bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk factors associated with malaria infection identified through reactive case detection in Zanzibar, 2012–2019
Authors: Mkali Humphrey R. , Reaves Erik J. , Lalji Shabbir M. , Al-mafazy Abdul-Wahid , Joseph Joseph J. , Ali Abdullah S. , Abbas Faiza B. , Ali Mohamed H. , Hassan Wahida S. , Kitojo Chonge , Serbantez Naomi , Kabula Bilali I. , Nyinondi Ssanyu S. , Bisanzio Donal , McKay Mike , Eckert Erin , Reithinger Richard , Ngondi Jeremiah M. 
Published: December 2021

Abstract
Background
Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar.

Methods
Surveillance data from Zanzibar’s Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level.

Results
A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3–39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3–2.8) and living in Unguja (OR = 1.2; 95% CI 1.0–1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7–0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7–0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7–0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6–0.8).

Conclusions
The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5–14 years and travellers are needed.
Health equity impact of community-initiated kangaroo mother care: a randomized controlled trial
Authors: Choudhary Tarun Shankar , Mazumder Sarmila , Haaland Øystein Ariansen , Taneja Sunita , Bahl Rajiv , Martines Jose , Bhan Maharaj Kishan , Johansson Kjell Arne , Sommerfelt Halvor , Bhandari Nita , Norheim Ole F 
Published: December 2021

Abstract
Background
Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival.

Methods
In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant’s sex, and religion.

Results
Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu.

Conclusions
We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival.

Trial registration
ClinicalTrials.gov, NCT02653534. Registered January 12, 2016—Retrospectively registered.
Surface plasmon resonance biosensor for exosome detection based on reformative tyramine signal amplification activated by molecular aptamer beacon
Authors: Chen Wenqin , Li Zhiyang , Cheng Wenqian , Wu Tao , Li Jia , Li Xinyu , Liu Lin , Bai Huijie , Ding Shijia , Li Xinmin , Yu Xiaolin 
Published: December 2021

AbstractHuman epidermal growth factor receptor 2 (HER2)-positive exosomes play an extremely important role in the diagnosis and treatment options of breast cancers. Herein, based on the reformative tyramine signal amplification (TSA) enabled by molecular aptamer beacon (MAB) conversion, a label-free surface plasmon resonance (SPR) biosensor was proposed for highly sensitive and specific detection of HER2-positive exosomes. The exosomes were captured by the HER2 aptamer region of MAB immobilized on the chip surface, which enabled the exposure of the G-quadruplex DNA (G4 DNA) that could form peroxidase-like G4-hemin. In turn, the formed G4-hemin catalyzed the deposition of plentiful tyramine-coated gold nanoparticles (AuNPs-Ty) on the exosome membrane with the help of H2O2, generating a significantly enhanced SPR signal. In the reformative TSA system, the horseradish peroxidase (HRP) as a major component was replaced with nonenzymic G4-hemin, bypassing the defects of natural enzymes. Moreover, the dual-recognition of the surface proteins and lipid membrane of the desired exosomes endowed the sensing strategy with high specificity without the interruption of free proteins. As a result, this developed SPR biosensor exhibited a wide linear range from 1.0 × 104 to 1.0 × 107 particles/mL. Importantly, this strategy was able to accurately distinguish HER2-positive breast cancer patients from healthy individuals, exhibiting great potential clinical application.
Graphical Abstract
Predictors of poor health-related quality of life among hemodialysis patients with anemia in Jordan
Authors: Alshogran Osama Y. , Shatnawi Esraa A. , Altawalbeh Shoroq M. , Jarab Anan S. , Farah Randa I. 
Published: December 2021

Abstract
Objective
This study examined health-related quality of life (HRQoL) and factors associated with poor HRQoL among hemodialysis (HD) patients.

Methods
A multicenter cross-sectional study was conducted on HD patients with anemia in Jordan (n = 168). Validated questionnaires were utilized to collect data on HRQoL using EQ-5D-5L, psychiatric symptoms using Hospital Anxiety and Depression Scale (HADS), and comorbidities score using the modified Charlson Comorbidity Index (mCCI). Multiple linear regression analysis was conducted to identify the variables which are independently associated with HRQoL among patients.

Results
The mean (± SD) age of study participants was 52.2 (± 14.6) years. The mean utility value of EQ-5D-5L was 0.44 (± 0.42). Participants reported extreme problems mostly in pain/discomfort domain (19.6%). Increased age, increased mCCI and patient complains, more years under dialysis, decreased exercise, and low family income were significantly associated with poor HRQoL (p < 0.05).

