bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity-specific improvement of lung cancer outcomes and immunotherapy efficacy with metformin
Authors: Smith Randall J , Zollo Robert , Kalvapudi Sukumar , Vedire Yeshwanth , Pachimatla Akhil Goud , Petrucci Cara , Shaller Garrison , Washington Deschana , Rr Vethanayagam , Sass Stephanie N , Srinivasan Aravind , Kannisto Eric , Bawek Sawyer , Jain Prantesh , Rosario Spencer , Barbi Joseph , Yendamuri Sai
Published: November 2024

Background

Preclinical cancer studies ascribe promising anticancer properties to metformin. Yet, clinical findings vary, casting uncertainty on its therapeutic value for non–small cell lung cancer (NSCLC) patients. We hypothesized that metformin could benefit obese and overweight patients with NSCLC.

Methods

We retrospectively analyzed 2 clinical cohorts and employed complementary mouse models to test our hypothesis. One cohort included NSCLC patients with overweight body mass index (≥25 kg/m2, n = 511) and nonoverweight body mass index (<25 kg/m2, n = 232) who underwent lobectomy, evaluating metformin’s impact on clinical outcomes. Another cohort examined metformin’s effect on progression-free survival after immune checkpoint inhibitors in overweight (n = 284) vs nonoverweight (n = 184) NSCLC patients. Metformin’s effects on tumor progression, antitumor immunity, and immune checkpoint inhibitor response in obese and normal-weight mice were assessed with lung cancer models.

Results

Metformin is associated with increased recurrence-free survival in overweight patients (hazard ratio [HR] = 0.47, 95% confidence interval [CI] = 0.24 to 0.94; P = .035) after lobectomy. It also corrected accelerated tumor growth in diet-induced obese mouse models in a lymphocyte-specific manner while reversing several mechanisms of immune suppression potentiated by obesity. Programmed cell death 1 blockade coupled with metformin was more effective at limiting tumor burden in obese mice and correlated with progression-free survival only in overweight patients on immunotherapy (HR = 0.60, 95% CI = 0.39 to 0.93; P = .024).

Conclusions

Metformin may improve lung cancer–specific clinical outcomes in obese and overweight lung cancer patients and enhance immunotherapy efficacy in this growing population. This work identifies obesity as a potential predictive biomarker of metformin’s anticancer and immunotherapy-enhancing properties in lung cancer while shedding light on the underlying immunological phenomena.
A case of post-traumatic acute appendicitis: uncommon consequence of blunt abdominal trauma
Authors: Alabdulaaly Norah I , Alghamdi Shahad , Albahli Mashael , Alabdullah Hisham , Alghuliga Abdullah
Published: November 2024

Acute appendicitis is known to be caused by intraluminal obstruction of the appendiceal lumen. Nonobstructive causes of acute appendicitis are rarely reported. Posttraumatic appendicitis is uncommon, and few cases have been reported in the literature. We present a case of acute appendicitis in a 21-year-old male confirmed via a computed tomography scan 5 days after a blunt abdominal injury. A laparoscopic appendectomy was performed, and the diagnosis of acute perforated appendicitis and peri appendicitis was confirmed histopathologically. The patient had an uneventful recovery following surgery.
“No doctor ever asked me…so I thought it wasn't a valid concern”: endometriosis patients’ perspectives of barriers and facilitators to sexual health communication in general practice
Authors: Davenport Rebekah Allison , Mills Jacqueline , McHardy Hannah , Lores Taryn , Sherman Kerry , Misajon RoseAnne , Van Niekerk Leesa
Published: November 2024

Background

Sexual health communication between general practitioners (GPs) and individuals with chronic diseases is well documented as an important component of sexual well-being. However, a notable gap exists in understanding factors that contribute to sexual health communication in the endometriosis context. Endometriosis-related research has focused on the assessment of sexual functioning and its role in influencing health-related quality of life, with a limited understanding of the management of sexual well-being in primary healthcare settings.

Aim

To explore how individuals with endometriosis perceive their experiences of sexual health communication with GPs to understand the barriers and facilitators of this communication in general practice.

Methods

This study formed part of a larger online quantitative survey measuring psychological and sexual well-being in individuals with endometriosis. In total 141 participants provided responses via open-ended unlimited free-text questions focused on their experiences of sexual health communication with GPs, including their perspectives on barriers and facilitators.

Results

Four overarching themes regarding barriers to sexual health communication were identified through thematic template analysis: (1) systemic factors; (2) practitioner factors; (3) patient factors; and (4) interpersonal factors. Facilitators mirrored strategies to address these barriers. Additionally, participants offered recommendations for developing resources to improve sexual health communication.

Clinical Implications

Despite patients’ interest, sexual health concerns in endometriosis are commonly overlooked in general practice due to various barriers, which individuals suggest could be addressed through comprehensive GP education and practical aids including communication tools.

Strengths and Limitations

Although the sample is large for a qualitative study, the potential selection bias—stemming from participants’ high levels of sexual dysfunction and motivation to discuss sexual health with a GP—may limit the diversity of perspectives. GP perspectives were not evaluated, precluding any assessment of the accuracy of individuals’ perceptions of practitioner factors.

