bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Practice Guidelines: Rehabilitation Interventions for Urgency Urinary Incontinence, Urinary Urgency, and/or Urinary Frequency in Adult Women
Authors: McAuley J. Adrienne , Mahoney Amanda T. , Austin Mary M.
Published: August 2023

Background/Rationale:

The body of evidence for interventions specific to urgency urinary incontinence (UUI), urinary urgency, and/or urinary frequency is not as readily accessible to consumers or health care providers when compared with stress urinary incontinence. This clinical practice guideline (CPG) is presented to help inform readers of the current evidence for physical therapy intervention of UUI, urinary urgency, and/or urinary frequency, as well as identify the areas in which further research is needed.

Purpose of the CPG:

The aim of this CPG is to provide evidence-based recommendations for rehabilitation interventions of UUI, urinary urgency, or urinary frequency in adult women.

Methodology:

Five electronic databases (OVID Medline, EMBASE, Cochrane Library, CINAHL, and ProQuest) were used to search for scientific literature published from January 1, 1995, to June 30, 2017. Critical readers formally assessed the procured articles. The authors collaborated to establish the levels of evidence and create the recommendations.

Results:

Thirty-one articles informed the development of 7 of the recommendations for intervention of UUI, urinary urgency, and/or urinary frequency. Summary tables of the articles that support each of the recommendations are presented. Two additional recommendations for best practice are presented as expert opinion.

Conclusion:

The CPG offers guidance to health care providers and patients for the treatment of urinary urge incontinence, urinary urgency, and urinary frequency. Recommendations, in order of strength of evidence, include behavioral interventions and pelvic floor muscle training (grade A) followed by electrical stimulation (grade B), and then lifestyle modifications (grades B and C).

See the Supplemental Digital Content Video Abstract, available at: http://links.lww.com/JWHPT/A115.
Novel approaches to measure transfusion effectiveness
Authors: Yee Marianne Elaine McPherson , Fasano Ross M.
Published: August 2023

Purpose of review

This review encompasses different considerations of transfusion effectiveness based upon clinical scenario and transfusion indication. Tissue oxygenation, cerebral metabolic oxygen use, and red blood cell (RBC) survival are important elements of transfusion effectiveness in individuals with acute and chronic transfusion requirements.

Recent findings

Noninvasive measures of tissue and cerebral oxygen extraction include near-infrared spectroscopy (NIRS) and specialized MRI sequences. RBC survival timepoints including 24 h posttransfusion recovery, 50% recovery timepoint, and mean potential lifespan may be accurately measured with biotin-labeling of RBC prior to transfusion. Labeling at different cell surface densities allows survival of multiple RBC populations to be determined.

Although past trials of optimal transfusion thresholds have focused on Hb as a singular marker for transfusion needs, measures of oxygenation (via NIRS or specialized MRI) and RBC survival (via biotin labeling) provide the opportunity to personalize transfusion decisions to individual patient's acute health needs or chronic transfusion goals.
Challenges with the current United Network for Organ Sharing heart allocation system
Authors: Gong Timothy A. , Hall Shelley A.
Published: August 2023

Purpose of review

The revised United States heart organ allocation system was launched in October 2018. In this review, we summarize this United Network for Organ Sharing (UNOS) policy and describe intended and unintended consequences.

Recent findings

Although early studies published after the change suggested postheart transplant survival declined at 6 months and 1 year, recent publications with longer follow-up time have confirmed comparable posttransplant survival in adjusted models and several patient cohorts. Moreover, the new allocation decreased overall waitlist time from 112 to 39 days (P < 0.001). Mean ischemic time increased because of greater distances traveled to acquire donor hearts under broader sharing. Despite the intention to decrease exception requests by expanding the number of priority tiers to provide more granular risk stratification, ∼30% of patients remain waitlisted under exception status. Left-ventricular assist device (LVAD) implants are declining and the number of LVAD patients on the transplant list has decreased dramatically after the allocation system change.

As the next allocation system is developed, it is imperative to curtail the use of temporary mechanical support as a strategy solely for listing purposes, identify attributes that more clearly stratify the severity of illness, provide greater oversight of exception requests, and address concerns regarding patients with durable LVADs.
New technologies for nephron-sparing surgery in upper urinary tract cancers
Authors: Gallioli Andrea , Basile Giuseppe , Territo Angelo , Breda Alberto
Published: August 2023

Purpose of review

Nephron-sparing surgery (NSS) is the preferred treatment in patients with low-risk upper tract urothelial carcinoma (UTUC). Improving both instruments and topical chemotherapy regimens efficacy is crucial to achieve better outcomes. The purpose of this review is to summarize the most recent evidence on technological advances for the conservative management of UTUC with implications on diagnosis and treatment.

Recent findings

Novel diagnostic tools, lasers, and topical chemotherapy systems delivery have been implemented to optimize NSS outcomes for UTUC.

