bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and analysis considerations for investigating patient subgroups of interest within cancer clinical trials
Authors: Mazza Gina L , Culakova Eva , Enserro Danielle M , Dignam James J , Unger Joseph M
Published: February 2025

Examining treatment effects in subgroups of patients defined by demographic, genetic, or clinical characteristics is increasingly of interest given the pursuit of personalized medicine and the importance of representation and equity in treatment decisions. The magnitude or even the direction of the treatment effect may vary across subgroups, and these differential treatment effects could have clinical implications. Subgroup analyses require caution in their interpretation, however, because of the high probability of a false-positive or false-negative conclusion. We outline study design and analysis considerations for responsibly investigating and reporting differential treatment effects across subgroups in oncology trials, with examples from the National Cancer Institute’s National Clinical Trials Network and Community Oncology Research Program. Recommendations include ensuring appropriate representation of patients from subgroups of interest, recognizing power and multiplicity limitations, and treating exploratory subgroup analyses as hypothesis generating rather than practice changing.
When to adjust for multiplicity in cancer clinical trials
Authors: Unger Joseph M , Mazza Gina L , Elsaid Mohamed I , Duan Fenhai , Dressler Emily V , Snavely Anna C , Enserro Danielle M , Pugh Stephanie L
Published: February 2025

Interpreting cancer clinical trial results often depends on addressing issues of multiplicity. When testing multiple hypotheses, unreliable findings can occur by chance due to the inflation of the type I error rate, the probability of mistakenly rejecting the null hypothesis when the null hypothesis is true. In this setting, researchers may often set the type I error rate (or the alpha level) low to limit false positive findings and the interpretation of a causal relationship where none exists. Conversely, overly conservative type I error control may result in declaring findings, that do not meet multiplicity-adjusted alpha levels, as false when they are actually true, reducing opportunities for new discovery. This presentation focuses on multiplicity adjustment in the context of clinical trials conducted within the NCI’s Community Oncology Research Program (NCORP). Because federally sponsored trials often require long-term participation from patients and represent a substantial investment by taxpayers, striking the right balance between optimizing what is learned from these trials, while avoiding false positive results, should be a priority.
Multicultural Education for Transnational Democratic Citizenship
Authors: Culp Julian
Published: February 2025

On Will Kymlicka’s conception of multicultural citizenship, group membership enables personal autonomy by way of providing individuals with meaningful options. Many educational and political theorists have employed Kymlicka’s argument to defend a multicultural education as proper preparation for democratic citizenship in socially diverse liberal societies. Multicultural education includes the study of a variety of cultures and is meant to promote the development of a cultural identity, inter-cultural empathy and tolerance, and the cross-cultural construction of shared positions. Recently, however, Elizabeth Anderson has challenged multicultural citizenship and education on the grounds that they lead to the formation of group-specific biases, stereotypes, and inequalities in cultural and social capital. Therefore, she proposes an integrationist conception of citizenship education that requires citizens from different groups to collaborate within educational and public contexts. This article takes issue with the nationalist framing of this debate and Anderson’s integrationist conception because they neglect how large-scale social transformations like economic globalization and global governance have generated the need for transnationalizing democracy and democratic citizenship. Adopting a transnational perspective, this article ascribes an important role to multicultural education for learning the attitudes, knowledge, and skills that empower citizens to exercise democratic control both across and beyond national borders. The article emphasizes how the formation of intercultural empathy through multicultural education facilitates engagement in transnational social movements and political discourses. Finally, the article responds to objections concerning the lack of feasibility, cosmopolitan bias, and counter-productiveness of multicultural education and transnational democratic citizenship.
Adaptive experiments toward learning treatment effect heterogeneity
Authors: Wei Waverly , Ma Xinwei , Wang Jingshen
Published: February 2025

Understanding treatment effect heterogeneity has become an increasingly popular task in various fields, as it helps design personalized advertisements in e-commerce or targeted treatment in biomedical studies. However, most of the existing work in this research area focused on either analysing observational data based on strong causal assumptions or conducting post hoc analyses of randomized controlled trial data, and there has been limited effort dedicated to the design of randomized experiments specifically for uncovering treatment effect heterogeneity. In the manuscript, we develop a framework for designing and analysing response adaptive experiments toward better learning treatment effect heterogeneity. Concretely, we provide response adaptive experimental design frameworks that sequentially revise the data collection mechanism according to the accrued evidence during the experiment. Such design strategies allow for the identification of subgroups with the largest treatment effects with enhanced statistical efficiency. The proposed frameworks not only unify adaptive enrichment designs and response-adaptive randomization designs but also complement A/B test designs in e-commerce and randomized trial designs in clinical settings. We demonstrate the merit of our design with theoretical justifications and in simulation studies with synthetic e-commerce and clinical trial data.
Peroxisomal dependent signalling and dynamics modulate plant stress responses: reactive oxygen and nitrogen species as key molecules
Authors: Molina-Moya E , Rodríguez-González A , Peláez-Vico M A , Sandalio Luisa M , Romero-Puertas María C
Published: February 2025

