bluuebunny/crossref_metadata_2025_split huggingface dataset:
In need of age‐appropriate cardiac models: Impact of cell age on extracellular matrix therapy outcomes
Authors: Ozcebe S. Gulberk , Zorlutuna Pinar 
Published: October 2023

AbstractAging is the main risk factor for cardiovascular disease (CVD). As the world's population ages rapidly and CVD rates rise, there is a growing need for physiologically relevant models of aging hearts to better understand cardiac aging. Translational research relies heavily on young animal models; however, these models correspond to early ages in human life, therefore cannot fully capture the pathophysiology of age‐related CVD. Here, we first investigated the transcriptomic and proteomic changes that occur with human cardiac aging. We then chronologically aged human induced pluripotent stem cell‐derived cardiomyocytes (iCMs) and showed that 14‐month‐old iCMs exhibited a similar aging profile to the human CMs and recapitulated age‐related disease hallmarks. Using aged iCMs, we studied the effect of cell age on the young extracellular matrix (ECM) therapy, an emerging approach for myocardial infarction (MI) treatment and prevention. Young ECM decreased oxidative stress, improved survival, and post‐MI beating in aged iCMs. In the absence of stress, young ECM improved beating and reversed aging‐associated expressions in 3‐month‐old iCMs while causing the opposite effect on 14‐month‐old iCMs. The same young ECM treatment surprisingly increased SASP and impaired beating in advanced aged iCMs. Overall, we showed that young ECM therapy had a positive effect on post‐MI recovery; however, cell age was determinant in the treatment outcomes without any stress conditions. Therefore, “one‐size‐fits‐all” approaches to ECM treatments fail, and cardiac tissue engineered models with age‐matched human iCMs are valuable in translational basic research for determining the appropriate treatment, particularly for the elderly.
Differential sperm histone retention in normozoospermic ejaculates of infertile men negatively affects sperm functional competence and embryo quality
Authors: Pandya Riddhi Kirit , Jijo Ameya , Cheredath Aswathi , Uppangala Shubhashree , Salian Sujith Raj , Lakshmi Vani R , Kumar Pratap , Kalthur Guruprasad , Gupta Sanjay , Adiga Satish Kumar 
Published: October 2023

AbstractBackgroundThe unique epigenetic architecture that sperm cells acquire during spermiogenesis by retaining <15% of either canonical or variant histone proteins in their genome is essential for normal embryogenesis. Whilst heterogeneous levels of retained histones are found in morphologically normal spermatozoa, their effect on reproductive outcomes is not fully understood.MethodsProcessed spermatozoa (n = 62) were tested for DNA integrity by sperm chromatin dispersion assay, and retained histones were extracted and subjected to dot‐blot analysis. The impact of retained histone modifications in normozoospermic patients on sperm functional characteristics, embryo quality, metabolic signature in embryo spent culture medium and pregnancy outcome was studied.ResultsDot‐blot analysis showed heterogeneous levels of retained histones in the genome of normozoospermic ejaculates. Post‐wash sperm yield was affected by an increase in H3K27Me3 and H4K20Me3 levels in the sperm chromatin (p < 0.05). Also, spermatozoa with higher histone H3 retention had increased DNA damage (p < 0.05). Spermatozoa from these cohorts, when injected into donor oocytes, correlated to a significant decrease in the fertilisation rate with an increase in sperm histone H3 (p < 0.05) and H3K27Me3 (p < 0.01). An increase in histone H3 negatively affected embryo quality (p < 0.01) and clinical pregnancy outcome post‐embryo transfer (p < 0.05). On the other hand, spent culture medium metabolites assessed by high‐resolution (800 MHz) nuclear magnetic resonance showed an increased intensity of the amino acid methionine in the non‐pregnant group than in the pregnant group (p < 0.05) and a negative correlation with sperm histone H3 in the pregnant group (p < 0.05).Discussion and conclusionHistone retention in spermatozoa can be one of the factors behind the development of idiopathic male infertility. Such spermatozoa may influence embryonic behaviour and thereby affect the success rate of assisted reproductive technology procedures. These results, although descriptive in nature, warrant further research to address the underlying mechanisms behind these clinically important observations.
Can 24 h of ambulatory ECG be used to triage patients to extended monitoring?
Authors: Johnson Linda S. , Måneheim Alexandra , Slusarczyk Magdalena , Grotek Agnieszka , Witkowska Olga , Bacevicius Justinas , Sörnmo Leif , Dziubinski Marek , Bhavnani Sanjeev , Healey Jeffrey S. , Engström Gunnar 
Published: October 2023

