bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the unpredictable: a robust nomogram for predicting recurrence in patients with ampullary carcinoma
Authors: Chen Ruiqiu , Zhu Lin , Zhang Yibin , Cui Dongyu , Chen Ruixiang , Guo Hao , Peng Li , Xiao Chaohui
Published: February 2024

Objective

To screen the risk factors affecting the recurrence risk of patients with ampullary carcinoma (AC)after radical resection, and then to construct a model for risk prediction based on Lasso-Cox regression and visualize it.

Methods

Clinical data were collected from 162 patients that received pancreaticoduodenectomy treatment in Hebei Provincial Cancer Hospital from January 2011 to January 2022. Lasso regression was used in the training group to screen the risk factors for recurrence. The Lasso-Cox regression and Random Survival Forest (RSF) models were compared using Delong test to determine the optimum model based on the risk factors. Finally, the selected model was validated using clinical data from the validation group.

Results

The patients were split into two groups, with a 7:3 ratio for training and validation. The variables screened by Lasso regression, such as CA19-9/GGT, AJCC 8th edition TNM staging, Lymph node invasion, Differentiation, Tumor size, CA19-9, Gender, GPR, PLR, Drinking history, and Complications, were used in modeling with the Lasso-Cox regression model (C-index = 0.845) and RSF model (C-index = 0.719) in the training group. According to the Delong test we chose the Lasso-Cox regression model (P = 0.019) and validated its performance with time-dependent receiver operating characteristics curves(tdROC), calibration curves, and decision curve analysis (DCA). The areas under the tdROC curves for 1, 3, and 5 years were 0.855, 0.888, and 0.924 in the training group and 0.841, 0.871, and 0.901 in the validation group, respectively. The calibration curves performed well, as well as the DCA showed higher net returns and a broader range of threshold probabilities using the predictive model. A nomogram visualization is used to display the results of the selected model.

Conclusion

The study established a nomogram based on the Lasso-Cox regression model for predicting recurrence in AC patients. Compared to a nomogram built via other methods, this one is more robust and accurate.
Dual effect of vitamin D3 on breast cancer-associated fibroblasts
Authors: Łabędź Natalia , Anisiewicz Artur , Stachowicz-Suhs Martyna , Banach Joanna , Kłopotowska Dagmara , Maciejczyk Adam , Gazińska Patrycja , Piotrowska Aleksandra , Dzięgiel Piotr , Matkowski Rafał , Wietrzyk Joanna
Published: February 2024

Background

Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Despite the well-known in vitro antitumoral effect of vitamin D3 (VD3), its impact on breast CAFs is almost unknown. In this study, we analyzed the ex vivo effects of calcitriol on CAFs isolated from breast cancer tissues.

Methods

CAFs were cultured with 1 and 10 nM calcitriol and their phenotype; gene expression, protein expression, and secretion were assessed. Calcitriol-treated CAFs-conditioned media (CM) were used to analyze the effect of CAFs on the migration and protein expression of MCF-7 and MDA-MB-231 cells.

Results

Tumor tissues from VD3-deficient patients exhibited lower levels of β-catenin and TGFβ1, along with higher levels of CYP24A1 compared to VD3-normal patients. In VD3-deficient patients, CAF infiltration was inversely associated with CYP24A1 levels and positively correlated with OPN levels. Calcitriol diminished CAFs’ viability, but this effect was weaker in premenopausal and VD3-normal patients. Calcitriol reduced mRNA expression of CCL2, MMP9, TNC, and increased PDPN, SPP1, and TIMP1. It also decreased the secretion of CCL2, TNC, and the activity of MMP-2, while increasing cellular levels of TIMP1 in CAFs from all patient groups. In nonmetastatic and postmenopausal patients, PDPN surface expression increased, and CAFs CM from these groups decreased MCF-7 cell migration after ex vivo calcitriol treatment. In premenopausal and VD3-deficient patients, calcitriol reduced IDO1 expression in CAFs. Calcitriol-treated CAFs CM from these patients decreased OPN expression in MCF-7 and/or MDA-MB-231 cells. However, in premenopausal patients, calcitriol-treated CAFs CM also decreased E-cadherin expression in both cell lines.

Conclusion

The effects of calcitriol on breast CAFs, both at the gene and protein levels, are complex, reflecting the immunosuppressive or procancer properties of CAFs. The anticancer polarization of CAFs following ex vivo calcitriol treatment may result from decreased CCL2, TNC (gene and protein), MMP9, and MMP-2, while the opposite effect may result from increased PDPN, TIMP1 (gene and protein), and SPP1. Despite these multifaceted effects of calcitriol on molecule expression, CAFs’ CMs from nonmetastatic and postmenopausal patients treated ex vivo with calcitriol decreased the migration of MCF-7 cells.
Acceptability and operational feasibility of community health worker-led home phototherapy treatment for neonatal hyperbilirubinemia in rural Bangladesh
Authors: Jahan Farjana , Parvez Sarker Masud , Rahman Mahbubur , Billah Sk Masum , Yeasmin Farzana , Jahir Tania , Hasan Rezaul , Darmstadt Gary L. , Arifeen Shams El , Hoque Md. Mahbubul , Shahidullah Mohammod , Islam Muhammad Shariful , Ashrafee Sabina , Foote Eric M.
Published: February 2024