Conclusion
The study findings revealed poor HRQoL among HD patients with anemia. Various dimensions of health were negatively affected among HD patients. Development and implementation of appropriate approaches with adequate education and psychosocial support to HD patients by healthcare professionals targeting improved HRQoL and clinical outcomes would be necessary.
The impact of treatment delay on skin cancer in COVID-19 era: a case-control study
Authors: Seretis Konstantinos , Boptsi Eleni , Boptsi Anastasia , Lykoudis Efstathios G. 
Published: December 2021

Abstract
Background
The outbreak of COVID-19 pandemic led to a 2-month lockdown in Europe. Elective surgeries, including skin cancer excisions, were postponed. The purpose of this prospective case-control study was to assess the impact of the treatment delay on patients with non-melanoma skin cancer (NMSC) or melanoma operated in the first post-lockdown period.

Methods
A comparative study of skin cancer operations performed in a 4-month period either in 2020 or in 2019 was conducted. All data were collected from a prospectively maintained clinic database and the pathological reports. Continuous variables were compared with t test or Mann-Whitney U test according to their distribution. Categorical variables were compared with Fisher exact test. Odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the risk of excising high-risk NMSC in 2020 compared with 2019.

Results
Skin cancer excision was performed in 158 cases in 2020 compared to 125 cases in 2019 (26.4% increase). Significantly, more SCC were excised in 2020 (p = 0.024). No significant difference for several clinical parameters regarding BCC, SCC, and melanoma was identified. However, the reconstructive method applied, following NMSC excision, was significantly different, requiring frequently either skin grafting or a flap.

Conclusion
These results indicate that skin cancer treatment delay, due to COVID-19 pandemic, is related to an increased incidence of SCC and more complicated methods of reconstruction. Considering the relapsing COVID-19 waves, significant skin cancer treatment delays should be avoided.

Trial registration
The study adhered to the STROBE statement for case-control studies.
Challenges and opportunities for Iranian global health diplomacy: lessons learned from action for prevention and control of noncommunicable diseases
Authors: Asadi-Lari Mohsen , Ahmadi Teymourlouy Ahmad , Maleki Mohammadreza , Eslambolchi Leila , Afshari Mahnaz 
Published: December 2021

Abstract
Background
The steady rise in noncommunicable diseases (NCDs) worldwide has been a key global health challenge. Governments have the primary responsibility for taking action to prevent and control NCDs. Given the growing importance of globalization of healthcare as well as the increasing use of soft power, governments need to identify challenges and opportunities to enhance global health diplomacy (GHD) for NCD prevention and control. The purpose of this qualitative research was to explain the challenges and opportunities of GHD for NCDs in Iran.

Methods
This study was conducted in 2020 using a qualitative approach and through in-depth, semi-structured interviews with 21 experts and specialists in related fields such as health policy, healthcare management, epidemiology and other related specialties. The participants were selected from all levels of diplomacy, including global, regional and national levels, with at least 3 years of experience in managerial, executive and scientific activities. Data analysis was performed by content analysis with an inductive approach. Data were analysed using inductive content analysis.

Results
The identified challenges were categorized into five main themes, including content challenges, structural challenges, process challenges, governance challenges and cultural challenges. Opportunities extracted from the interviews were also categorized into four main themes, including strong political will, utilizing the capacity of nongovernmental organizations (NGOs), multisectoral collaborations and a well-developed health system.

Conclusions
NCD prevention and control requires a multilateral collaboration-based solution. Recognition of the challenges and opportunities in GHD can help draw significant lessons for building the necessary capacities and implementing more effective policies to prevent and control NCDs.
A novel staging system and clinical predictive nomogram for more accurate staging and prognosis of malignant pancreatic intraductal papillary mucinous neoplasms: a population-based study
Authors: Zhang Haoxiang , Gao Chenggang , Chen Jiaoshun , Wu Shihong , Bai Jianwei , Yin Tao 
Published: December 2021

Abstract
Background
The current guidelines of the American Joint Committee on Cancer (AJCC) for the staging of exocrine pancreatic tumors seem inapplicable to malignant pancreatic intraductal papillary mucinous neoplasms (IPMN). Therefore, we aimed to improve the accuracy of clinical staging and prognosis for malignant IPMN by modifiing current AJCC system.

Methods
We extracted data of 2001 patients with malignant IPMN from the Surveillance, Epidemiology, and End Results database between 2000 and 2016. Of these, 1401 patients were assigned to the primary cohort and 600 patients to the validation cohort.