Photodynamic ureteroscopy has been reported to improve cancer detection rate as compared with conventional imaging or ureteroscopy, especially in case of carcinoma in situ. However, refinements in photosensitizer administration and dedicated instruments are needed. The armamentarium of lasers for UTUC ablation is composed of several devices with peculiar characteristics. Together with Ho:YAG and Tm:YAG lasers, the Thulium Fiber Laser (TFL) is gaining momentum in UTUC ablation. Strengths and weaknesses of each laser must be considered to maximize oncological and safety outcomes. Several novel endocavitary chemotherapy delivery systems have been tested to reduce tumor recurrence and progression after NSS. Administration of gel-based chemotherapeutic agents has been proven to be effective in humans; conversely, drug-eluting ureteral stent systems are still conceptual.
TRPS1, a New Promising Marker for Assessment of Distant Metastatic Breast Cancer
Authors: McIntire Patrick J. , Duckworth Lauren A. , Van Arnam John , Abdelwahab Hala , Shin Sandra J.
Published: August 2023

This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and GATA3, compared with the novel immunohistochemical stain, Trichorhinophalangeal syndrome-1 (TRPS1). We review previous studies evaluating TRPS1 staining, which were conducted using cytology specimens, as well as our recently conducted study evaluating this stain using surgical tissue samples, both from primary and distant metastatic invasive breast carcinoma. In summary, although no immunohistochemical stain is 100% specific or sensitive, in the metastatic setting where tissue available for ancillary studies is limited, TRPS1 was a reliable and even a standalone marker for breast origin, particularly in cases of triple-negative breast cancer.
Early Diagnosis of Acute Myocarditis or Dilated Cardiomyopathy in Children Younger Than 2 Years
Authors: Ahmed Yasir , Heidemann Sabrina M.
Published: August 2023

Objective

Diagnosis of acute myocarditis or dilated cardiomyopathy (DCM) on initial presentation is difficult in children younger than 2 years because most present with complaints suggestive of a respiratory infection. The objective of this study is to determine whether signs, symptoms, and diagnostic studies excluding those of heart failure, done routinely in the emergency department could distinguish children younger than 2 years with acute myocarditis or DCM from those with respiratory illnesses.

Methods

Sixty-four infants' charts, 32 cases and 32 controls, were reviewed from January 1, 2009, through December 31, 2020. Controls were matched to cases with respect to age, reason, and time of admission. Signs, symptoms, and blood gases were reviewed.

Results

The median age is 6.5 (0.5–22) months in both groups. Infants presenting with signs of heart failure including murmurs (P = 0.002), prolonged capillary refill (P = 0.024), cool, mottled extremities (P = 0.002), poor perfusion (P = 0.001), or hepatomegaly (P < 0.001) were more likely to be diagnosed with acute myocarditis or DCM when compared with the control group with respiratory disease. Infants with fever (P = 0.017), nasal congestion (P < 0.001), rhinorrhea (P < 0.001), cough (P < 0.001), and wheezing (P < 0.001) were more likely to have a respiratory illness than acute myocarditis or DCM. The presence of a lower pco
2 (30 [14–116] vs 40 [31–59] mm Hg, P < 0.001), lower bicarbonate (16.7 [6.3–23.4] vs 21.7 [16–28.4], P < 0.001), or an oxygen saturation > 95% (P = 0.004) was observed in infants with acute myocarditis or DCM compared with those with respiratory illness. By multivariable analysis, infants with tachycardia in the absence of fever, metabolic acidosis, and an oxygen saturation > 95% were more likely to have acute myocarditis or DCM than those without this disease.

Conclusions

Children younger than 2 years presenting to the emergency department with tachycardia and no fever, metabolic acidosis, and a high oxygen saturation should be investigated for acute myocarditis or DCM.
Predictors of Post-COVID-19 Functional Status Scale in hospitalized patients recovering from SARS-CoV-2 infection
Authors: dos Santos Tamires Daros , Alves Souza Juliana , Cardoso Dannuey Machado , Berni Viviane Bohrer , Pasqualoto Adriane Schmidt , de Albuquerque Isabella Martins
Published: August 2023

Objective

The study aimed to investigate whether peripheral and inspiratory muscle strength and architecture, functional capacity, functional mobility, fatigue and health-related quality of life (HRQoL) are predictors of the PCFS scale score in patients with post-COVID-19 syndrome who were hospitalized.

Design

A cross-sectional study included 69 patients (53.3 ± 13.2 years, 36 men) with post-COVID-19 syndrome. The following outcomes were assessed: peripheral (dynamometry) and inspiratory (manovacuometry) muscle strength, muscle architecture (ultrasound), functional capacity (six-minute walk test), functional mobility (Timed Up and Go), fatigue (Functional Assessment of Chronic Illness Therapy), HRQoL (36-item Short Form Health Survey) and functional status (PCFS scale).

Results

Functional mobility (β = 0.573; P < 0.001), vastus intermedius echogenicity (β = -0.491; P = 0.001), length of stay (β = 0.349; P = 0.007) and female sex (β = 0.415; P = 0.003) influenced the PCFS scale.

Conclusion

Functional mobility, muscle quality of the vastus intermedius, length of stay and female sex influence the PCFS scale score in this population. It is noteworthy that functional mobility is an independent predictor of PCFS scale.
Attachment patterns, self-compassion, and coping strategies in patients with chronic pain
Authors: Nasika Iliana-Nefeli , Wiart Catherine , Bonvarlet Anne-Sophie , Guillaume Jessica , Yavchitz Amélie , Tereno Susana
Published: August 2023

Introduction:

In the recent year's literature, attachment insecurity is described as a vulnerability factor among patients with chronic pain, associated with poor pain coping, anxiety, depression, catastrophizing, greater pain intensity, and disability. Self-compassion, on the other hand, is described as a protective factor, associated with lower levels of negative affect, catastrophizing, depression, and anxiety in patients with chronic pain.