Plant peroxisomes are organelles housing different key metabolic pathways in the cell such as photorespiration and fatty acid β-oxidation. The metabolism of phytohormones, polyamines and other key signalling molecules such as reactive oxygen and nitrogen species (ROS and RNS) are housed in these organelles. The presence of a complex antioxidant system that may regulate ROS/RNS level makes peroxisomes a key organelle governing its dependent signalling. The evolution of -omics technologies and the existence of mutants with specifically altered ROS metabolism in peroxisomes, have provided us with a large amount of data and genes that could be regulated in plant responses to stress. All these data point to the existence of a specific transcriptomic footprint associated with peroxisomes. Furthermore, advances in microscopy and the implementation of new molecules have allowed us to visualize organelles in vivo and obtain detailed information about the dynamics of these organelles involving changes in their velocity, peroxules formation and proliferation. In this review, we update the latest information about peroxisomal metabolism and signalling, mainly related to ROS/RNS under control and stress conditions and how the different stimuli affect the plasticity and dynamic of the organelles, which can contribute in turn to plant responses to these stimuli.
Follicular development of fetal gonads under the skin of adult mice
Authors: Chen Jiyu , Liu Chang , Yu Yongqin , Ye Xiaoying , Liu Lin , Zhu Zhengmao
Published: February 2025

Adult ovarian tissues or biopsies isolated from patients prior to chemotherapy or irradiation can reconstitute ovarian functions when transplanted either in the abdomen or subcutaneously. This approach avoids invasive surgery and potential risks associated with internal procedures. We investigated whether functional ovaries could develop subcutaneously from early E12.5 fetal gonads without entering meiosis in mouse model. Unexpectedly, the subcutaneously transplanted fetal gonads failed to undergo folliculogenesis in the recipient mice. The transplanted gonads experienced meiotic deficiency and exhibited significant defects in DNA repair and recombination, along with elevated apoptosis levels. Meiotic defects in the subcutaneous grafts were partly attributable to variations in temperature and oxygen concentration. However, completion of meiotic prophase I was effectively achieved through in vitro culture of the gonads at 37°C. Subsequently, the in vitro cultured E12.5 gonads, following subcutaneous transplantation, became competent in folliculogenesis, restoring endocrine functions. This finding may have implications for rejuvenating ovarioids from fetal gonad-like cells using pluripotent stem cell technologies, as well as for enhancing endocrine recovery and health span.
Nutritional and Psychological Support as a Multidisciplinary Coordinated Approach in the Management of Chronic Liver Disease: A Scoping Review
Authors: Romeo Mario , Dallio Marcello , Cipullo Marina , Coppola Annachiara , Mazzarella Chiara , Mammone Simone , Iadanza Giorgia , Napolitano Carmine , Vaia Paolo , Ventriglia Lorenzo , Federico Alessandro
Published: February 2025

Objectives

This review emphasizes a novel, multidisciplinary, coordinated approach in the management of chronic liver diseases (CLDs).

Background

Chronic liver diseases represent a significant global health burden, marked by a notable shift in the prevalence patterns from virus-related to metabolic and alcohol-related entities. Malnutrition, frailty, and sarcopenia exert a substantial impact on patients with cirrhosis, affecting 75%-90% of cases and escalating as the disease progresses. The European Association for the Study of the Liver recommends a comprehensive approach to nutritional care, emphasizing the need for detailed assessments in patients with cirrhosis, using diverse tools such as computed tomography scans, bioelectrical impedance analysis, and evaluations of muscle function. Considering the prevalence of nutritional and psychological disorders in the CLD population, the treatment of these patients should be founded indispensably on a multidisciplinary approach.

Methods

A systematic search was conducted of the PubMed, MEDLINE, and SCOPUS databases to identify trials investigating the health effects of nutritional and psychological assessments in patients with CLD.

Results

In dealing with the treatment of patients with CLD, an exploration of the psychological domain emerges as crucial, because psychological distress, especially depression, exerts a tangible influence on patient outcomes. Thus, the engagement of psychologists and/or psychotherapists, who might use techniques such as cognitive behavioral therapy, could enhance patients' comprehension of nutritional implications in their treatment and make them more aware of their illness.

Conclusion

The review emphasizes the relevance of both nutritional and psychological assessments in patients with CLD that could improve patient education on the pivotal role of nutrition in disease management. Randomized controlled trials evaluating the combined impact of nutritional and psychological support are recommended to further investigate this complex clinical landscape.
Prevalence of injecting-related bacterial and fungal infection among people who inject drugs: a systematic review and meta-analysis
Authors: Wheeler Alice , Masters Jeffrey , Pradhan Alyssa , Roth Jess Monineath , Degenhardt Prof Louisa , Dore Gregory J , Matthews Gail V , Cunningham Evan B , Peacock Amy , Colledge-Frisby Samantha , Grebely Jason , Hajarizadeh Behzad , Martinello Marianne
Published: February 2025

Background

Despite increasing burden of injecting-related bacterial and fungal infection, there has been no recent synthesis of their epidemiology. We performed a systematic review and meta-analysis evaluating prevalence and incidence of injecting-related infection among people who inject drugs.

