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Simultaneous Administration of Human Papillomavirus (HPV) Vaccine With Other Recommended Vaccines Among Adolescents Aged 13-17 years, National Immunization Survey-Teen (NIS-Teen), United States, 2023.

PURPOSE: To investigate the percent of adolescents who receive human papillomavirus (HPV) vaccine with one or more other vaccines recommended for adolescents in a single medical visit. METHODS: Data from the 2023 National Immunization Survey-Teen were analyzed. Timing of receipt of HPV vaccine, tetanus, diphtheria, and acellular pertussis vaccine (Tdap), quadrivalent meningococcal conjugate vaccine (MenACWY), and influenza vaccine was assessed using provider-reported vaccination histories. RESULTS: In 2023, among adolescents aged 13-17 years, 69.5% received HPV vaccine with one or more other vaccines recommended for adolescents in a single medical visit. In addition, 47.8% received specifically HPV vaccine, Tdap, and MenACWY together in a single medical visit. DISCUSSION: The HPV vaccine is commonly given with other vaccines recommended for adolescents in a single medical visit. These findings demonstrate variation in simultaneous vaccination patterns, suggesting that flexibility in the recommended adolescent vaccination schedule allows for different approaches to vaccination across clinical settings and family preferences while maintaining adherence to the recommended schedule.

Humans

Instruments for measuring body image in breast cancer patients: a systematic review of measurement properties.

PURPOSE: To evaluate the psychometric properties of PROMs for measuring body image in breast cancer patients. METHODS: In December 2024, a psychometric systematic review was performed in the nine databases. The COSMIN checklist was employed to evaluate the methodological quality and psychometric properties of the included body image measures. The level of evidence was assessed using the GRADE framework, and final recommendations were formulated for the scale. RESULTS: Thirty-eight articles evaluating fifteen PROMs were included in this review. Structural validity, internal consistency, and hypothesis testing had been most frequently evaluated. Measurement error had not been assessed for all PROMs. Twelve instruments show potential application value but require further research. The BAS-BC, PSPP, and ASI-R are not recommended for use, as these instruments do not meet the strict COSMIN thresholds for full recommendation. CONCLUSION: The BIS can be recommended as a temporary screening tool for assessing body image outcome in clinical practice. The BIRS can be tentatively advised for measuring specific postoperative body image changes. However, further comprehensive studies are required to validate the psychometric properties of existing PROMs.

Female

Assessing the Frequency of VEXAS-Related Canonical UBA1 Mutations in Myelodysplastic Syndrome Patients.

OBJECTIVES: Somatic mutations in the UBA1 gene cause VEXAS syndrome, which presents with inflammatory and hematological symptoms. Case studies show a strong overlap between VEXAS and myelodysplastic syndrome (MDS). Recognizing VEXAS is important for differential diagnosis in patients with both inflammation and MDS, as accurate identification guides treatment. The study focuses on determining how often canonical UBA1 mutations linked to VEXAS occur in MDS patients. METHODS: Patients diagnosed with MDS were enrolled in the study, and genomic DNA was isolated from bone marrow FFPE samples. Molecular analysis was performed using a specifically designed ARMS-PCR approach. Additionally, protein-protein interaction (PPI) studies combined with bioinformatic analyses were carried out to explore potential links between UBA1 and pyroptosis. RESULTS: Among the 149 MDS patients analyzed, none exhibited high-Variant Allele Frequency (VAF) the canonical UBA1 point mutations linked to VEXAS syndrome. PPI analysis revealed a possible association between UBA1 and the NLRP3 inflammasome component. CONCLUSIONS: Expanding the sample size and using targeted NGS or ddPCR would improve mutation detection sensitivity and could reveal UBA1 canonical and non-canonical variants and more accurately estimate the frequency of VEXAS-related mutations in the MDS population.

Humans

A profile of abandoned fetal and neonatal remains admitted to the Diepkloof forensic pathology service medico-legal mortuary during the COVID-19 and post-COVID-19 periods.

