bluuebunny/crossref_metadata_2025 huggingface dataset:
Finding accreted stars in the Milky Way: clues from NIHAO simulations
Authors: Buder S , Mijnarends L , Buck T
Published: June 2024

Exploring the marks left by galactic accretion in the Milky Way helps us understand how our Galaxy was formed. However, finding and studying accreted stars and the galaxies they came from has been challenging. This study uses a simulation from the Numerical Investigation of a Hundred Astronomical Objects project, which now includes a wider range of chemical compositions, to find better ways to spot these accreted stars. By comparing our findings with data from the GALAH spectroscopic survey, we confirm that the observationally established diagnostics of [Al/Fe] versus [Mg/Mn] also show a separation of in situ and accreted stars in the simulation, but stars from different accretion events tend to overlap in this plane even without observational uncertainties. Looking at the relationship between stellar age and linear or logarithmic abundances, such as [Fe/H], we can clearly separate different groups of these stars if the uncertainties in their chemical makeup are less than 0.15 dex and less than 20 per cent for their ages. This method shows promise for studying the history of the Milky Way and other galaxies. Our work highlights how important it is to have accurate measurements of stellar ages and chemical content. It also shows how simulations can help us understand the complex process of galaxies merging and suggest how these events might relate to the differences we see between our Galaxy’s thin and thick disc stars. This study provides a way to compare theoretical models with real observations, opening new paths for research in both our own Galaxy and beyond.
iMab antibody binds single-stranded cytosine-rich sequences and unfolds DNA i-motifs
Authors: Boissieras Joseph , Bonnet Hugues , Susanto Maria Fidelia , Gomez Dennis , Defrancq Eric , Granzhan Anton , Dejeu Jérôme
Published: June 2024

i-Motifs (iMs) are non-canonical, four-stranded secondary structures formed by stacking of hemi-protonated CH+·C base pairs in cytosine-rich DNA sequences, predominantly at pH < 7. The presence of iM structures in cells was a matter of debate until the recent development of iM-specific antibody, iMab, which was instrumental for several studies that suggested the existence of iMs in live cells and their putative biological roles. We assessed the interaction of iMab with cytosine-rich oligonucleotides by biolayer interferometry (BLI), pull-down assay and bulk-FRET experiments. Our results suggest that binding of iMab to DNA oligonucleotides is governed by the presence of runs of at least two consecutive cytosines and is generally increased in acidic conditions, irrespectively of the capacity of the sequence to adopt, or not, an iM structure. Moreover, the results of the bulk-FRET assay indicate that interaction with iMab results in unfolding of iM structures even in acidic conditions, similarly to what has been observed with hnRNP K, well-studied single-stranded DNA binding protein. Taken together, our results strongly suggest that iMab actually binds to blocks of 2–3 cytosines in single-stranded DNA, and call for more careful interpretation of results obtained with this antibody.
Challenges and opportunities in newly diagnosed glioblastoma in the United Kingdom: A Delphi panel
Authors: Bulbeck Helen , Noble Karen , Oliver Kathy , Skinner Tina Mitchell
Published: June 2024

Background

Glioblastoma is the deadliest primary malignant brain tumor in adults with limited treatment options and an average survival time of 12–18 months in the United Kingdom. In addition, glioblastoma has a highly detrimental impact on physical, cognitive, and emotional well-being, leaving substantial unmet needs for patients and caregivers. This study aimed to identify unmet needs in people with newly diagnosed glioblastoma and opportunities to mitigate them.

Methods

Utilizing Delphi methodology, an initial roundtable discussion with patient advocacy experts from 5 brain tumor organizations in the United Kingdom informed the development of 2 rounds of surveys across 9 domains (diagnosis, treatment, integrated care, support beyond treatment, quality of life, access to new treatments, access to trials, measures to ease the burden, and impact of COVID-19). Consensus was predefined as ≥70% agreement.

Results

A total of 17 Delphi panelists (glioblastoma patients, caregivers, and patient representatives) completed the first round of questionnaires and 26 completed the second. Consensus was reached on 16/21 questions (76.2%) and 7/9 domains. Panelists reached a consensus on key questions including the high frequency of diagnosis via emergency departments, the lack of effective personalized treatments and holistic care, the high caregiver burden, the lack of awareness and availability of access to clinical trials, and the negative impact of COVID-19 on glioblastoma care.