Results
In Kaplan–Meier analysis of the primary cohort, the current AJCC guidelines were unable to distinguish between certain tumor substages (IA and IB in the 7th, IB and IIA in the 8th). The modified system that we regrouped based on the median overall survival and hazard ratios, was superior in tumor stage classifications. Age > 70 years, tumors located in the body or tail, high-grade differentiated tumors, surgery, chemotherapy, and tumor, lymph node, and metastasis (TNM) stage were identified as independent predictive factors for overall survival. Compared to that of TNM-based systems, the concordance index of the clinical predictive nomogram significantly improved (0.819; 95% confidence interval, 0.805–0.833), with excellent area under the receiver operating characteristic curves (1-, 3-, and 5-year: 0.881, 0.889, and 0.879, respectively). The calibration curves also showed good agreement between prediction and actual observation. The analysis of treatment modalities revealed that surgery resulted in better survival for all resectable malignant IPMN. The analysis of chemotherapy data reveals its potential in improving the prognosis of treatment for patients with locally advanced or distant metastases.

Conclusions
Our modified staging system improves the distinction of tumor stages. The nomogram was a more accurate and clinically reliable tool for prognosis prediction of patients with malignant IPMN.
Long-term memory T cells as preventive anticancer immunity elicited by TuA-derived heteroclitic peptides
Authors: Mauriello Angela , Cavalluzzo Beatrice , Manolio Carmen , Ragone Concetta , Luciano Antonio , Barbieri Antonio , Tornesello Maria Lina , Buonaguro Franco M. , Tagliamonte Maria , Buonaguro Luigi 
Published: December 2021

AbstractThe host’s immune system may be primed against antigens during the lifetime (e.g. microorganisms antigens—MoAs), and swiftly recalled upon growth of a tumor expressing antigens similar in sequence and structure. C57BL/6 mice were immunized in a preventive setting with tumor antigens (TuAs) or corresponding heteroclitic peptides specific for TC-1 and B16 cell lines. Immediately or 2-months after the end of the vaccination protocol, animals were implanted with cell lines. The specific anti-vaccine immune response as well as tumor growth were regularly evaluated for 2 months post-implantation. The preventive vaccination with TuA or their heteroclitic peptides (hPep) was able to delay (B16) or completely suppress (TC-1) tumor growth when cancer cells were implanted immediately after the end of the vaccination. More importantly, TC-1 tumor growth was significantly delayed, and suppressed in 6/8 animals, also when cells were implanted 2-months after the end of the vaccination. The vaccine-specific T cell response provided a strong immune correlate to the pattern of tumor growth. A preventive immunization with heteroclitic peptides resembling a TuA is able to strongly delay or even suppress tumor growth in a mouse model. More importantly, the same effect is observed also when tumor cells are implanted 2 months after the end of vaccination, which corresponds to 8 – 10 years in human life. The observed potent tumor control indicates that a memory T cell immunity elicited during the lifetime by a antigens similar to a TuA, i.e. viral antigens, may ultimately represent a great advantage for cancer patients and may lead to a novel preventive anti-cancer vaccine strategy.
Analysis and validation of m6A regulatory network: a novel circBACH2/has-miR-944/HNRNPC axis in breast cancer progression
Authors: Lv Wenchang , Tan Yufang , Xiong Mingchen , Zhao Chongru , Wang Yichen , Wu Min , Wu Yiping , Zhang Qi 
Published: December 2021

Abstract
Background
N6-methyladenosine (m6A), the most abundant and reversible modification of mRNAs in eukaryotes, plays pivotal role in breast cancer (BC) tumorigenesis and progression. Circular RNAs (circRNAs) can act as tumor promoters or suppressors by microRNA (miRNA) sponges in BC. However, the underlying mechanism of circRNAs in BC progression via regulating m6A modulators remains unclear.

Methods
Prognostic m6A RNA methylation regulators were identified in 1065 BC patients from The Cancer Genome Atlas (TCGA) project. Differentially expressed (DE) miRNAs and DE circRNAs were identified between BC and normal samples in TCGA and GSE101123, respectively. MiRNA-mRNA interactive pairs and circRNA-miRNA interactive pairs were verified by MiRDIP and Circular RNA Interactome. GSEA, KEGG, and ssGSEA were executed to explore the potential biological and immune functions between HNRNPC-high and HNRNPC-low expression groups. qRT-PCR and Western blot were used to quantify the expression of HNRNPC and circBACH2 in MCF-7 and MDA-MB-231 cells. The proliferation of BC cells was assessed by CCK-8 and EdU assay.