There is an unmet need for phototherapy treatment in low- and middle-income countries (LMICs) to prevent disability and death of newborns with neonatal hyperbilirubinemia. Home phototherapy deployed by community health workers (CHWs) in LMICs may help increase access to essential newborn postnatal care in a more acceptable way for families and lead to an increase in indicated treatment rates for newborns with hyperbilirubinemia. We aimed to investigate the operational feasibility and acceptability of a CHW-led home phototherapy intervention in a rural sub-district of Bangladesh for families and CHWs where home delivery was common and a treatment facility for neonatal hyperbilirubinemia was often more than two hours from households. We enrolled 23 newborns who were ≥ 2 kg in weight and ≥ 35 weeks gestational age, without clinical danger signs, and met the American Academy of Pediatric treatment criteria for phototherapy for hyperbilirubinemia. We employed a mixed-method investigation to evaluate the feasibility and acceptability of home phototherapy through surveys, in-depth interviews and focus group discussions with CHWs, mothers, and grandparents. Mothers and family members found home phototherapy worked well, saved them money, and was convenient and easy to operate. CHWs found it feasible to deploy home phototherapy and identified hands-on training, mHealth job aids, a manageable workload, and prenatal education as facilitating factors for implementation. Feasibility and acceptability concerns were limited amongst parents and included: a lack of confidence in CHWs’ skills, fear of putting newborn infants in a phototherapy device, and unreliable home power supply. CHW-led home phototherapy was acceptable to families and CHWs in rural Bangladesh. Further investigation should be done to determine the impact of home phototherapy on treatment rates and on preventing morbidity associated with neonatal hyperbilirubinemia. Clinical Trial (CT) registration ID: NCT03933423, full protocol can be accessed at https://doi.org/10.1186/s13102-024-00824-6. Name of the trial registry: clinicaltrials.gov. Clinical Trial (CT) registration Date: 01/05/2019.
Real world outcomes of distributing Lucira Check-It® COVID self-tests in Ontario, Canada: the GetaKit COVID study
Authors: Orser Lauren , Squires Janet E. , Musten Alexandra , Ho Nikki , Lindsay Jennifer , Pai Nitika Pant , O’Byrne Patrick
Published: February 2024

Background

In Ontario, Canada we developed and implemented an online screening algorithm for the distribution of HIV self-tests, known as GetaKit. During the COVID pandemic, we adapted the GetaKit algorithm to screen for COVID based on population and infection data and distributed COVID rt-LAMP self-tests (using the Lucira Check-It®) to eligible participants.

Methods

GetaKit/COVID was a prospective observational study that occurred over a 7-month period from September 2021 to April 2022. All potential participants completed an online registration and risk assessment, including demographic information, COVID symptoms and risk factors, and vaccination status. Bivariate comparisons were performed for three outcomes: results reporting status, vaccination status, and COVID diagnosis status. Data were analysed using Chi-Square for categorial covariates and Independent Samples T-Test and Mann-Whitney U test for continuous covariates. Bivariate logistic regression models were applied to examine associations between the covariates and outcomes.

Results

During the study period, we distributed 6469 COVID self-tests to 4160 eligible participants; 46% identified as Black, Indigenous or a Person of Colour (BIPOC). Nearly 70% of participants reported their COVID self-test results; 304 of which were positive. Overall, 91% also reported being vaccinated against COVID. Statistical analysis found living with five or fewer people, having tested for COVID previously, and being fully vaccinated were positive factors in results reporting. For COVID vaccination, people from large urban centers, who identified their ethnicity as white, and who reported previous COVID testing were more likely to be fully vaccinated. Finally, being identified as a contact of someone who had tested positive for COVID and the presence of COVID-related symptoms were found to be positive factors in diagnosis.

Conclusions

While most participants who accessed this service were vaccinated against COVID and the majority of diagnoses were identified in participants who had symptoms of, or an exposure to, COVID, our program was able to appropriately link participants to recommended follow-up based on reported risks and results. These findings highlight the utility of online screening algorithms to provide health services, particularly for persons with historical barriers to healthcare access, such as BIPOC or lower-income groups.
“So that’s why I found PrEP to be safest way to protect yourself”: exploring IPV experiences and impact on HIV prevention among pregnant and postpartum women in Cape Town, South Africa
Authors: Miller Amanda P. , Dean Sarah Schoetz , Court Lara , Mvududu Rufaro , Mashele Nyiko , Wara Nafisa J. , Myer Landon , Shoptaw Steven , Davey Dvora L. Joseph
Published: February 2024