Conclusions

Significant unmet needs exist for newly diagnosed glioblastoma patients in the United Kingdom, highlighting the demand for increased research funding, comprehensive patient care, caregiver support, enhanced awareness and access to clinical trials, and new treatments.
The effectiveness and safety of natural food and food-derived extract supplements for treating functional gastrointestinal disorders—current perspectives
Authors: Liu Tianxu , Asif Ismail Muhammad , Bai Chengmei , Huang Yutian , Li Bin , Wang Ling
Published: June 2024

Functional gastrointestinal disorders (FGIDs) were highly prevalent and involve gastrointestinal discomfort characterized by non-organic abnormalities in the morphology and physiology of the gastrointestinal tract. According to the Rome IV criteria, irritable bowel syndrome and functional dyspepsia are the most common FGIDs. Complementary and alternative medicines are employed by increasing numbers of individuals around the world, and they include herbal and dietary supplements, acupuncture, and hypnosis. Of these, herbal and dietary supplements seem to have the greatest potential for relieving FGIDs, through multiple modes of action. However, despite the extensive application of natural extracts in alternative treatments for FGIDs, the safety and effectiveness of food and orally ingested food-derived extracts remain uncertain. Many randomized controlled trials have provided compelling evidence supporting their potential, as detailed in this review. The consumption of certain foods (eg, kiwifruit, mentha, ginger, etc) and food ingredients may contribute to the alleviation of symptoms associated with FGID,. However, it is crucial to emphasize that the short-term consumption of these components may not yield satisfactory efficacy. Physicians are advised to share both the benefits and potential risks of these alternative therapies with patients. Furthermore, larger randomized clinical trials with appropriate comparators are imperative.
Conference of the Parties (COP) 28 Takeaways at the Intersection of Health, Climate, and Food
Authors: Varyvoda Yevheniia
Published: June 2024

The 28th session of the Conference of the Parties (COP 28) to the UN Framework Convention on Climate Change brought together 85 000 climate stakeholders to leverage solutions and accelerate climate actions in 4 key areas: energy transition; issue of funding and financing of climate actions; emphasis on nature, people’s lives, and livelihoods; and ensuring inclusivity for all. This commentary highlights insights at the intersection of health, climate, and food gained by the author from participating in COP 28 events. The objective is to inform policymakers, researchers, and practitioners on emerging opportunities to scale specific, measurable, achievable, relevant, and time-based (SMART) climate actions that prioritize health and boost the resilience of food and public health systems.
Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer
Authors: Tian Chun-Fang , Jing Hai-Yan , Sinicrope Frank A , Wang Jin-Shen , Gao Bin-Bin , Sun Xiao-Gang , Yao Zhi-Gang , Li Le-Ping , Saberzadeh-Ardestani Bahar , Song Wei , Sha Dan
Published: June 2024

Background

Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy.

Methods

TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression.

Results

Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%).

Conclusions

Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.
Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients
Authors: Wang Mingda , Qian Guojun , Xiao Hongmei , Liu Xingkai , Sun Liyang , Chen Zhong , Lin Kongying , Yao Lanqing , Li Chao , Gu Lihui , Xu Jiahao , Sun Xiaodong , Qiu Wei , Pawlik Timothy M , Yee Lau Wan , Lv Guoyue , Shen Feng , Yang Tian
Published: June 2024

Background

The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection.

Methods

A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS).

Results

Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001).

Conclusion

The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.
Quality of life in women with early-stage and metastatic hormone receptor-positive, HER2-negative breast cancer receiving endocrine therapy
Authors: O’Reilly David , Farooq Abdul Rehman , Nevins Selvadurai Paul , Sheehan Laura , Molan Karen , Krishnanivas Bindu , Mullen Valerie , McMahon David , Hadi Danial , Ahmed Ahmed , Jennings Maeve , Carroll Hailey , Chew Sonya , Macanovic Bojan , O’Hanlon Brown Ciara , Noonan Sinéad A , O Reilly Seamus , Connolly Roisin M , Cahir Caitriona , Kelly Catherine M
Published: June 2024

Introduction

Early discontinuation of endocrine therapy (ET) is higher among patients with early breast cancer (EBC) compared to patients with metastatic hormone receptor-positive (HR+) breast cancer (MBC). In our clinical experience the reasons for this may include a significant burden of ET side effects impacting quality of life (QOL) in patients with EBC. We hypothesized that QOL is lower in patients with HR + EBC compared to patients with HR + MBC on ET.

Methods

We conducted a cross-sectional observational study to assess QOL utilizing FACT-ES & EORTC QLQ C30 tools among patients with EBC and MBC receiving ET across 5 Irish hospitals.

Results

A total of 417 patients were enrolled—EBC (79% n = 331) and MBC 21% (n = 86). Using the FACT-ES, we found no difference in overall QOL by stage (139.2 vs 141, P  = .33). Patients with HR + MBC had a lower symptom burden from ET compared to HR + EBC (61.4 vs 54, P < .01). In adjusted multivariate linear regression models, there was no difference in QOL for patients with EBC and MBC receiving ET.