Methods

We searched EMBASE, MEDLINE, Web of Science, and PsycINFO for articles published from January 1, 2010. Eligible studies assessed the prevalence or incidence of at least one injecting-related infection among people who recently injected drugs. Random-effects meta-analysis was used to calculate pooled estimates of infection prevalence, according to infection type and prevalence period.

Results

Of 8,097 articles identified, 87 were eligible for inclusion (78 prevalence, 9 incidence). Data were available for 25 countries including 10 low- or middle-income countries. Prevalence of skin and soft tissue infections (including skin abscess and cellulitis) was 13% in the past month (11 studies; 95%CI 9-19%), 30% in the past 3-12 months (23 studies; 95%CI 23-37%), and 47% across the lifetime (7 studies; 95%CI 29-66%). Prevalence of endocarditis was 2% in the past month (4 studies; 95%CI 1-3%), 2% in the past 3-12 months (5 studies; 95%CI 2-3%), and 6% across the lifetime (8 studies; 95%CI 3-10%). Prevalence of sepsis and/or bloodstream infection was 1% in the past month (2 studies; 95%CI 1-2%), 7% in the past 3-12 months (3 studies; 95%CI 4-13%), and 8% across the lifetime (5 studies; 95%CI 3-19%).

Conclusions

Injecting-related infections are a common complication of injecting drug use. Interventions to reduce their occurrence and associated disease burden are needed.
Osr40g3 Imparts Salt Tolerance by Regulating GF14e-mediated Gibberellin Metabolism to Activate EG45 in Rice
Authors: Roy Chandan , Sahid Salman , Debgupta Jadav , Roy Ananya , Shee Dibyendu , Datta Riddhi , Paul Soumitra
Published: February 2025

Under changing environmental conditions, salt stress is a serious threat to agriculture. The R40 family lectins are known to be associated with osmotic stress response, although their mechanism of action remains unclear. Here, we report that Osr40g3, upregulated by salt, improves salt tolerance but causes pollen sterility and poor seed development in rice when constitutively overexpressed. Osr40g3 knockout lines, on the other hand, display salt sensitivity with no other phenotypic aberration. Further studies revealed that the gene exhibits a precise tissue-specific expression pattern essential for seed development. Overexpressing the Osr40g3 with its native promoter alleviates pollen sterility and improves salt tolerance. In-depth molecular studies demonstrated that Osr40g3 positively regulates an expansin protein, OsEG45, while decreasing the stability of a 14-3-3 protein, OsGF14e. Correspondingly, OsEG45 overexpression, OsGF14e silencing lines and the double mutants display salt tolerance, supporting the involvement of the Osr40g3-OsGF14e-OsEG45 module in salt tolerance. Moreover, constitutive overexpression of Osr40g3 or silencing of OsGF14e diminishes gibberellic acid (GA) accumulation that activates the OsEG45 gene. Together, our study highlights that the Osr40g3 confers salt tolerance by negatively regulating OsGF14e while positively regulating OsEG45 via a GA-dependent pathway.
Polysubstance toxicity deaths in Newfoundland and Labrador: a retrospective study
Authors: Raza Syed Z , Whitten Cindy , Randell Shane , Sparkes Brooklyn , Denic Nash
Published: February 2025

Objective

The present study examined the prevalence of polysubstance toxicity deaths in Newfoundland and Labrador between 2018 and 2023, describing sociodemographics of decedents and the most common substances contributing to death.

Methods

Death investigation data from the Office of the Chief Medical Examiner pertaining to polysubstance toxicity was obtained. Polysubstance toxicity deaths were defined as drug toxicity deaths in which substances from more than one drug class contributed to death. Trends in sociodemographics and substance combinations were quantitatively summarized.

Results

313 individuals died from drug toxicity in the province between 2018 and 2023. Most deaths (n = 185, 59%) were determined to be caused by polysubstance toxicity. Polysubstance deaths increased 46% from 26 in 2018 to 38 in 2023. Most deaths were accidental in manner and the proportion of yearly accidental deaths increased sharply through the study period from 69% in 2018 to 89% in 2023. Male decedents outnumbered female decedents across the study period except for 1 year (2022), and young people (< 40 years old) had the highest death rate in the most recent study year. Cocaine was the most prevalent substance in toxicology reports and the combination of stimulants-opioids was the most prevalent drug class combination, followed by benzodiazepines-opioids and sedatives-opioids.

