bluuebunny/crossref_metadata_2025_split huggingface dataset:
A narrative review about the intricate crosstalk among endometrium, adipose tissue, and neurons in endometriosis. The multifaceted role of leptin
Authors: Neves Delminda , Neto Ana Catarina , Salazar Maria , Fernandes Ana Sofia , Martinho Margarida , Charrua Ana , Rodrigues Adriana Raquel , Gouveia Alexandra Maria , Almeida Henrique 
Published: December 2024

SummaryEndometriosis is a highly prevalent gynecological disease characterized by the presence of endometrium‐like tissue outside the uterus, whose etiopathology is far from being elucidated. The most frequent complains of patients are pelvic pain and infertility. Increasing evidence supports the systemic impact of endometriosis suggesting that an intricate crosstalk among distinct organs underlies the development of the disease. In this setting, endometriosis patients present an increased risk for developing other diseases, such as cancer, cardiovascular pathologies, and autoimmune diseases, and manifest neurologic disturbances, including neuropathic hyperalgesia. Whilst the ovary‐secreted estrogen dependency of ectopic endometrium growth is well established, we conjecture that adipose tissue‐secreted molecules also intervene in endometriosis development and pain manifestation. In fact, women with endometriosis present a peculiar pattern of adipokine secretion that ensues the disease onset. Unexpectedly, the levels of adipose tissue‐secreted molecules in those women present similarities with those found in patients with obesity, despite the recognized association of low body mass index with endometriosis. Taking this evidence into consideration, we hypothesize that endometriosis patients present a dysfunctional adipose tissue, which is associated with enhanced metabolism and unregulated browning that not only intervene in the control of body weight but also in peculiar pain processing pathways.
Phenotypic Spectrum of GNA11R183C Mosaicism
Authors: Zhang Donglin , Sánchez‐Espino Luis Fernando , Ivars Marta , Pope Elena , Nopper Amy J. , Arkin Lisa M. , Tollefson Megha M. , Lavarino Cinzia E. , Muldowney Maya , Olaciregui Nagore Gené , Paco Sonia , Drolet Beth A. , Baselga Eulàlia 
Published: December 2024

ABSTRACTBackgroundMany vascular anomalies harbor postzygotic somatic variants in GNAQ and GNA11; however, the phenotype of specific G‐protein variants has not been well described. We report the clinical characteristics of 17 patients with a GNA11 R183C variant.MethodsThis case series is derived from a multinational cohort of vascular anomaly patients whose pathogenic mutations were identified using high‐depth next generation sequencing. Data include vascular anomaly features, imaging reports, and extracutaneous manifestations of the GNA11 R183C variant.ResultsWe identified 17 subjects (median age 18 years [range 6–67]) with somatic GNA11 R183C variant. All patients had vascular lesions of the skin that presented as pink‐to‐red in children and deeper red in adults. Most lesions were large, poorly demarcated, and reticulated patches that were often bilaterally distributed. Nevus anemicus was observed in 53% (N = 9) and dermal melanocytosis in 13.3% (N = 2) of individuals. 82% (N = 14) of patients had limb growth discrepancies, and 1 patient had marked thoracic hypoplasia. 47% (N = 8) of patients had facial involvement, and 41% (N = 7) had forehead involvement. One patient experienced seizures due to right hemispheric leptomeningeal angiomatosis consistent with Sturge–Weber syndrome. Other findings included glaucoma (29%, N = 5) and psychomotor delay (29%, N = 5).ConclusionThese findings contribute to our understanding of the clinical spectrum of GNA11 R183C capillary malformations (CMs); patients characteristically present with extensive, bilateral, poorly demarcated, pink‐to‐red CMs associated with nevus anemicus. Glaucoma and growth discrepancies (overgrowth or undergrowth) are common. Leptomeningeal angiomatosis and developmental delay can occur, appearing potentially less prevalent and severe than GNAQ‐associated disease.
Spectrum of bacterial keratitis at a tertiary eye center in Indonesia
Authors: Lutfiamida Rifna , Widyasari Rien , Kalandra Kara Citra 
Published: December 2024