The abandonment of neonates is a global concern, with a higher prevalence of cases present in South Africa. This study aimed to review cases admitted to the Diepkloof Forensic Pathology Service during the COVID-19 (2020-2021) and post-COVID-19 (2023) periods. A total of 158 cases were analysed to determine prevalence, demographic characteristics, circumstances and causes of death, with a comparative analysis between the COVID-19 and post-COVID-19 periods. Most cases were classified as natural. However, many were undetermined due to decomposition. Non-viable fetuses (< 26 wk gestation) comprised 47% of the cases. Among the viable births (n&#x2009;=&#x2009;72), 23 (32%) were classified as stillbirths, while 11 (15%) were live births. A minority of cases were deemed unnatural, with deaths attributed to trauma (8 cases) or abandonment (2 cases). No statistically significant difference was found between the COVID-19 and post-COVID-19 periods. Decedents were most often found in open spaces, roads or streets, or dumping sites, most commonly wrapped in plastic materials. These findings highlight the severity of fetal and neonatal abandonment. They underscore a pressing need for targeted preventative measures, community outreach, and enhanced support systems in maternal healthcare to address this growing concern.

Humans

Comparison of conventional and micro-surgical techniques for gingival recession using collagen matrix: Randomised controlled split-mouth clinical trial.

BACKGROUND: The present study aimed to determine the effectiveness of the microsurgical approach in treating gingival recession with collagen matrix by comparing it with Conventional surgery in terms of clinical and patient-centered outcomes. METHODS: A total of 29 patients with bilateral gingival recession in the maxillary canine and/or premolar region were selected. After randomisation, bilateral recession sites were grouped into the test group (Microsurgery under 3.5 X magnification) and the control group (Conventional surgery). All the clinical and patient-reported parameters were recorded at baseline, 1, 3 and 6 months. RESULTS: Both groups showed statistically significant differences in terms of reduction in gingival recession height (GRH), gingival recession width (GRW), clinical attachment level gain (CAL gain), increase in keratinized tissue thickness (KTT) and keratinized tissue width (KTW) after 6 months. But intergroup comparison showed no significant difference in terms of clinical parameters. The only significant difference was noted in terms of patient-centred parameters (Patient satisfactory score, Hypersensitivity score, Root aesthetic scores), which favoured the microsurgical group. CONCLUSIONS: Both groups demonstrated comparable clinical improvement; However, Patient-centred parameters were significantly better with the Microsurgical approach. Selection of the surgical approach should balance patient needs with practical considerations like cost, time, and clinician proficiency.

Adult

Catecholaminergic Contributions to Inhibitory Control Following Physical Fatigue: Behavioral and Neurophysiological Findings.

Acute physical fatigue can impair cognitive control, yet its underlying neurochemical mechanisms remain unclear. This study investigated whether catecholaminergic modulation influences behavioral and neural markers of inhibitory control following physical fatigue. Eighteen healthy, recreationally active adults (9 males, 9 females; 23.4&#xa0;&#xb1;&#xa0;2.2&#xa0;years) completed a randomized, triple-blind, placebo-controlled crossover study. On separate visits, participants received methylphenidate (MPH; 20&#xa0;mg; a dopamine and noradrenaline reuptake inhibitor), reboxetine (REB; 8&#xa0;mg; a noradrenaline reuptake inhibitor), or placebo. Physical fatigue was induced by repeated bilateral leg extensions to task failure. Cognitive performance was assessed before and after physical fatigue using a Go/No-Go task with electroencephalographic recording. Behavioral outcomes included reaction time and accuracy, while event-related potentials measured neural stages of response execution and inhibition (N2 and P3). Mixed-effects models were used for statistical analysis. For No-Go trials, a significant MPH&#xa0;&#xd7;&#xa0;Time interaction was observed for accuracy (p&#xa0;=&#xa0;0.008), with improved post-fatigue performance following MPH administration (p&#xa0;=&#xa0;0.048). At the neural level, MPH was associated with shorter fronto-central No-Go N2 latency (p&#xa0;=&#xa0;0.038) and altered fatigue-related changes in No-Go P3 latency (p&#xa0;=&#xa0;0.047). REB did not produce comparable behavioral or neural effects. These findings provide pharmacological evidence that catecholaminergic mechanisms contribute to inhibitory control following physical fatigue. The differential effects of MPH and REB suggest that selective noradrenergic enhancement alone is insufficient to maintain inhibitory control following physical fatigue. Instead, the findings implicate broader&#xa0;dopaminergic and noradrenergic mechanisms, potentially involving alterations in the temporal dynamics of inhibitory processing. TRIAL REGISTRATION: (G095422N and identifier NCT05880342).

