI 9.27 [5.16–16.65]). Among the 236 patients in the prospective validation cohort, pneumothorax occurred in 18% and 8% were drained. A negative score (<73 points) predicted a probability of pneumothorax occurrence of 7.4% and late evacuation of 2.5% (OR 95% CI respectively 0.18[0.08–0.39] and 0.15[0.04–0.55]) and suggested a reduced length of hospital stay (P=0.009).

Conclusion:

This predictive score for pneumothorax secondary to PTLB has high prognostic performance and accuracy to direct patients toward outpatient management.

Clinical Trials:

NCT03488043
Safety of Augmenting Breast Volume in Direct-to-Implant Breast Reconstruction With Contralateral Breast Augmentation
Authors: Woo Soo Hyun , Lee Seok Joon , Kim Eun Key , Han Hyun Ho , Eom Jin Sup
Published: August 2023

Background

Direct-to-implant breast reconstruction is a standard method of implant-based reconstruction; however, the risk of skin necrosis and implant failure exists. During simultaneous contralateral augmentation, an implant larger than the resected tissue must be inserted to balance both sides, which may increase the risk of complications. This study examined the differences in the incidence of complications between the single-stage direct-to-implant reconstruction and 2-stage reconstruction when contralateral augmentation was performed simultaneously.

Methods

This study included 99 patients who underwent implant-based breast reconstruction with contralateral augmentation between 2012 and 2020. A retrospective chart review was conducted and the patients were divided into 2 groups: the single-stage reconstruction (n = 61) and 2-stage reconstruction (TSR, n = 38) groups. Demographic data and surgical and oncological information were collected. Complications including skin necrosis and reconstruction failure were investigated as the primary outcome.

Results

Implant volume and contralateral implant volume were significantly greater in TSR group than in the single-stage reconstruction group. There were no significant differences in the incidence of complications and reconstruction failure rates between both groups. The nipple-sparing mastectomy was the risk factor for complications. Furthermore, the risk factors for mastectomy skin necrosis were implant volume and differences in the volume of both implants.

Conclusions

Single-stage reconstruction did not increase the risk of complications compared with TSR when implants that were larger than the resected tissue were inserted after mastectomy. Proper patient selection and selection of implants that are not excessively large could satisfy patients' cosmetic needs in a single operation.
Treatment of a Patient With Meningioma With Complicated Blood Supply
Authors: Yan Xuelei , Tao Xiaowei , Zheng Junfei , Liu Jinkai , Qin Shiqiang
Published: August 2023

Meningiomas account for ~30% of primary intracranial tumors, making them the second most common type of brain tumor. Most meningiomas are benign, and surgical resection is curative. By utilizing 3-dimensional slicer technology for multimodal image fusion, a wealth of 3-dimensional anatomic information can be obtained, enabling more effective treatment of meningiomas with complex tumor locations and surrounding structures. Guided by the 3-dimensional structural models, we conducted detailed preoperative planning for 1 case of highly vascularized meningioma and utilized combined surgery for complete tumor removal, effectively avoiding intraoperative bleeding and postoperative complications.
Correction of Asymmetry of Palpebral Folds by Adopting Interrupted and Continuous Buried Suture Techniques Respectively on Different Eyelid
Authors: Zhang Zhilu , Di Wenjun , Wang Yongqian
Published: August 2023

People with an obvious palpebral fold on 1 eye and a narrow or no palpebral fold on the other eye are usually more satisfied with the shape of the obvious palpebral fold and want to acquire symmetry by minimally invasive surgical methods that preserve the shape of the original folds they are more satisfied with. This study introduced a minimally invasive approach using 2 different buried suture techniques on different eyelids to acquire symmetry. The continuous suture method aimed to build palpebral folds, whereas the 3-point interrupted suture method aimed to enhance naturally formed palpebral folds. The 3-point interrupted buried suture method was used on the eye with an obvious palpebral fold, and the continuous buried suture method was performed on the eye with a narrow or no palpebral fold. Twenty patients underwent this procedure to correct the asymmetry between June 2010 and July 2022. The mean follow-up period was 18.12 months. The average swelling period was 7 days on the side using the interrupted buried suture technique and 10 days on the side using the continuous suture method. It took ~3 weeks to recover a relatively natural appearance. According to postoperative follow-up data, all patients were satisfied with the results. Our surgical approach of adopting 2 different buried suture techniques on different eyelids allowed the building of the palpebral fold on one eyelid while enhancing the original fold on the other eyelid, leading to satisfactory results of palpebral fold symmetry.
Jaw Osteomyelitis of Impacted Tooth After Radiotherapy: A Report of a Case
Authors: Yue Haiqiong , Liu Yudong , Zhou Libin
Published: August 2023