AbstractBackgroundAccess to long‐term ambulatory recording to detect atrial fibrillation (AF) is limited for economical and practical reasons. We aimed to determine whether 24 h ECG (24hECG) data can predict AF detection on extended cardiac monitoring.MethodsWe included all US patients from 2020, aged 17–100 years, who were monitored for 2–30 days using the PocketECG device (MEDICALgorithmics), without AF ≥30 s on the first day (n = 18,220, mean age 64.4 years, 42.4% male). The population was randomly split into equal training and testing datasets. A Lasso model was used to predict AF episodes ≥30 s occurring on days 2–30.ResultsThe final model included maximum heart rate, number of premature atrial complexes (PACs), fastest rate during PAC couplets and triplets, fastest rate during premature ventricular couplets and number of ventricular tachycardia runs ≥4 beats, and had good discrimination (ROC statistic 0.7497, 95% CI 0.7336–0.7659) in the testing dataset. Inclusion of age and sex did not improve discrimination. A model based only on age and sex had substantially poorer discrimination, ROC statistic 0.6542 (95% CI 0.6364–0.6720). The prevalence of observed AF in the testing dataset increased by quintile of predicted risk: 0.4% in Q1, 2.7% in Q2, 6.2% in Q3, 11.4% in Q4, and 15.9% in Q5. In Q1, the negative predictive value for AF was 99.6%.ConclusionBy using 24hECG data, long‐term monitoring for AF can safely be avoided in 20% of an unselected patient population whereas an overall risk of 9% in the remaining 80% of the population warrants repeated or extended monitoring.
The prophylactic value of TNF‐α inhibitors against retinal cell apoptosis and optic nerve axon loss after corneal surgery or trauma
Authors: Paschalis Eleftherios I. , Zhou Chengxin , Sharma Jyoti , Dohlman Thomas H. , Kim Sarah , Lei Fengyang , Chodosh James , Vavvas Demetrios , Urtti Arto , Papaliodis George , Dohlman Claes H. 
Published: October 2023

AbstractBackground and PurposeLate secondary glaucoma is an often‐severe complication after acute events like anterior segment surgery, trauma and infection. TNF‐α is a major mediator that is rapidly upregulated, diffusing also to the retina and causes apoptosis of the ganglion cells and degeneration of their optic nerve axons (mediating steps to glaucomatous damage). Anti‐TNF‐α antibodies are in animals very effective in protecting the retinal cells and the optic nerve—and might therefore be useful prophylactically against secondary glaucoma in future such patients. Here we evaluate (1) toxicity and (2) efficacy of two TNF‐α inhibitors (adalimumab and infliximab), in rabbits by subconjunctival administration.MethodsFor drug toxicity, animals with normal, unburned corneas were injected with adalimumab (0.4, 4, or 40 mg), or infliximab (1, 10, or 100 mg). For drug efficacy, other animals were subjected to alkali burn before such injection, or steroids (for control). The rabbits were evaluated clinically with slit lamp and photography, electroretinography, optical coherence tomography, and intraocular pressure manometry. A sub‐set of eyes were stained ex vivo after 3 days for retinal cell apoptosis (TUNEL). In other experiments the optic nerves were evaluated by paraphenylenediamine staining after 50 or 90 days. Loss of retinal cells and optic nerve degeneration were quantified.ResultsSubconjunctival administration of 0.4 mg or 4.0 mg adalimumab were well tolerated, whereas 40.0 mg was toxic to the retina. 1, 10, or 100 mg infliximab were also well tolerated. Analysis of the optic nerve axons after 50 days confirmed the safety of 4.0 mg adalimumab and of 100 mg infliximab. For efficacy, 4.0 mg adalimumab subconjunctivally in 0.08 mL provided practically full protection against retinal cell apoptosis 3 days following alkali burn, and infliximab 100 mg only slightly less. At 90 days following burn injury, control optic nerves showed about 50% axon loss as compared to 8% in the adalimumab treatment group.ConclusionsSubconjunctival injection of 4.0 mg adalimumab in rabbits shows no eye toxicity and provides excellent neuroprotection, both short (3 days) and long‐term (90 days). Our total. accumulated data from several of our studies, combined with the present paper, suggest that corneal injuries, including surgery, might benefit from routine administration of anti‐TNF‐α biologics to reduce inflammation and future secondary glaucoma.
LGBTQ+ new and expectant parents' experiences of perinatal services during the UK's first COVID‐19 lockdown
Authors: Greenfield Mari , Darwin Zoe 
Published: October 2023