Methods:

In this study, we aim to explore the association between attachment, self-compassion quality, and coping strategies, in patients with chronic pain. Thus, 134 eligible patients with chronic pain were recruited at the certified Evaluation and Treatment Pain Center of the A. de Rothschild Foundation in Paris. We used a sociodemographic questionnaire, the Relationship Scale Questionnaire (RSQ-RC), the Self-Compassion Scale, and the Brief COPE.

Results:

Results supported our principal hypothesis; securely attached participants reported a significantly higher global self-compassion score compared with insecurely attached ones. Secure attachment and higher self-compassion levels were positively correlated with functional coping strategies and negatively correlated with dysfunctional ones.

Discussion:

Attachment patterns may be the basis of someone's ability to be compassionate to himself and to cope adequately with a difficult situation, such as a chronic pain condition. An attachment-informed approach to pain management could offer a better understanding of the complexity of this clinical condition and potentially provide appropriate support for both patients and health professionals, aiming to improve the effectiveness of interventions.
Lower Body Mass Index at Baseline Is Related to Steeper Cognitive Decline in the Alzheimer’s Disease Neuroimaging Initiative Cohort
Authors: Haley Andreana P. , Clark Alexandra L. , Duarte Audrey ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: August 2023

Objective

Midlife obesity is a risk factor for dementia, whereas obesity in older age may be protective of cognition, a phenomenon known as the “obesity paradox.” The mechanisms underlying this phenomenon and the relationship between body mass index (BMI) and cognitive function over time remain unclear.

Methods

In 1399 adults with and without mild cognitive impairment (median age 73.6 years) from the Alzheimer’s Disease Neuroimaging Initiative, we modeled the effects of baseline BMI on within-person trajectories of cognitive decline using Latent Growth Curve Modeling. We also tested if the effects of BMI on cognitive decline are global or specific to memory, executive function, or language.

Results

Higher baseline BMI was associated with better memory (β
BMI = 0.06, p < .05) and worse executive function (β
BMI = −0.05, p < .05) and not associated with language. Independent of baseline diagnosis, higher baseline BMI was associated with slower rate of decline in executive function, memory, and language (β
BMI = 0.13, 0.12, and 0.12, respectively; p < .01). Higher BMI was not associated with the intercept (β
BMI = 0.04, p = .059) or change (β
BMI = 0.04, p = .415) in a global cognitive factor.

Conclusions

We found that higher baseline BMI was associated with slower cognitive decline in participants with and without mild cognitive impairment diagnosis. Higher BMI in this context seems to be protective of cognitive function for people at risk for dementia. Our findings also support domain-specific effects of obesity on various cognitive functions rather than a final common pathway.
Gut microbiome and its clinical implications: exploring the key players in human health
Authors: Koneru Sindhuja , Thiruvadi Varshini , Ramesh Mayur
Published: August 2023

Purpose of review

The human gut harbors a diverse community of microorganisms known as the gut microbiota. Extensive research in recent years has shed light on the profound influence of the gut microbiome on human health and disease. This review aims to explore the role of the gut microbiome in various clinical conditions and highlight the emerging therapeutic potential of targeting the gut microbiota for disease management.

Recent findings

Knowledge of the influence of gut microbiota on human physiology led to the development of various therapeutic possibilities such as fecal microbiota transplant (FMT), phage therapy, prebiotics, and probiotics. Recently, the U.S. FDA approved two FMT products for the treatment of recurrent Clostridioides difficile infection with ongoing research for the treatment of various disease conditions.

Advancement in the knowledge of the association between gut microbiota and various disease processes has paved the way for novel therapeutics.
Resistance in Enteric Shigella and nontyphoidal Salmonella: emerging concepts
Authors: Yang Chaojie , Xiang Ying , Qiu Shaofu
Published: August 2023

Purpose of review

The emergence of globally resistant enteric Shigella and nontyphoidal Salmonella strains (NTS) has limited the selection of effective drugs, which has become a major challenge for the treatment of infections. The purpose of this review is to provide the current opinion on the antimicrobial-resistant enteric Shigella and nontyphoidal Salmonella.

Recent findings

Enteric Shigella and NTS are resistant to almost all classes of antimicrobials in recent years. Those with co-resistance to ciprofloxacin, azithromycin and ceftriaxone, the first-line antibiotics for the treatment of infectious diarrhoea have emerged worldwide. Some of them have caused interregional and international spread by travel, trade, MSM, and polluted water sources. Several strains have even developed resistance to colistin, the last-resort antibiotic used for treatment of multidrug-resistant Gram-negative bacteria infections.