Maxillofacial radiotherapy has a significant negative impact on oral health and impacted teeth often lead to diseases such as jaw cysts and periapical periodontitis. This article reports a case of jaw osteomyelitis (with both impacted teeth and periodontitis) occurring 10 years after radiotherapy for nasopharyngeal carcinoma. There is no systematic treatment plan for patients with both pathogenic factors in clinical practice, so it is important to develop a systematic and complete treatment plan before radiotherapy and chemotherapy. The periodontal treatment of patients receiving radiotherapy and the timing of extraction of impacted teeth are mainly discussed.
Transoral Endoscopy-Assisted Tongue-Lip Adhesion With Modified Tongue Base Suspension in a Pierre-Robin Sequence: A Safe and Effective Technique
Authors: Kim Ji-hyun , Ryu Jae-young , Jung Seung-gon , Kook Min-seok , Oh Hee-kyun , Park Hong-ju
Published: August 2023

Life-threatening airway obstruction is a major concern in patients with Pierre-Robin sequence. Tongue-lip adhesion (TLA) has been used to manage airway obstruction. The authors present the case of a female neonate with Pierre-Robin sequence who presented with airway obstruction and a cleft palate. She underwent a TLA procedure with modified tongue base suspension (TBS). Endoscopy was used to check and control the traction of the tongue base to enable unobstructed self-ventilation. Positive outcomes including improved O2 saturation and weight gain were noted. The effectiveness of TLA was enhanced by using TBS with real-time endoscopy to evaluate the oropharyngeal airway space required to alleviate airway obstruction. The use of endoscopy enabled us to check and determine how much the tongue base should be tracted by manipulating the tongue anteriorly and posteriorly. The authors report transoral endoscopy-assisted TLA and modified TBS.
Higher-Order Dynamics Beyond Repolarization Alternans in Ex-Vivo Human Ventricles are Independent of the Restitution Properties
Authors: Iravanian Shahriar , Uzelac Ilija , Shah Anand D , Toye Mikael J , Lloyd Michael S. , Burke Michael A. , Daneshmand Mani A , Attia Tamer S , Vega J David , El-Chami Michael , Merchant Faisal M. , Cherry Elizabeth M , Bhatia Neal K. , Fenton Flavio H.
Published: August 2023

Background

Repolarization alternans, defined as period-2 oscillation in the repolarization phase of the action potentials, provides a mechanistic link between cellular dynamics and ventricular fibrillation (VF). Theoretically, higher-order periodicities (e.g., periods 4, 6, 8,…) are expected but have minimal experimental evidence.

Methods

We studied explanted human hearts obtained from recipients of heart transplantation at the time of surgery. Optical mapping of the transmembrane potential was performed after staining the hearts with voltage-sensitive fluorescent dyes. Hearts were stimulated at an increasing rate until VF was induced. Signals recorded from the right ventricle endocardial surface prior to induction of VF and in the presence of 1:1 conduction were processed using the Principal Component Analysis and a combinatorial algorithm to detect and quantify higher-order dynamics. Results were correlated to the underlying electrophysiological characteristics as quantified by restitution curves and conduction velocity.

Results

A prominent and statistically significant global 1:4 peak (corresponding to period-4 dynamics) was seen in three of the six studied hearts. Local (pixel-wise) analysis revealed the spatially heterogeneous distribution of periods 4, 6, and 8, with the regional presence of periods greater than two in all the hearts. There was no significant correlation between the underlying restitution properties and the period of each pixel.

Discussion

We present evidence of higher-order periodicities and the co-existence of such regions with stable non-chaotic areas in ex-vivo human hearts. We infer from the independence of the period to the underlying restitution properties that the oscillation of the excitation-contraction coupling and calcium cycling mechanisms is the primary mechanism of higher-order dynamics. These higher-order regions may act as niduses of instability that can degenerate into chaotic fibrillation and may provide targets for substrate-based ablation of VF.
The Burden of Digestive Diseases in the United States Population
Authors: Unalp-Arida Aynur , Ruhl Constance E.
Published: August 2023