Conclusions

Individuals with endometriosis encounter various systematic, practitioner, personal, and interpersonal factors that hinder or facilitate sexual health communication in general practice. Future research should prioritize strategies to improve sexual health communication for both GPs and patients.
Bacterial composition and cultural dynamics of microgreens-associated microbiota during selective enrichment for Listeria monocytogenes
Authors: Haniford Laura S E , Dussault Forest , Shay Julie A , Cooper Ashley , Blais Burton W , Lau Calvin Ho-Fung
Published: November 2024

Widely regarded as a so-called “superfood,” microgreens have become an increasingly significant food crop from both nutritional and agricultural standpoints. However, similar to other produce commodities that are also cultivated using modernized indoor farming methods, there have been mounting concerns over the potential risks of consuming microgreens contaminated by Listeria monocytogenes. To gain insights into the microbial properties of microgreens, this study characterized the bacterial composition of fresh microgreen retail products using amplicon sequencing of 16S rRNA genes. Dominated by Gammaproteobacteria, a total of 36 shared genera were identified as putative constituents of the microgreen core microbiome. By monitoring the dynamics of microgreen-borne bacteria undergoing a Listeria-selective cultural enrichment procedure, it was revealed that, regardless of the presence or absence of L. monocytogenes, off-target bacteria of the Klebsiella and Enterococcus genera were significantly enriched from microgreens by the primary enrichment step, with the secondary enrichment step continuing to promote the expansion of Enterococcus population. While Listeria was generally neither the most-enriched nor the dominant taxon in cultures sampled at different enrichment stages, significant enrichment of Lysinibacillus and Bacillus bacteria was detected in microgreens contaminated with L. monocytogenes, suggesting they could be co-enriched in competition with Listeria.
Predictions for the abundance and clustering of H α emitting galaxies
Authors: Madar Makun S , Baugh Carlton M , Shi Difu
Published: November 2024

We predict the surface density and clustering bias of H $\alpha$ emitting galaxies for the Euclid and Nancy Grace Roman Space Telescope redshift surveys using a new calibration of the galform galaxy formation model. We generate 3000 galform models to train an ensemble of deep learning algorithms to create an emulator. We then use this emulator in a Markov Chain Monte Carlo (MCMC) parameter search of an eleven-dimensional parameter space, to find a best-fitting model to a calibration data set that includes local luminosity function data, and, for the first time, higher redshift data, namely the number counts of H $\alpha$ emitters. We discover tensions when exploring fits for the observational data when applying a heuristic weighting scheme in the MCMC framework. We find improved fits to the H $\alpha$ number counts while maintaining appropriate predictions for the local universe luminosity function. For a flux limited Euclid-like survey to a depth of $2\times 10^{-16}~\textrm {erg}^{-1}~\textrm {s}^{-1}~\textrm {cm}^{-2}$ for sources in the redshift range $0.9< z< 1.8$, we estimate 2962–4331 H $\alpha$ emission-line sources deg$^{-2}$. For a Nancy Grace Roman survey, with a flux limit of $1\times 10^{-16}~\textrm {erg}^{-1}~\textrm {s}^{-1}~\textrm {cm}^{-2}$ and a redshift range $1.0< z< 2.0$, we predict 6786–10 322 H $\alpha$ emission-line sources deg$^{-2}$.
Immunotherapy benefits for large brain metastases in non-small cell lung cancer
Authors: Sadagopan Narayanan , Komlodi-Pasztor Edina , Veytsman Irina
Published: November 2024

Introduction

Non-small cell lung cancer (NSCLC) patients with large brain metastases (BrM) defined as >2 cm in diameter historically face grim prognoses. With immunotherapy emerging as a promising avenue for BrM management and being commonly used in NSCLC, its application in addressing large BrM remains underexplored.

Methods

This retrospective study conducted across the MedStar Georgetown Cancer Network aimed to assess the efficacy of immunotherapy in non-biomarker driven NSCLC patients with large BrM following initial treatment.

Results

Thirty-six patients were included, all of whom underwent neurosurgery and/or radiation before commencing immunotherapy. The median intracranial progression-free survival (PFS) was 9.2 months and the median overall survival (OS) reached 31 months. Utilizing multivariable Cox penalized regression, the intracranial PFS hazard ratio (HR) was 0.07 (95% confidence interval (CI), 0.02-0.26) for patients who received at least 90 days of immunotherapy compared to those who did not. Each additional 30 days of immunotherapy was associated with an OS HR 0.77 (95% CI, 0.67-0.90).