Adult

K-wire versus screw fixation in Scarf-Akin osteotomy for hallux valgus: A retrospective cohort study.

BACKGROUND: Retention of metal implants after Scarf-Akin osteotomy (SAO) may cause irritation and psychological discomfort, often necessitating a hardware removal procedure. This study aimed to introduce K-wire fixation, allowing for outpatient removal, and to compare it with screw fixation. METHODS: This retrospective study included 64 patients with hallux valgus, comprising 32 in the K-wire fixation group and 32 in the screw fixation group. Clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS), and patient satisfaction. Radiographic parameters included hallux valgus angle(HVA), intermetatarsal angle(IMA), and distal metatarsal articular angle(DMAA). RESULTS: Both groups showed significant clinical and radiographic improvement (P&#x202f;<&#x202f;0.01). No significant between-group differences were observed in the other clinical or radiographic outcomes (P&#x202f;>&#x202f;0.05). Treatment costs were significantly lower in the K-wire group (P&#x202f;<&#x202f;0.001). CONCLUSIONS: K-wire fixation provides clinical and radiographic outcomes comparable to screw fixation, while avoiding the need for an additional procedure to remove the implant. LEVEL OF EVIDENCE: Level III.

Humans

Effects of Cognitive Behavioral Couple Therapy With Integrated Mindfulness on Mindful Attention, Depressive Symptoms, and Dyadic Adjustment in Low-Income Couples: A Pilot Randomized Clinical Trial.

Psychosocial distress can exacerbate marital conflict, maladjustment, and mental health vulnerability. This pilot randomized clinical trial examined cognitive-behavioral couple therapy (CBCT) integrated with mindfulness in low-income Brazilian couples (per-capita household income up to one minimum wage). Thirty-four participants (17 heterosexual couples) were randomized (independent computer-generated sequence) to an experimental (n&#x2009;=&#x2009;16) or waitlist control group (n&#x2009;=&#x2009;18). We assessed dyadic adjustment, mindful attention, marital social skills, and depressive symptoms (R-DAS, MAAS, IHSC, BDI-II) at baseline, post-treatment, and 3-month follow-up. The intervention was eight 80-min conjoint sessions plus daily home exercises. Time&#x2009;&#xd7;&#x2009;group effects favored the experimental group for dyadic adjustment, mindful attention, and depressive symptoms (all p&#x2009;<&#x2009;0.001,&#x2009;=&#x2009;0.20-0.37), but not marital social skills (p&#x2009;=&#x2009;0.14). Because two outcomes differed at baseline, effects were confirmed with baseline- and dependence-adjusted sensitivity analyses. These findings provide preliminary evidence that CBCT with mindfulness may benefit disadvantaged couples.

Adult

Assessment of the Potential of Different Anthropometric Indices in Predicting the Risk of Diabetes and Associated Co-morbidities.

Diabetes, a chronic disorder, is showing a rapidly increasing trend globally. India holds the second position in the global diabetes epidemic. The present investigation is an assessment of different anthropometric measurements and their association with type 2 diabetes to determine their diagnostic potential for diabetes as well as its co-morbidities. In this cross-sectional study, we have measured anthropometric parameters and blood biomarkers in subjects with diabetes. We have presented the comparisons of cost- and time-effective anthropometric variable with costly and time-dependent biochemical variables in control and diabetic groups (n = 233/group). Correlations between anthropometric variables and biochemical measurements, as well as the diagnostic utility of anthropometric variables for diabetes, were evaluated. The diagnostic utility of anthropometric variables for diabetes was assessed through receiver operating characteristic (ROC) curves. Neck circumference, sagittal abdominal diameter (SAD), skinfold thickness, and body roundness index (BRI) displayed high specificity and diagnostic utility for diabetes, emphasizing their potential in predicting diabetes and the further development of metabolic syndrome. The study highlights the importance of cost- and time-effective anthropometric assessments in diabetes risk evaluation and calls for further research to elucidate this intricate relationship and develop personalized management strategies.