Background and rationale.Digestive diseases are common and lead to significant morbidity, mortality, and health care utilization. We used national survey and claims databases to expand on earlier findings and investigate current trends in the digestive disease burden in the United States.Methods.The National Ambulatory Medical Care Survey, Nationwide Emergency Department Sample, National Inpatient Sample, Vital Statistics of the U.S., Surveillance, Epidemiology, and End Results Program, Optum Clinformatics® Data Mart, and Centers for Medicare and Medicaid Services Medicare 5% Sample databases were used to estimate medical care, mortality, cancer incidence, and claims-based prevalence with a digestive disease diagnosis. Rates were age-adjusted (for national databases) and shown per 100,000 population.Results.For all digestive diseases, prevalence (claims-based, all-listed diagnoses) was 30.5% among commercial insurance enrollees (2020) and 53.1% among Medicare beneficiaries (2019). In the U.S. population, digestive diseases contributed to approximately 126 million ambulatory care visits (2015), 41 million emergency department visits (2018), 16 million hospital discharges (2018), and 472,000 deaths (2019) annually. Prevalence, medical care, and mortality rates with a digestive disease diagnosis were higher among children and younger adults (except for emergency department visits) and then increased with age. Women had higher prevalence and medical care rates with a digestive disease diagnosis, but mortality rates were higher among men. Prevalence and medical care rates with a digestive disease diagnosis were higher among Blacks, followed by Whites, then Hispanics, and lowest among Asians. Mortality rates were higher among Blacks compared with Whites and lower among Hispanics compared with non-Hispanics. Between 2004 and the most recent year, ambulatory care visit rates with a digestive disease diagnosis increased by 4%, hospital discharge rates decreased by 3%, and mortality rates decreased by 7%. Among commercial insurance enrollees, rates were higher compared with national data for ambulatory care visits and hospital discharges, but lower for emergency department visits. The medical care use and mortality burdens varied among individual digestive diseases.Conclusion.The digestive disease burden in the United States is substantial, particularly among Blacks and older adults.
The impact of live dietary microbes on health: a scoping review
Authors: Iyer Ajay , Mukherjee Arghya , Gómez-Sala Beatriz , O’Connor Eibhlís M. , Kenny John G. , Cotter Paul D.
Published: August 2023

Background

A systematic approach to collect, peruse and summarise the available information relating to the potential benefits of consuming dietary microbes was pursued in this scoping review. This review focused on the research endpoints, experimental designs, and microbial exposure in experimental as well as observational research work.

Approach

Using a structured-set of keywords, scientific databases were systematically searched to retrieve publications reporting outcomes pertaining to the use of dietary-microbes in healthy, non-patient populations. Searches were further tailored to focus on eight different health categories, namely, “antibiotic associated diarrhoea” (AAD), “gastrointestinal health” (GIH), “immunological health” (ImH), “cardiovascular health and metabolic syndrome” (CvHMS), “cancer prevention” (CanPr), “respiratory health” (ReH), “weight management” (WtMgt), and “urogenital health” (UrGH). Quality of evidence available in each publication was assessed using the Jadad scoring system.

Result

The search yielded 228 relevant publications describing 282 experimental cases comprising 62 research endpoints overall. A microbial dose of≥2 × 109CFU·day−1was associated with non-negative reported outcomes. Older population groups with a median age of 39 years were associated with positive outcomes.

Conclusion

More high-quality research is required investigating the role of dietary microbes in maintaining general health, particularly in the health categories of urogenital health, weight management and cancer prevention.
Order-of-mutation effects on cancer progression: models for myeloproliferative neoplasm
Authors: Wang Yue , Shtylla Blerta , Chou Tom
Published: August 2023

In some patients with myeloproliferative neoplasms (MPN), two genetic mutations are often found, JAK2 V617F and one in the TET2 gene. Whether or not one mutation is present will influence how the other subsequent mutation affects the regulation of gene expression. When both mutations are present, the order of their occurrence has been shown to influence disease progression and prognosis. We propose a nonlinear ordinary differential equation (ODE), Moran process, and Markov chain models to explain the non-additive and non-commutative mutation effects on recent clinical observations of gene expression patterns, proportions of cells with different mutations, and ages at diagnosis of MPN. These observations consistently shape our modeling framework. Our key proposal is that bistability in gene expression provides a natural explanation for many observed order-of-mutation effects. We also propose potential experimental measurements that can be used to confirm or refute predictions of our models.
Metabolomic Alterations in Crimean Congo Hemorrhagic Fever Explored Through a Nationwide Study Using NMR Spectroscopy
Authors: Göcenler Oktay , Kahraman Kerem , Yapar Derya , Kahraman Yaren , Büyükdağ Cengizhan , Esken Gülen , Ozabrahamyan Serena , Barlas Tayfun , Karadağ Yüksel , Çelikbaş Aysel Kocagül , Can Füsun , Baykam Nurcan , Kuşkucu Mert , Ergönül Önder , Dağ Çağdaş
Published: August 2023

Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne viral disease with high mortality rates and significant public health implications. Despite its global prevalence, the mechanisms underlying its pathogenesis remain poorly understood, and effective diagnostic and therapeutic tools are limited. Metabolomics, as a powerful tool for exploring host-pathogen interactions, offers a promising avenue for identifying biomarkers and elucidating disease mechanisms. In this study, we investigated the metabolic alterations in CCHF patients using non-targeted metabolomics to enhance understanding of disease pathogenesis, improve diagnostic capabilities, and identify potential therapeutic targets. A nationwide analysis was conducted on the blood serum of 29 CCHF patients and 10 healthy controls, employing Nuclear Magnetic Resonance (NMR) spectroscopy. Serum samples were collected over four consecutive days, and metabolic profiling was performed using Partial Least Squares Discriminant Analysis (PLS-DA) and Variable Importance in Projection (VIP) scoring to identify key metabolic pathways and compounds. Significant disruptions in metabolic pathways were observed in CCHF patients, particularly in purine and pyrimidine metabolism, the TCA cycle, and redox-related processes. Elevated levels of metabolites such as S-adenosyl homocysteine (SAH), guanosine triphosphate (GTP), inosine monophosphate (IMP), adenosine monophosphate (AMP), carnosine, 2’-deoxyuridine, nicotinamide adenine dinucleotide phosphate (NADP+), and maleate were identified. These metabolites demonstrated potential as biomarkers for disease severity and progression, with distinct metabolic profiles observed between moderate and severe cases. This study provides the first comprehensive metabolomic analysis of CCHF, highlighting critical metabolic pathways disrupted during infection. The findings underscore the utility of NMR-based metabolomics for identifying biomarkers that facilitate early diagnosis, prognosis, and therapeutic development. These results pave the way for future research to validate the identified biomarkers and explore targeted treatment strategies to improve patient outcomes in this severe viral infection.
Penetration of Topically Applied Polymeric Nanoparticles across the Epidermis of Thick skin
Authors: Antony Andrea , Raju Gayathri , Job Ahina , Joshi Meet , Shankarappa Sahadev
Published: August 2023

The natural barrier function of the epidermal skin layer poses a significant challenge to nanoparticle-mediated topical delivery. A key factor in this barrier function is the thickness of the stratum corneum (SC) layer within the epidermis, which varies across different anatomical sites. The epidermis from the palms and soles, for instance, have thicker SC compared to those from other areas. Previous studies have attempted to bypass the SC layer for nanoparticle penetration by using physical disruption; however, these studies have mostly focused on non-thick skin. In this study, we investigate the role of mechano-physical strategies on SC of thick skin for transdermal nanoparticle penetration. We characterize and compare two mechano-physical strategies, namely tape-stripping and microneedle abrasion, for epidermal disruption in both thick and thin skin. Furthermore, we examine the impact of SC disruption in thick and thin skin on the penetration of topically applied 100 nm sized polystyrene nanoparticles using an ex-vivo model. Our findings show that tape-stripping reduced the overall thickness of SC in thick skin by 87%, from 67.4 ± 17.3 µm to 8.2 ± 8.5 µm, whereas it reduced thin skin SC by only 38%, from 9.9 ± 0.6 µm to 6.2 ± 3.2 µm. Compared to non-thick skin, SC disruption in thick skin resulted in higher nanoparticle diffusion. Tape-stripping effectively reduces SC thickness of thick skin and can be potentially utilized for enhanced penetration of topically applied nanoparticles in skin conditions that affect thick skin.
Structural flexibility of apolipoprotein E-derived arginine-rich peptides improves their cell penetration capability
Authors: Takechi-Haraya Yuki , Ohgita Takashi , Usui Akiko , Nishitsuji Kazuchika , Uchimura Kenji , Abe Yasuhiro , Kawano Ryuji , Konaklieva Monika I. , Reimund Mart , Remaley Alan T. , Sato Yoji , Izutsu Ken-ichi , Saito Hiroyuki
Published: August 2023

Amphipathic arginine-rich peptide, A2-17, exhibits moderate perturbation of lipid membranes and the highest cell penetration among its structural isomers. We investigated the direct cell-membrane penetration mechanism of the A2-17 peptide. We designed structurally constrained versions of A2-17, stapled (StpA2-17) and stitched (StchA2-17), whose α-helical conformations were stabilized by chemical crosslinking. Circular dichroism confirmed that StpA2-17 and StchA2-17 had higher α-helix content than A2-17 in aqueous solution. Upon liposome binding, only A2-17 exhibited a coil-to-helix transition. Confocal microscopy revealed that A2-17 had higher cell penetration efficiency than StpA2-17 in HeLa cells. Partitioning into lipid membranes was more prominent for StchA2-17 than for A2-17 or StpA2-17; StchA2-17 remained on the cell membrane without cell penetration. Tryptophan fluorescence analysis suggested that A2-17 and its analogs had similar membrane-insertion positions between the interface and hydrophobic core. Atomic force microscopy demonstrated that A2-17 reduced the mechanical rigidity of liposomes to a greater extent than StpA2-17 and StchA2-17. Finally, electrophysiological analysis showed that A2-17 induced a higher charge influx through transient pores in a planer lipid bilayer than StpA2-17 and StchA2-17. These findings indicate that structural flexibility, which enables diverse conformations of A2-17, leads to a membrane perturbation mode that contributes to cell membrane penetration.
CYP2C19 and effect of clopidogrel for secondary prevention of major ischemic events: systematic review and meta-analysis
Authors: Kremers Femke C.C. , van den Biggelaar Jochem , Lingsma Hester F. , van Schaik Ron H.N. , Roozenbeek Bob , Dippel Diederik W.J.
Published: August 2023

Background

Carriers of the CYP2C19 Loss of Function (LoF) allele may experience decreased efficacy of clopidogrel in secondary prevention after cardiovascular events. Randomized clinical trials of clopidogrel in patients with known CYP2C19 carrier status provided inconsistent results. Our aim was to pool the evidence on the effect of clopidogrel on outcome, according to CYP2C19 LoF status, in a meta-analysis.