Conclusion

This real-world data highlights the potential of immunotherapy in large BrM NSCLC patients, a population often excluded from clinical trials. This study contributes insights that can inform future treatment approaches, emphasizing the need for further exploration of immunotherapy’s role in enhancing outcomes for this challenging patient population.
Smads and AP‐1 activation of TGF‐β signaling upregulate transcription of Osteoprotegerin in Cementoblasts to inhibit osteoclastogenesis
Authors: Mo Lijuan , Zhu Jiaqi , Li Mengying , Zhang Gengming , Cao Zhengguo , Li Biao , Du Mingyuan , He Hong
Published: November 2024

Orthodontically induced root resorption (OIRR) is a common side effect during orthodontic tooth treatment (OTM). The function of osteoprotegerin (OPG) is considered to protect cementum from excessive resorption to maintain root integrity. In this study, we observed that the expression of TGF‐β1 and OPG was upregulated under the loading of orthodontic force in periodontal tissues. However, the specific molecular mechanisms of TGF‐β1‐induced OPG expression in cementoblasts are not fully elucidated. This study aims to investigate the effect of Smads and AP‐1 stimulated by TGF‐β signaling on the transcription of OPG in cementoblasts. In vitro, we demonstrated that TGF‐β/Smad and AP‐1 signaling involved in TGF‐β1‐induced extracellular secretion of OPG in conditioned media (CM) from cementoblasts, which further inhibited osteoclastogenesis. Reporter gene plasmids containing OPG promoter sequences of different lengths (0.5–3 kb) were constructed to investigate the potential binding sites of Smads and AP‐1. We identified nine binding sites of Smads and AP‐1 concentrated in the 0–0.5 and 2.3–3 kb regions of OPG promoter in cementoblasts. ChlP results showed that Smad2/3/4 and c‐Jun were bound more to the OPG promoter under TGF‐β1 stimulation. In vivo, localized administration of TGF‐β1 in the OTM model increased OPG expression, which resulted in the inhibition of OIRR. In summary, TGF‐β1‐induced Smads and AP‐1 can bind to the OPG promoter to promote the transcription, expression, and secretion of OPG in cementoblasts, which inhibits osteoclast differentiation and protects cementum from excessive resorption.
miR‐203 modulates pregnant myometrium contractility via transient receptor potential vanilloid 4 channel expression
Authors: Ying Lihua , Fornes Daiana D. , Dobberfuhl Amy D. , Ansari Jessica R. , Alvira Cristina M. , Cornfield David N.
Published: November 2024

Preterm labor is the leading cause of neonatal death and major morbidity but remains a poorly understood process with no effective tocolytic therapies. Recent work has identified the transient receptor potential vanilloid 4 (TRPV4) channel, a membrane calcium channel upregulated in uterine smooth muscle through gestation, as integral in the transition from quiescence to contraction in the gravid uterus. The present study builds upon these findings and investigates regulation of the TRPV4 channel during pregnancy in the murine and human uterus by micro‐RNA 203 (miR‐203). We find a progressive decrease in miR‐203 expression during gestation, accompanied by a reciprocal increase in TRPV4 mRNA and protein expression. In human uterine smooth muscle cells (UtSMC), miR‐203 overexpression reduces, and si‐RNA‐mediated silencing increases, TRPV4 expression. Studies using murine UtSMC demonstrate that miR‐203 expression modulates TRPV4‐mediated cytosolic calcium entry and contractility. Consistent with these findings, the response to pharmacologic TRVP4 agonists is increased in myometrial tissue from miRNA203 −/− mice compared to control mice. Moreover, we demonstrate that miR‐203 binds specifically on the promoter region of TRPV4 to decrease expression. In murine inflammatory models of preterm labor, miR‐203 overexpression prolongs pregnancy. Estradiol (E2) decreases miR‐203 and increases TRPV4 expression, providing a potential physiologic link for the unique reciprocal relationship in UtSMC. Taken together, these findings provide evidence that miR‐203 modulates uterine contractility during pregnancy via negative regulation of TRPV4. These findings support the hypothesis that targeting miR‐203 holds the promise of an entirely novel approach to prevent prematurity and treat preterm labor.
Barriers to Nursing School Admissions for Students With Physical or Sensory Disabilities: Do Essential Abilities Requirements Align With Licensure Standards and Legal Precedence?
Authors: Llewellyn Sarah , Alderden Jenny , Madsen Leslie , Christenson Jadison , Mecham Sharece , Trujillo Tanner Corinna
Published: November 2024

AIM

The aim of the study was to examine sensory and motor essential abilities required by nursing boards and assess their inclusion in prelicensure nursing program admissions.

BACKGROUND

The nursing workforce should mirror diverse patient populations for better concordance; however, essential abilities restrictions hinder admissions for students with disabilities.

METHOD

Requirements for licensure were collected from state boards of nursing and compared with essential abilities admissions requirements from 58 prelicensure programs.

RESULTS

No state boards mandated sensory or motor abilities for licensure. Thirty-one (53%) programs had restrictive essential abilities criteria. Some criteria conflicted with safety standards or the Americans with Disabilities Act.

CONCLUSION

Disparity of essential abilities requirements was observed. Restrictive essential abilities criteria may create barriers to admission of students with disabilities, thus limiting the diversity and capacity of the nursing workforce.
The “F-Words” in Pediatric Oncology: Improving Pediatric Cancer Care Through Innovative Thinking and Rehabilitation for Optimal Quality of Life
Authors: Wright Marilyn , Gorter Jan Willem
Published: November 2024

Conceptual frameworks inform and advance clinical practice, research, and education. The “F-words for child development” is a child/youth/family friendly model that embeds the words fitness, functioning, family, friends, fun, and future into the International Classification of Functioning, Disability and Health (ICF). This perspectives paper explores how the concepts and use of the F-words for child development are conducive to the practice of pediatric oncology rehabilitation and promotion of quality of life of children and their families.