Humans

Blinding integrity in psychedelic research: Evidence from a comparative randomized controlled trial of psilocybin, MDMA, and methylphenidate in healthy volunteers.

Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced-choice substance guesses, certainty ratings, decision factors, and subjective substance effects, the analyses characterize blinding integrity and its relation to the substance experience. Results indicate that overall blinding was insufficient, with psilocybin showing the highest rates of functional unblinding, MDMA moderate levels, and methylphenidate the lowest. As an active placebo, methylphenidate provided more effective blinding for MDMA than for psilocybin. Incorporating certainty levels of substance guesses revealed a more differentiated pattern, with lower functional unblinding rates. Decision factors and subjective substance experiences were associated with phenomenological substance effects. Prior substance experiences did not influence accuracy of forced-choice substance guesses. These findings provide empirical guidance for the design and reporting of blinding procedures in psychedelic trials and underscore the value of systematic, multi-level assessment of blinding integrity.

Humans

Efficacy of targeted neuromodulation treatments: a clinical report.

BACKGROUND: Peripheral neuropathy is a debilitating condition characterized by chronic pain, numbness, tingling, burning, and tightness/swelling. Conventional therapies often focus on symptom management, and some patients experience chronic and refractory symptoms. RESEARCH DESIGN AND METHODS: This retrospective clinical analysis evaluated the clinical outcomes of neuromodulation neuropathy treatment using the NeuroGen-Series device in patients with diabetic peripheral neuropathy (DPN) or idiopathic peripheral neuropathy (IPN). 9,805 unique patients who underwent 133,741 treatments between 18 August 2017, and 23 July 2024, were analyzed. Patients were divided into treatment completers (&#x2265;24 sessions) and noncompleters (<24 sessions). Paired t-tests confirmed statistically significant reductions in pre- and post-treatment symptom scores (p&#x2009;<&#x2009;0.001). RESULTS: Among completers, symptom severity decreased by an average of 46.2%. Tingling and pain showed the greatest improvement, while tightness/swelling and numbness showed the least reduction. 64% of patients reported improvement after one session, and 84% reported improvement after 24 sessions. Nonresponders accounted for 5.8% of patients overall. Younger patients and those with higher initial symptom severity were more likely to discontinue treatment. CONCLUSIONS: Overall, neuromodulation treatment resulted in statistically significant reductions in symptom severity, though nonresponders and high attrition rate highlight the need for individualized treatment strategies and further investigation.

Humans

Access to maternity services for women asylum seekers and refugees: A transnational document analysis of international, European regional, and United Kingdom governance.

Women asylum seekers and refugees face persistent barriers to maternity care (antenatal, intrapartum and postnatal care) across high-income countries, yet the upstream governance shaping access remains under-examined. Although legally distinct, both groups share protection-seeking experiences and are addressed jointly in governance documents. This study examined and synthesised how international (macro), European regional (meso), and United Kingdom (UK, micro) governance documents frame and operationalise maternity service access. Sixty-four documents were analysed using the READ framework. Inductive analysis of macro and meso documents identified six access dimensions: universal coverage; cultural and linguistic adaptation; rights-based approaches; multi-agency collaboration; data, monitoring and accountability; and quality of care. These dimensions structured assessment of UK governance, with jurisdictions rated strong, moderate or weak. Alignment was fragmented: Wales, Scotland and Northern Ireland exempted asylum seekers from charging, whereas England retained charging provisions. Multi-agency collaboration was consistently articulated, yet none of the 35 UK government documents focused on maternity access for this population, and none required outcome monitoring disaggregated by asylum or refugee status. UK governance appears coordinated in form but fragmented in substance. UK-wide minimum standards and routine recording of these data, with safeguards against immigration-related use, could strengthen coherence and accountability and improve visibility of inequities.

Refugees

Cancer statistics for Asian American, Native Hawaiian, and Pacific Islander people, 2026.