ABSTRACT

The purpose of this study is to analyze the bacterial spectrum and antibiotic susceptibility patterns in bacterial keratitis at a tertiary eye center in Jakarta, Indonesia. The study design is a retrospective analytic study. A retrospective cross-sectional analytic review of medical records was conducted for patients with bacterial keratitis who underwent corneal cultures over an 8-year period. The study exclusively included eyes with culture-positive bacterial keratitis. The data were divided into two distinct periods: January 2012 to December 2017 and January 2018 to June 2020. A total of 129 eyes with keratitis were examined, and culture-positive bacteria were found in 74 eyes. Gram-negative bacteria were identified in 65 eyes (69.1%), and Gram-positive bacteria were identified in 29 eyes (30.9%). The most common bacteria identified was
Pseudomonas aeruginosa
(34 positive cultures, 36.2%). Gram-negative bacteria had the highest susceptibility toward ceftazidime (94.7%; 95% CI, 88.9–100). Gram-positive bacteria had the highest susceptibility toward vancomycin (100%; 95% CI, 98.8–100). Gentamicin demonstrated broad sensitivity across all bacterial types (85.7%; 95% CI, 78.2–93.2%), surpassing fluoroquinolones. There were no significant changes in antibiotic susceptibility patterns between the two periods studied (
P
> 0.05). The stability observed in both the bacterial spectrum and antibiotic susceptibility patterns throughout the study period indicates that the current empirical treatment is still effective. However, the results highlight gentamicin as a highly valuable option for the empirical treatment of bacterial keratitis, while targeted treatment with ceftazidime should be considered for Gram-negative infections and vancomycin for Gram-positive infections when culture results are available.

IMPORTANCE
Bacterial keratitis poses a significant public health concern in Indonesia due to its potential for vision loss and morbidity. Understanding the spectrum of bacterial pathogens causing keratitis is crucial for guiding appropriate treatment strategies and improving patient outcomes. This study aims to investigate the prevalence, antibiotic susceptibility patterns, and risk factors associated with bacterial keratitis cases, providing valuable insights for clinicians to optimize management protocols and enhance the overall ocular health landscape in Indonesia or in other countries that have similar geographical conditions.
Palmitoleic acid sensitizes vancomycin-resistant
Staphylococcus aureus
to vancomycin by outpacing the expression of resistance genes
Authors: Tabashsum Zajeba , Angeles-Solano Michelle , Sidders Ashelyn E. , Parsons Joshua B. , Rowe Sarah E. 
Published: December 2024

ABSTRACT

The rise in antibiotic resistance limits the availability of antibiotics to treat bacterial infections. Despite this, antibiotic development pipelines remain sparse which makes using adjuvants to reverse antibiotic resistance a promising therapeutic strategy. The use of vancomycin, a frontline antibiotic used to treat hospitalized patients with methicillin-resistant
Staphylococcus aureus
(MRSA) infections, is complicated by high rates of treatment failure. Vancomycin binds to the D-ala-D-ala terminus of the nascent peptidoglycan precursor lipid II, preventing cell wall biosynthesis. Vancomycin-resistant strains of
S. aureus
and
Enterococci
typically express a
van
gene cluster that is induced in response to vancomycin and results in the synthesis of an alternative lipid precursor with a peptide chain ending in D-ala-D-lac. Vancomycin has low affinity for the D-ala-D-lac terminus, and the bacteria can resume growth even in the presence of an otherwise lethal dose of vancomycin. We previously showed that palmitoleic acid, a host-produced monounsaturated fatty acid, combined with vancomycin led to an accumulation of large fluid patches in the bacterial membrane, resulting in membrane destabilization and cell death. In this study, we observed that palmitoleic acid increases the rate of vancomycin killing by more than 50-fold, compared to vancomycin alone. This rapid bactericidal activity by the combined treatment sensitized vancomycin-resistant
S. aureus
(VRSA) and vancomycin-resistant
Enterococcus
(VRE) to vancomycin, likely by outpacing the expression of vancomycin resistance genes. This study represents an important step in the ongoing effort to mitigate antibiotic resistance.

IMPORTANCE

The development of antibiotics has transformed medicine, reducing the incidence and severity of bacterial infections and allowing for advancements in healthcare, including invasive surgeries and organ transplants. However, the rise of antibiotic resistance poses a significant threat to these medical advancements, leading to treatment failures that result in increased patient morbidity and mortality, as well as substantial healthcare costs. Vancomycin-resistant
Enterococcus
(VRE) species are prevalent in hospital settings and chronic infections. Although high-level vancomycin resistance in
S. aureus
is rare,
S. aureus
can acquire plasmids expressing vancomycin resistance genes from resistant Enterococcal species during infection, further complicating treatment. In this study, we find that palmitoleic acid increases the rate of vancomycin killing and restores sensitivity to vancomycin-resistant
S. aureus
(VRSA) and VRE isolates.
Infection of nonclassic monocytes by respiratory syncytial virus induces an imbalance in the CD4
+
T-cell subset response
Authors: Han Lianlian , Li Danyang , Wang Conghui , Ren Lili , Guo Li , Wang Jianwei 
Published: December 2024