Conclusions

There was no significant difference in overall QOL for patients with EBC and MBC. However, patients with EBC experienced more endocrine symptoms. In adjusted multivariate linear regression models, the stage did not predict QOL. Our results suggest that endocrine symptoms are significant contributors to impaired QOL for patients with EBC but the role of other determinants of QOL (eg, stage) is less clear. Future work could include the development of stage-specific QOL tools and utilization of electronic patient-reported outcomes (ePROs) to identify and manage emergent toxicities.
Astrocytic GPCR signaling in the anterior cingulate cortex modulates decision making in rats
Authors: Akter Mastura , Fu Zhongqi , Zheng Xianlin , Iqbal Zafar , Zhang Na , Karim Anwarul , Li Ying
Published: June 2024

Decision making is a process of selecting a course of action by assessing the worth or value of the potential consequences. Rat Gambling Task (RGT) is a well-established behavioral paradigm that allows for assessment of the decision-making performance of rats. Astrocytes are emerging as key players in modulating cognitive functions. Using repeated RGTs with short intersession time intervals (48 h), the current study demonstrates that Gi pathway activation of astrocytes in the anterior cingulate cortex (ACC) leads to impaired decision-making in consistently good decision-making rats. On the other hand, ACC astrocytic Gq pathway activation improves decision-making in a subset of rats who are not consistently good decision-makers. Furthermore, we show that astrocytic Gq activation is associated with an increase in the L-lactate level in the extracellular fluid of the ACC. Together, these results expand our knowledge of the role of astrocytic GPCR signaling in modulating cognitive functions.
‘The system is engineered to do this’: Multilevel Disempowerment and Climate Injustice in Regulating Colorado’s Oil and Gas Development
Authors: Ryder Stacia , Malin Stephanie A
Published: June 2024

Continuing to emit greenhouse gases (GHGs) moves our planet closer to crossing critical tipping points, making ongoing development of fossil fuels an act of climate injustice. Yet, the United States has doubled down on unconventional oil and gas (UOG), becoming the top global producer of hydrocarbons. Significant segments of the public resist UOG drilling, mobilizing to limit or stop production due to intersecting climate, environmental, and public health concerns. However, regulatory conflicts complicate the power of public resistance and problematize the role of the state in facilitating industry. UOG production has rapidly expanded with little capacity for public participation in decision-making. We contend this is a climate injustice—where procedural injustices across levels of governance make it difficult for the public to prevent fossil fuel extraction. We examine these injustices across state legislative, judicial, and executive governance processes in Colorado where residents have actively resisted UOG production. We demonstrate how the public consistently faces procedural inequities and power disadvantages across multiple sites and levels of decision-making, resulting in multilevel disempowerment. In this high-stakes context, our policy ethnography illustrates how these multilevel procedural injustices can facilitate rapid expansion of UOG production, where state-sanctioned activities also constitute broader acts of climate violence and injustice.
Identification of weight loss interventions for translation among endometrial cancer survivors: A RE-AIM analysis
Authors: Harden Samantha M , Brow Katie , Zoellner Jamie , Armbruster Shannon D
Published: June 2024

Interventions for obesity-related cancers that combine nutrition and physical activity for weight loss exist; however, their application to survivors of endometrial cancer is unknown. Furthermore, little is known about pre-implementation perceptions of existing programs from a variety of interested persons (physicians, researchers) who may be part of the implementation team. Adapting an existing intervention rather than developing a new intervention may speed the translational lag time as long as intervention characteristics and fit within the delivery system are considered during the planning phase. To describe the process of determining the core elements of obesity-related interventions for cancer survivors and determine which one might be best delivered by an urban healthcare system that predominantly serves individuals who live in rural areas of Virginia and West Virginia. A pragmatic review of the literature was conducted via PubMed and Google Scholar with broad search terms of cancer survivor AND weight loss AND health intervention. Identified interventions were scored related to the Practical, Robust Implementation and Sustainability Model—which is an extension of RE-AIM framework to guide the understanding of who, what, where, when, and how the intervention was conducted. Intervention characteristics are reported. In addition, ratings from three independent reviewers on the validated 5-point Likert scale of an intervention’s acceptability, appropriateness, and feasibility in the intended delivery system were collected and summarized. Twelve interventions were identified with an average sample size of 241(±195) and a range of 48–683 participants. Target populations included survivors of colorectal, breast, and endometrial cancers as well as general cancer survivors and included both men and women or only women. Most participants (74%) identified as white/Caucasian and average age ranged from 47.1 to 65.9 years. Program duration ranged from 4 weeks to 18 months, with an average duration of 32 weeks. Intervention dosage ranged from three times a week to once a month. Intervention acceptability, appropriateness, and feasibility had average and standard deviation ratings of 3.52(±0.46), 3.41(±0.45), and 3.21(±0.46), respectively, out of 5. The four interventions with the highest combined acceptable, appropriate, and feasible scores are being considered for potential use as an obesity-related intervention for survivors of endometrial cancer. Future work is needed to determine relevant adaptations and efficacy among survivors of endometrial cancer with obesity. Our approach may be beneficial for other interventionists aiming to speed intervention development and implementation.
Evolution of DS-1-like G8P[8] rotavirus A strains from Vietnamese children with acute gastroenteritis (2014–21): Adaptation and loss of animal rotavirus-derived genes during human-to-human spread
Authors: Hoa-Tran Thi Nguyen , Nakagomi Toyoko , Vu Hung Manh , Nguyen Trang Thu Thi , Dao Anh Thi Hai , Nguyen Anh The , Bines Julie E , Thomas Sarah , Grabovac Varja , Kataoka-Nakamura Chikako , Taichiro Takemura , Hasebe Futoshi , Kodama Toshio , Kaneko Miho , Dang Huyen Thi Thanh , Duong Hong Thi , Anh Dang Duc , Nakagomi Osamu
Published: June 2024