BACKGROUND: Cancer statistics for Asian American and Native Hawaiian and Pacific Islander (NHPI) people are usually aggregated, masking substantial variation within this heterogeneous population. Herein, the American Cancer Society reports cancer incidence and survival for 8 Asian American and 3 NHPI ethnic groups. METHODS: The authors used population-based cancer registry data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program, for Asian American and NHPI ethnic groups from 2000 through 2022. RESULTS: During 2018-2022, overall cancer incidence ranged from 218.3 per 100,000 Kampuchean people to 474.5 per 100,000 Native Hawaiian people, which was 1.5 times higher than the rate for the aggregated Asian American and NHPI population (307.3 per 100,000). High incidence among Native Hawaiian people is largely driven by the highest rates of female breast, colorectal, and prostate cancers, whereas infection-related cancers were highest among Asian American ethnic groups. For example, liver and stomach cancer incidence is highest among Vietnamese (22.2 per 100,000) and Korean people (17.8 per 100,000), respectively, both of which were nearly twice that in Native Hawaiian people (12.9 and 9.6 per 100,000, respectively). Native Hawaiian and Samoan women are twice and 3 times as likely, respectively, to be diagnosed with uterine corpus cancer as aggregated Asian American and NHPI women or White women. Five-year relative survival ranges from 42% in Laotians to 74% in Asian Indians/Pakistanis, with largest differences for colorectal (43% in Laotians to 72% in Asian Indians/Pakistanis) and prostate (63% in Kampucheans to 97% in Japanese) cancers. CONCLUSIONS: Wide variation in cancer risk within the Asian American and NHPI population highlights the critical need for disaggregated data to effectively target cancer prevention and control interventions.

Adolescent

ENLIGHTENme: Translating the Benefits of Self-Administered Daytime Light Supplementation to Older Adults in the Real World.

Controlled studies have demonstrated that light supplementation benefits circadian entrainment, sleep and mood. Translating these findings into effective, real-world usage of light supplementation is, however, challenging because naturalistic and supplemental light exposure are shaped by personal habits and environmental light conditions. Bridging this translation gap is especially critical for older adults, given the reduced ocular light sensitivity associated with natural ageing, which exacerbates low daytime indoor light exposure in urban housing. We therefore set out to investigate the determinants of self-directed light supplementation in this population, and what the real-world feasibility and efficacy of daytime light supplementation is. We recruited 202 participants (63-92 years; 139 females) to our interventional, prospective, randomised study in three major EU cities at different latitudes (Amsterdam, Bologna, Tartu). Participants underwent a 2-week baseline assessment of light exposure, rest-activity patterns and sleep through wearables and daily diaries. Participants were then randomised to either 12 weeks of self-implemented indoor light supplementation using a lamp placed in their most frequently used room (>&#x2009;8000 melanopic EDI, N&#x2009;=&#x2009;98) or a no-intervention group. A subsequent 2-week reassessment showed that greater naturalistic light exposure was associated with increased daytime activity, consolidated wakefulness, better subjective sleep quality, and reduced metabolic disorder incidence. Individuals with lower naturalistic light exposure self-initiated earlier and longer indoor light supplementation across seasons, in which supplementation onset before 10:00 was associated with greater daytime activity and lower rest-activity fragmentation. These results confirm that this simple, non-pharmacological, and low-cost intervention has broad potential to support healthy ageing in urban settings.

Humans

CNOT1 is a potential YTHDF2 target that orchestrates maternal mRNA decay and zygotic genome activation during goat embryogenesis.

Timely and efficient degradation of maternal mRNA is essential for early embryonic development, which occurs from fertilization through the initiation of zygotic genome activation (ZGA). Yet, the regulatory mechanisms governing this process remain poorly characterized. In the present study, we investigated the function of CCR4-NOT transcription complex subunit 1 (CNOT1) during goat embryogenesis. We found that CNOT1 was upregulated during mammalian ZGA, and that its knockdown led to developmental arrest and a marked reduction in blastocyst formation. Moreover, CNOT1 knockdown impaired nascent RNA activity, resulting in 814 upregulated and 1014 downregulated genes, which were enriched for RNA splicing, regulation of chromosome organization, and RNA localization. RNA splicing analysis revealed differential splicing events in 2959 genes, of which 259 were downregulated following CNOT1 knockdown. Notably, CNOT1 was predicted to crosstalk with the m6A reader YTHDF2. Knockdown of YTHDF2 resulted in CNOT1 downregulation at the 8-cell stage in goats and increased transcription levels around polyadenylation sites during ZGA in mice. Together, these findings indicate that CNOT1 is a potential YTHDF2 target that orchestrates maternal mRNA decay and ZGA during goat embryogenesis. Our work provides new insight into the complex regulatory landscape underlying ZGA and may inform strategies to improve the efficiency of goat embryogenesis.