Conclusion

Polysubstance toxicity is rising in Newfoundland and Labrador in recent years and our findings provide important information about sociodemographics and substance combinations to policymakers to aid in addressing this public health issue.
Knowing receipt, characterisation, and proper law: a persistent duty and the cloak of invisibility
Authors: Tsui Zealot Kenneth , Lam Wang Tat Max
Published: February 2025

The categorisation of knowing receipt remains uncertain in both domestic and private international law contexts, despite efforts by judges and scholars to clarify it. This article argues that knowing receipt is viewed as a breach of a continuing restorative and custodial duty owed to the beneficiary. It explains how these duties arise and outlines their content. Under this view, the traditional proprietary and fault-based perspectives on knowing receipt can be reconciled while establishing an equitable nexus for the claim. Additionally, this article suggests that this perspective aligns with the sui generis characterisation in private international law, preventing circumvention of liability.
Artificial Intelligence Meets Holistic Review: Promises and Pitfalls of Automating the Medical Education Admissions Process
Authors: Rosenthal Jacob T. , Hafferty Frederic W. , Kulasegaram Kulamakan (Mahan) , Wendland Claire L. , Taylor Janelle S.
Published: February 2025

Holistic review has been widely adopted in medical education as a means of promoting equity in the application process and diversity in the medical workforce. Artificial intelligence (AI) is a rapidly emerging technology already having an impact on the medical school and residency application process as students and faculty alike increasingly turn to AI tools to automate some steps in the preparation and evaluation of application materials. While AI may have the potential to improve the holistic admissions process by increasing efficiency and adding some measure of standardization among reviewers, the authors caution that this promise does not come without certain pitfalls. AI models may introduce new sources of bias and amplify existing ones, which when combined with a lack of transparency regarding their use in the admissions process, may perpetuate the very inequities that holistic review seeks to minimize. The authors call for the medical education community to establish clear regulations to govern the acceptable use of AI in the admissions process and for a principled adoption of AI tools in a way that is sustainable for applicants and reviewers in the future.
Type IV Tibial Tubercle Fractures in Adolescents—Is Operative Treatment Necessary?
Authors: Feijoo Emilio , Nihalani Shrey , Lane Pearce , Bloodworth Adele , McGwin Gerald , Ashley Philip , Williams Kevin A. , Gilbert Shawn R. , Conklin Michael J.
Published: February 2025

Background:

Tibial tubercle fractures (TTF) in adolescents can be treated operatively or nonoperatively depending on fracture configuration and displacement. In the modified Ogden classification, the type IV fracture is extra-articular and exits through the posterior physis or metaphysis. No previous publications have reviewed a series of these injuries and compared clinical and radiographic outcomes of operative and nonoperative treatment.

Methods:

Patients under the age of 18 with Ogden type IV TTFs treated at a single institution between 2013 and 2023 were evaluated. Mechanism of injury, weight percentile, concern for compartment syndrome, time to full weight bearing, time to return to sport/activity, method of treatment, follow-up time, and complications were collected from the electronic medical record (EMR). Posterior tibial slope angle (PTSA), medial proximal tibial angle (MPTA), and anterior fracture gap were measured from the initial injury, postreduction, and final follow-up radiographs.

Results:

A total of 36 limbs in 33 patients were followed for an average of 182 days, 18 of which were treated nonoperatively and 18 operatively. The mean pretreatment PTSA was 22.4°﻿ in the nonoperative and 25.0° in the operative group (P=0.25). The mean final follow-up PTSA was 15.1° in the nonoperative and 14.3° in the operative group (P=0.54). The mean pretreatment MPTA was 84.7° for both groups (P=0.99). The final follow-up mean MPTA was 84.2° in the nonoperative and 85.5° in the operative group (P=0.08). There were no significant differences noted in time to full weight bearing, return to sport/activity, or total follow-up. There were 7 cases with complications, 4 in the nonoperative and 3 in the operative group.

Conclusions:

The present study suggests that nonoperative and operative treatment for type IV TTFs are equivalent in terms of radiographic and clinical outcomes. Given that joint incongruity is not an issue in these fractures, closed reduction can be attempted unless contraindicated by impending compartment syndrome. Operative management should be performed for failure of closed reduction.

Level of Evidence:

Level IV.
A Review of Cardiac Preoperative Screening Guidelines for Liver Transplantation
Authors: Garg Jasmine , Sharma Tanya , Bali Atul D. , Frishman William H. , Aronow Wilbert S.
Published: February 2025

Orthotopic liver transplant (OLT) medicine is a constantly evolving field, especially with the demographics of individuals with advanced liver disease drastically changing. OLT candidates are now older, and there is an increase of nonalcoholic steatohepatitis cirrhosis due to the epidemic of obesity, which has also resulted in an increase in cardiac comorbidities in this population. The pathophysiology of liver cirrhosis creates many complexities during the pre- and postoperative management of OLT. We discuss the role of screening for common co-existent cardiovascular comorbidities, including coronary artery disease, congestive heart failure, arrhythmias, and portopulmonary hypertension, as well as challenges in the standardization of pre-liver transplant cardiovascular care.
Infant Crawling Variation Related to Subsequent Development
Authors: Yamamoto Shimpei , Lee Yeonghee , Matsumura Umi , Tsurusaki Toshiya
Published: February 2025