Methods

A systematic review and meta-analysis of randomized controlled trials (RCTs) on the effect of clopidogrel according to CYP2C19 LoF status in patients with cardiovascular disease and recent TIA or stroke was performed. The primary outcomes were 1) ischemic stroke and 2) major adverse cardiac events (MACE). We used random effects analysis to estimate the effect of clopidogrel as a pooled odds ratio (OR) in carriers and non-carriers of the LoF variant and tested for interaction between clopidogrel and CYP2C19.

Results

We included six RCTs with a total of 15,141 participants comparing combined clopidogrel and aspirin therapy to aspirin monotherapy. The effect of clopidogrel on MACE was OR=0.70 in CYP2C19 non-variant carriers compared to OR=0.84 in CYP2C19 variant carriers (pinteraction=0.13). In patients with a recent TIA or minor ischemic stroke, the OR for the effect of clopidogrel on MACE was OR=0.52 in CYP2C19 non-variant carriers compared to OR=0.84 in CYP2C19 variant carriers (pinteraction=0.02) while in patients with cardiovascular disease the difference in effect was not evident (non-variant carriers OR=0.76, variant carriers OR= 0.84, pinteraction=0.50).

Conclusion

Our meta-analysis could not establish that overall, clopidogrel is less effective in patients with a recent MI, minor stroke or TIA and a CYP2C19 LoF genotype. However, the size and direction of the difference in effect warrants further research.

Registration - URL:https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021242993.
Occupational Farm Work Activities Influence Workers’ Indoor Home Microbiome
Authors: Dalton Kathryn R. , Lee Mikyeong , Wang Ziyue , Zhao Shanshan , Parks Christine G. , Beane-Freeman Laura E. , Motsinger-Reif Alison A. , London Stephanie J.
Published: August 2023

Abstract

Background

Farm work entails a heterogeneous mixture of exposures that vary considerably across farms and farmers. Farm work is associated with various health outcomes, both adverse and beneficial. One mechanism by which farming exposures can impact health is through the microbiome, including the indoor built environment microbiome. It is unknown how individual occupational exposures shape the microbial composition in workers’ homes.

Objectives

We investigated associations between farm work activities, including specific tasks and pesticide use, and the indoor microbiome in the homes of 468 male farmers.

Methods

Participants were licensed pesticide applicators, mostly farmers, enrolled in the Agricultural Lung Health Study from 2008-2011. Vacuumed dust from participants’ bedrooms underwent whole-genome shotgun sequencing for indoor microbiome assessment. Using questionnaire data, we evaluated 6 farm work tasks (processing of either hay, silage, animal feed, fertilizer, or soy/grains, and cleaning grain bins) and 19 pesticide ingredients currently used in the past year, plus 7 persistent banned pesticide ingredients ever used.

Results

All 6 work tasks were associated with increased within-sample microbial diversity, with a positive dose-response for the sum of tasks (p=0.001). All tasks were associated with altered overall microbial compositions (weighted UniFrac p=0.001) and with higher abundance of specific microbes, including soil-based microbes such asHaloterrigena. Among the 19 pesticides, only current use of glyphosate and past use of lindane were associated with increased within-sample diversity (p=0.02-0.04). Ten currently used pesticides and all 7 banned pesticides were associated with altered microbial composition (p=0.001-0.04). Six pesticides were associated with differential abundance of certain microbes.

Discussion

Specific farm activities and exposures can impact the dust microbiome inside homes. Our work suggests that occupational farm exposures could impact the health of workers and their families through modifying the indoor environment, specifically the microbial composition of house dust, offering possible future intervention targets.
Ready-To-Use Investigational Stem Cells in Patients with recent Acute Myocardial Infarction
Authors: Ueng KC , Tsai CF , Chuang YT , Huang JY , Liu JTK
Published: August 2023

BACKGROUND

Cardiovascular diseases are a major health concern, and stem cell therapy holds promise as a potential treatment. However, obtaining stem cells from patients who are already ill poses challenges, as does limited access to specialized laboratories. We aimed to assess the safety and preliminary effectiveness of a read-to-use investigational stem cell product, MiSaver, in patients with recent acute myocardial infarction (AMI).