Animal rotaviruses A (RVAs) are considered the source of emerging, novel RVA strains that have the potential to cause global spread in humans. A case in point was the emergence of G8 bovine RVA consisting of the P[8] VP4 gene and the DS-1-like backbone genes that appeared to have jumped into humans recently. However, it was not well documented what evolutionary changes occurred on the animal RVA-derived genes during circulation in humans. Rotavirus surveillance in Vietnam found that DS-1-like G8P[8] strains emerged in 2014, circulated in two prevalent waves, and disappeared in 2021. This surveillance provided us with a unique opportunity to investigate the whole process of evolutionary changes, which occurred in an animal RVA that had jumped the host species barrier. Of the 843 G8P[8] samples collected from children with acute diarrhoea in Vietnam between 2014 and 2021, fifty-eight strains were selected based on their distinctive electropherotypes of the genomic RNA identified using polyacrylamide gel electrophoresis. Whole-genome sequence analysis of those fifty-eight strains showed that the strains dominant during the first wave of prevalence (2014–17) carried animal RVA-derived VP1, NSP2, and NSP4 genes. However, the strains from the second wave of prevalence (2018–21) lost these genes, which were replaced with cognate human RVA-derived genes, thus creating strain with G8P[8] on a fully DS-1-like human RVA gene backbone. The G8 VP7 and P[8] VP4 genes underwent some point mutations but the phylogenetic lineages to which they belonged remained unchanged. We, therefore, propose a hypothesis regarding the tendency for the animal RVA-derived genes to be expelled from the backbone genes of the progeny strains after crossing the host species barrier. This study underlines the importance of long-term surveillance of circulating wild-type strains in order to better understand the adaptation process and the fate of newly emerging, animal-derived RVA among the human population. Further studies are warranted to disclose the molecular mechanisms by which spillover animal RVAs become readily transmissible among humans, and the roles played by the expulsion of animal-derived genes and herd immunity formed in the local population.
Effect of Drought Stress During Seed Development on Charcoal Rot and Yield of Soybean
Authors: Zaccaron Marcio , Holland Robert , Gbur Edward , Thompson Kevin , Rojas J. Alejandro , Rupe John C.
Published: June 2024

The primary controls for charcoal rot in soybean, caused by the fungal pathogen Macrophomina phaseolina, are to avoid drought stress and to plant a moderately resistant cultivar. The effects of irrigation and cultivar were determined in 2011 and 2013 at the Lon Mann Cotton Research Station, Marianna, AR. Four soybean cultivars (Hutcheson, Osage, Ozark, and R01581F) were planted in plots with or without added M. phaseolina inoculum and subjected to three furrow irrigation regimes: full-season irrigation (Full), irrigation terminated at R5 (CutR5), and nonirrigated (NonIrr). Normalized difference vegetation index (NDVI) was measured at R3 and R6. At harvest, plants and yields were collected. Roots and stems were split and the extent of visible colonization by M. phaseolina microsclerotia was assessed in the roots with a 1 to 5 scale (RSS) and the percent plant height stem discoloration measured. Precipitation in September and October was 54 and 65% below the 30-year average in 2011 and 2013, respectively. The CutR5 irrigation treatment resulted in one less irrigation than Full each year, but CutR5 NDVIs at R6 and yields were significantly lower than those with Full and not significantly different from those of NonIrr. The CutR5 RSS ratings were greater than either Full or NonIrr. Plant colonization by M. phaseolina was negatively correlated to yield in 2011 but not in 2013. No premature plant death caused by charcoal rot was observed in either year. These results indicated that late-season drought stress may be more important to charcoal rot development than drought stress throughout the season, but other factors are needed to trigger early plant death and subsequent yield losses observed in grower fields.
Night‐restricted feeding improves colonic barrier function and reduces inflammation by optimizing gut microbial composition in growing pigs during the hot season
Authors: Zhang Lei , Yao Chun‐Yan , Wang Qiang‐Jun , Shan Chun‐Hua , Zhang Ke‐Hao , Guo Yao , Li Qin , Liu Zhong‐Ying , Liu Peng , Geng Shi‐Xia , Hu Yu‐Pei , Huang Jie , Yao Fu‐Sheng , Lu Jin‐Lun , Wu Zhong‐Hong
Published: June 2024