Intimate partner violence (IPV) occurs at alarmingly high rates towards pregnant women in South Africa. Experiences of emotional, physical, and sexual IPV in pregnancy can adversely impact the health and safety of mother and fetus. Furthermore, IPV is associated with increased risk of HIV, exacerbating the public health impact of violence among pregnant women in this HIV endemic setting. In-depth understanding of cultural and contextual drivers of experiences of IPV is a critical precursor to development of interventions effectively addressing this issue among pregnant women in South Africa. The present study examines factors contributing to IPV among pregnant women to identify potential points of intervention. We conducted twenty in-depth interviews with postpartum women who used oral pre-exposure prophylaxis (PrEP) in pregnancy and reported recent experiences of IPV and/or ongoing alcohol use in a township near Cape Town, South Africa that experiences a heavy burden of both HIV and IPV. Interpretive thematic analysis was used. Several patterns of IPV during pregnancy were identified and violence was frequently described as co-occurring with male partner alcohol use. A majority of women referenced oral PrEP as their preferred method for HIV prevention, highlighting the agency and discretion it provided as beneficial attributes for women experiencing IPV. Fear of judgement from peers for remaining with an abusive partner and a lack of clear community messaging around IPV were identified as barriers to disclosure and support-seeking. Addressing the lack of social support received by women experiencing IPV during pregnancy in South Africa is essential to comprehensive IPV programming.
Cross-country health inequalities of four common nutritional deficiencies among children, 1990 to 2019: data from the Global Burden of Disease Study 2019
Authors: Jiang Wenkai , Li Xiao , Wang Ruiying , Du Yan , Zhou Wence
Published: February 2024

Background

Nutritional deficiencies remain serious medical and public health issues worldwide, especially in children. This study aims to analyze cross-country inequality in four common nutritional deficiencies (protein-energy malnutrition, dietary iron deficiency, vitamin A deficiency and iodine deficiency) among children from 1990 to 2019 based on Global Burden of Disease (GBD) 2019 data.

Methods

Prevalence and disability-adjusted life years (DALYs) data as measures of four nutritional deficiency burdens in people aged 0 to 14 years were extracted from the GBD Results Tool. We analyzed temporal trends in prevalence by calculating the average annual percent change (AAPC) and quantified cross-country inequalities in disease burden using the slope index.

Results

Globally, the age-standardized prevalence rates of dietary iron deficiency, vitamin A deficiency and iodine deficiency decreased, with AAPCs of -0.14 (-0.15 to -0.12), -2.77 (-2.96 to -2.58), and -2.17 (-2.3 to -2.03) from 1999 to 2019, respectively. Significant reductions in socio-demographic index (SDI)-related inequality occurred in protein-energy malnutrition and vitamin A deficiency, while the health inequality for dietary iron deficiency and iodine deficiency remained basically unchanged. The age-standardized prevalence and DALY rates of the four nutritional deficiencies decreased as the SDI and healthcare access and quality index increased.

Conclusions

The global burden of nutritional deficiency has decreased since 1990, but cross-country health inequalities still exist. More efficient public health measures are needed to reduce disease burdens, particularly in low-SDI countries/territories.
Risk factors and prognosis of perioperative acute heart failure in elderly patients with hip fracture: case-control studies and cohort study
Authors: Zhao Wei , Fu Mingming , Wang Zhiqian , Hou Zhiyong
Published: February 2024

Background

Elderly patients with hip fracture who develop perioperative acute heart failure (AHF) have a poor prognosis. The aim of the present study is to investigate the potential risks of AHF in elderly hip-fracture patients in the postoperative period and to evaluate the prognostic significance of AHF.

Methods

A retrospective analysis was conducted on hip fracture patients at the Third Hospital of Hebei Medical University, who were continuously in hospital from September 2018 to August 2020. To identify independent risk factors for AHF in elderly patients with hip fracture, univariate and multivariate Logistic regression analysis was employed. The Kaplan-Meier survival curve illustrated the relationship between all-cause mortality in the AHF and non-AHF groups. An assessment of the correlation between baseline factors and all-cause mortality was conducted by means of univariable and multivariable Cox proportional hazards analysis.

Results

We eventually recruited 492 patients,318 of whom were in the AHF group. Statistical significance was found between the two groups for age group, concomitant coronary heart disease, COPD, haemoglobin level below 100 g/L on admission, albumin level below 40 g/L on admission, and increased intraoperative blood loss. Age over 75, concomitant coronary artery disease, hemoglobin level below 100 g/L and albumin level below 40 g/L on admission were independent risk factors for AHF in older hip fracture patients. The AHF group exhibited a higher incidence of perioperative complications, such as anemia, cardiovascular issues, and stress hyperglycemia, as well as all-cause mortality. Based on our COX regression analysis, we have identified that the main risk factors for all-cause mortality in AHF patients are concomitant coronary heart disease, absence of pulmonary infection, absence of diabetes, absence of cancer, and absence of urinary tract infection.