The drug resistance of enteric Shigella and NTS is largely driven by the use of antibiotics and horizontal gene transfer of mobile genetic elements. These two species show various drug resistance patterns in different regions and serotypes. Hence treatment decisions for Shigella and Salmonella infections need to take into consideration prevalent antimicrobial drug resistance patterns. It is worth noting that the resistance genes such as bla
CTX,
mph, ermB, qnr and mcr, which can cause resistance to ciprofloxacin, cephalosporin, azithromycin and colistin are widespread because of transmission by IncFII, IncI1, IncI2 and IncB/O/K/Z plasmids. Therefore, continuous global monitoring of resistance in Shigella and Salmonella is imperative.
Heterogeneity of Orofacial Clefts and Associated Anomalies in China
Authors: Jiang Leheng , Jiang Chanyuan , Wang Yongqian , Song Tao , Yin Ningbei
Published: August 2023

Despite the large number of affected individuals in China, information on the descriptive epidemiology of orofacial clefts in the Chinese population remains limited. Therefore, the authors aimed to report a detailed clinical classification of orofacial clefts, including microform cleft lip (CL), and associated malformations in patients from a major cleft surgical unit in China. The authors reviewed the medical records of 718 patients who underwent primary cleft repair surgery at their center between December 2016 and April 2023. The sex distribution varied with cleft type and extent, and males had a higher proportion of clefts with increased severity than females. In patients with a unilateral CL, the ratio of left-to-right–sided clefts was 1.85:1. The frequency of associated congenital malformations in patients with microform CL only, overt CL only, CL and palate, and cleft palate only was 8.0%, 7.6%, 14.9%, and 30.9%, respectively. A total of 98 malformations were observed in 69 patients with congenital anomalies of unknown origin. Among these, cardiovascular anomalies were the most common, identified in 27 patients (39.1%), followed by head and neck and musculoskeletal anomalies. The high risk of heart defects highlights the importance of routine echocardiography. Microform CL exhibited increased prevalence and a similar frequency of associated malformations with overt CL, suggesting that this mild phenotype requires further attention by clinicians.
Web-based cognitive assessment in older adults: Where do we stand?
Authors: Belleville Sylvie , LaPlume Annalise Aleta , Purkart Rudy
Published: August 2023

Purpose of review

The use of digital tools for remote cognitive measurement of older adults is generating increasing interest due to the numerous advantages offered for accessibility and scalability. However, these tools also pose distinctive challenges, necessitating a thorough analysis of their psychometric properties, feasibility and acceptability.

Recent findings

In this narrative review, we present the recent literature on the use of web-based cognitive assessment to characterize cognition in older adults and to contribute to the diagnosis of age-related neurodegenerative diseases. We present and discuss three types of web-based cognitive assessments: conventional cognitive tests administered through videoconferencing; unsupervised web-based assessments conducted on a computer; and unsupervised web-based assessments performed on smartphones.

There have been considerable progress documenting the properties, strengths and limitations of web-based cognitive assessments. For the three types of assessments reported here, the findings support their promising potential for older adults. However, certain aspects, such as the construct validity of these tools and the development of robust norms, remain less well documented. Nonetheless, the beneficial potential of these tools, and their current validation and feasibility data, justify their application [see Supplementary Digital Content (SDC), http://links.lww.com/CONR/A69].
A Case of Bing–Neel Syndrome Presenting Like Giant Cell Arteritis
Authors: Hepschke Jenny L. , Ramalingam Satheesh , Pohl Ute , Amel-Kashipaz Rasoul M. , Blanch Richard J.
Published: August 2023

A 55-year-old woman presented with new-onset headache, scalp tenderness, shoulder arthralgias, night sweats, and loss of appetite. She was diagnosed with giant cell arteritis by her primary care physician and commenced on oral corticosteroids. However, her headache, scalp tenderness, and night sweats persisted. She then developed right Horner syndrome and trigeminal hypoesthesia. Extensive blood work-up revealed mildly elevated inflammatory markers and a paraproteinemia. Subsequent bone marrow biopsy showed lymphoplasmacytic lymphoma, with 10% of hemopoiesis, and staging led to the diagnosis of Waldenstrom macroglobulinemia without nodal or central nervous system (CNS) lesions. Immunohistochemical staining of a temporal artery biopsy showed perivascular lymphoplasmacytic cells and paraprotein deposits. She was diagnosed with CNS involvement of her macroglobulinemia—Bing–Neel syndrome (BNS). Identification of rare CNS involvement of lymphoma is challenging when a patient is already on steroid immunosuppression. In the absence of clear diagnostic criteria, the rare and heterogenous BNS remains a clinical diagnosis.
How suitable is freshwater sponge Ephydatia fluviatilis (Linnaeus, 1759) for time-integrated biomonitoring of microbial water quality?
Authors: Cartwright Allison , Dooley James S.G. , McGonigle Chris D. , Arnscheidt Joerg
Published: August 2023