Circadian rhythm disruptions and heat stress can cause gut microbiota dysbiosis and intestinal barrier damage, increasing the risk of inflammatory bowel disease. However, whether eating according to the circadian rhythm during the day when the ambient temperature is higher or eating against the circadian rhythm at night when the ambient temperature is relatively suitable, is better for the gut health of diurnal animals in summer has not been clarified. In this study, growing pigs were randomly assigned to a daytime‐restricted feeding or nighttime‐restricted feeding (NRF) group and raised for 18 days in summer with mild heat stress. Our results showed that NRF alleviated heat stress in pigs, as reflected by increased feed intake and decreased drinking. Microbiome analysis revealed that NRF increased the diversity of gut microbiota and abundance of short‐chain fatty acids (SCFAs)‐producing bacteria and decreased the abundance of gram‐negative and potentially pathogenic bacteria, thereby increasing SCFAs and reducing lipopolysaccharide production in the colon. These changes enhanced colonic barrier function and reduced colitis and systemic inflammation by upregulating tight junction proteins and mucin. Our findings indicate that although nighttime eating does not align with the biological habits of pigs, consuming food at a relatively suitable ambient temperature is more beneficial for gut health and homeostasis during hot seasons. Our research provides a reference for guiding the healthy feeding of farm animals in summer and a basis for developing a lifestyle that promotes gut health for individuals in tropical regions.
NF2 regulates IP3R‐mediated Ca2+ signal and apoptosis in meningiomas
Authors: Lei Zhaoying , Niu Jie , Cai Huajian , Kong Zhengyi , Ding Xue , Dong Yufei , Zhang Dong , Li Xu , Shao Jianzhong , Lin Aifu , Zhou Ruhong , Yang Shuxu , Yan Qingfeng
Published: June 2024

Meningiomas are the most common primary intracranial tumors and account for nearly 30% of all nervous system tumors. Approximately half of meningioma patients exhibit neurofibromin 2 (NF2) gene inactivation. Here, NF2 was shown to interact with the endoplasmic reticulum (ER) calcium (Ca2+) channel inositol 1,4,5‐trisphosphate receptor 1 (IP3R1) in IOMM‐Lee, a high‐grade malignant meningioma cell line, and the F1 subdomain of NF2 plays a critical role in this interaction. Functional assays indicated that NF2 promotes the phosphorylation of IP3R (Ser 1756) and IP3R‐mediated endoplasmic reticulum (ER) Ca2+ release by binding to IP3R1, which results in Ca2+‐dependent apoptosis. Knockout of NF2 decreased Ca2+ release and promoted resistance to apoptosis, which was rescued by wild‐type NF2 overexpression but not by F1 subdomain deletion truncation overexpression. The effects of NF2 defects on the development of tumors were further studied in mouse models. The decreased expression level of NF2 caused by NF2 gene knockout or mutation affects the activity of the IP3R channel, which reduces Ca2+‐dependent apoptosis, thereby promoting the development of tumors. We elucidated the interaction patterns of NF2 and IP3R1, revealed the molecular mechanism through which NF2 regulates IP3R1‐mediated Ca2+ release, and elucidated the new pathogenic mechanism of meningioma‐related NF2 variants. Our study broadens the current understanding of the biological function of NF2 and provides ideas for drug screening of NF2‐associated meningioma.
Nonpharmacological Interventions to Mitigate Procedural Pain in the NICU
Authors: Sutton Rana , Lemermeyer Gillian
Published: June 2024

Background:

Small infants experience a myriad of stimuli while in the Neonatal Intensive Care Unit (NICU), with many being painful or stressful experiences, although medically necessary.

Purpose:

To determine what is known about nonpharmacological developmental care interventions used in the NICU to mitigate procedural pain of infants born under 32 weeks gestation.

Search/Strategy:

Five electronic databases were searched: Medline, CINAHL, Scopus, Embase and the Cochrane Library. The inclusion criteria were as follows: experimental and nonexperimental studies from all publication years with infants born at less than 32 weeks gestational age; peer-reviewed research articles studying nonpharmacological interventions such as skin-to-skin care, facilitated tucking, nonnutritive sucking, hand hugs, and swaddling; and English language articles. Our search yielded 1435 articles. After the elimination of 736 duplicates, a further 570 were deemed irrelevant based on their abstract/titles. Then, 124 full-text articles were analyzed with our inclusion and exclusion criteria.