Conclusion

Enhancing hip fracture prevention for AHF is particularly important. It is crucial to make informed decisions to avoid poor prognoses. Patients whose age over 75 years old, concomitant coronary heart disease, hemoglobin < 100 g/L and album< 40 g/L on admission are more likely to develop perioperative AHF. To avert complications and potential fatalities, patients with AHF must receive appropriate care during the perioperative period.
Heterogeneity of work alienation and its relationship with job embeddedness among Chinese nurses: a cross-sectional study using latent profile analysis
Authors: Chen Changchang , Zheng Xutong , Cui Yi , Mu Hezi , Yang Qian , Zhang Man , Xu Huan , Guan Jian , Chen Wenjie , Lang Hongjuan
Published: February 2024

Objective

To identify the distinct profiles of work alienation among Chinese nurses, examine the demographic factors associated with profile memberships, and then explore the relationship between latent categories of work alienation and job embeddedness.

Methods

A cross-sectional survey of 523 nurses was conducted from July to August 2023. Latent profile analysis (LPA) was performed to identify distinct profiles of nurses based on three aspects: powerlessness, helplessness, and meaningfulness. A multinomial logistic regression analysis was conducted to explore the predictors of profile membership. Hierarchical regression analysis was carried out to examine the association between profile memberships and job embeddedness.

Results

Three subgroups of work alienation of nurses were identified: 23.1%, 57.8%, and 19.1% in the low work alienation group (profile 1), the moderate work alienation group (profile 3), and the high work alienation group (profile 2), respectively. Nurses with college degrees were more likely to be grouped into moderate work alienation. Nurses who did not work night shifts were more likely to have low or moderate levels of work alienation. Nurses earning 2,000–3,000 and 3,001–5,000 yuan per month were likely to be in the low work alienation group. The different categories of work alienation significantly predicted job embeddedness among nurses (ΔR2 = 0.103, p < 0.001).

Conclusions

Work alienation has an important impact on clinical nurses’ job embeddedness. Nursing managers should pay attention to the differences in individual work alienation status and adopt reasonable management strategies to improve the level of job embeddedness, ensure the quality of care, and reduce nursing turnover.
Transcultural nursing: a qualitative analysis of nursing students’ experiences in a multicultural context in North-Eastern Namibia
Authors: Nuuyoma Vistolina , Muvumwaeni Sitembile , Chihururu Leonard
Published: February 2024

Background

Culture is a fundamental concept in healthcare settings due to the reason that care provided to patients is holistic and encompasses their perspectives on health, which are greatly influenced by the patients’ cultures. To prepare culturally competent nursing graduates, it is important to understand the experiences of students on transcultural nursing during clinical practice. However, there are limited studies that have explored experiences of students on transcultural nursing, specifically those located in multicultural societies. In addition, studies focus on experiences of international students who visit with student - exchange programme. Nevertheless, their experiences of transcultural nursing may differ since they are not residents and have limited exposure to transcultural nursing, and therefore cannot be generalized to undergraduate resident students. This study aimed to explore and describe transcultural nursing experiences of nursing students during clinical practice at an intermediate hospital in north-eastern Namibia.

Methods

Descriptive and explorative qualitative designs were used, data were collected via individual interviews from 16 final year nursing students, who were sampled using maximum variation purposive and snowballing sampling. During data collection, an interview guide was used together with audiotape and field notes. Data analysis followed Tesch’s eight steps in qualitative coding process. Trustworthiness was ensured using four principles of Lincoln and Guba, Moreover, ethical clearance and permission were granted by research ethics committees from two institutions.

Findings

Four main themes emerged as findings of the study are: nursing students’ exposure to different cultural practices and beliefs; personal feelings experienced by nursing students during transcultural nursing; challenges experienced by students during transcultural nursing; and nursing students coping mechanisms.

Conclusions

Nursing students had mixed experiences on transcultural nursing which touch on aspects such as exposure to cultural aspects, personal feelings, challenges, and coping mechanisms. These findings are useful in helping nurse educators, clinical mentors, students, and future researchers to understand experiences of students on transcultural nursing. Consequently, assist in enriching transcultural nursing issues in curricula and for adequate preparation of graduates to become culturally competent when providing nursing care.
Healthcare provider perspectives on emergency department-initiated buprenorphine/naloxone: a qualitative study
Authors: Badke Katherin , Small Serena S. , Pratt Megan , Lockington Julie , Gurney Lara , Kestler Andrew , Moe Jessica
Published: February 2024

Background

Take-home buprenorphine/naloxone is an effective method of initiating opioid agonist therapy in the Emergency Department (ED) that requires ED healthcare worker buy-in for large-scale implementation. We aimed to investigate healthcare workers perceptions of ED take-home buprenorphine/naloxone, as well as barriers and facilitators from an ED healthcare worker perspective.

Methods

In the context of a take-home buprenorphine/naloxone feasibility study at a tertiary care teaching hospital we conducted a descriptive qualitative study. We conducted one-on-one in person or telephone interviews and focus groups with ED healthcare workers who cared for patients given take-home buprenorphine/naloxone in the feasibility study at Vancouver General Hospital from July 2019 to March 2020. We conducted 37 healthcare worker interviews from December 2019 to July 2020. We audio recorded interviews and focus groups and transcribed them verbatim. We completed interviews until we reached thematic saturation.