AbstractBackgroundCOVID‐19 created specific challenges for new and expectant parents and perinatal services. Services changed rapidly in the United Kingdom (UK), including the withdrawal of home birth services, birth center closures, and restrictions on the number of birth partners allowed in the birth room. The purpose of this study was to examine how these changes affected the experiences of LGBTQ+ parents in the UK.MethodsAn online survey was conducted in April 2020 to provide real‐time data capture of new and expectant families' experiences. It was open to those in the third trimester, or to those who had given birth since the beginning of the first UK lockdown period, and their partners. The survey asked open‐ended questions about perinatal experiences. Demographic data were also collected, including sexual orientation and gender. Responses were collected from 1754 participants, including 76 who self‐identified as LGBTQ+.ResultsThematic analysis identified that LGBTQ+ new and expectant parents faced similar issues to cisgendered, heterosexual expectant parents, though additional concerns were also noted relating to support and recognition. Heterocentric policies negatively affect lesbian families. Non‐birthing co‐mothers feared invalidation as parents. Sexual minority pregnant women were more likely than heterosexual pregnant women to consider additional birth supporters and to consider freebirthing.DiscussionService changes introduced in the pandemic were cisheteronormative, creating additional challenges for LGBTQ+ new and expectant parents and compounding existing inequalities. When planning, changing, or evaluating perinatal services, specific consideration is needed to include birthing parents who are not mothers and mothers who did not give birth. If appropriate care is not available, consequences may include impaired perinatal wellbeing and restricted birth choices. Including sexual orientation and gender in data collection enables different perspectives to be considered.
Natural history of blood pressure in sickle cell disease pregnancy
Authors: Early Macy L. , Luo Amy , Solow Marissa , Matusiak Kristine , Eke Ahizechukwu C. , Shehata Nadine , August Phyllis , Kuo Kevin H. M. , Lanzkron Sophie , Malinowski Ann Kinga , Pecker Lydia H. 
Published: October 2023

SummaryIn this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD‐related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non‐SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSβ0 group than in the non‐SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSβ0 group and non‐SCD controls, whereas the mean SBP and DBP in the HbSC/HbSβ+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSβ0.
Exploring dual effects of dinutuximab beta on cell death and proliferation of insulinoma
Authors: Karatug Kacar Ayse 
Published: October 2023

AbstractInsulinoma INS‐1 cells are pancreatic beta cell tumors. Dinutuximab beta (DB) is a monoclonal antibody used in the treatment of neuroblastoma. The aim of this study is to investigate the effects of DB on pancreatic beta cell tumors at the molecular level. DB (Qarziba®) was available from EUSA Pharma. Streptozotocin (STZ) was used induce to cell cytotoxicity. DB was applied to the cells before or after the STZ application. KCND3, KCNN4, KCNK1, and PTHrP gene expression levels were analyzed by q‐RT‐PCR, and protein levels were analyzed by Western blotting. Analysis of glucose‐stimulated insulin secretion was performed. Ca+2 and CA19‐9 levels were determined by the ELISA kit. PERK, CHOP, HSP90, p‐c‐Jun, p‐Atf2, and p‐Elk1 protein levels were analyzed by simple WES. Decreased KCND3, KCNK1, and PTHrP protein levels and increased KCND3, KCNN4, KCNK1, and PTHrP gene expression levels were observed with DB applied after STZ application. Cell dysfunction was detected with DB applied before and after STZ application. Ca19‐9 and Ca+2 levels were increased with DB applied after STZ application. PERK, CHOP, and p‐Elk1 levels decreased, while HSP90 levels increased with DB applied after STZ application. CHOP, p‐Akt‐2, and p‐c‐Jun levels increased in the DB group. As a result, INS‐1 cells go to cell death via the ERK signaling pathway without ER stress and release insulin with the decrease of K+ channels and an increase in Ca+2 levels with DB applied after STZ application. Moreover, the cells proliferate via JNK signaling with DB application. DB holds promise for the treatment of insulinoma. The study should be supported by in vivo studies.
LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes
Authors: Li Yuqian , Zhang Qiang , Tan Qing , Sha Xuan , Gao Yang , Hua Rong , Zhou Ping , Wei Zhaolian , He Xiaojin , Cao Yunxia , Li Tao , Wu Huan 
Published: October 2023