Animals

Implicit and explicit statistical learning in reading: Evidence from a randomized controlled-learning study and computational modeling.

A key challenge in reading acquisition is understanding how learners extract the complex probabilistic mappings between print, meaning, and sound. Statistical learning (SL) theory offers a mechanistic account of how such mappings are acquired, whether implicitly through exposure or explicitly through instruction. We conducted a randomized controlled-learning study in Chinese, a writing system characterized by multiple sub-lexical regularities linking orthography, semantics, and phonology. Ninety-five 2nd-3rd graders with or at risk for dyslexia were randomly assigned to one of three groups: an implicit-SL training group exposed to repeated lexical and sublexical orthography-semantics-phonology associations, an explicit-SL training group receiving the same input plus explicit instruction on the sublexical print-sound mapping, and a no-SL control group. Both SL groups outperformed controls on the characters they were trained on, as well as on untrained characters that required generalization. However, only the explicit group demonstrated abstraction of print-sound mapping to novel items. Neural network simulations further revealed distinct mechanisms supporting implicit and explicit SL, consistent with a dual-system account of reading acquisition. Together, these findings (1) clarify how implicit and explicit learning distinctly support the discovery of statistical structure in written language and (2) underscore the implicit-explicit dual learning mechanism underlying reading acquisition.

Humans

The Effect of Slow Deep Breathing Relaxation Exercise on Pain and Anxiety Levels During and Post-Chest Tube Removal After CABG.

Chest tube removal after coronary artery bypass graft is frequently reported by patients as stressful and painful, highlighting the need for effective nonpharmacological interventions. Slow deep breathing relaxation exercises (SDBREs) may serve as a simple nursing strategy to reduce discomfort. In this study, we aimed to evaluate the effect of SDBRE on pain and anxiety during and after chest tube removal following coronary artery bypass grafting in Nablus hospitals. An experimental design was used with 80 patients recruited from 2 hospitals. Participants were randomly assigned to either an intervention group (n = 40) that practiced SDBRE or a control group (n = 40) that received standard care. Data were collected through a self-administered questionnaire, the Numeric Pain Scale, and the Visual Anxiety Scale. Data collection occurred from March to October 2024. The intervention group reported significantly lower pain scores during removal (M: 5.325 vs 7.125, P < .001) and after removal (P < .001). Anxiety scores were significantly lower both during and after removal (P < .001). Pain correlated with duration, with more complex operations and prolonged chest tube insertion linked to higher scores. SDBRE significantly reduced pain and anxiety during and after chest tube removal, supporting its integration into routine postoperative nursing care.

Humans

Handle with care: packaging the oocyte epigenome for the next generation.

During oocyte growth, substantial epigenetic programming occurs to establish a distinctive epigenome including appropriately patterned DNA methylation and histone modifications. Oocyte epigenetic programming must be tightly spatiotemporally regulated to ensure that a wide variety of epigenetic modifiers correctly establish their respective modifications to mediate precise control of gene expression. Furthermore, epigenetic modifications in oocytes include canonical and non-canonical genomic imprints, which are transmitted through meiosis to offspring. Significantly, disruptions in oocyte epigenetic programming can cause aberrant developmental outcomes in the next generation mediated by altered imprinting. Polycomb repressive complex 2 is an important epigenetic modifier that establishes histone 3 lysine 27 trimethylation and non-canonical imprints during mouse oogenesis, which are important for normal offspring development. While it is widely recognised that altered oocyte epigenetic programming can disrupt offspring development, mechanisms controlling maternal epigenetic inheritance remain poorly understood. The possibility remains that non-canonical imprinting exists in humans, although this requires confirmation. This review discusses mouse and human oocyte epigenetic programming including interactions between various epigenetic modifiers and modifications that form the unique oocyte epigenome. Understanding how oocyte epigenetic programming is regulated will be crucial in discerning how changes to the oocyte epigenome can disrupt epigenetic memory and alter developmental outcomes in offspring.

Animals