Data analysis

We inductively coded a sample of transcripts to generate a provisional coding structure and to identify emerging themes, which were reviewed by our multidisciplinary team. We then used the final coding structure to analyze the transcripts. We present our findings descriptively.

Results

Participants identified a number of context-specific facilitators and barriers to take-home buprenorphine/naloxone provision in the ED. Participants highlighted ED conditions having either facilitative or prohibitive effects: provision of buprenorphine/naloxone was feasible when ED volume was low and space was available but became less so as ED volume increased and space decreased. Similarly, participants noted that patient-related factors could have a facilitative or prohibitive effect, such as willingness to wait (willing to stay in the ED for study-related activities and buprenorphine/naloxone initiation activities), receptiveness to buprenorphine/naloxone, and comprehension of the instructions. As for staff-related factors, time was identified as a consistent barrier. Time included time available and time required to initiate buprenorphine/naloxone (including time building rapport). Healthcare worker familiarity with buprenorphine/naloxone was noted as either a facilitating factor or a barrier, and healthcare workers indicated that ongoing training would have been advantageous. Many healthcare workers identified that the ED is an important first point of contact for the target patient population.

Conclusion

Integrating a buprenorphine/naloxone program into ED care requires organizational supports (e.g., for managing buprenorphine/naloxone within limitations of ED volume, space, and time), and ongoing education of healthcare workers to minimize identified barriers.
Using serological diagnostics to characterize remaining high-incidence pockets of malaria in forest-fringe Cambodia
Authors: Grimée Mathilde , Tacoli Costanza , Sandfort Mirco , Obadia Thomas , Taylor Aimee R. , Vantaux Amélie , Robinson Leanne J. , Lek Dysoley , Longley Rhea J. , Mueller Ivo , Popovici Jean , White Michael T. , Witkowski Benoît
Published: February 2024

Background

Over the last decades, the number of malaria cases has drastically reduced in Cambodia. As the overall prevalence of malaria in Cambodia declines, residual malaria transmission becomes increasingly fragmented over smaller remote regions. The aim of this study was to get an insight into the burden and epidemiological parameters of Plasmodium infections on the forest-fringe of Cambodia.

Methods

950 participants were recruited in the province of Mondulkiri in Cambodia and followed up from 2018 to 2020. Whole-blood samples were processed for Plasmodium spp. identification by PCR as well as for a serological immunoassay. A risk factor analysis was conducted for Plasmodium vivax PCR-detected infections throughout the study, and for P. vivax seropositivity at baseline. To evaluate the predictive effect of seropositivity at baseline on subsequent PCR-positivity, an analysis of P. vivax infection-free survival time stratified by serological status at baseline was performed.

Results

Living inside the forest significantly increased the odds of P. vivax PCR-positivity by a factor of 18.3 (95% C.I. 7.7–43.5). Being a male adult was also a significant predictor of PCR-positivity. Similar risk profiles were identified for P. vivax seropositivity. The survival analysis showed that serological status at baseline significantly correlated with subsequent infection. Serology is most informative outside of the forest, where 94.0% (95% C.I. 90.7–97.4%) of seronegative individuals survived infection-free, compared to 32.4% (95% C.I.: 22.6–46.6%) of seropositive individuals.

Conclusion

This study justifies the need for serological diagnostic assays to target interventions in this region, particularly in demographic groups where a lot of risk heterogeneity persists, such as outside of the forest.
TGFβ1-induced hedgehog signaling suppresses the immune response of brain microvascular endothelial cells elicited by meningitic Escherichia coli
Authors: Sun Jinrui , Yang Ruicheng , Fu Jiyang , Huo Dong , Qu Xinyi , Tan Chen , Chen Huanchun , Wang Xiangru
Published: February 2024

Background

Meningitic Escherichia coli (E. coli) is the major etiological agent of bacterial meningitis, a life-threatening infectious disease with severe neurological sequelae and high mortality. The major cause of central nervous system (CNS) damage and sequelae is the bacterial-induced inflammatory storm, where the immune response of the blood-brain barrier (BBB) is crucial.

Methods

Western blot, real-time PCR, enzyme-linked immunosorbent assay, immunofluorescence, and dual-luciferase reporter assay were used to investigate the suppressor role of transforming growth factor beta 1 (TGFβ1) in the immune response of brain microvascular endothelial cells elicited by meningitic E. coli.

Result

In this work, we showed that exogenous TGFβ1 and induced noncanonical Hedgehog (HH) signaling suppressed the endothelial immune response to meningitic E. coli infection via upregulation of intracellular miR-155. Consequently, the increased miR-155 suppressed ERK1/2 activation by negatively regulating KRAS, thereby decreasing IL-6, MIP-2, and E-selectin expression. In addition, the exogenous HH signaling agonist SAG demonstrated promising protection against meningitic E. coli-induced neuroinflammation.