Crawling is considered an important motor skill for infants. Although infants show variations in their crawling, the association between crawling variations and subsequent development is unexplored. This study investigates the difference in amount of crawling variation between infants with and without subsequent developmental delays. This longitudinal study evaluated crawling variations using crawling movement codes for infants with no noted structural anomaly in their central nervous system. Their developmental level was evaluated with the DENVER II (Japanese version) after age 2 years, and the cumulative numbers of crawling variations (CNCVs) between groups with and without suspected developmental delays were compared. Those infants with suspected developmental delays had significantly lower CNCV than their counterparts. Furthermore, the former were commonly suspected to have a delay in the DENVER II subdomain of fine motor/adaptive and language skills. Infants who experience fewer crawling variations may be at risk for subsequent developmental delays, especially in fine motor and language skills.
Experiences of Pediatricians and Part C EI Personnel With Identification, Referral, and Evaluation Amidst COVID-19
Authors: Yadav Asha , Phelps Randall Alan , Squires Jane
Published: February 2025

The impact of the coronavirus (COVID-19) pandemic on families of young children with disabilities is well documented; however, there is little published research on the experiences of pediatricians and Part C Early Intervention (EI) personnel during the pandemic. This study examined the collective experiences of general pediatricians and Part C EI personnel related to delivering services to children and their families during the pandemic. Qualitative analyses of semi-structured interviews conducted between November 2020 and February 2021 revealed a significant decline in the number of children identified and referred to EI programs.

Additionally, the 14 Part C EI providers and four pediatricians who were interviewed suggested that those children and families who were referred were either not linked with the EI program or experienced delayed evaluations. There was consensus among EI personnel and pediatricians that telehealth was not an ideal platform for conducting developmental screening and eligibility evaluations for children aged birth to 3 during the pandemic, particularly with new families where there was limited contextual information, and a rapport had not yet been established between the provider and the family.
Prevention of Commercial Sexual Exploitation of Children
Authors: Hornor Gail
Published: February 2025

Commercial sexual exploitation of children (CSEC) is a global public health crisis. CSEC is defined as the use of a child under the age of 18 years in a range of crimes and activities involving the sexual abuse or exploitation of the child for the financial benefit of any person or in exchange for anything of value given or received by any person. CSEC is a problem of epidemic proportions throughout the world including the United States. It is difficult to determine the true number of CSEC victims in the United States. However, the National Center for Missing & Exploited Children states that, in 2021, more than 17,200 reports of child sex trafficking were received from all 50 U.S. states and estimates that of the 25,000 children reported missing, one in six were likely victims of sex trafficking. CSEC can result in significant physical and mental health consequences for victims, even death. Studies indicate that CSEC victims are consumers of healthcare. Up to this point, the focus of healthcare related to CSEC has primarily been upon recognizing red flags that should raise CSEC concerns and the identification of victims. Although victim identification is critical, it is time for forensic nurses to understand their role in the prevention of CSEC. This narrative review will discuss the prevention of CSEC using a multitiered healthcare approach.
Establishing a Frontline Medical Response During Human Trafficking Recovery Operations
Authors: Saye Jamie , Barnett Katherine , Beidler Susan M.
Published: February 2025

In the southeastern United States, sexual assault nurse examiners, registered nurses, and advanced practice registered nurses partnered with local, state, and federal law enforcement to provide comprehensive medical services to recovered persons of human trafficking. Medical services were provided in conjunction with Homeland Security Investigation's human trafficking recovery operations. Over five operations, 31 trafficked women were recovered and provided trauma-informed, holistic medical care. Medical services provided included pelvic exams, sexually transmitted infection testing and treatment, cancer screenings, pregnancy testing, and contraception. Supportive services such as nourishment, comfort items, and initial counseling sessions were also offered.
Psychotherapy and Psychotherapeutic Techniques for the Treatment of Vulvodynia: A Systematic Review and Meta-Analysis
Authors: Queiroz Janice F. , Sarmento Ayane C.A. , Aquino Antonio C.Q. , de Souza Amaxsell Thiago Barros , de Medeiros Kleyton Santos , Falsetta Megan L. , Gonçalves Ana Katherine
Published: February 2025

Objectives

To assess the effectiveness of psychotherapy and psychotherapeutic techniques for reduction of vulvar pain and the improvement of sexual function and psychological adjustment in vulvodynia.

Material and Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed, Embase, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, PsycInfo, and Clinical Trial Databases were searched on July 19, 2024. We included randomized controlled trials comparing psychotherapy interventions and psychotherapeutic techniques for vulvodynia. The risk of bias was assessed using the Cochrane Risk of Bias (RoB 2.0) tool. RevMan 5.4 was used for data synthesis. The Grading of Recommendations Assessment Development (GRADE) and Evaluation method was used to assess the strength of the evidence.

Results

A total of 1,884 articles were retrieved. Eight studies met the eligibility criteria and were included in the systematic review, comprising 689 participants. Two studies were included in the meta-analysis, these with 143 participants. When comparing the Acceptance and Commitment Therapy (ACT) with the control group, the mean difference (MD) in the pooled analysis for the Chronic Pain Acceptance Questionnaire did not differ significantly between ACT therapy and other therapies for posttreatment assessment (MD = 0.77; 95% CI = 3.45–4.99). Only 1 study was at high risk of bias due to a lack of clarity about the outcome measurement process. The GRADE rating for the certainty of the evidence for vulvar pain acceptance using ACT was considered low.