Faecal pollution of water by bacteria has a negative effect on water quality and can pose a potential health hazard. Conventional surveillance of microbial water quality relies on the analysis of low frequency spot samples and are thus likely to miss episodic or periodic pollution. This study aimed to investigate the potential of filter feeding sponges for time-integrated biomonitoring of microbial water quality. Laboratory trials tested the effects of different ratios of bacterial abundance and the sequence of exposure on bacterial retention by the freshwater sponge Ephydatia fluviatilis (Linnaeus, 1759) to establish their potential to indicate bacterial exposure.
Gemmule grown sponges were simultaneously exposed to Escherichia coli and Enterococcus faecalis but at different ratios (Trial 1) or individually exposed to each of bacterial species but in different sequential order (Trial 2). The E. coli and E. faecalis retained in each sponge was quantified by culture on selective agars. Data analysis was conducted using Kruskal- Wallis test and/ or Mann Whitney U test to compare between the numbers of bacteria retained in each treatment. Additionally, the Wilcoxon Matched-Paired Signed-Rank test was used for comparison of the different bacterial abundance retained within each individual sponge.
Sponges from all trials retained E. coli and E. faecalis in small numbers relative to the exposure (<0.05% Trial 1 and <0.07% Trial 2) but exhibited preference for retention of E. coli. Higher abundance of either bacterial species resulted in significantly lower (p<0.005) retention of the same species within sponges (Trial 1). An initial exposure to E. coli resulted in significantly higher (p=0.040) retention of both bacterial species than when sponges were exposed to E. faecalis first (Trial 2).
Bacterial retention by sponges was neither representative of bacterial abundance in the ambient water nor the sequence of exposure. This implies either selective filtration or an attempt by sponges to prevent infection. However, freshwater sponges may be useful in biomonitoring as qualitative time-integrated samplers of faecal indicator bacteria.
PEPhub: a database, web interface, and API for editing, sharing, and validating biological sample metadata
Authors: LeRoy Nathan J. , Khoroshevskyi Oleksandr , O’Brien Aaron , Stepień Rafał , Arslan Alip , Sheffield Nathan C.
Published: August 2023

Background

As biological data increases, we need additional infrastructure to share it and promote interoperability. While major effort has been put into sharing data, relatively less emphasis is placed on sharing metadata. Yet, sharing metadata is also important, and in some ways has a wider scope than sharing data itself.

Results

Here, we present PEPhub, an approach to improve sharing and interoperability of biological metadata. PEPhub provides an API, natural language search, and user-friendly web-based sharing and editing of sample metadata tables. We used PEPhub to process more than 100,000 published biological research projects and index them with fast semantic natural language search. PEPhub thus provides a fast and user-friendly way to finding existing biological research data, or to share new data.

Availability

https://pephub.databio.org
JQ1 Epigenetic Modulation of Pancreatic β-Cells (INS-1) Normalizes Glucose Sensitivity under Hyperglycemia: Therapeutic Preventive Implications for Type II Diabetes Mellitus
Authors: Hernández Mateo H. , Uçar Nazlı , Deeney Jude T.
Published: August 2023

Chronic hyperinsulinemia and insulin resistance are prequels to type II diabetes mellitus (T2D), a disease that affects over 10% of Americans and is closely associated with obesity, as nearly 90% of diabetic patients are overweight or obese. Chronic excess nutrient exposure leads to glucolipotoxicity in pancreatic β-cells, which is characterized by a left shift in glucose concentration-dependent insulin secretion. Previous studies from our laboratory have demonstrated that the Bromodomain and Extra-Terminal (BET) protein inhibitor JQ1 (400 nM) increases fatty acid (FA) oxidation in clonal pancreatic β-cells (INS-1), leading to a partial reversal of glucolipotoxicity. The present research investigates the effect of JQ1 on the glucose sensitivity of INS-1 cells under hyperglycemic conditions. INS-1 cells were pre-treated with dimethyl sulfoxide-based 400 nM JQ1 for 3 days and cultured for 5 days in RPMI 1640 media (11 mM glucose). Subsequently, INS-1 cells were pre-incubated in a modified Krebs-Henseleit buffer (1 mM glucose) before adding test solutions (1-12 mM glucose). Samples for insulin release and cellular content were measured using a Homogeneous Time-Resolved Fluorescence insulin assay kit. Insulin secretion from INS-1 cells cultured in 11 mM glucose was maximally stimulated at 4 mM glucose. Treatment with JQ1 for one day right-shifted maximal glucose-stimulated insulin secretion (GSIS) to 6 mM glucose compared to control but did not prevent stimulated insulin secretion at 4 mM glucose. Three-day treatment with JQ1 reduced secretion at 4 mM glucose to basal level (1 mM) while maintaining the right-shifted concentration-dependent GSIS, an effect described herein for the first time. Total insulin content (TIC) and release as its percentage were also measured, indicating a higher TIC and lower percentage use in JQ1-treated cells. Additionally, lipid concentration was photographically fluorescent analyzed, showing significant depletion of lipid droplets in JQ1-treated cells. Results imply that epigenetic modulation of pancreatic β-cells with JQ1 beneficially alters signal transduction pathways that maintain insulin-glucose homeostasis by ameliorating glucolipotoxicity through the preservation of a low GSIS basal level, increment of GSIS maximum capacity, delay of GSIS cuspid level at 12 mM glucose, more efficient spend of total insulin content resources, and diminished lipid accumulation due to increased FA oxidation—thereby suggesting JQ1 returning hyperglycemic β-cells to physiological conditions. Suggested future directions include improving the efficacy and accuracy of JQ1 and similar small-molecule BET inhibitors through tests in human subjects’ isolated islets, as this presents an innovative course of research for the prevention of T2D and comorbidities.
A reproducible and generalizable software workflow for analysis of large-scale neuroimaging data collections using BIDS Apps
Authors: Zhao Chenying , Jarecka Dorota , Covitz Sydney , Chen Yibei , Eickhoff Simon B. , Fair Damien A. , Franco Alexandre R. , Halchenko Yaroslav O. , Hendrickson Timothy J. , Hoffstaedter Felix , Houghton Audrey , Kiar Gregory , Macdonald Austin , Mehta Kahini , Milham Michael P. , Salo Taylor , Hanke Michael , Ghosh Satrajit S. , Cieslak Matthew , Satterthwaite Theodore D.
Published: August 2023