METHODS

We enrolled 10 participants with AMI and reduced left ventricular ejection fraction (LVEF ≤45%). Group A (n=5) received a low dosage of 0.5×107cells/kg, and Group B (n=5) received a high dosage of 1.6×107cells/kg of cells. Additionally, 20 control patients who received standard care were included for statistical analysis. The primary outcome was the occurrence of side effects or graft-versus-host disease (GVHD) associated with the stem cell treatment. Secondary outcomes included changes in LVEF.

RESULTS

During the 12-month follow-up period, no study-related adverse effects or GVHD were observed. Baseline LVEF values for Group A and Group B were 42.0% and 41.3%, respectively, increasing to 53.0% and 53.7% at 12 months. Furthermore, no signs or symptoms of graft-versus-host disease (GVHD) were reported. Significant improvements in LVEF were observed in non-morbidly obese treated patients (cases 1-9), with baseline values of 41.3% and 12-month values of 53.7%, compared to the control group with baseline and 12-month values of 42.35% and 47.5%, respectively (p<0.05).

CONCLUSIONS

This trial demonstrated the safety and tolerability of MiSaver stem cells in patients with recent AMI. Preliminary evidence suggests efficacy in improving outcomes in non-morbidly obese participants.
Prevalence and Prescribers’ Knowledge of Psychotropic Polypharmacy in the Bono, Bono East, and Ahafo Regions, Ghana
Authors: Dumba James , Barimah Antwi Joseph , Ibrahim Mohammed Mohammed , Allotey Solomon Saka , Alorvi Semefa , Appertey William , Sopaal Luke , Acheampong Frank , Niriwa Benjamin Pulle
Published: August 2023

The use of psychotropic medications for treating simple and complex psychological and emotional problems is common and relevant among prescribers. This, therefore, come with the tendency to prescribe many medications to a patient on a single visit due to varied reasons. The study, therefore, sought to ascertain the prevalence and prescribers’ knowledge of psychotropic polypharmacy. A quantitative, descriptive study was conducted using a simple random approach to select and review the prescription records of three hundred and ten (309) patients’ folders retrospectively within seven (7) mental health units across the study area to ascertain the prevalence of Psychotropic Polypharmacy (PP). Fifty-eight (58) prescribers were also selected using probability method (simple random) to respond to the study questionnaire. Psychotropic Polypharmacy was prevalent (66.0%) in the study area with antipsychotic polypharmacy (74.0%) being the common form with the co-prescription of Chlorpromazine (CPZ) + Hadol (70.0%) being frequent. This was more predominant among male patients (78.0%) than female patients (22.0%). Prescribers had high (82.8%) knowledge of Psychotropic Polypharmacy and the majority (68.9%) disagreed that the practice of Psychotropic Polypharmacy should be promoted. The continuous training of prescribers (i.e. mental health officers) on rational prescriptions would help reduce the prevalence of Psychotropic Polypharmacy.
The Metabolic Usage and Glycan Destinations of GlcNAz inE. coli
Authors: Eddenden Alexander , Dooda Manoj K. , Morrison Zachary A. , Subramanian Adithya Shankara , Howell P. Lynne , Troutman Jerry M. , Nitz Mark
Published: August 2023

Bacteria use a diverse range of carbohydrates to generate a profusion of glycans, with amino sugars such asN-acetylglucosamine (GlcNAc) being prevalent in the cell wall and in many exopolysaccharides. The primary substrate for GlcNAc-containing glycans, UDP-GlcNAc, is the product of the bacterial hexosamine pathway, and a key target for bacterial metabolic glycan engineering. Using the strategy of expressing NahK, to circumvent the hexosamine pathway, it is possible to directly feed the analogue of GlcNAc,N-azidoacetylglucosamine (GlcNAz), for metabolic labelling inE. coli. The cytosolic production of UDP-GlcNAz was confirmed using fluorescence assisted polyacrylamide gel electrophoresis. The key question of where GlcNAz is incorporated, was interrogated by analyzing potential sites including: peptidoglycan (PGN), the biofilm-related exopolysaccharide poly-β-1,6-N-acetylglucosamine (PNAG), lipopolysaccharide (LPS) and the enterobacterial common antigen (ECA). The highest levels of incorporation were observed in PGN with lower levels in PNAG and no observable incorporation in LPS or ECA. The promiscuity of the PNAG synthase (PgaCD) towards UDP-GlcNAzin vitroand lack of undecaprenyl-pyrophosphoryl-GlcNAz intermediates generatedin vivoconfirmed the incorporation preferences. The results of this work will guide the future development of carbohydrate-based probes and metabolic engineering strategies.
Left Out: The Effect of Handedness on fMRI Activation in Memory Paradigms
Authors: Goulding Loriana , Hamm Isaac , Kirwan C. Brock
Published: August 2023