Results
2 m6A RNA methylation regulators with prognostic value, including HNRNPC and YTHDF3, were identified in BC patients. Then, the regulatory network of circRNA-miRNA-m6A modulators was constructed, which consisted of 2 DE m6A modulators (HNRNPC and YTHDF3), 12 DE miRNAs, and 11 DE circRNAs. Notably, BC patients with high expression of HNRNPC and low expression of hsa-miR-944 were correlated with late clinical stages and shorter survival times. Besides, the results from the KEGG inferred that the DE HNRNPC was associated with the MAPK signaling pathway in BC. Moreover, the circBACH2 (hsa_circ_0001625) was confirmed to act as hsa-miR-944 sponge to stimulate HNRNPC expression to promote BC cell proliferation via MAPK signaling pathway, thus constructing a circBACH2/hsa-miR-944/HNRNPC axis in BC.

Conclusions
Our findings decipher a novel circRNA-based m6A regulatory mechanism involved in BC progression, thus providing attractive diagnostic and therapeutic strategies for combating BC.
“Forever young at the table”: metabolic effects of eating speed in obesity
Authors: Barrea Luigi , Vetrani Claudia , Verde Ludovica , Napolitano Bruno , Savastano Silvia , Colao Annamaria , Muscogiuri Giovanna 
Published: December 2021

Abstract
Background
Cardiometabolic diseases (CMD) are recognized as the main causes of morbidity and mortality in developed countries. In recent years eating speed (ES) has been of particular interest since some studies have associated it with the development of obesity and CMD. However, the different impact of the ES at which main meals are eaten on the risk of developing these diseases has not yet been identified. Thus, we aimed to investigate the effect of ES at the main meals (breakfast, lunch, and dinner) on the risk of developing cardiometabolic diseases (type 2 diabetes mellitus, dyslipidaemia and hypertension) in middle-aged Caucasian subjects with obesity.

Methods
For this purpose we carried out a cross-sectional, observational study. One hundred and eighty-seven middle-aged subjects aged 43.6 ± 16 years were enrolled of which anthropometric parameters and lifestyle habits were studied. A dietary interview was performed to collect information about meal duration and eating habits at the main meals. According to median value of meal duration, meals were classified in two groups: fast eating group (FEG) and slow eating group (SEG).

Results
The prevalence of dyslipidaemia was more than twice in FEG compared to SEG at lunch and dinner. For all main meals, FEG had a significantly higher risk of dyslipidaemia than SEG (p < 0.05) in unadjusted model. However, when the model was adjusted for age, BMI, physical activity, smoking and alcohol use and medication, the result remained significant for lunch and dinner (p < 0.05).

Conclusion
The results of our study suggest that fast eating increases at lunch and dinner increase the risk of developing dyslipidaemia in obesity.
Prognostic significance of natural killer cell-associated markers in gastric cancer: quantitative analysis using multiplex immunohistochemistry
Authors: Na Hee Young , Park Yujun , Nam Soo Kyung , Koh Jiwon , Kwak Yoonjin , Ahn Sang-Hoon , Park Do Joong , Kim Hyung-Ho , Lee Kyu Sang , Lee Hye Seung 
Published: December 2021

Abstract
Background
Natural killer (NK) cells mediate the anti-tumoral immune response as an important component of innate immunity. The aim of this study was to investigate the prognostic significance and functional implication of NK cell-associated surface receptors in gastric cancer (GC) by using multiplex immunohistochemistry (mIHC).

Methods
We performed an mIHC on tissue microarray slides, including 55 GC tissue samples. A total of 11 antibodies including CD57, NKG2A, CD16, HLA-E, CD3, CD20, CD45, CD68, CK, SMA, and ki-67 were used. CD45 + CD3-CD57 + cells were considered as CD57 + NK cells.

Results
Among CD45 + immune cells, the proportion of CD57 + NK cell was the lowest (3.8%), whereas that of CD57 + and CD57- T cells (65.5%) was the highest, followed by macrophages (25.4%), and B cells (5.3%). CD57 + NK cells constituted 20% of CD45 + CD57 + immune cells while the remaining 80% were CD57 + T cells. The expression of HLA-E in tumor cells correlated with that in tumoral T cells, B cells, and macrophages, but not CD57 + NK cells. The higher density of tumoral CD57 + NK cells and tumoral CD57 + NKG2A + NK cells was associated with inferior survival.

Conclusions
Although the number of CD57 + NK cells was lower than that of other immune cells, CD57 + NK cells and CD57 + NKG2A + NK cells were significantly associated with poor outcomes, suggesting that NK cell subsets play a critical role in GC progression. NK cells and their inhibitory receptor, NKG2A, may be potential targets in GC.