Pediatric oncology rehabilitation is explored in the context of the ICF and F-words through a review of relevant literature, clinical expertise, and child/youth/family perspectives. The F-words framework is congruent with recognized rehabilitation strategies, preferences, and best practices during and after treatment for cancer in children and youth. The concepts can be used to promote the engagement, health, well-being, and quality of life of children/youth and their families.
Nonabstinence among US Adults in Recovery from an Alcohol or Other Drug Problem
Authors: Pasman Emily , Evans-Polce Rebecca J. , Schepis Ty S. , Engstrom Curtiss W. , McCabe Vita V. , Drazdowski Tess K. , McCabe Sean Esteban
Published: November 2024

Objectives

Most US treatment and recovery services are abstinence-based. However, many people in recovery from an alcohol or other drug (AOD) use problem do not abstain completely. This study estimated the prevalence of and characteristics associated with nonabstinence among US adults in recovery.

Methods

Nonabstinence—operationalized as past-month use of alcohol, illicit drugs, or nonmedical use of prescription drugs—was estimated among a sample of 3763 US adults in self-identified recovery from the 2022 National Survey on Drug Use and Health, weighted to be nationally representative. Multivariable logistic regression identified factors associated with nonabstinence.

Results

An estimated 65.2% (95% confidence interval [CI] = 62.6–67.8) of adults in self-identified recovery reported past-month AOD use. Half (50.8%) reported alcohol use, and one-third (33.2%) reported cannabis use. Females had lower odds of use than males (adjusted odds ratio [AOR] = 0.73, 95% CI = 0.54–0.99), and lesbian/gay-identified individuals had greater odds of use than heterosexual/straight-identified individuals (AOR = 2.39, 95% CI = 1.13–5.07). Greater religiosity (AOR = 0.90, 0.84–0.96) and mutual aid attendance (AOR = 0.16, 95% CI = 0.06–0.27) were associated with lower odds of use. Significant differences were not detected for self-reported health, psychological distress, and other measures of functioning. However, relative to those without a past-year substance use disorder (SUD), odds of nonabstinence were greater among those with one mild (AOR = 14.60, 9.05–23.55), one moderate or severe (AOR = 13.05, 7.06–24.14), and multiple (AOR = 23.33, 10.59–51.37) past-year SUDs.

Conclusions

Most US adults who self-identified as in recovery from an AOD use problem were nonabstinent. Treatment and recovery services may improve engagement and outcomes by supporting nonabstinent goals.
Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review
Authors: Blacker Samuel N. , Burbridge Mark , Chowdhury Tumul , Gouker Lindsey N. , Heller Benjamin J. , Kang Mia , Moreton Elizabeth , Nadler Jacob W. , Sindelar LTC Brian D. , Vincent Anita N. , Williams James H. , Lele Abhijit V.
Published: November 2024

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded. Nine studies meeting the inclusion criteria were identified after screening 1885 abstracts and full text review of 276 articles. Six of the 9 included studies were prospective and 3 were retrospective, and included sample sizes ranging between 48 and 373 patients. All were single center studies. Three studies examined anesthetic technique (volatile vs. intravenous), 1 examined osmotic diuresis, 1 examined extubation in the operating room, 1 examined quality metrics, and 3 examined intracranial pressure and changes in vital sign. There was insufficient evidence to perform a meta-analysis. Overall, there was limited evidence regarding the anesthetic management of patients having urgent/emergent craniotomy or craniectomy for intracranial hypertension or herniation due to any cause.
Continuing Education Certificate in Trauma Skills Among Emergency Nurses: A National Sample Survey Analysis
Authors: Castner Jessica , Zazzera Erin A. , Burchill Christian N.
Published: November 2024

Background:

Trauma population health indicators are worsening in the United States. Nurses working in trauma care settings require specialized training for patient care. Little is known about national enumeration of nurses who hold skill-based trauma certificates.

Objective:

The purpose of this project was to estimate (1) skill-based certificate status among U.S. nurses who primarily work with emergency or trauma patients, (2) demographic and work characteristic differences between those who report skill-based trauma certificates and those who do not, and (3) continuing education learning needs among nurses who hold skill-based trauma certificates.

Methods:

This was an applied epidemiologic analysis of the 2022 National Sample Survey of Registered Nurses.

Results:

The weighted analysis of 239,893 emergency nurses indicated 57% held skill-based trauma certificates with disparities by rural practice, racial identity, age, and marital status. Among those who held skill-based trauma certificates, the greatest need for continuing education was on topics of mental health, quality improvement, and substance use disorders. Approximately 87% of emergency nurses with trauma skill-based certificates only spoke English fluently.