About 11% of the population is left-handed, a significant minority of the potential participant pool for functional MRI (fMRI) studies. However, convention in fMRI research dictates these potential participants be excluded due to the supposition that left-handed (LH) people may have different lateralization of neural functioning than right-handed (RH) people. This difference in lateralization may cause different areas of the brain to be activated by the same task. The current study investigates the lateralization differences between N=49 LH and N=50 RH during encoding and recognition memory tasks for verbal and non-verbal stimuli. Additionally, we measured participants’ laterality index by administering a semantic fluency task. We found no difference between groups for memory encoding activation for either verbal or non-verbal stimuli. Similarly, we found no group differences for verbal retrieval activation. There were quantitative differences between groups in non-verbal retrieval activation, primarily driven by greater spatial extent of activation in the RH group rather than by differences in lateralization in the LH group. To measure if including LH in fMRI studies would dilute results, we calculated memory effects ina prioriregions of interest (ROI) for the RH group only and then examined the effect of substituting in progressively more LH for RH. We found significant memory effects in 14a prioriROIs, 10 of which retained significant effects when adding LH participants. The remaining ROIs had significant memory-related activation in more than 80% of simulations with statistically likely numbers of LH participants. Taken together, these results indicate that the inclusion of left-handed participants does not have a strong detrimental effect on memory-related fMRI activation. On this basis we advocate for the inclusion of left-handed participants in cognitive neuroscience of memory research.
Cryo-EM of soft-landedβ-galactosidase: Gas-phase and native structures are remarkably similar
Authors: Esser Tim K. , Böhning Jan , Önür Alpcan , Chinthapalli Dinesh K. , Eriksson Lukas , Grabarics Marko , Fremdling Paul , Konijnenberg Albert , Makarov Alexander , Botman Aurelien , Peter Christine , Benesch Justin L. P. , Robinson Carol V. , Gault Joseph , Baker Lindsay , Bharat Tanmay A. M. , Rauschenbach Stephan
Published: August 2023

Native mass spectrometry (native MS) is a powerful technique that provides information on stoichiometry, interactions, homogeneity and shape of protein complexes. However, the extent of deviation between protein structures in the mass spectrometer and in solution remains a matter of debate. Here, we uncover the gas-phase structure ofβ-galactosidase using single particle electron cryomicroscopy (cryo-EM) down to 2.6 Å resolution, enabled by soft-landing of mass-selected protein complexes onto cold TEM grids and in-situ ice coating. We find that large parts of the secondary and tertiary structure are retained from solution, with dehydration-driven subunit reorientation leading to consistent compaction in the gas phase. Our work enables visualizing the structure of gas-phase protein com-plexes from numerous experimental scenarios at side-chain resolution and demonstrates the possibility of more controlled cryo-EM sample preparation.

One Sentence Summary

Electrospray ion-beam deposition on cold grids and in-vacuum ice growth enable cryo-EM of mass-selected proteins at 2.6 Å.
Central and peripheral tau retention modulated by an anti-tau antibody
Authors: Solorzano Alexander , Brady Molly , Bhatt Nemil , Johnson Angelique , Burgess Brooke , Leyva Hannah , Puangmalai Nicha , Jerez Cynthia , Wood Ronald , Kayed Rakez , Deane Rashid
Published: August 2023

Tau protein blood levels dependent on its distribution to peripheral organs and possible elimination from the body. Thus, the peripheral distribution of CSF-derived tau protein was explored, especially since there is a transition to blood-based biomarkers and the emerging idea that tau pathology may spread beyond brain. Near infrared fluorescence (NIRF) was mainly used to analyze tau (tau-NIRF) distribution after its intracisternal or intravenous injection. There was a striking uptake of blood- or CSF-derived tau-NIRF protein by the skeletal structures, liver, small intestine (duodenum), gall bladder, kidneys, urinary bladder, lymph nodes, heart, and spleen. In aging and in older APP/PS1 mice, tau uptake in regions, such as the brain, liver, and skeleton, was increased. In bone (femur) injected tau protein was associated with integrin-binding sialoprotein (IBSP), a major non-collagenous glycoprotein that is associated with mineralization. Tau-NIRF was cleared slowly from CSF via mainly across the cribriform plate, and cervical lymph nodes. In brain, some of the CSF injected tau protein was associated with NeuN-positive and PDGFRý-positive cells, which may explain its retention. The presence of tau in the bladders suggested excretion routes of tau. CSF anti-tau antibody increased CSF tau clearance, while blood anti-tau antibody decreased tau accumulation in the femur but not in liver, kidney, and spleen. Thus, the data show a body-wide distribution and retention of CSF-derived tau protein, which increased with aging and in older APP/PS1 mice. Further work is needed to elucidate the relevance of tau accumulation in each organ to tauopathy.
PP2A Dephosphorylates Phytochrome-Interacting Factor 3 to Modulate Photomorphogenesis inArabidopsis
Authors: Cai Xingbo , Lee Sanghwa , Gomej-Jaime Andrea , Tang Wenqiang , Sun Yu , Huq Enamul
Published: August 2023