AbstractAsthenozoospermia (AZS) is the primary cause of infertility in males. The radial spoke (RS) is an axonemal structure, connecting the peripheral doublet microtubules with the central pair of microtubules. This T‐shaped multiprotein complex functions as a mechanochemical sensor to promote sperm motility. LRRC23 is a novel subunit of the RS complex that is necessary for flagellar assembly and movement in mice. However, the importance of LRRC23 in modulating RS formation in humans remains unclear. Here, we identified a homozygous nonsense mutation in LRRC23 (c.376C>T:p. Arg126X) in an infertile AZS patient whose parents were consanguineous. We verified the adversity of this novel mutation because of its ability to disrupt LRRC23 synthesis and impair RSs integrity. Furthermore, we demonstrated an interaction between LRRC23 and RSPH3 in vitro, indicating that LCCR23 is associated with RS in humans. Meanwhile, the LRRC23‐mutant patient had a good prognosis following intracytoplasmic sperm injection. This study provides strong preliminary evidence that LRRC23 defects are potential causative factors of AZS in humans, which expands our knowledge for improved genetic counseling and better reproductive recommendations for patients with AZS.
Comparison of patient‐centered outcomes measures between low‐speed drilling without irrigation and high‐speed drilling with irrigation: A randomized clinical trial
Authors: Bernabeu‐Mira Juan Carlos , Peñarrocha‐Diago Miguel , Peñarrocha‐Diago María , Romero‐Gavilán Francisco , Camacho‐Alonso Fabio , Peñarrocha‐Oltra David 
Published: October 2023

AbstractObjectiveTo compare patient satisfaction during surgery, postoperative pain and inflammation and quality of life between high‐speed drilling with irrigation and low‐speed drilling without irrigation for implant bed preparation.Materials and MethodsSixty‐six posterior single edentulous patients were included in a randomized controlled clinical trial. Implant beds were created using high‐speed drilling with irrigation (control group) or low‐speed drilling without irrigation (test group). Patient satisfaction during surgery (in relation to drilling‐time perception, vibration, pressure, noise, comfort, and drowning sensation) and postoperative pain and inflammation were evaluated using a 100‐mm visual analogue scale (VAS)‐based questionnaire. Quality of life was analyzed with a Likert scale (in relation to mouth opening, chewing, speaking, sleeping, daily routine, and job). The follow‐up period was 7 days.ResultsPatient satisfaction in relation to drilling‐time perception, vibration, pressure, and noise did not show statistically significant differences (p > .05). The highest scores of drowning sensation (p < .05) were correlated (moderate correlation (r = .57)) with lowest scores of comfort (p < .005). Both postoperative pain and inflammation means were significantly higher in the control group than in the test group. No significant differences in quality of life were observed during the postoperative period (p > .05).ConclusionLow‐speed drilling without irrigation for single implant site preparation was more comfortable for patients than high‐speed drilling with irrigation, due to the correlation between important drowning sensation and low perceived comfort. Postoperative pain and inflammation were lower for low‐speed drilling without irrigation. Further studies are needed to validate or refute these results.
Natural language processing for identification of refractory status epilepticus in children
Authors: Chafjiri Fatemeh Mohammad Alizadeh , Reece Latania , Voke Lillian , Landschaft Assaf , Clark Justice , Kimia Amir A. , Loddenkemper Tobias 
Published: October 2023