ABSTRACT

Respiratory syncytial virus (RSV) causes lower respiratory tract infections in infants and young children, leading to a pathogenesis-associated imbalance in CD4
+
T-cell subsets and monocyte subsets. To investigate whether RSV affects the imbalance of CD4
+
T-cells through monocytes, we examined the effects of the RSV-infected monocyte subset on CD4
+
T-cell subsets, namely, Th1, Th2, Th17, and regulatory T (Treg) subsets, on proliferation
in vitro
and identified key monocyte-derived cytokines. We found that RSV efficiently infects CD16
+
monocytes, but not CD16
-
monocytes,
via
cocultures of CD4
+
T-cells with RSV-infected CD16
+
monocytes, inhibits Treg cell proliferation and increases Th2 cell frequency, suggesting that RSV causes an imbalance in the CD4
+
T-cell subset by primarily infecting CD16
+
monocytes. Our data also revealed that IL-1β and IL-10 are key cytokines responsible for the activities of RSV-infected CD16
+
monocytes. In a mouse model, we found that high-efficiency RSV infection of mouse Ly6C
-
monocytes, corresponding to CD16
+
monocytes in humans, and adoptive transfer of Ly6C
-
monocytes during RSV infection decreased the Treg frequency in the lungs and aggravated pneumonia. Our data indicate that RSV can increase its pathogenesis through infection of nonclassic monocytes, leading to a CD4
+
T-cell imbalance.

IMPORTANCE

This study identified a pathogenesis pathway related to the RSV-nonclassic monocyte–IL-1β/IL-10-CD4
+
T-cell subset balance, which links the heterogeneity of monocytes to RSV pathogenesis and elucidates a new mechanism by which RSV infection disrupts the balance of CD4
+
T cells during RSV infection. These new findings provide potential therapeutic targets for RSV infection.
Access to and utilisation of COVID-19 antigen rapid diagnostic tests (Ag-RDTs) among the general population in Phnom Penh: a cross-sectional study
Authors: Seang Kennarey , Vogt Florian , Ky Sovathana , Ouk Vichea , Kaldor John , Vallely Andrew John , Saphonn Vonthanak 
Published: December 2024

ObjectivesGlobally, there is a lack of evidence regarding access to and utilisation of antigen rapid diagnostic tests (Ag-RDTs). This might hinder public health interventions to increase testing. We conducted a survey to understand access to and utilisation of COVID-19 Ag-RDT among residents in Phnom Penh, Cambodia.DesignThis is a representative household survey using linear regression models with random effects to account for clustering and a logistic model with random effects to assess factors associated with Ag-RDT access.SettingWe conducted the study in 10 villages in Phnom Penh between August and mid-September 2022.ParticipantsWe enrolled one member per household (n=280), aged between 18 and 65 years.Outcome measuresBoth access and utilisation were defined at the individual level (self-reports). We defined access as having undergone COVID-19 rapid testing within 6 months and utilisation as having administered this test (to themselves or others) within 12 months, prior to the study interview.ResultsIn a clustering-adjusted linear model, access to Ag-RDTs among the general population from the 10 villages was 34% (n=95) and utilisation was 28% (n=77). Price and advice from the pharmacist were commonly reported to be the main selection criteria for Ag-RDTs, with 41% (n=111) and 62% (n=175), respectively. In the logistic model, those with higher educational attainment were more likely to have access to the Ag-RDT compared with those with lower education levels (adjusted OR4.42, 95% CI 1.82 to 10.74).ConclusionsUnfamiliarity with Ag-RDT tests and low education levels negatively affect access and utilisation of Ag-RDTs among the general population in Phnom Penh.
Promoting Intensive Transitions for Children and Youth with Medical Complexity from Paediatric to Adult Care: the PITCare study—protocol for a randomised controlled trial
Authors: Santos Sara , Thomson Donna , Diaz Sanober , Soscia Joanna , Adams Sherri , Amin Reshma , Bernstein Stacey , Blais Brenda , Bruno Natasha , Colapinto Kimberly , Espin Sherry , Fayed Nora , Greenaway Jon , Henze Megan , Ivers Noah M , LeGrow Karen , Lim Audrey , Lippett Robyn , Lunsky Yona , Macarthur Colin , Mahant Sanjay , Malecki Sarah , Miranda Susan , Moharir Mahendranath , Moretti Myla E , Phillips Lacey , Robeson Paula , Taryan Monica , Thorpe Kevin , Toulany Alene , Vandepoele Eryn , Weitzner Brenda , Orkin Julia , Cohen Eyal 
Published: December 2024