Neuroimaging research faces a crisis of reproducibility. With massive sample sizes and greater data complexity, this problem becomes more acute. Software that operates on imaging data defined using the Brain Imaging Data Structure (BIDS) – BIDS Apps – have provided a substantial advance. However, even using BIDS Apps, a full audit trail of data processing is a necessary prerequisite for fully reproducible research. Obtaining a faithful record of the audit trail is challenging – especially for large datasets. Recently, the FAIRly big framework was introduced as a way to facilitate reproducible processing of large-scale data by leveraging DataLad – a version control system for data management. However, the current implementation of this framework was more of a proof of concept, and could not be immediately reused by other investigators for different use cases. Here we introduce theBIDSAppBootstrap (BABS), a user-friendly and generalizable Python package for reproducible image processing at scale. BABS facilitates the reproducible application of BIDS Apps to large-scale datasets. Leveraging DataLad and the FAIRly big framework, BABS tracks the full audit trail of data processing in a scalable way by automatically preparing all scripts necessary for data processing and version tracking on high performance computing (HPC) systems. Currently, BABS supports jobs submissions and audits on Sun Grid Engine (SGE) and Slurm HPCs with a parsimonious set of programs. To demonstrate its scalability, we applied BABS to data from the Healthy Brain Network (HBN; n=2,565). Taken together, BABS allows reproducible and scalable image processing and is broadly extensible via an open-source development model.
Direct RNA-binding by MYCN mediates feedback from RNA processing to transcription control
Authors: Papadopoulos Dimitrios , Ha Stefanie Anh , Fleischhauer Daniel , Uhl Leonie , Schneider Katharina , Mikicic Ivan , Russell Timothy J. , Brem Annika , Valanju Omkar Rajendra , Gallant Peter , Schuelein-Voelk Christina , Maric Hans Michael , Beli Petra , Büchel Gabriele , Vos Seychelle M. , Eilers Martin
Published: August 2023

The MYCN oncoprotein broadly binds active promoters in a heterodimer with its partner protein MAX. MYCN also interacts with the nuclear exosome, a 3’-5’ exoribonuclease complex, suggesting a function in RNA metabolism. Here we show that MYCN forms stable high molecular weight complexes with the exosome and multiple RNA-binding proteins. In cells, MYCN binds to thousands of intronic RNAs; recombinant MYCN directly binds RNA via a short, highly conserved sequence termed MYCBoxI. Perturbing exosome function results in global re-localization of MYCN from promoters to intronic RNAs. At promoters, MYCN is then replaced by the MNT(MXD6) repressor protein, which inhibits MYCN-dependent transcription. MYCN promotes the degradation of its bound introns via the nuclear exosome targeting (NEXT) complex. Our data demonstrate that MYCN is an RNA-binding protein that regulates nascent transcript turnover and show that competition between its RNA– and DNA-bound states links the dynamics of the MYCN/MAX/MXD network to mRNA processing.
Single cell multi-omics analysis of chronic myeloid leukemia links cellular heterogeneity to therapy response
Authors: Warfvinge Rebecca , Ulfsson Linda Geironson , Dhapola Parashar , Safi Fatemeh , Sommarin Mikael N.E. , Soneji Shamit , Hjorth-Hansen Henrik , Mustjoki Satu , Richter Johan , Thakur Ram Krishna , Karlsson Göran
Published: August 2023

The advent of tyrosine kinase inhibitors (TKIs) as treatment of chronic myeloid leukemia (CML) is a paradigm in molecularly targeted cancer therapy. Nonetheless, TKI insensitive leukemia stem cells (LSCs) persist in most patients even after years of treatment. The sustained presence, heterogeneity and evolvability of LSCs are imperative for disease progression as well as recurrence during treatment-free remission (TFR). However, dynamic changes among LSC sub-populations upon TKI therapy impede their measurement and targeting. Here, we used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to generate high-resolution single cell multiomics maps from CML patients at diagnosis, retrospectively stratified by BCR::ABL1IS(%) following 12 months of TKI therapy as per European LeukemiaNet (ELN) recommendations. Simultaneous measurement of global gene expression profiles together with >40 surface markers from the same cells revealed that each patient harbored a unique composition of stem and progenitor cells at diagnosis demonstrating that cellular heterogeneity is a hallmark of CML. The patients with treatment failure after 12 months of therapy had markedly higher abundance of molecularly defined primitive cells at diagnosis compared to the optimal responders. Furthermore, deconvolution of an independent dataset of CML patient-derived bulk transcriptomes (n=59) into constituent cell populations showed that the proportion of primitive cells versus lineage primed sub-populations significantly connected with the TKI-treatment outcome. The multiomic feature landscape enabled visualization of the primitive fraction as a heterogenous mixture of molecularly distinct Lin−CD34+CD38−/lowBCR::ABL1+LSCs and BCR::ABL1−hematopoietic stem cells (HSCs) in variable ratio across patients and guided their prospective isolation by a combination of CD26 and CD35 cell surface markers. We for the first time show that BCR::ABL1+LSCs and BCR::ABL1−HSCs can be distinctly separated as CD26+CD35−and CD26−CD35+respectively. In addition, we found the relative proportion of CD26−CD35+HSCs to be higher in optimal responders when compared to treatment failures, at diagnosis as well as following 3 months of TKI therapy, and that the LSC/HSC ratio was increased in patients with prospective treatment failure. Collectively, the patient-specific cellular heterogeneity multiomics maps build a framework towards understanding therapy response and adapting treatment by devising strategies that either extinguish TKI-insensitive LSCs or engage the immune effectors to suppress the residual leukemogenic cells.
TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content
Authors: Gunalp Sinem , Helvacı Derya Goksu , Oner Aysenur , Bursalı Ahmet , Conforte Alessandra , Güner Hüseyin , Karakülah Gökhan , Szegezdi Eva , Sag Duygu
Published: August 2023