Conclusion

Our work revealed the effect of TGFβ1 antagonism on E. coli-induced BBB immune response and suggested that activation of HH signaling may be a potential protective strategy for future bacterial meningitis therapy.
Detecting the impacts of humidity, rainfall, temperature, and season on chikungunya, dengue and Zika viruses in Aedes albopictus mosquitoes from selected sites in Cebu city, Philippines
Authors: Edillo Frances , Ymbong Rhoniel Ryan , Navarro Anthoddiemn Olin , Cabahug Maureen Mathilde , Saavedra Kristilynn
Published: February 2024

Background

Aedes albopictus is the secondary vector for dengue virus (DENV) in the Philippines, and also harbors chikungunya (CHIKV) and Zika (ZIKV) viruses. This study aimed to determine the minimum infection rates (MIRs) of CHIKV, DENV serotypes, and ZIKV in Ae. albopictus collected from selected two-site categories by altitude (highland [H] and lowland [L] sites) in Cebu city, Philippines during the wet (WS) and dry seasons (DS) of 2021–2022, and to explore the relationships between these arboviral MIRs and the local weather.

Methods

The viral RNA extracts in pooled and reared adult Ae. albopictus collected during the DS and WS from two-site categories were subjected to RT-PCR to amplify and detect gene loci specific for CHIKV, DENV-1 to DENV-4, and ZIKV and analyzed with the weather data.

Results

The range of CHIKV MIRs was higher in the WS (13.61–107.38 infected individuals per 1,000 mosquitoes) than in the DS (13.22–44.12), but was similar between the two-site categories. Rainfall (RF) influenced the CHIKV MIR. The MIR ranges of both DENV-2 (WS: H = 0, L = 0; DS: H = 0–5.92; L = 0–2.6) and DENV-4 (WS: H = 0, L = 0–2.90; DS: H = 2.96–6.13, L = 0–15.63) differed by season but not between the two-site categories. Relative humidity (RH), RF, and temperature did not influence DENVs’ MIRs. The MIR range of ZIKV was similar in both seasons (WS: 11.36–40.27; DS: 0–46.15) and two-site categories (H = 0–90.91, L = 0–55.56). RH and temperature influenced ZIKV MIR.

Conclusions

RF influenced CHIKV MIR in Ae. albopictus, whereas RH and temperature influenced that of ZIKV. Season influenced the MIRs of CHIKV and DENVs but not in ZIKV. Ae. albopictus were co-infected with CHIKV, DENVs, and ZIKV in both highland and lowland sites in Cebu city. Recommendations include all-year-round implementation of the Philippine Department of Health’s  4S enhanced strategy and installation of water pipelines in rural highlands for vector and disease control. Our findings are relevant to protect public health in the tropics in this climate change.
Acute neutrophilic vasculitis (leukocytoclasia) in 36 COVID-19 autopsy brains
Authors: Rhodes Roy H. , Love Gordon L. , Da Silva Lameira Fernanda , Sadough Shahmirzadi Maryam , Fox Sharon E. , Vander Heide Richard S.
Published: February 2024

Background

Hypercytokinemia, the renin-angiotensin system, hypoxia, immune dysregulation, and vasculopathy with evidence of immune-related damage are implicated in brain morbidity in COVID-19 along with a wide variety of genomic and environmental influences. There is relatively little evidence of direct SARS-CoV-2 brain infection in COVID-19 patients.

Methods

Brain histopathology of 36 consecutive autopsies of patients who were RT-PCR positive for SARS-CoV-2 was studied along with findings from contemporary and pre-pandemic historical control groups. Immunostaining for serum and blood cell proteins and for complement components was employed. Microcirculatory wall complement deposition in the COVID-19 cohort was compared to historical control cases. Comparisons also included other relevant clinicopathological and microcirculatory findings in the COVID-19 cohort and control groups.

Results

The COVID-19 cohort and both the contemporary and historical control groups had the same rate of hypertension, diabetes mellitus, and obesity. The COVID-19 cohort had varying amounts of acute neutrophilic vasculitis with leukocytoclasia in the microcirculation of the brain in all cases. Prominent vascular neutrophilic transmural migration was found in several cases and 25 cases had acute perivasculitis. Paravascular microhemorrhages and petechial hemorrhages (small brain parenchymal hemorrhages) had a slight tendency to be more numerous in cohort cases that displayed less acute neutrophilic vasculitis. Tissue burden of acute neutrophilic vasculitis with leukocytoclasia was the same in control cases as a group, while it was significantly higher in COVID-19 cases. Both the tissue burden of acute neutrophilic vasculitis and the activation of complement components, including membrane attack complex, were significantly higher in microcirculatory channels in COVID-19 cohort brains than in historical controls.