Conclusions

Psychotherapy significantly improves vulvar pain, psychological adjustment, and sexual function in women with vulvodynia. Additionally, our meta-analysis showed that ACT and other psychotherapeutic interventions improve psychological adjustment through pain acceptance. However, more rigorous studies are needed to improve the quality of evidence and inform clinical practice.
Mesenteric Ischemia During Intra-Aortic Balloon Counterpulsation Therapy: Case Series
Authors: Wohlfahrt Alyssa , Ablavsky Alex , John Kevin John , Kiernan Michael , Kapur Navin K. , Kawabori Masashi , Chweich Haval
Published: February 2025

Intra-aortic balloon pumps (IABPs) are commonly used circulatory support devices. Mesenteric ischemia is a serious and poorly studied complication of IABP use. Here, we examine six cases of mesenteric ischemia associated with IABPs from a single urban academic medical center. We examine patient, device, and radiographic characteristics, and hypothesize several mechanisms behind IABP-associated mesenteric ischemia including anatomic-to-device length mismatch, atheroembolism, and mechanical obstruction. We highlight the high morbidity and mortality of such complication and the need for future studies to examine risk factors that may predispose IABP-treated patients to the development of mesenteric ischemia.
Code-ICH: time is brain
Authors: Yakhkind Aleksandra , Yu Wenzheng , Goldstein Joshua N. , Mayer Stephan A.
Published: February 2025

Purpose of review

Intracerebral hemorrhage (ICH) is the most devastating type of stroke resulting in severe disability and mortality. This review summarizes the emerging body of evidence supporting a new paradigm for care of patients called Code-ICH. It highlights the need for the adoption of time-based care bundles based on recent evidence, akin to those used in the management of acute ischemic stroke.

Recent findings

Numerous trials aimed at decreasing hematoma expansion through single interventions have historically failed to show significant effects on primary outcomes. Time-sensitive, multifaceted, bundled care approaches have emerged with substantial promise in improving functional outcomes in patients with ICH. These bundles include early aggressive control of blood pressure and reversal of anticoagulation, strict normalization of blood sugar and temperature, early surgical evaluation, and minimizing early withdrawal of care.

The paradigm of Code-ICH empowers acute care providers to continuously measure system performance, reflect on best practices, improve outcomes, and tackle disparities for patients with ICH.
Early diagnostic value of neurotransmitter changes in vulnerable brain regions of patients with subjective cognitive decline detected using proton magnetic resonance spectroscopy
Authors: Zeng Zhen , He Jing , Yao Tao
Published: February 2025

This study utilized proton magnetic resonance spectroscopy (1H-MRS) to analyze changes in glutamate-to-creatine ratios (Glu/Cr) in specific brain regions of patients with subjective cognitive decline (SCD) and explored their clinical value for early diagnosis and intervention. Sixty participants, including 30 SCD patients and 30 healthy controls (HCs), were enrolled. Brain imaging was performed using a 3.0T superconducting magnetic resonance scanner. Single-voxel point-resolved spectroscopy sequence (PRESS) was applied for 1H-MRS, focusing on the left posterior cingulate gyrus, hippocampus, and temporal lobe. Glu/Cr ratios were calculated and compared between groups. Correlations between Glu/Cr ratios and cognitive function scores were analyzed. Glu/Cr ratios in the left posterior cingulate gyrus were significantly lower in the SCD group compared to the healthy control group (P = .002), suggesting early metabolic disturbances in this region. However, no significant differences in Glu/Cr ratios were observed in the left hippocampus (P = .312) or temporal lobe (P = .073). Additionally, the Glu/Cr ratio in the posterior cingulate gyrus negatively correlated with cognitive function scores (r = −0.45, P < .001), further emphasizing its potential as a biomarker for early cognitive impairment. This study highlights the diagnostic value of reduced Glu/Cr ratios in the posterior cingulate gyrus for identifying SCD patients at risk of cognitive decline. The findings support the application of 1H-MRS as a noninvasive tool for early detection and monitoring of metabolic changes associated with neurodegenerative processes. Future longitudinal studies are needed to confirm these findings and explore their utility in guiding clinical interventions.
Causal role of common autoimmune diseases in interstitial cystitis/bladder pain syndrome: Mendelian randomization (MR) study
Authors: Wu Liming , Wang Tianwei , Bai Ming , Chen Jinbang , Ning Jiang , Jin Qingyang , Ma Yuanchun , Xu Xinyan , Hao Zihan , Yang Rong
Published: February 2025