Conclusions:

Population health management interventions are needed to enhance workforce equity and continuing education opportunities for trauma nurses. Professional nursing organizations, emergency nursing employers, and academic settings should offer continuing education in mental health and quality improvement. These findings also support the need for ongoing activities to enhance language accessibility for non-English speaking patients in the trauma care system.
The Influence of Genital Lichen Sclerosus on Sexual Health and Well-being: A Tripartite Comparative Analysis
Authors: Bettolini Luca , Maione Vincenzo , Arisi Mariachiara , Rovaris Sara , Romanò Carola , Tomasi Cesare , Calzavara-Pinton Piergiacomo , Zerbinati Nicola , Bighetti Stefano
Published: November 2024

Objectives

Genital lichen sclerosus (LS) is a chronic mucocutaneous disorder causing considerable discomfort. Despite this, comprehensive comparison of LS impacts on quality of life (QoL), particularly on men's health or relative to other dermatological conditions like pemphigus, are sparse. This research aims to discern the effects of LS on sexual functionality and overall QoL, benchmarking against pemphigus patients and healthy controls. The study's intent is to broaden the understanding of sexual dysfunction, satisfaction, and psychological distress attributable to LS.

Materials and Methods

From March 2021 to September 2023, this observational multicenter study at the affiliated university hospitals involved 176 individuals, 120 females and 56 males, with LS, pemphigus, or as controls. Questionnaires employed were the Female Sexual Function Index or the International Index of Erectile Function depending upon subject's gender, the General Health Questionnaire-12, the Clinical Lichen Sclerosus Score, and Pemphigus Disease Area Index. Differences in QoL were analyzed using either the Fisher exact test or the Mann-Whitney U test, and the correlation between Clinical Lichen Sclerosus Score sexual QoL using Spearman's coefficient.

Results

LS patients faced more sexual health challenges than pemphigus patients and healthy people. Women with LS had difficulties with lubrication and pain, men had less satisfaction during intercourse, and all had increased psychological distress, although less than those with pemphigus. A strong link between LS severity and worse sexual QoL, especially for women, was identified.

Conclusions

LS significantly affects sexual function and psychological well-being, both for men and women, reaffirming the need for comprehensive management.
Restrictive Versus Liberal Transfusion in Symptomatic Coronary Artery Disease and Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials
Authors: Singh Sahib , Tantry Udaya S. , Bliden Kevin , Gurbel Paul A. , Navarese Eliano , Garg Aakash
Published: November 2024

Background:

In patients with coronary artery disease (CAD) and/or myocardial infarction (MI), anemia is associated with an increased risk of adverse cardiovascular (CV) outcomes. Transfusion goals in such patients remain unclear.

Study question:

A meta-analysis of the available randomized controlled trials (RCTs) was conducted comparing restrictive and liberal transfusion strategies in patients with symptomatic CAD/MI.

Data sources:

Multiple online databases including Cochrane, Pubmed, Embase, and MEDLINE were searched for RCTs.

Study design:

End points of interest were major adverse CV events (MACEs), MI, all-cause death, CV death, revascularization, heart failure (HF), and infection. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model.

Results:

A total of 5 RCTs with 4518 patients—2258 in the restrictive transfusion group and 2260 in the liberal transfusion group—were included. The mean age was 72 years, and 59% of patients were men. At 30 days, MACE and MI were similar in the 2 transfusion groups. However, at the longest available follow-up, the restrictive strategy was associated with increased risks of MACE (OR 1.18, 95% CI, 1.02–1.37; P = 0.03) and MI (1.27, 95% CI, 1.02–1.58; P = 0.04), along with the higher trend of all-cause death (1.21, 95% CI, 1.00–1.46; P = 0.05) as compared with liberal transfusion. The 2 groups had comparable rates of CV death, revascularization, HF, and infection.

Conclusions:

Liberal transfusion strategy may be associated with improved CV outcomes among patients with symptomatic CAD/MI as compared with a restrictive transfusion strategy.
Treatment With Long-Acting Injectable Aripiprazole During Pregnancy in Bipolar Disorder: A Scoping Review
Authors: Teodorescu Andreea , Dima Lorena , Petric Paula Simina , Necula Ruxandra Mihaela , Banciu Roxana , Moga Marius Alexandru , Marian-Pavlenco Angela , Ifteni Petru
Published: November 2024

Background:

The management of bipolar disorder during pregnancy presents a significant challenge, particularly regarding the safety and effectiveness of long-acting injectable (LAI) antipsychotics like aripiprazole. Despite the growing use of LAI antipsychotics in psychiatric disorders, data on their use during pregnancy are limited, especially for bipolar disorder. This study aimed to shed light on this issue through a scoping review.

Areas of Uncertainty:

The level of evidence concerning the safety of second-generation antipsychotics during pregnancy is limited. Data on LAI aripirazole are even more limited.

Data Sources:

We conducted a scoping review following the PRISMA-ScR guidelines, systematically searching multiple electronic databases for studies published between January 2008 and February 2024. The review focused on the administration of aripiprazole during pregnancy among patients with psychiatric disorders, examining outcomes related to maternal health, fetal well-being, and neonatal outcomes.

Results:

The scoping review identified 11 case reports that met the inclusion criteria and 4 additional studies (prospective and retrospective cohort studies).