Conclusions

Acute neutrophilic vasculitis with leukocytoclasia, acute perivasculitis, and associated paravascular blood extravasation into brain parenchyma constitute the first phase of an immune-related, acute small-vessel inflammatory condition often termed type 3 hypersensitivity vasculitis or leukocytoclastic vasculitis. There is a higher tissue burden of acute neutrophilic vasculitis and an increased level of activated complement components in microcirculatory walls in COVID-19 cases than in pre-pandemic control cases. These findings are consistent with a more extensive small-vessel immune-related vasculitis in COVID-19 cases than in control cases. The pathway(s) and mechanism for these findings are speculative.
Natural products in osteoarthritis treatment: bridging basic research to clinical applications
Authors: Fang Shunzheng , Zhang Bin , Xiang Wei , Zheng Liujie , Wang Xiaodong , Li Song , Zhang Tongyi , Feng Daibo , Gong Yunquan , Wu Jinhui , Yuan Jing , Wu Yaran , Zhu Yizhen , Liu Enli , Ni Zhenhong
Published: February 2024

Osteoarthritis (OA) is the most prevalent degenerative musculoskeletal disease, severely impacting the function of patients and potentially leading to disability, especially among the elderly population. Natural products (NPs), obtained from components or metabolites of plants, animals, microorganisms etc., have gained significant attention as important conservative treatments for various diseases. Recently, NPs have been well studied in preclinical and clinical researches, showing promising potential in the treatment of OA. In this review, we summed up the main signaling pathways affected by NPs in OA treatment, including NF-κB, MAPKs, PI3K/AKT, SIRT1, and other pathways, which are related to inflammation, anabolism and catabolism, and cell death. In addition, we described the therapeutic effects of NPs in different OA animal models and the current clinical studies in OA patients. At last, we discussed the potential research directions including in-depth analysis of the mechanisms and new application strategies of NPs for the OA treatment, so as to promote the basic research and clinical transformation in the future. We hope that this review may allow us to get a better understanding about the potential bioeffects and mechanisms of NPs in OA therapy, and ultimately improve the effectiveness of NPs-based clinical conservative treatment for OA patients.
Psychotic illness in people with Prader–Willi syndrome: a systematic review of clinical presentation, course and phenomenology
Authors: Aman Lucie C. S. , Lester Suzannah D. , Holland Anthony J. , Fletcher Paul C.
Published: February 2024

Background

Prader–Willi syndrome (PWS) is a rare and complex neurodevelopmental disorder resulting from absent paternal expression of maternally imprinted genes at chromosomal locus 15q11-13. This absence of expression occurs as a consequence of a deletion on the chromosome 15 of paternal origin (ca. 70%), a chromosome 15 maternal uniparental disomy (mUPD; ca. 25%), or an imprinting centre defect (IC; ca. 1–3%). At birth, individuals with PWS are severely hypotonic and fail to thrive. Hyperphagia and characteristic physical and neuropsychiatric phenotypes become apparent during childhood. The risk for the development of a co-morbid psychotic illness increases during the teenage years, specifically in those with PWS due to the presence of an mUPD. The primary aim of this literature review is to inform clinical practice. To achieve this, we have undertaken a systematic analysis of the clinical research literature on prevalence, presentation, course, characteristics, diagnosis and treatment of psychotic illness in people with PWS. The secondary aim is to identify clinical aspects of psychotic illness in PWS in need of further investigation.

Methods and findings

A systematic literature review on psychosis in PWS was conducted on the databases Web of Knowledge, PubMed and Scopus, using the terms “((Prader–Willi syndrome) OR (Prader Willi Syndrome)) AND ((psychosis) OR (psychotic illness))”. All articles written in English and reporting original human research were reviewed. In all but three of the 16 cohort studies in which the genetic types were known, the authors reported higher rates of psychosis in people with PWS resulting from an mUPD, compared to those with the deletion subtype of PWS. When psychosis was present the presentation was psychosis similar regardless of genetic type and was usually characterised by an acute onset of hallucinations and delusions accompanied by confusion, anxiety and motor symptoms.

Conclusions

The onset of confusion, an affective cyclical pattern with the presence of abnormal mental beliefs and experiences, usually of rapid onset is suggestive of the development of psychotic illness. Phenomenologically, this psychosis in people with PWS is atypical in comparison to schizophrenia and bipolar disorder in the general population. The relationship to psychosis in the general population and the optimum treatments remain uncertain.
Transcriptional profiling of peripheral blood mononuclear cells identifies inflammatory phenotypes in Ataxia Telangiectasia
Authors: Michki Nigel S. , Singer Benjamin D. , Perez Javier V. , Thomas Aaron J. , Natale Valerie , Helmin Kathryn A. , Wright Jennifer , Cheng Leon , Young Lisa R. , Lederman Howard M. , McGrath-Morrow Sharon A.
Published: February 2024

Introduction

Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy.

Methods

Participants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features.

Results

People with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls.

Conclusion

Using a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.
Rare neurodevelopmental conditions and parents’ mental health – how and when does genetic diagnosis matter?
Authors: Chi Zhaotian , Devine Rory T. , Wolstencroft Jeanne , Skuse David , Hughes Claire , Baker Kate ,   IMAGINE-ID consortium
Published: February 2024

Background

Parents of individuals with rare neurodevelopmental conditions and intellectual disabilities (ID) are vulnerable to mental health difficulties, which vary between parents and within parents over time. The underlying cause of a child’s condition can influence parents’ mental health, via uncertain pathways and within unknown time-windows.