Observational studies suggest that interstitial cystitis/bladder pain syndrome (IC/BPS) indices might be influenced by autoimmune diseases (AIDs), though it is difficult to infer causal relationships based on observational data due to risk of residual confounding. We utilized Mendelian randomization (MR) to explore causal relevance of multiple AIDs on IC/BPS. Our bidirectional two-sample MR analysis was based on summary statistics from the most recent and comprehensive genome-wide association studies. This particular approach was used to delve into the relationships of cause and effect between IC/BPS and a group of 14 AIDs. We examined a range of AIDs such as ulcerative colitis, Crohn disease, celiac disease, Sjogren syndrome, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, primary biliary cirrhosis, psoriasis, asthma, eczema, ankylosing spondylitis, type 1 diabetes, and primary sclerosing cholangitis. Our primary analytical approach involved using the inverse variance weighting method to establish causal relationships across various AIDs and IC/BPS conditions. Furthermore, we carried out additional examinations, such as utilizing the weighted median technique, MR-Egger regression, MR-PRESSO, and evaluating reverse causality, in order to strengthen the dependability of our results. Our findings indicate a strong association between genetically predicted asthma and the risk of developing IC/BPS with a weighted odds ratio of 1.692, a confidence interval of 1.147 to 2.496, and P = .008, while the Cochran Q test P = .589 and the MR-Egger intercept test P = .554, MR-PRESSO global test P = .600. No evidence was found for causal relationships between other AIDs and IC/BPS. Individuals with asthma show an increased vulnerability to IC/BPS according to our findings. More randomized controlled trials are necessary to validate these results. These results underscore the importance for healthcare providers to assess the potential risk in asthma patients, offering a novel genetic perspective on studying interstitial cystitis.
Plasma proteins and coronary atherosclerosis: A Mendelian randomization study
Authors: Pan Henan , Wu Zongkai , Gao Yaran , Yao Wentao , Feng Ge , Wang Hebo
Published: February 2025

Coronary atherosclerosis (AS) is a complicated and severe chronic pathological process that contributes to the basis of various cardiovascular diseases, which causes a serious challenge to the global healthcare system. AS is the underlying physiopathological mechanism. Despite recent advances in the research of biomarkers and therapeutic targets for AS, there remain significant limitations in the current targeted therapies for AS. This study utilizes Mendelian randomization analysis to leverage genetic variations in order to identify plasma proteins with causal relationships to coronary AS. Utilizing publicly available genome-wide association study datasets, 4907 plasma proteins were assessed as exposure factors, with coronary AS being the outcome variable. The primary analytical method employed was the inverse variance weighted approach to ensure the robustness and accuracy of the causal relationships. In addition, to verify the reliability of the results, we employed several complementary methods, including the weighted median, Mendelian randomization-Egger, weighted mode, and simple mode approaches, to thoroughly assess the heterogeneity and pleiotropy of the findings. To ensure the robustness of the results and to exclude potential biases, a leave-one-out sensitivity analysis was performed. Twenty potential therapeutic targets were analyzed and identified (P < .05), combined with multiple bioinformatic analyses; among them, fibronectin 1 was identified as a key target. These findings may provide a new theoretical basis for future research in coronary AS drug development and therapeutic strategies.
Threshold effect of non-high-density lipoprotein to high-density lipoprotein cholesterol ratio and hypertension in U.S. adults: NHANES 2005–2016
Authors: Sha Yanming , Cai Yuzhou , Zeng Yujian , Fu Jingyun
Published: February 2025

Hypertension is a prevalent chronic non-communicable disease associated with cardiovascular issues, strokes, kidney disorders, and depression. Most hypertensive patients have dyslipidemia and metabolic abnormalities. The non-high-density lipoprotein to high-density lipoprotein cholesterol ratio (NHHR) is a novel index that more accurately assesses the risk of atherosclerotic cardiovascular diseases and metabolic issues like insulin resistance. The association between NHHR and hypertension prevalence is still unclear. The study aims to examine the link between NHHR and hypertension prevalence in American adults. N10,410 adults from the National Health and Nutrition Examination Survey (NHANES) (2005–2016) were included in this cross-sectional analysis. Multivariable logistic regression constructed to analyze the relationship between NHHR and hypertension, with additional analyses including restricted cubic spline regression (RCS), threshold and saturation effect analyses, effect point calculations, subgroup analyses, and sensitivity analyses. Machine learning methods combined with the Boruta algorithm were employed to identify key predictors of hypertension risk. Of the 10,410 participants, 48% were male, with a hypertension prevalence of 37.03%. NHHR was higher in hypertensive patients compared to non-hypertensive individuals (2.74 vs 2.90, P < .001). In models that were completely confounded with factors including general demographic data, BMI, smoking status, alcohol consumption, diabetes, total cholesterol, history of coronary heart disease, LDL, and dietary cholesterol, NHHR showed a significant positive correlation with hypertension prevalence. RCS regression indicated a non-linear relationship, with a saturation effect point at 3.058. Subgroup analyses showed significant interactions by race and education level (P < .05). Machine learning models demonstrated AUCs > 0.8, affirming the importance of NHHR in predicting hypertension. NHHR levels are significantly elevated in hypertensive individuals compared to non-hypertensive adults in the U.S. Furthermore, a non-linear positive correlation exists between NHHR and hypertension risk, suggesting its potential as a predictive biomarker for early hypertension prevention.
Developing a health education program for home enteral nutrition after esophageal cancer surgery based on the Delphi method
Authors: Tian Weiran , Liu Wei , Wang Cuirong , Liu Lei , Zhang Liming , Chen Lu
Published: February 2025

