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Background: Indonesia launched a nationwide school-based HPV immunization program in August 2023. Despite this, regional disparities in vaccine uptake persist. Therefore, we undertook a study in North Sumatra Province to assess HPV vaccination coverage and analyze the main factors affecting the uptake of HPV vaccination. Methods: This study employed a mixed-methods approach and was carried out in Medan and Deli Serdang of North Sumatra Province. Quantitative data were used to examine HPV coverage rates among school-aged girls in 2024, while qualitative interviews with parents, teachers, and health officers explored administrative, social, and behavioral barriers and facilitators. Results: In 2024, HPV vaccine coverage in Deli Serdang reached 62.09%, while Kota Medan lagged behind at just 27.20%. High-coverage schools in the Galang subdistrict benefited from proactive engagement between Puskesmas (community health clinics) and parents. In contrast, lower-coverage areas experienced logistical and communication challenges. Parents expressed a preference for face-to-face communication over written consent forms and emphasized the importance of clear, empathetic messaging. Conclusions: The stark contrast in coverage—particularly the low uptake in urban Kota Medan—highlights the need for more responsive and localized implementation strategies. Strengthening direct communication, addressing administrative inefficiencies, and fostering trust through tailored community engagement are critical. These findings suggest a need for targeted improvements in urban settings and further research across diverse regions to inform policy development and strategies for improved coverage of HPV vaccinations.

BackgroundPrimary biliary cholangitis (PBC) demonstrates significant geographical variability in its epidemiology. This systematic review and meta-analysis aim to provide an updated estimate of the global and temporal trends of the prevalence and incidence of PBC from 1976 to 2024.MethodsWe systematically searched three electronic databases from inception to 20th August 2024 to include all studies reporting the incidence or prevalence of PBC. The outcomes of interest were the prevalence and incidence of PBC. Subgroup analysis was performed by study type, study period, geographical region, sex, Human Development Index (HDI), method of diagnosis, and latitude. The temporal trend of PBC prevalence and incidence was analyzed using meta-regression. The study protocol was registered with PROSPERO (CRD42024595102).ResultsA total of 59 studies, encompassing 381 million participants and 129,455 patients with PBC across 25 countries were included. The pooled global prevalence of PBC was 18.1 cases per 100,000 people (95% CI: 14.6–22.0, I2=99.9%, 55 studies) among population-based studies with a low risk of bias. The incidence rate of PBC was 1.8 per 100,000 person-years (95% CI: 1.5–2.3, I2=99.6%, 46 studies). PBC prevalence was higher in countries with higher latitude, higher HDI, in America and amongst the female sex. PBC prevalence increases with latitude (below 30°: 6.8 per 100,000 people, 95%CI: 2.8–12.7; 30°-60°: 18.2 per 100,000 people, 95%CI: 14.6–22.2; >60°: 27.3 per 100,000 people, 95%CI: 15.2–42.8), p=0.0016, 54 studies). Meta-regression showed higher HDI was significantly associated with a higher prevalence of PBC (p=0.03). Temporal analysis showed that the global prevalence of PBC has increased over time, with the Western Pacific region experiencing the greatest rise in PBC prevalence over time. Both the funnel plot and Egger’s test showed no evidence of publication bias.ConclusionsThe rising prevalence of PBC represents a growing healthcare burden in the Western Pacific region. The positive association between latitude and PBC prevalence requires further studies.

Epigenetic mechanisms govern the transcriptional activity of lineage-specifying enhancers; but recent work challenges the dogma that joint chromatin accessibility and DNA demethylation are prerequisites for transcription. To understand this paradox, we established a highly-resolved timeline of DNA demethylation, chromatin accessibility, and transcription factor occupancy during neural progenitor cell differentiation. We show thousands of enhancers undergo rapid, transient accessibility changes associated with distinct periods of transcription factor expression. However, most DNA methylation changes are unidirectional and delayed relative to chromatin dynamics, creating transiently discordant epigenetic states. Genome-wide detection of 5-hydroxymethylcytosine further revealed active demethylation begins ahead of chromatin and transcription factor activity, while enhancer hypomethylation persists long after these activities have dissipated. We demonstrate that these timepoint specific methylation states predict past, present and future chromatin accessibility using machine learning models. Thus, chromatin and DNA methylation collaborate on different timescales to mediate short and long-term enhancer regulation during cell fate specification.

Background. A patient- and assessor-blinded randomized controlled trial was conducted to examine the effectiveness of auricular transcutaneous electrical nerve stimulation (TENS) in relieving posthysterectomy pain. Method. Forty-eight women who had undergone a total abdominal hysterectomy were randomly assigned into three groups (n=16 each) to receive either (i) auricular TENS to therapeutic points (the true TENS group), (ii) auricular TENS to inappropriate points (the sham TENS group), or (iii) 20 minutes of bed rest with no stimulation (the control group). The intervention was delivered about 24 hours after the operation. A visual analogue scale was used to assess pain while resting (VAS-rest) and upon huffing (VAS-huff) and coughing (VAS-cough), and the peak expiratory flow rate (PEFR) was assessed before and at 0, 15, and 30 minutes after the intervention. Result. As compared to the baseline, only the true TENS group reported a significant reduction in VAS-rest (P=.001), VAS-huff (P=.004), and VAS-cough (P=.001), while no significant reduction in any of the VAS scores was seen in the sham TENS group (all P>.05). In contrast, a small rising trend was observed in the VAS-rest and VAS-huff scores of the control group, while the VAS-cough score remained largely unchanged during the period of the study. A between-group comparison revealed that all three VAS scores of the true TENS group were significantly lower than those of the control group at 15 and 30 minutes after the intervention (all P<.02). No significant between-group difference was observed in PEFR at any point in time. Conclusion. A single session of auricular TENS applied at specific therapeutic points significantly reduced resting (VAS-rest) and movement-evoked pain (VAS-huff, VAS-cough), and the effects lasted for at least 30 minutes after the stimulation. The analgesic effects of auricular TENS appeared to be point specific and could not be attributed to the placebo effect alone. However, auricular TENS did not produce any significant improvement in the performance of PEFR.