Results

We analysed baseline data from the IMAGINE-ID cohort, comprising 2655 parents of children and young people with ID of known genetic origin. First, we conducted a factor analysis of the SDQ Impact scale to isolate specific pathways from genetic aetiology to parents’ mental health. This suggested a two-factor structure for the SDQ Impact scale, with a “home & distress” dimension and a “participation” dimension. Second, we tested via structural equation modelling (SEM) whether genetic diagnosis affects Impact and mental health directly, or indirectly via children’s characteristics. This analysis identified an indirect pathway linking genetic aetiology to parents’ mental health, serially through child characteristics (physical disabilities, emotional and behavioural difficulties) and Impact: home & distress. Third, we conducted moderation analysis to explore the influence of time elapsed since genetic diagnosis. This showed that the serial mediation model was moderated by time since diagnosis, with strongest mediating effects among recently diagnosed cases.

Conclusions

There are multiple steps on the pathway from ID-associated genetic diagnoses to parents’ mental health. Pathway links are strongest within 5 years of receiving a genetic diagnosis, highlighting opportunities for better post-diagnostic support. Recognition and enhanced support for children’s physical and behavioural needs might reduce impact on family life, ameliorating parents’ vulnerabilities to mental health difficulties.
Assessing support for mental health policies among policy influencers and the general public in Alberta and Manitoba, Canada
Authors: Nykiforuk Candace I. J. , Thomson Mathew , Curtin Kimberley D. , Colman Ian , Wild T. Cameron , Hyshka Elaine
Published: February 2024

Background

There is a need to improve mental health policy in Canada to address the growing population burden of mental illness. Understanding support for policy options is critical for advocacy efforts to improve mental health policy. Our purpose was to describe support for population-level healthy public policies to improve mental health among policy influencers and the general public in Alberta and Manitoba; and, identify associations between levels of support and sociodemographic variables and relative to the Nuffield Bioethics Intervention Ladder framework.

Methods

We used data from the 2019 Chronic Disease Prevention Survey, which recruited a representative sample of the general public in Alberta (n = 1792) and Manitoba (n = 1909) and policy influencers in each province (Alberta n = 291, Manitoba n = 129). Level of support was described for 16 policy options using a Likert-style scale for mental health policy options by province, sample type, and sociodemographic variables using ordinal regression modelling. Policy options were coded using the Nuffield Council on Bioethics Intervention Ladder to classify support for policy options by level of intrusiveness.

Results

Policy options were categorized as ‘Provide Information’ and ‘Enable Choice’ according to the Nuffield Intervention Ladder. There was high support for all policy options, and few differences between samples or provinces. Strong support was more common among women and among those who were more politically left (versus center). Immigrants were more likely to strongly support most of the policies. Those who were politically right leaning (versus center) were less likely to support any of the mental health policies. Mental health status, education, and Indigenous identity were also associated with support for some policy options.

Conclusions

There is strong support for mental health policy in Western Canada. Results demonstrate a gap between support and implementation of mental health policy and provide evidence for advocates and policy makers looking to improve the policy landscape in Canada.
Mapping mental health care services for children and youth population in Colombia’s Pacific: potential for boundary spanning between community and formal services
Authors: Weber Sanne , Carranza Francy , Rengifo Juan Roberto , Romero Camilo , Arrieta Sergio , Martínez Karina , Pinilla-Roncancio Mónica , Fenton Sarah-Jane , Casas Germán , Jackson Paul , Aranguren Juan Pablo
Published: February 2024

Background

Conflict and violence can impact on the mental health of children and young people, who are in a crucial stage of their personal growth. Not much is known about the provision of mental health care to young people in conflict-affected areas. Community-based care can be essential, as state-led services are often scarce in conflict contexts, like Colombia’s Pacific region where this research was conducted. According to the WHO, such care is ideally provided in the form of a network of interconnected services, offered by different actors beyond the formal health sector. This article describes the relationship between the formal and community mental health systems in Colombia’s Pacific region, and identifies ways of improving their interaction.

Methods

Qualitative data were collected through 98 semi-structured interviews with community organisations, schools, international organisations and state institutions. These interviews aimed to identify the strategies used to promote young people’s mental health and the interactions between the different providers. Boundary spanning theory was used to analyse how different actors and forms of mental health care provision could coordinate better.

Results

Community organisations and schools use a wide array of strategies to attend to the mental health of children and young people, often of a collective and psychosocial nature. State institutions offer more clinically focused strategies, which are however limited in terms of accessibility and continuity. International organisations aim to strengthen state capacity, but often struggle due to high staff turnover. Although mental health care pathways exist, their effectiveness is limited due to ineffective coordination between actors.

Conclusions

To make sure that the variety of strategies to improve young people’s mental health effectively reach their beneficiaries, better coordination is needed between the different actors. Mental health care pathways should therefore integrate community organisations, while community connectors can help to manage the coordination between different actors and forms of clinical and psychosocial support.