To develop a health education program for home enteral nutrition (HEN) after Esophageal cancer (EC) surgery based on Delphi method, providing reference opinions for clinical nursing education and patient home care. The health education program for HEN after EC surgery was constructed through literature research, theoretical analysis and group discussion. From February to June 2024, experts in clinical nursing, clinical medicine, and nutrition of EC were invited to conduct 2 rounds of Delphi expert consultation to initially determine the items of the program. The weight and assignment of each items were determined through analytic hierarchy process (AHP), and then the final health education program for HEN after EC surgery was established. The authoritative coefficients of the 2 rounds consulting experts were 0.918 and 0.929 and the positive coefficients were 100% and 95%, respectively; The mean range of importance assignment for the second round of consultation indicators was 4.26 to 5.00 points, with a full score range of 40.90% to 95.45%. The mean harmony coefficients for expert opinions from 2 rounds were 0.206 and 0.218 (P < .01), respectively. The final health education program for postoperative HEN in EC includes 6 primary items, 27 secondary items, and 18 tertiary items. The results of the AHP showed that the consistency coefficients (CR values) of each matrix for the tertiary items were all < 0.1, meeting the requirements of consistency testing. The constructed health education program for postoperative HEN patients with EC in this study has high scientific and practical value, and can provide reference for the health education of postoperative HEN patients with EC.
Risk factors for age-related macular degeneration: Updated systematic review and meta-analysis
Authors: Babaker Raghad , Alzimami Lama , Al Ameer Abdullah , Almutairi Majed , Alam Aldeen Rahaf , Alshatti Hamad , Al-Johani Najwan , Al Taisan Abdulaziz
Published: February 2025

Background:

Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in the elderly population, affecting millions of the people worldwide. AMD has a substantial effect on quality of life in older individuals. Understanding and identifying risk factors are crucial for developing preventive strategies.

Methods:

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search across databases including PubMed, Scopus, and Web of Science up to January 28, 2024. Studies were selected using standardized inclusion and exclusion criteria, and the quality of the studies was assessed via the Newcastle Ottawa Scale. Meta-analysis was conducted using Review Manager software to pool the odds ratio (OR) of each included risk factors at the 95% confidence interval (CI).

Results:

Eighteen of the 2640 identified studies met the inclusion criteria for the meta-analysis. Older age compared to younger age, male gender compared to female gender, smoking, hypertension, cardiovascular diseases, and diabetes were statistically significant predictors for AMD occurrence, with ORs of 1.11 (95% CI = 1.06–1.15, P < .00001), 1.63 (95% CI = 1.13–2.35, P = .009), 1.86 (95% CI = 1.33–2.6, P = .0003), 1.24 (95% CI = 1.09–1.4, P = .0007), 1.44 (95% CI = 1.11–1.87, P = .006), and 1.44 (95% CI = 1.3–1.6, P < .00001), respectively. Other factors, such as body mass index, cerebrovascular diseases, cholesterol, and triglycerides, were not significantly associated with AMD.

Conclusion:

This updated meta-analysis highlights the significance of modifiable risk factors for AMD, including smoking, hypertension, cardiovascular diseases, and diabetes. Early identification of AMD accompanied by strategic management of these modifiable risk factors may preserve patients’ visual acuity without advancing to advanced stages.
Unraveling the role of macrophages in diabetes: Impaired phagocytic function and therapeutic prospects
Authors: Rong Bing , Jiang Hailun , Zhu Weiming , Yang Guanhu , Zhou Xuancheng , Lyu Zhongxi , Li Xiangyi , Zhang Jieying
Published: February 2025

The rising aging population and changing lifestyles have led to a global increase in diabetes and its complications, making it one of the most prevalent diseases worldwide. Chronic inflammation is a key pathogenic feature of diabetes and its complications, yet the precise mechanisms remain unclear, impeding the development of targeted therapies. Recent studies have highlighted the β cell-macrophage crosstalk pathway as a crucial factor in chronic low-grade inflammation and glucose homeostasis imbalance in both type 1 and type 2 diabetes. Furthermore, impaired macrophage phagocytic functions, including pathogen phagocytosis, efferocytosis, and autophagy, play a significant role in diabetes complications. Given their high plasticity, macrophages represent a promising research target. This review summarizes recent findings on macrophage phagocytic dysfunction in diabetes and its complications, and explores emerging therapies targeting macrophage phagocytic function. We also discuss the current challenges in translating basic research to clinical practice, aiming to guide researchers in developing targeted treatments to regulate macrophage status and phagocytic function, thus preventing and treating metabolic inflammatory diseases.