AbstractObjectivePediatric status epilepticus is one of the most frequent pediatric emergencies, with high mortality and morbidity. Utilizing electronic health records (EHRs) permits analysis of care approaches and disease outcomes at a lower cost than prospective research. However, reviewing EHR manually is time intensive. We aimed to compare refractory status epilepticus (rSE) cases identified by human EHR review with a natural language processing (NLP)‐assisted rSE screen followed by a manual review.MethodsWe used the NLP screening tool Document Review Tool (DrT) to generate regular expressions, trained a bag‐of‐words NLP classifier on EHRs from 2017 to 2019, and then tested our algorithm on data from February to December 2012. We compared results from manual review to NLP‐assisted search followed by manual review.ResultsOur algorithm identified 1528 notes in the test set. After removing notes pertaining to the same event by DrT, the user reviewed a total number of 400 notes to find patients with rSE. Within these 400 notes, we identified 31 rSE cases, including 12 new cases not found in manual review, and 19 of the 20 previously identified cases. The NLP‐assisted model found 31 of 32 cases, with a sensitivity of 96.88% (95% CI = 82%–99.84%), whereas manual review identified 20 of 32 cases, with a sensitivity of 62.5% (95% CI = 43.75%–78.34%).SignificanceDrT provided a highly sensitive model compared to human review and an increase in patient identification through EHRs. The use of DrT is a suitable application of NLP for identifying patients with a history of recent rSE, which ultimately contributes to the implementation of monitoring techniques and treatments in near real time.
Seasonally variable and sex‐specific motivation for cooperative resource defence in a duetting songbird—The Chubb's cisticola
Authors: Budka Michał , Kokociński Patryk , Osiejuk Tomasz Stanisław 
Published: October 2023

AbstractDuets are one of the most complex forms of acoustic displays, involving two individuals vocalising in a coordinated way to defend resources cooperatively. However, motivation to defend resources may be sex specific and variable in time and space, which should be reflected in the changes in duet singing behaviour. We experimentally examined whether the motivation to defend resources is sex specific and seasonally variable in an Afrotropical, sedentary songbird living in pairs or small groups—the Chubb's cisticola. We broadcasted songs of males, females and duets in a random order, both at the beginning and the end of the breeding season. We quantified the birds' responses from the perspective of the entire group as well as its individual members. We found cooperative responses to each type of intruder, with the birds flying and singing. Groups consisting of two to four individuals responded significantly more strongly towards intrusions by females than pairs, and at the beginning than at the end of breeding season. Solo syllables comprised less than 4% of all recorded syllables, and in most cases were sung within a song also containing duet and chorus syllables (only 12 from 1773 songs analysed were solo songs). Males sang solo syllables more often than females (83% vs. 17% of all solo syllables) and did it significantly more often towards intruding females than males or pairs. The number of solo syllables sung by females was independent of treatment and season. Together, our results suggests that Chubb's cisticola uses duets to cooperatively defend resources located within its territory, but the intensity of reaction is sex specific and seasonally variable. We suggest that defended resources could be mates, group stability or reproductive effort. Looking at the function of duets from the perspective of the group and its particular members, various stages of the season and different resources defended by birds allow for a better understanding of cooperative singing.
Explaining Ukraine's resilience to Russia's invasion: The role of local governance
Authors: Rabinovych Maryna , Brik Tymofii , Darkovich Andrii , Savisko Myroslava , Hatsko Valentyn , Tytiuk Serhii , Piddubnyi Igor 
Published: October 2023

AbstractResilience of local communities (territorial hromadas) is an increasingly salient matter in the academic and policy debate on the factors which have determined Ukraine's resilience to Russia's 2022 invasion. Building on existing literature on institutional resilience and its predictors, this article explains the ability of Ukrainian self‐governed municipalities to withstand the threats to institutional stability stemming from the invasion. First, it uses an exploratory qualitative design to operationalize the concept of resilience and its predictors with an account of varying experiences of Ukrainian hromadas during the full‐scale invasion (e.g., hromadas near the frontline and in the rear). Next, it presents data from open sources and the results of a regression analysis to test the impact of various groups of predictors on hromadas' resilience to the full‐scale invasion. Our models show a significant relationship between hromadas' resilience and geographical, politico‐administrative and economic predictors influenced by the outcomes of the decentralization reform conducted in Ukraine since 2014.