Background

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can either induce cell death or activate survival pathways after binding to death receptors (DRs) DR4 or DR5. TRAIL is investigated as a therapeutic agent in clinical trials due to its selective toxicity to transformed cells.

Macrophages can be polarized into pro-inflammatory/tumor-fighting M1 macrophages or anti-inflammatory/tumor-supportive M2 macrophages and an inbalance between M1 and M2 macrophages can promote diseases. Therefore, identifying modulators that regulate macrophage polarization is important to design effective macrophage-targeted immunotherapies. The impact of TRAIL on macrophage polarization is not known.

Methods

Primary human monocyte-derived macrophages were pre-treated with either TRAIL or with DR4 or DR5-specific ligands and then polarized into M1, M2a, or M2c phenotypesin vitro. The expression of M1 and M2 markers in macrophage subtypes was analyzed by RNA sequencing, qPCR, ELISA, and flow cytometry. Furthermore, the cytotoxicity of the macrophages against U937 AML tumor targets was assessed by flow cytometry. TCGA datasets were also analyzed to correlate TRAIL with M1/M2 markers, and the overall survival of cancer patients.

Results

TRAIL increased the expression of M1 markers at both mRNA and protein levels while decreasing the expression of M2 markers at the mRNA level in human macrophages. TRAIL also shifted M2 macrophages towards an M1 phenotype. Our data showed that both DR4 and DR5 death receptors play a role in macrophage polarization. Furthermore, TRAIL enhanced the cytotoxicity of macrophages against the AML cancer cellsin vitro. Finally, TRAIL expression was positively correlated with increased expression of M1 markers in the tumors from ovarian and sarcoma cancer patients and longer overall survival in cases with high, but not low, tumor macrophage content.

Conclusions

TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype via both DR4 and DR5. Our study defines TRAIL as a new regulator of macrophage polarization and suggests that targeting DRs can enhance the anti-tumorigenic response of macrophages in the tumor microenvironment by increasing M1 polarization.
Development of an optimized, non-stem cell line for intranasal delivery of therapeutic cargo to the central nervous system
Authors: El-Ayoubi Ali , Arakelyan Arsen , Klawitter Moritz , Merk Luisa , Hakobyan Siras , Gonzalez-Menendez Irene , Quintanilla-Fend Leticia , Holm Per Sonne , Mikulits Wolfgang , Schwab Matthias , Danielyan Lusine , Naumann Ulrike
Published: August 2023

Neural stem cells (NSC) are considered to be valuable candidates for delivering a variety of anti-cancer agents to brain tumors, including oncolytic viruses. However, owing to the previously reported tumorigenic potential of NSC cell line after intranasal administration (INA), here we identified the human hepatic stellate cell line (LX-2) as a cell type capable of longer resistance to replication of oncolytic adenoviruses (OAV) as therapeutic cargo, and being non-tumorigenic after INA. Our data show that LX-2 cells can longer withstand the OAV XVir-N-31 replication and oncolysis than NSCs. By selecting the highly migratory cell population out of LX-2, an offspring cell line with a higher and more stable capability to migrate was generated. Additionally, as a safety backup, we applied genomic HSV-TK integration into LX-2 leading to the high vulnerability to Ganciclovir. Histopathological analyses confirmed the absence of neoplasia in the respiratory tracts and brains of immuno-compromised mice 3 months after INA of LX-2 cells. Our data suggest that LX-2 is a novel robust and safe cell line for delivering anti-cancer and other therapeutic agents to the brain.
A Hybrid Transistor with Transcriptionally Controlled Computation and Plasticity
Authors: Gao Yang , Zhou Yuchen , Ji Xudong , Graham Austin J. , Dundas Christopher M. , Mahfoud Ismar E. Miniel , Tibbett Bailey M. , Tan Benjamin , Partipilo Gina , Dodabalapur Ananth , Rivnay Jonathan , Keitz Benjamin K.
Published: August 2023

Organic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacteriumShewanella oneidensisthat enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) fromS. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT- based biosensing and biocomputing systems with genetically controllable and modular design elements.
Texans support mountain lion conservation management
Authors: Ohrens Omar , Ghasemi Benjamin , Gulas-Wroblewski Bonnie E. , Elbroch L. Mark
Published: August 2023