Findings:

Twenty-seven studies were reviewed. Sucrose, facilitated tucking, pacifier, skin-to-skin care, and human milk appeared to lessen pain experienced during heel sticks, suctioning, nasogastric tube insertions, and echocardiograms. All nonpharmacological interventions failed to prove efficacious to adequately manage pain during retinopathy of prematurity (ROP) examinations.

Implications for Practice:

Evidence review demonstrates that healthcare practitioners should use nonpharmacological measures to help prevent pain from day-to-day procedures in the NICU including heel sticks, nasogastric tube insertions, suctioning, echocardiograms, and subcutaneous injections.

Implications for Research:

Future research is necessary to better understand and measure how pain is manifested by very small premature infants. Specific research on mitigating the pain of examinations for retinopathy of prematurity is also needed.
Defining the Concept of Acoustic Neuroprotection in the Neonate
Authors: Chumley Peyton Lewis , Dudding Katherine M. , Patrician Patricia
Published: June 2024

Background:

It has long been understood and acknowledged that the Neonatal Intensive Care Unit (NICU) environment and the transport environments are extremely loud, with both long- and short-term sequelae to the neonate, being well over the recommended amount of noise by the American Academy of Pediatrics (AAP). This problem has yet to be properly addressed. The purpose of this manuscript is to define and explain the concept of acoustic neuroprotection. While we cannot change the internal structures of the neonates’ auditory system, we could change the acoustics of the environment to be support neuroprotection of these sensitive patients.

Evidence acquisition:

Walker and Avant’s concept analysis steps were followed to create and define the idea of acoustic neuroprotection, as it has not had a definition before. A total of 45 articles from multiple search engines were chosen. A combination of 2 concepts were used: acoustic protection and neurodevelopmental protection/support. The search was expanded past 20 years for lack of research and importance of seminal works.

Results:

To achieve acoustic neuroprotection, a neonate should not be exposed to sound greater than 45 decibels (dBa) for longer than 10 s, and exposure to sound above 80 dBa should never occur. Appropriate interventions need to include supporting the neurodevelopment of the neonate through therapeutic sound, while decreasing the amount of toxic noise exposure to safe levels.

Implications for Practice and research:

By further understanding and having a quantifiable goal of acoustic neuroprotection for neonates, neonatal clinicians can work together to create new interventions for how to better protect and support the care of our tiniest patients.
Let’s Talk Safety – Data from the Neonatal Intensive Care Unit Safety and Bed Capacity Huddles
Authors: O’Malley Teresa , Capone Jamie , Perla Brittanie , Vasbinder Sheila
Published: June 2024

Background:

Huddles are brief team meetings designed to communicate essential information. Safety huddles provide a forum to identify and review patient safety events. In a just culture, everyone is accountable for patient safety.

Purpose:

The purpose of this project is to discuss safety issues/events at the twice daily bed capacity huddles in a Level IV Neonatal Intensive Care Unit (NICU) utilizing a just culture model. Having daily discussions of patient safety and the escalation process for follow-up promotes a just culture. The aims are to improve the unit’s culture of safety and learn from patient safety issues.

Methods:

A just culture model was adopted to promote discussion of safety events during the huddles. A structured checklist of safety events was utilized along with a script of ground rules. Twice a day, a multidisciplinary group gathers to huddle. Nurse leaders facilitate the discussion, track the results, and provide follow-up.

Results:

The structured safety huddle began in May of 2020 and continues twice daily. All required staff attend. The escalation process is defined and has prevented recurrence of some safety issues. The NICU experienced a 14% increase in favorable results on the Agency for Healthcare Research and Quality (AHRQ) culture of safety survey since the inception of the structured safety huddles.

Implications for Practice and Research:

Safety huddle discussions have impacted the culture of safety on this unit. Tracking of discussions can help to identify trends, improve processes, and impact patient safety.
Postoperative Access and Compliance Following Medial Patellofemoral Ligament Reconstruction in Hispanic Adolescents Mirrors the Non-Hispanic Adolescent Population
Authors: Howard Roland A. , Morales Jose A. , Ordaz Angel , Bryan Tracey P. , Edmonds Eric W.
Published: June 2024

Background:

Disparity in surgical care of patellar instability patients has not been fully investigated in the adolescent Hispanic population. This demographic has been shown to have differences in their care, including a lower rate of surgical treatment for patellar instability. Socioeconomic factors have been cited as a factor that influences patient outcomes and its relationship with ethnicity in context of patellar instability has not been evaluated.

Methods:

Review performed of patients <19 years of age who underwent MPFL reconstruction between September 2008 and December 2015. Demographics, patient median household income data, and clinical variables were collected. Generalized linear mixed model (GLMM) with subject as random effects factor was utilized to evaluate differences between ethnicity groups due to nonindependence of data. It was then expanded to incorporate interactions between ethnicity and income.