IntroductionChildren with medical complexity (CMC) have chronic, intensive care needs managed by many healthcare practitioners. Medical advances have enabled CMC to survive well into adulthood. However, the availability of supports as CMC transition into the adult care system remain suboptimal, contributing to poor care coordination, and discontinuity. Promoting Intensive Transitions for Children and Youth with Medical Complexity from Paediatric to Adult Care (PITCare) aims to assess whether intensive patient and caregiver-oriented transition support beyond age 18 will improve continuity of care for CMC compared with usual care.Methods and analysisThis is a pragmatic superiority randomised controlled trial in a parallel group, two-arm design with an embedded qualitative component. CMC turning 17.5 years old will be recruited (n=154), along with their primary caregiver. Participants randomised to the intervention arm will be provided with access to a multidisciplinary transition team who will support patients and caregivers in care planning, integration with an adult primary care provider (PCP), adult subspecialty facilitation and facilitation of resource supports for 2 years. Outcomes will be measured at baseline, 12 and 24 months. The primary outcome measure is successful transfer completion, defined as continuous care in the 2 years after age 18 years old. Secondary outcomes include satisfaction with transitional care, self-management, care coordination, healthcare service use, caregiver fatigue, family distress, utility and cost-effectiveness. Qualitative interviews will be conducted to explore the experiences of patients, caregivers, the transition team, and healthcare providers with the PITCare intervention.Ethics and disseminationInstitutional approval was obtained from the Hospital for Sick Children Research Ethics Board. Our findings and resources will be shared with child health policymakers and transitions advocacy groups provincially, nationally, and internationally.Trial registration numberClinicalTrials.gov, US National Library of Medicine, National Institutes of Health, #NCT06093386.
Service availability and readiness to provide maternal and newborn healthcare services in Kilimanjaro region, Tanzania: a cross sectional study
Authors: Kimario Agathon Avelin , Mahmoud Ashraf , Thomas Jonaviva A , Mallilah Benardine P , Mlay Pendo S , Olomi Gaudensia , Mmbaga Blandina 
Published: December 2024

ObjectiveTo assess service availability and readiness of health facilities to provide maternal and newborn care in the Kilimanjaro region, northern Tanzania: a study conducted between August to October 2022.DesignThe study used a cross-sectional design by adopting WHO Service Availability and Readiness Assessment tool to assess basic maternal, newborn and child health services delivery in the health facilities of the Kilimanjaro region.SettingThe study was conducted in seven districts of Kilimanjaro region at health facilities with a labour ward and where delivery and maternal services for women and neonatal care were offered.ParticipantsThe study included all district hospitals, two selected health centres and two dispensaries within every district with high utilisation of delivery services as well as the regional hospital of Kilimanjaro region making a total of 37 health facilities that were assessed.Primary outcomeBasic emergency obstetric and newborn care (BEmONC) service availability, BEmONC service readiness, comprehensive emergency obstetric and newborn care (CEmONC) service availability and CEmONC service readiness.ResultsA total of 37 facilities were enrolled that included 14 dispensaries, 14 health centres, 8 district hospitals and 1 regional hospital. The study highlights that majority of the signal functions are available in all levels of health facilities with overall readiness scores in BEmONC and CEmONC being 83% and 98.87%, respectively. However, the study reports that 40.5% of health facilities do not conduct death reviews. Similarly, on-job trainings regarding maternal and newborn healthcare was low, with only 29.8% of all healthcare workers in the region received training for the past 2 years.ConclusionDespite progress, challenges persist in delivering tailored maternal and newborn healthcare services in Kilimanjaro region. The study revealed strong readiness in essential care functions, but shortcomings in maternal and neonatal death reviews and training, emphasise the need for improved practices to further enhance maternal and newborn health outcomes.
Cost-effectiveness of long-acting progestogens versus the combined oral contraceptives pill for preventing recurrence of endometriosis-related pain following surgery: an economic evaluation alongside the PRE-EMPT trial
Authors: Melyda Melyda , Monahan Mark , Cooper Kevin G , Bhattacharya Siladitya , Daniels Jane P , Cheed Versha , Middleton Lee , Roberts Tracy E 
Published: December 2024