The state of Texas encompasses an estimated 7% of the United States mountain lion (Puma concolor) population, a likely overestimate due to their nongame status, unregulated take and high mountain lion mortality rates. In August 2022, Texas Parks and Wildlife Department (TPWD) denied a petition to amend state mountain lion management policies, but was mandated by the Texas Wildlife Commission to form a stakeholder group to assess the potential to initiate mountain lion management and policy. Herein, we synthesize survey data collected and previously published in a report by Ghasemi et al. (2022) to provide members of this mountain lion stakeholder working group, the Commission, and TPWD with succinct summaries of Texas residents’ knowledge and attitudes salient to the evaluation of mountain lion management in the state. We analyzed responses to represent the opinion of all Texans as well as to compare the sentiments of four key stakeholder groups: hunters vs. nonhunters; livestock owners vs. people without livestock; urban vs. rural residents; and Hispanics vs. non-Hispanics. Overall, Texans expressed a positive sentiment about mountain lions and supported management to conserve the species. Respondents exhibited very high consensus regarding the value of scientific research about mountain lions and expressed overwhelming support for mandatory reporting of any mountain lion killed for any purpose by hunters, trappers, or state or federal agents. Texas residents also backed a compensation program supporting livestock producers who lose animals to mountain lions and rapid checking of set traps. Contrary to expectation, hunters and livestock owners were more positive about mountain lions than non-hunters and people without livestock, and we detected no differences in the responses of urban versus rural residents or Hispanics versus non-Hispanics on any topic.
Metacognition and Problem Solving: How Self-Coaching Helps First-Year Students Move Past the Discomfort of Monitoring
Authors: Halmo Stephanie M. , Yamini Kira A. , Stanton Julie Dangremond
Published: August 2023

Stronger metacognitive regulation skills are linked to increased academic achievement. Metacognition has primarily been studied using retrospective methods, but these methods limit access to students’ in-the-moment metacognition. We investigated first-year life science students’ in-the-moment metacognition while they solved challenging problems, and asked 1) What metacognitive regulation skills are evident when first-year life science students solve problems on their own? and 2) What aspects of learning self-efficacy do first-year life science students reveal when they solve problems on their own? Think aloud interviews were conducted with 52 first-year life science students across three institutions and analyzed using qualitative content analysis. Our results reveal that first-year life science students use an array of monitoring and evaluating skills while solving problems, which challenges the deficit-oriented notion that students enter college with poor metacognitive skills. Additionally, a handful of students self-coached or encouraged themselves as they confronted aspects of the problems that were unfamiliar. These verbalizations suggest ways we can encourage students to couple their metacognitive regulation skills and self-efficacy to persist when faced with challenging disciplinary problems. Based on our findings, we offer recommendations for how instructors can help first-year life science students develop and strengthen their metacognition to achieve improved problem-solving performance.
A neurogenetic toolkit to decodeAnopheles gambiaeolfaction
Authors: Giraldo Diego , Hammond Andrew M. , Wu Jinling , Feole Brandon , Al-Saloum Noor , McMeniman Conor J.
Published: August 2023

The African malaria mosquitoAnopheles gambiaeexhibits a strong innate sensory drive to seek out human scent. To detect human odorants,An. gambiaeuses olfactory sensory neurons (OSNs) that can be divided into different classes by unique repertoires of chemoreceptor gene expression. We applied CRISPR-Cas9-mediated T2A-In Frame Fusions and theQF2/QUASsystem to gain genetic access to specific OSN subsets inAn. gambiaeexpressing the chemoreceptor genesIr25a,Ir76b,Gr22andorco. We first optimized methods to generate cell-type specificQF2driver andQUASresponder lines to map expression patterns of these chemoreceptors across mosquito sensory appendages. We next applied transcuticular calcium imaging to record neurophysiological responses to select human-related odorants for each OSN class. This neurogenetic toolkit tiling OSN subsets inAn. gambiae, including those responsive to CO2, stands to support systematic efforts to decode olfaction in this prolific disease vector at high-resolution to combat malaria.
Strain generated by the stacking faults in epitaxial SrO(SrTiO3)
N
Ruddlesden–Popper structures
Authors: Saint-Girons Guillaume , Furgeaud Clarisse , Largeau Ludovic , Danescu Alexandre , Bachelet Romain , Bouras Mohamed
Published: August 2023

Ruddlesden–Popper (RP) phases present outstanding physical properties triggering significant academic interest. Out-of-plane stacking faults (OP-SFs), which are the main channel for accommodating stoichiometry imbalance in RP thin layers, affect these properties. The mechanisms underlying the formation and spatial distribution of these defects remain largely unknown to date. This work shows that the residual mismatch related to the presence of OP-SFs in SrTiO3-based RP thin layers is accommodated by a delocalized mechanism of lateral strain transfer from the disturbed regions to the RP structure, generating a distribution of compressive strain in the latter. Analysing the RP X-ray diffractograms in the light of this mechanism allows the assessment of the OP-SF distribution along the growth axis. It also allows the separate and accurate determination of the SrTiO3 lattice parameter (c = 3.9214 ± 0.0003 Å) and the SrO–SrO inter-reticular distance (d = 2.549 ± 0.001 Å) in the RP structure.