To evaluate attitudes of Chinese patients towards day-case surgery. Prospective cross-sectional questionnaire survey. District public hospital, Hong Kong. Two hundred patients attending a preanaesthetic assessment clinic between 1 January and 30 June 2004 were invited to participate. Demographic profiles, understanding and attitudes towards day-case surgery, preference for day-case surgery before and after the experience, postoperative adverse effects, and patient satisfaction. The mean age of the patients was 28 (standard deviation, 19) years. In all 200 respondents completing the survey, 180 preferred day-case surgery. Important reasons for this view were: shorter duration of hospitalisation, dislike of hospital environments, belief that hospitals are highly infectious, need to look after their families, desire to return to work early, and doctors' advice. Small home environments and belief that day-case surgery was unsafe were not important. Respondents who did not prefer day-case surgery stressed the importance of better care available for hospital in-patients, concerns about surgical complications, postoperative nausea and vomiting, and doctors' advice. Only 11% patients complained of postoperative adverse effects. Demographic characteristics and previous day-case surgery experience did not have any effect on patient preferences. However, experiencing a postoperative adverse effect significantly affected the preference (P=0.005) and satisfaction (P=0.001) of respondents for day-case surgery. Local Chinese patients attending our institution have a high preference for day-case surgery. Postoperative adverse effects might influence the respondents' satisfaction and preference after their surgical experience.

The basic idea behind this volume is to probe the nature of grammaticalization. Its contributions focus on the following questions: (i) In how far can grammaticalization be considered a universal diachronic process or mechanism of change and in how far is it conditioned by synchronic factors? (ii) What is the role of the speaker in grammaticalization? (iii) Does grammaticalization itself provide a cause for change or is it an epiphenomenon, i.e. a conglomeration of causal factors/mechanisms which elsewhere occur independently? (iv) If it is epiphenominal, how do we explain that similar pathways so often occur in known cases of grammaticalization? (v) Is grammaticalization unidirectional? (vi) What is the nature of the parameters guiding grammaticalization? The overall aim of the book is to enrich our understanding of what grammaticalization does or does not entail via detailed case studies in combination with theoretical and methodological discussions.

The front feet of six adult free-ranging southern giraffe (Giraffa giraffa ) were opportunistically examined to characterize normal hoof anatomy, focusing on the corium (dermis), which provides vascular supply, metabolic support, and structural templates for the overlying epidermis that generates the keratinized hoof capsule. Gross dissection and histology identified two types of corium on the surface of the distal phalanx (Pd): laminae and papillae. On the parietal surface of Pd, laminae covered approximately its distal two-thirds and, as in other ruminants, secondary laminae were absent. Papillae varied regionally, with the longest and thickest located at the distal margins of Pd. On the solar surface, horn tubules were oriented obliquely in a palmar-proximal to dorso-distal direction. Within the hoof, the digital cushion consisted of a proximal adipose-rich region and a distal fibroelastic region. Histological findings were unremarkable and supported gross observations of normal anatomy. Examination of Pd and the navicular (distal sesamoid) regions revealed no evidence of pedal osteitis, navicular pathology, laminitis, or other lesions. These data provide a reference for normal giraffe foot anatomy and histology. Improved understanding of the corium and associated structures that support hoof capsule growth may inform preventative hoof care, reduce risk of overgrowth, and assist in managing lameness in both zoo-housed and free-ranging giraffe.

Background Effective clinician-patient communication is essential for delivering quality end-of-life care. However, there are no validated measures to assess the quality of end-of-life communication for Chinese patients. Methods This study aims to cross-culturally adapt and validate the patient-reported Quality of Communication Questionnaire (QOC) for Chinese speaking patients. The QOC was translated and adapted using a standardized methodology consisting of forward translations, backward translations, expert panel review, and testing with patients. We conducted a cross-sectional study to perform principal component, content validity, internal consistency, convergent and discriminant validity analyses of the 16-item Chinese QOC (C-QOC). Subjects were Chinese-speaking advanced cancer ( n  = 82) and advanced chronic kidney disease ( n  = 68) patients attending outpatient clinics in five hospitals or receiving home-based palliative care in Hong Kong. Results The content validity of the C-QOC was established by an expert panel. The C-QOC has a 3-component structure (general communication skills, communication about illness trajectory, and end-of-life care planning subscales) and demonstrated good internal consistency (Cronbach’s α = 0.88; subscales 0.84–0.90). Convergent validity was supported by positive association between C-QOC score and overall clinician communication quality ( r  = 0.47, p  < 0.001) and clinician comfort in discussing dying ( r  = 0.63, p  < 0.001). Discriminant validity was demonstrated by the stronger association between overall clinician communication quality and general communication skills, compared to the other two subscales. Conclusions The C-QOC is a valid, reliable, and culturally relevant instrument for evaluating the quality of clinician end-of-life care communication by Chinese patients with advanced cancer and chronic kidney disease.