ObjectivesTo evaluate the cost-effectiveness of long-acting progestogens (LAP), including levonorgestrel-releasing intrauterine system (LNG-IUS) and depot-medroxyprogesterone acetate (DMPA), compared with the combined oral contraceptives pill (COCP) in preventing recurrence of endometriosis-related pain postsurgery.DesignWithin-trial economic evaluation alongside a multicentre, pragmatic, parallel-group, open-label, randomised controlled trial (Preventing Recurrence of Endometriosis by means of Long-Acting Progestogen Therapy trial).SettingThirty-four UK hospitals recruiting participants from November 2015 to March 2019.PatientsFour hundred and five women aged 16–45 years undergoing conservative endometriosis surgery.InterventionsThe ratio of 1:1 randomisation to receive LAPs (LNG-IUS or DMPA) or COCP.Main outcome measuresThe primary evaluation was a cost-utility analysis based on cost per quality-adjusted life-year (QALY) gained at 3 years. We adopted a UK National Health Service perspective. Secondary analyses in the form of cost-effectiveness analysis based on a range of outcomes were also undertaken.ResultsFor the primary analysis, the COCP group incurred an additional cost of £533 (95% CI £52 to £983) per woman compared with LAPs. Treatment with COCP generated additional QALYs of 0.031 (95% CI −0.079 to 0.139) compared with the LAP group over 36-month follow-up. The incremental cost-effectiveness ratio for COCP compared with LAPs is therefore approximately £17 193 per QALY. The probabilistic sensitivity analysis suggested that there was a 54.7% probability that COCP would be cost-effective at the £20 000/QALY threshold. The secondary analyses revealed results more in favour of LAPs.ConclusionAlthough the COCP has a slightly higher probability of being cost-effective at £20 000/QALY threshold, there remains considerable uncertainty, with only marginal differences in outcomes between the two treatments. The lower rates of further surgery and second-line medical treatment for women allocated to LAPs may make this option preferable for some women.Trial registration numberISRCTN 97865475.
Exploring symptoms perception and barriers to medication adherence among Thai Muslim patients with non-communicable diseases in a rural community in southern Thailand: a mixed-methods study
Authors: Buathong Napakkawat , Naruephai Surawut , Wanichanon Worawit , Rodkitvitthaya Kananas , Thananinkul Peeraphol , Jankaew Napat , Wessamanon Phisit , Khaotrakul Samatchaya , Boonmak Ratthakorn , Choo-eard Nichamon , Nintap Thanakrit , Sarakitphan Teera , Kaewchuay Paweeorn , Naruephai Kittiya , Chaison Monchai 
Published: December 2024

ObjectivesThis study aimed to explore the prevalence of medication non-adherence and influence of symptom perception and various barriers on medication adherence among Thai Muslim patients in a rural subdistrict of southern Thailand.DesignExplanatory sequential mixed-methods approach.SettingA rural community in southern Thailand.MethodsData collection spanned from March to December 2023. In the quantitative phase, 138 Muslim patients diagnosed with non-communicable diseases were enrolled, and their medication adherence and associated factors were assessed. In the qualitative phase, 22 participants were selected for in-depth interviews, and their symptom perceptions and the obstacles they faced in adhering to medication were explored. A focus group discussion involving 10 healthcare workers from a subdistrict health-promoting hospital was conducted to gain insights into healthcare providers’ perspectives on patients’ perceptions of symptoms and barriers to medication adherence.Outcome measuresMedication non-adherence was assessed, and the influence of symptom perception and various barriers on medication adherence was evaluatedResultsThe prevalence of medication non-adherence in the study sample was 75.36%. The following factors were significantly associated with medication non-adherence: occupation (farmer) (adjusted OR=3.93; 95% CI 1.04 to 12.64), lack of recommendations on adjusting medication schedules/dosages during Ramadan (adjusted OR=2.65; 95% CI 1.06 to 6.61) and patients’ perception of no symptoms (adjusted OR=3.72; 95% CI 1.23 to 11.25). The qualitative analysis highlighted patient-related issues, such as lack of symptom perception, limited health literacy regarding disease information and treatment and personal reasons for non-adherence (eg, forgetfulness, occupational constraints and transportation challenges for medical appointments). Additionally, healthcare system-related factors, patient–doctor relationships and communication gaps in medication management during Ramadan were identified as factors influencing medication non-adherence.ConclusionsTo improve adherence, healthcare providers should prioritise fostering positive patient–provider relationships and promoting patient care through enhanced health literacy initiatives.