The phytochrome (phy) family of sensory photoreceptors modulates developmental programs in response to ambient light. phys control gene expression in part by directly interacting with the bHLH class of transcription factors, phytochrome-interacting factors (PIFs), and inducing their rapid phosphorylation and degradation. Several kinases have been shown to phosphorylate PIFs and promote their degradation. However, the phosphatases that dephosphorylate PIFs are less investigated. Here we describe the identification of four regulatory subunits ofArabidopsisprotein phosphatase 2A (PP2A) family (B’α, B’β, B’’α and B’’β) that interacted with PIF3 in yeast-two-hybrid,in vitroandin vivoassays. Thepp2ab’’αβandb’’αβ/b’αβdisplayed short hypocotyls, while the overexpression of the B subunits induced longer hypocotyls compared to wild type under red light. The light-induced degradation of PIF3 was faster inb’’αβ/b’αβquadruple mutant compared to wild type. Consistently, immunoprecipitated PP2A A and B subunits directly dephosphorylated PIF3-MYCin vitro. RNA-seq analyses showed that B’’α and B’’β alter global gene expression in response to red light.PIFs (PIF1, PIF3, PIF4andPIF5)are epistatic to these four B subunits in regulating hypocotyl elongation under red light. Collectively, these data show an essential function of PP2A in dephosphorylating PIF3 to modulate photomorphogenesis inArabidopsis.
Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes
Authors: Hernáez Álvaro , Skåra Karoline H. , Page Christian M. , Mitter Vera R. , Hernández Marta H. , Magnus Per , Njølstad Pål R. , Andreassen Ole A. , Corfield Elizabeth C. , Havdahl Alexandra , Næss Øyvind , Brumpton Ben , Åsvold Bjørn Olav , Lawlor Deborah A. , Fraser Abigail , Magnus Maria Christine
Published: August 2023

Background

Adverse pregnancy outcomes (APO) may unmask a woman’s underlying risk for coronary heart disease (CHD). To test this, we estimated associations between genetically predicted liability for CHD and risk of APOs in mothers and their male partners. We hypothesized that associations would be found for women, but not their partners (negative controls).

Methods

We studied up to 83,969 women (and up to 55,568 male partners) participating in the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and information on history of any APO in their pregnancies (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10-8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis.

Results

One standard deviation increase in the GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05-1.10), pre-eclampsia (OR 1.08, 95% CI 1.05-1.11), and small for gestational age (OR 1.04, 95% CI 1.01-1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96 to 1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98 to 1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners’ GRS and restricting analyses to stable couples. Associations for miscarriage, gestational diabetes, and spontaneous preterm birth were close to the null. In male partners, there was weak evidence of an association with spontaneous preterm birth (OR 1.02 [0.99 to 1.05]), but not with other APOs.

Conclusions

Hypertensive disorders of pregnancy, small for gestational age and stillbirth unmask women with a genetically predicted existing propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth needs further exploration.
Informant-rated change in personality traits, psychological distress, well-being, and social connection with dementia
Authors: Sutin Angelina R. , Luchetti Martina , Stephan Yannick , Terracciano Antonio
Published: August 2023

Objectives:Studies of retrospective personality change with dementia consistently find caregivers report large changes in personality (e.g., increases in neuroticism) of their care recipients compared to before dementia. This work seeks to replicate the established pattern of personality change, extend it to change in psychological distress, well-being, and social connection, and evaluate whether changes vary by stage of dementia.Methods:Caregivers of people with dementia (N=194) reported on the psychological and social health of their care recipient currently and how they were before they developed dementia. Personality was measured as five factor model traits. Psychological distress was measured as symptoms of depression and anxiety, perceived stress, and pessimism. Psychological well-being was measured as purpose in life, life satisfaction, happiness, self-efficacy, and optimism. Social connection was measured as loneliness, belonging, social support, and social strain.Results:There were substantial increases in neuroticism (d=1.10) and decreases in the other four personality traits (drange=-.82 to −1.31). There were significant increases in psychological distress (e.g.,d=1.05 for depression) and substantial decreases in well-being (e.g.,d=-1.07 for purpose in life) and social connection (e.g.,d=-1.09 for belonging). Change was apparent across dementia stage and generally larger in more severe dementia.Discussion:In addition to personality, there are large retrospective changes in psychological distress, well-being, and social connection with dementia. These quantitative findings complement clinical observations of the natural history of psychosocial changes in people with dementia, and can inform families, clinicians, and researchers on commonly observed changes and improve interventions to mitigate dementia burden.