Conclusions:

The scoping review emphasizes the need for further research to confirm its safety and efficacy. The limited data underscore the importance of individualized treatment plans and informed decision-making, considering the unique risks and benefits of LAI antipsychotic use during pregnancy. Further studies are imperative to provide more definitive guidance for managing bipolar disorder with LAI antipsychotics in pregnant patients.
EGb761 Trials for Mild-to-Moderate Dementia—What Have We Learned in the Past 18 years?
Authors: Necula Bogdan-Radu , Necula Radu Dan , Petric Paula Simina , Ifteni Petru Iulian , Irimie Marius , Dima Lorena
Published: November 2024

Background:

Dementia leads to cognitive decline affecting memory, thinking, and behavior. Current pharmaceutical treatments are symptomatic, with limited efficacy and significant drawbacks. Ginkgo biloba extract (EGb761) is being explored as an adjuvant therapy for dementia because of its potential neuroprotective effects.

Areas of Uncertainty:

Despite decades of study, EGb761 has not been incorporated into treatment guidelines for these conditions. This review evaluates research futility in EGb761 trials for dementia, analyzing efficacy and methodological challenges to inform future research directions.

Data Sources:

In this review, we investigate the efficacy and adverse reactions of Ginkgo biloba extract (EGb761) as a treatment for Alzheimer disease or vascular dementia. We searched the randomized controlled trials published between 2006 and 2023 on PubMed and ScienceDirect.

Results:

The 7 selected studies have shown that the degree of improvement in standard cognitive assessment scores [Mini-Mental State Examination (MMSE), short cognitive performance test (SKT), neuropsychiatric inventory (NPI)] was not significant enough for a substantial proportion of patients. Improvements of the SKT score with at least 3 points in the Alzheimer disease/vascular dementia groups were found only in 2 out of 7 studies, changes of less than 2 points in MMSE score were found in 2 of the studies, while an improvement of at least 4 points in NPI scores was reported in 4 out of 7 studies. We aim to understand why this extract has not reached the level of evidence to be included in guideline recommendation despite extensive research and what have we learned from systematic reviews performed since 2010? Studies included in this review have shown some improvement in outcome scores with EGb761 treatment compared with placebo, but these improvements did not reach the threshold for clinically significant enhancement in MMSE/SKT/NPI scores. Limitations such as small sample sizes, minimal score changes, predominantly placebo comparisons, and short follow-up durations make it challenging to determine the usefulness of EGb761 in dementia treatment. The changes observed and methodological constraints underscore the uncertainty surrounding the efficacy of EGb761.

Conclusion:

The findings do not consistently demonstrate the clinical utility of EGb761, and improved scores on cognitive and neuropsychiatric assessments may not necessarily translate into meaningful clinical outcomes for patients with dementia. Starting from the question “What have we learned in the past 18 years?”, the answer would be: not much. Consequently, the question raised is: how long should we go on with the same conclusion, continuing to spend time and financial resources to replicate these results? Research strategies should be refined to optimize decision making and advance evidence-based care for neurocognitive disorders.
Botox for Sleep Effectiveness
Authors: Getaneh Feven W. , Richter Lee Ann , Dabbas Mai , Chou Jiling , Iglesia Cheryl B. , Dieter Alexis A.
Published: November 2024

Importance

Nocturia is one of the most bothersome complaints in women with overactive bladder syndrome (OAB). Although small preliminary studies have shown that intradetrusor onabotulinum toxin A (BTX) injections reduce nocturia episodes, it is not known how reduction in nighttime urination affects sleep quality and quality of life.

Objectives

We aimed to assess the effect of BTX on nocturia frequency, sleep quality, and quality of life.

Study Design

This is a prospective observation study of adult women with ≥2 nocturia episodes and OAB planning to undergo treatment with BTX injections. Participants completed a 2-day bladder/sleep diary and sleep-related questionnaires at baseline and 5 weeks post-BTX.

Results

A total of 40 participants were included with a mean age of 71 ± 12 years and most (90%) undergoing 100 units of BTX injection. At baseline, the median nocturia episodes were 3.5 (IQR, 2.5–5.0), and nearly half (43%) of participants reported mild to moderate sleep disturbance. At 5 weeks post-BTX, we found a significant decrease in nocturia episodes (−2/night) and a 59% decrease in mild to moderate sleep disturbance (P = 0.006). There were significant increases in longest sleep interval (+1.5 hours), time to first awakening (+1.6 hours) and average sleep interval (+1.3 hours), and a significant increase in nocturia-related quality of life scores (P < 0.001 for all). Sixteen (40%) of participants had nocturia resolution defined as ≤1 mean nocturia episode post-BTX.

Conclusions

For women with OAB and >2 nocturia episodes/night, BTX injections reduce voids/night and improve sleep quality and nocturia-related quality of life.
Urinary Incontinence and Care Seeking Among Wisconsin Women
Authors: Warner Kristina J. , Schultz Amy A. , Barnet Jodi H. , Brown Heidi W.
Published: November 2024

Importance

Women who identify as Black or African American are underrepresented in research about pelvic floor disorders.

Objectives

The objectives of this study were to describe the prevalence of and factors associated with urinary incontinence (UI) and UI care-seeking among adult women in a Wisconsin household survey.

Study Design

This was a cross-sectional analysis of data collected by the Survey of the Health of Wisconsin (SHOW). Using community engagement, individuals who identified as Black or African American were purposively oversampled in the 2018–2019 wave. Descriptive analyses compared women with and without UI, and those who had and had not sought care.