Results:

Ninety-five patellar dislocation events met criteria in 85 adolescents (mean age: 15.5 y). Thirty-four (40%) adolescents identified as Hispanic. In univariate analysis no differences were found between Hispanic and non-Hispanic patients. The multivariate GLMM demonstrated a significant interaction between ethnicity and income. The Hispanic group in the >100% State median income category had the highest rate of postoperative clinic appointments attended (P=0.019). The Hispanic group in the <100% State median income category had the lowest rate of physical therapy appointments attended (P=0.044). No differences were observed for duration of follow-up (P=0.57) or final Kujala score (P=0.75).

Conclusions:

Hispanic ethnicity alone is not associated with inferior postoperative management after MPFL reconstruction in adolescents. However, when socioeconomic status is considered, Hispanic patients of lower-income backgrounds are found to have lower compliance with postoperative rehab recommendations.

Level of Evidence:

Level III.
Tibial Tubercle Osteotomy With and Without Medial Patellofemoral Ligament Reconstruction in Adolescent Patients Leads to Decrease in Patellar Height and Patella Tendon Length
Authors: McNamara Natalya E. , Shing Elaine Z. , Khalil Ameen Z. , Tabish Erin M. , Featherall Joseph T. , Rosenthal Reece M. , Maak Travis G. , Aoki Stephen K. , Ernat Justin J.
Published: June 2024

Objective:

Patellar height changes after tibial tubercle osteotomy (TTO) have not yet been described. We aimed to evaluate whether TTO ± medial patellofemoral ligament reconstruction (MPFL-R) influences patellar height and tendon length, hypothesizing that TTO would decrease patellar height and tendon length.

Methods:

A retrospective review was performed of skeletally mature adolescents (<18 y) receiving primary anteromedialization or medialization TTO ± MPFL-R. Patients with at least 6 months of radiographic follow-up were included in the study. Pre and postoperative patellar heights were assessed on lateral, weight-bearing, and flexion (30 to 70 degrees) radiographs using the Blackburne-Peel Index (BPI), Caton-Deschamps Index (CDI), and Insall-Salvati Ratio (ISR). Subgroup analyses were performed to compare patellar height changes in patients with preoperative patella alta, norma, and baja, as well as between patients undergoing medialization and anteromedialization TTO. Data were analyzed for normality using a Shapiro-Wilk test, and paired-sample t tests were performed.

Results:

Forty-nine knees were included (mean age: 15 y; range: 12 to 17). A significant decrease in mean patellar height after TTO ± MPFL-R was observed across all measures: BPI (0.12, P = 0.000783), CDI (0.08, P = 0.01062), and ISR (0.15, P = 0.00000075). Patellar tendon length decreased by 2.26 mm (P = 0.001272). Subgroup analyses demonstrated a decrease in mean patellar height across all 3 measurements (P < 0.001; BPI, CDI, and ISR) for patients with preoperative patella alta but not patella norma or baja. Additional subgroup analysis showed a patellar height decrease using BPI (0.15, P = 0.004583) and ISR (0.14, P = 0.0002806) for patients receiving medialization TTO but not anteromedialization. The anteromedialization cohort did not demonstrate patellar height change using BPI and CDI; ISR demonstrated a decrease (0.10, P = 0.00917).

Conclusions:

Mean patellar height and tendon length decreases after TTO ± MPFL-R in skeletally mature, adolescent patients. Subgroup analyses suggest these changes occur in patients with preoperative patella alta and/or patients who undergo medialization TTO. These data suggest that some distalization in patellar positioning may be achieved without formal distalization osteotomy.
What is the Association of the Subsections of the Oswestry Disability Index and Overall Improvement Two Years after Lumbar Surgery for Degenerative Lumbar Spondylolisthesis?
Authors: Hambrecht Jan , Köhli Paul , Duculan Roland , Lan Ranqing , Chiapparelli Erika , Guven Ali E. , Evangelisti Gisberto , Burkhard Marco D. , Tsuchiya Koki , Shue Jennifer , Sama Andrew A. , Cammisa Frank P. , Girardi Federico P. , Mancuso Carol A. , Hughes Alexander P.
Published: June 2024

Study Design.

Retrospective review of a prospective cohort study

Objective.

To identify the association between Oswestry Disability Index (ODI) subsections and overall improvement 2 years after lumbar surgery for degenerative lumbar spondylolisthesis (DLS).

Background.

DLS often necessitates lumbar surgery. The ODI is a trusted measure for patient-reported outcomes (PROMs) in assessing spinal disorder outcomes. Surgeons utilize the ODI for baseline functional assessment and post-surgery progress tracking. However, it remains uncertain if and how each subsection influences overall ODI improvement.

Methods.