Results

Among 237 study participants, 46% (110) had UI: 46% mild, 36% moderate, and 18% severe. Most participants (84%) self-identified as non-Hispanic Black (84%), with a mean age of 49 ± 16 years and mean body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 34 ± 9; 62% were insured by Medicaid. The prevalence of UI was 44% among women who identified as non-Hispanic Black versus 59% (P = 0.085) among other women. Older age, obesity, needing help to read medical instructions, and identifying as a race other than non-Hispanic Black were significantly associated with UI. Among 110 women with UI, 53% had previously sought care. Rates of UI care seeking were similar (P = 0.32) among women who identified as non-Hispanic Black (55%) and those who identified as another race or ethnicity (43%).

Conclusion

Needing help to read medical instructions emerged as a factor associated with UI diagnosis in this sample that included almost 200 women who identified as non-Hispanic Black.
Enhancing Gene Set Overrepresentation Analysis with Large Language Models
Authors: Zhu Jiqing , Wang Rebecca Y. , Wang Xiaoting , Azevedo Ricardo , Moreno Alexander , Kuhn Julia A. , Khan Zia
Published: November 2024

Gene set overrepresentation analysis is widely used to interpret high-throughput transcriptomics and proteomics data, but traditional methods rely on static, human-curated gene set databases that lack flexibility. We introducellm2geneset, a framework that leverages large language models (LLMs) to dynamically generate gene set databases tailored to input query genes, such as differentially expressed genes (DEGs) and a biological context specified in natural language. These databases integrate with methods, such as overrepresentation analysis (ORA), to assign biological functions to input genes. Benchmarking against human-curated gene sets demonstrates that LLMs generate gene sets comparable in quality to those curated by humans.llm2genesetalso identifies biological processes represented by input gene sets, outperforming traditional ORA and direct LLM prompting. Applying the framework to RNA-seq data from iPSC-derived microglia treated with a TREM2 agonist highlights its potential for flexible, context-aware gene set generation and improved interpretation of high-throughput biological data.llm2genesetis available as open source athttps://github.com/Alector-BIO/llm2genesetand via a web interface athttps://llm2geneset.streamlit.app.
Mu and beta power effects of fast response trait double dissociate during precue and movement execution in the sensorimotor cortex
Authors: Kamali Sara , Baroni Fabiano , Varona Pablo
Published: November 2024

A better understanding of the neural and muscular mechanisms underlying motor responses is essential for advancing neurorehabilitation protocols, brain-computer interfaces (BCI), feature engineering for biosignal classification algorithms, and identifying biomarkers of disease and performance enhancement strategies. In this study, we examined the neuromuscular dynamics of healthy individuals during a sequential finger-pinching task, focusing on the relationships between cortical oscillations and muscle activity in simultaneous electroencephalography (EEG) and electromyography (EMG) recordings. We contrasted two pairs of subsets of the dataset based on the latency of EMG onset: an across-subjects trait-based comparison and a within-subjects state-based comparison. Trait-based analyses showed that fast responders had higher baseline beta power, indicating stronger motor inhibition and efficient resetting of motor networks, and greater mu desynchronization during movement, reflecting enhanced motor cortex activation. Visual association areas also displayed more pronounced changes in different phases of the task in subjects with lower latency. Fast responders exhibited lower baseline EMG activity and stronger EMG power during movement initiation, showing effective motor inhibition and rapid muscle activation. State-based analyses revealed no significant EEG differences between fast and slow trials, while EMG differences were only detected after movement onset. These results highlight that fast response trait is related to electro-physiological differences at specific frequency bands and task phases, offering insights for enhancing motor function in rehabilitation, biomarker identification and BCI applications.

Highlights

We analyzed simultaneous EEG and EMG recordings during a sequential finger movement task

We identified neural correlates of response latency trait, but not state

Fast responders show higher baseline beta power, indicating stronger motor inhibition

Lower latency trait was linked to a sharper postcue sensorimotor mu power decrease

Fast responders have lower pre-movement EMG and higher EMG onset power
Regulating of Koisio technology-produced fluid on Vascular Adventitial Interstitial Fluid flow and its Effect on heart rate by delivering Esmolol
Authors: Li Bei , Cai Jin , Ma Chao , Hu Jun , Li Hongyi
Published: November 2024

Acupoint-originated interstitial fluid (ISF) circulatory network along the vasculature has been demonstrated to play a role as an extravascular drug delivery pathway. We aim to reveal the regulation of Koisio technology-produced fluid (KF), which is rich in Ultra-small Particle Size Nanobubbles (UsNBs), on vascular adventitial ISF flow and its Effect on heart rate by delivering Esmolol. In animal experiments, using real-time fluorescent imaging technology, it was found that: when normal saline-fluorescent liquid was given at Kunlun acupoint, the velocity of the adventitial ISF along the femoral vein was measured to be about 600 μm/sec, and the width of the tunica ISF channel on the adventitia surface of the femoral vein was about 210μm; when KF-fluorescent liquid was injected into the subcutaneous tissue of Kunlun acupoint, the velocity of the adventitia ISF slowed down by about 24% compared with before; the width of the tunica ISF channel on the adventitia surface of the femoral vein increased by about 35% compared with before; When 150μL of KF with high-concentration UsNBs was injected into Kunlun acupoint, it was observed that the adventitial ISF flow velocity was decreased by 43%, and recovered after 30 minutes. Administration of normal saline-esmolol solution at Kunlun acupoint caused the heart rate to drop from 410 bpm to 380 bpm, a decrease of 7.3%, which continued for 5 minutes before recovery. Administration of KF-esmolol solution at Kunlun acupoint caused the heart rate to drop from 410 bpm to 371 bpm, a decrease of 9.5%, which continued for 15 minutes before recovery. Thus, acupoint injection of KF can regulate the velocity of the adventitia ISF flow along the femoral vein and increase the width of the tunica ISF channel. These results may reveal a new mechanism of the physiological effect of Koisio drinking water rich in ultra-small particle size nanobubbles. KF may not only regulate the acupoint-originated ISF circulatory system, but also play a role in adventitial drug delivery, nutrient supply, and waste removal.
Poplar: A Phylogenetics Pipeline
Authors: Koning Elizabeth , Krishnakumar Raga
Published: November 2024