This retrospective cohort study analyzed patients who underwent lumbar surgery for DLS between 2016 and 2018. Preoperative and 2-year postoperative ODI assessments were conducted. The study analyzed postoperative subsection scores and defined ODI improvement as ODIpreop-ODIpostop >0. Univariate linear regression was applied, and receiver operating characteristic (ROC) analysis determined cut-offs for subsection changes and postoperative target values to achieve overall ODI improvement.

Results.

265 patients (60% female, mean age 67±8 y) with a baseline ODI of 50±6 and a postoperative ODI of 20±7 were included. ODI improvement was noted in 91% (242 patients). Achieving a postoperative target score of ≤2 in subsections correlated with overall ODI improvement. Walking had the highest predictive value for overall ODI improvement (AUC 0.91, sensitivity 79%, specificity 91%). Pain intensity (AUC 0.90, sensitivity 86%, specificity 83%) and changing degree of pain (AUC 0.87, sensitivity 86%, specificity 74%) were also highly predictive. Sleeping had the lowest predictability (AUC 0.79, sensitivity 84%, specificity 65%). Except for sleeping, all subsections had a Youden-index >50%.

Conclusion.

These findings demonstrate how the different ODI subsections associate with overall improvement post-lumbar surgery for DLS. This understanding is crucial for refining preoperative education, addressing particular disabilities, and evaluating surgical efficacy. Additionally, it shows that surgical treatment does not affect all subsections equally.
Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration
Authors: Rehman Obaid Ur , Fatima Eeshal , Imran Hiba , Akram Umar , Ahmad Amna Badar , Nadeem Zain Ali , Fatima Laveeza , Hussain Ahmad , Mabrouk Manar Alaa , Farooq Muhammad Zain
Published: June 2024

Objective:

This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period.

Methods:

We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2).

Results:

After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P<0.0001, I
2=90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P<0.0001, I
2=80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P=0.02, I
2=0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P=0.77, I
2=30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P=0.26, I
2=10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P=0.50, I
2=0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P=0.0008, I
2=82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P=0.30, I
2=94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events.

Conclusion:

Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.
Hypofractionated Radiation Therapy
Authors: Ritter Alex R. , Prasad Rahul N. , Jhawar Sachin R. , Bazan Jose G. , Gokun Yevgeniya , Vudatala Sundari , Diaz Dayssy A.
Published: June 2024

Objectives:

For many malignancies, hypofractionated radiotherapy (HFRT) is an accepted standard associated with decreased treatment time and costs. United States provider beliefs regarding HFRT likely impact its adoption but are poorly studied. We surveyed US-based radiation oncologists (ROs) to gauge HFRT utilization rates for prostate (PC), breast (BC), and rectal cancer (RC) and to characterize the beliefs governing these decisions.

Methods:

From July to October 2021, an anonymized, online survey was electronically distributed to ROs actively practicing in the United States. Demographic and practice characteristic information was collected. Questions assessing rates of offering HFRT for PC, BC, and RC and perceived limitations towards using HFRT were administered.

Results:

A total of 203 eligible respondents (72% male, 72% White, 53% nonacademic practice, 69% with 11+ years in practice) were identified. Approximately 50% offered stereotactic body radiation therapy (SBRT) for early/favorable intermediate risk PC. Although >90% of ROs offered whole-breast HFRT for early-stage BC, only 33% offered accelerated partial-breast irradiation (APBI). Overall, 41% of ROs offered short-course neoadjuvant RT for RC. The primary reported barriers to HFRT utilization were lack of data, inexperience, and referring provider concerns.

Conclusions:

HFRT is safe, effective, and beneficial, yet underutilized—particularly prostate SBRT, APBI, and short-course RT for RC. Skills retraining and education of ROs and referring providers may increase utilization rates.
Optimization Strategies in CAR T-cell Therapy
Authors: Qureshi Zaheer , Altaf Faryal , Jamil Abdur , Siddique Rimsha
Published: June 2024

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for various hematological malignancies. Still, its remarkable efficacy is accompanied by unique adverse events that must be carefully managed. This comprehensive literature review evaluates the safety profile of CAR T-cell therapy, focusing on cytopenia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), and other potential complications. Cytopenia, characterized by reduced blood cell counts, affects a significant proportion of patients, with rates of anemia, neutropenia, and thrombocytopenia reaching up to 60%, 70%, and 80%, respectively. Risk factors include high tumor burden, prior chemotherapy, and bone marrow involvement. Cytokine release syndrome (CRS) occurs in 13% to 77% of patients and is linked to the cytokine storm induced by CAR T cells, target antigen expression, and preexisting immune dysregulation. Other notable adverse events discussed are cytokine release syndrome, neurotoxicity, and infections. Understanding the mechanisms, risk factors, and management strategies for these adverse events is crucial for optimizing patient outcomes and unlocking the full potential of this revolutionary therapy. The review highlights the need for continued research, interdisciplinary collaboration, and evidence-based approaches to enhance the safety and efficacy of CAR T-cell therapy.