Motivation

Generating phylogenetic trees from genomic data is essential in understanding biological systems. Each step of this complex process has received extensive attention in the literature, and has been significantly streamlined over the years. Given the volume of publicly available genetic data, obtaining genomes for a wide selection of known species is straightforward. However, analyzing that same data in order to generate a phylogenetic tree is a multi-step process with legitimate scientific and technical challenges, and often requires a significant input from a domain-area scientist.

Results

We present Poplar, a new, streamlined computational pipeline, to address the computational logistical issues that arise when constructing phylogenetic trees. It provides a framework that runs state-of-the-art software for essential steps in the phylogenetic pipeline, beginning from a genome with or without an annotation, and resulting in a species tree. Running Poplar requires no external databases. In the execution, it enables parallelism for execution for clusters and cloud computing. The trees generated by Poplar match closely with state-of-the-art published trees. The usage and performance of Poplar is far simpler and quicker than manually running a phylogenetic pipeline.

Availability and Implementation

Freely available on GitHub athttps://github.com/sandialabs/poplar. Implemented using Python and supported on Linux.

Supplementary Information

Newick versions of the reference and generated trees.
Sulfur-species in Zinc-specific Condylar Zones of a Rat Temporomandibular Joint
Authors: Lee Brandon H. , Yang Zhiyuan , Ho Tiffany , Wang Yongmei , Tamura Nobumichi , Webb Samuel , Bone Sharon , Ho Sunita P.
Published: November 2024

In this study, we performed synchrotron-based micro-X-ray fluorescence (μ-XRF) imaging of elements Zn and S, and X-ray absorption near edge spectroscopy (XANES) coupled with μ-XRF for identification of Zn and S species in the condylar zones of a rat temporomandibular joint (TMJ). Histologic localization of Zn and hypoxia-inducible factor-1α (HIF-1α) were mapped using an optical microscope. These data were visually correlated with μ-XRF and XANES data to provide insights into plausible biological S-species in Z-enriched condylar zones of a rat TMJ. Furthermore, μ-XRF coupled with micro-X-ray diffraction (μ-XRD) was used to underline Z-incorporated biological apatite in the subchondral bone and bone of the rat TMJ.

Results illustrated the potential dependence between biometal Zn and nonmetal S and their collective governance of cell and tissue functions in a zone-specific manner. Elemental Zn with organic and inorganic S-species at the cartilage-bone interface and transformation of plausible Zn-enriched mineralization kinetics of biological apatite from subchondral bone to condylar bone were ascertained using μ-XRF-XANES and μ-XRD. The coupled μ-XRF-XANES complementing with μ-XRD and immunohistology provided an informative view of S and Zn and their association with zone-specific biological pathwaysin situ. Understanding the spatial distributions of the main S-species with redox-inert Zn in regions of cartilage, bone, and the interface is essential for further unlocking questions surrounding formation and resorption-related biomineralization pathways as related to osteoarthritis or genetically inherited diseases. Using these complementary techniques with microspectroscopic spatial information provided insights into the associations between biometal Zn and nonmetal S and a window into detecting the plausible early-stage diagnostic biomarkers for humans with TMJ osteoarthritis.
Protein-protein interaction is a major source of epistasis in genetic interaction networks
Authors: Castellanos-Girouard Xavier , Serohijos Adrian WR , Michnick Stephen W
Published: November 2024

Genetic interaction (GI) and protein-protein interaction (PPI) networks have proved among the most important tools for inference of gene function and genotype-phenotype relationship1–6. It remains unclear, however, how these two networks are related to each other. Here we demonstrate that the strengths of epistatic genetic interactions between two genes strongly correlate with the binding free energies of interactions between their cognate proteins, for both yeast and human genomes. Consequently, we show that GI and PPI networks can reciprocally predict each other. Further, we observe that functional divergence and redundancy in duplicated genes (paralogs) are reflected in the binding affinity of their interactions with other proteins and in their genetic interaction strengths. Finally, we demonstrate that the overall topologies of GI and PPI networks significantly overlap in two topological features: Modules, in which genes/proteins are organized by common function, and connectors, which link modules to each other. This opens avenues for new integrated network approaches in understanding cellular processes and flow of genomic information.