bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010–2020 surveillance-based study
Authors: García-Azorín David , Santana-López Laura , Lozano-Alonso José Eugenio , Ordax-Díez Ana , Vega-Alonso Tomas , Macias Saint-Gerons Diego , González-Osorio Yésica , Rojo-Rello Silvia , Eiros José M. , Sánchez-Martínez Javier , Sierra-Mencía Álvaro , Recio-García Andrea , Martín-Toribio Alejandro , Sanz-Muñoz Ivan , Guerrero-Peral Ángel Luis
Published: February 2024

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456–3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732–2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718–2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293–1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159–1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120–1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023–1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039–1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264–0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190–1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.
Investigation of mitochondria-dependent apoptosis pathway and lipid peroxidation level induced by biosynthesized silver nanoparticles: caspase-3 activation, BAK1/BCLx regulation and malondialdehyde production
Authors: Xiong Haiwei , Nie Xiaoyan , Cao Wei , Zhu Jia , Chen Jian , Liu Ruihao , Li Yingliang
Published: February 2024

Nowadays, silver nanoparticles (AgNPs) have attracted the attention of many researchers due to their special physical, chemical, and biological properties. There is strong evidence that biogenic AgNPs can act as potent anticancer agents through the production of reactive oxygen species (ROS) and initiate the mitochondrial pathway of apoptosis. That is why we decided to use Nepeta bracteata Benth flower extract for the first time to bio-synthesize AgNPs and study their cytotoxic and apoptotic effects on SK-BR-3 cells. AgNPs were biosynthesized at 70 °C after mixing silver nitrate and flower extract with a specific ratio and concentration, then were characterized using various analytical techniques, such as FESEM, FTIR, EDS, and zeta potential. Studies have shown that AgNPs have an irregular and circular shape, with about 99% by weight of silver, carbon, and oxygen. On the other hand, the appropriate size (below 57 nm) and surface charge (− 11.52 mV) make them stable in biological fluids. The better cytotoxic effect of AgNPs compared to flower extract on SK-BR-3 cells was investigated using the MTT method. The positive effect of AgNPs on inhibiting the growth of SK-BR-3 breast cancer cells was again confirmed by the sulforhodamine B staining method, so that AgNPs were able to decrease the density of cancer cells in a concentration-dependent manner. In addition, the flow cytometry test proved that biosynthesized AgNPs using Nepeta bracteata Benth flower extract can induce apoptosis in SK-BR-3 cancer cells. Real-time PCR then proved that the ratio of Bak1/Bclx, as well as caspase-3 expression, was increased due to active ROS-producing biomolecules present in the plant extract, and therefore, AgNPs can activate the mitochondria-dependent apoptosis pathway in breast cancer cells. Finally, their negligible oxidative stress on erythrocytes was confirmed by the lipid peroxidation method and showed that biosynthesized AgNPs can be used for breast cancer treatment without showing adverse effects on erythrocytes.
Sex-biased genetic regulation of inflammatory proteins in the Dutch population
Authors: Boahen Collins K. , Abee Hannah , Ponce Isis Ricaño , Joosten Leo A. B. , Netea Mihai G. , Kumar Vinod
Published: February 2024

Background

Significant differences in immune responses, prevalence or susceptibility of diseases and treatment responses have been described between males and females. Despite this, sex-differentiation analysis of the genetic architecture of inflammatory proteins is largely unexplored. We performed sex-stratified meta-analysis after protein quantitative trait loci (pQTL) mapping using inflammatory biomarkers profiled using targeted proteomics (Olink inflammatory panel) of two population-based cohorts of Europeans.

Results

Even though, around 67% of the pQTLs demonstrated shared effect between sexes, colocalization analysis identified two loci in the males (LINC01135 and ITGAV) and three loci (CNOT10, SRD5A2, and LILRB5) in the females with evidence of sex-dependent modulation by pQTL variants. Furthermore, we identified pathways with relevant functions in the sex-biased pQTL variants. We also showed through cross-validation that the sex-specific pQTLs are linked with sex-specific phenotypic traits.

Conclusion

Our study demonstrates the relevance of genetic sex-stratified analysis in the context of genetic dissection of protein abundances among individuals and reveals that, sex-specific pQTLs might mediate sex-linked phenotypes. Identification of sex-specific pQTLs associated with sex-biased diseases can help realize the promise of individualized treatment.
Estimating cutoff values for diagnostic tests to achieve target specificity using extreme value theory
Authors: Pugh Sierra , Fosdick Bailey K. , Nehring Mary , Gallichotte Emily N. , VandeWoude Sue , Wilson Ander
Published: February 2024

Background

Rapidly developing tests for emerging diseases is critical for early disease monitoring. In the early stages of an epidemic, when low prevalences are expected, high specificity tests are desired to avoid numerous false positives. Selecting a cutoff to classify positive and negative test results that has the desired operating characteristics, such as specificity, is challenging for new tests because of limited validation data with known disease status. While there is ample statistical literature on estimating quantiles of a distribution, there is limited evidence on estimating extreme quantiles from limited validation data and the resulting test characteristics in the disease testing context.

Methods

We propose using extreme value theory to select a cutoff with predetermined specificity by fitting a Pareto distribution to the upper tail of the negative controls. We compared this method to five previously proposed cutoff selection methods in a data analysis and simulation study. We analyzed COVID-19 enzyme linked immunosorbent assay antibody test results from long-term care facilities and skilled nursing staff in Colorado between May and December of 2020.

Results

We found the extreme value approach had minimal bias when targeting a specificity of 0.995. Using the empirical quantile of the negative controls performed well when targeting a specificity of 0.95. The higher target specificity is preferred for overall test accuracy when prevalence is low, whereas the lower target specificity is preferred when prevalence is higher and resulted in less variable prevalence estimation.

Discussion

While commonly used, the normal based methods showed considerable bias compared to the empirical and extreme value theory-based methods.

Conclusions

When determining disease testing cutoffs from small training data samples, we recommend using the extreme value based-methods when targeting a high specificity and the empirical quantile when targeting a lower specificity.
Efficacy of endoscopic submucosal resection with a ligation device for small rectal neuroendocrine tumor: study protocol of a multicenter open-label randomized control trial (BANDIT trial)
Authors: Takada Kazunori , Imai Kenichiro , Yamada Takanori , Ohata Ken , Kanesaka Takashi , Nagami Yasuaki , Yamasaki Yasushi , Kobara Hideki , Inokuchi Yasuhiro , Chino Akiko , Yamaguchi Shinjiro , Ikehara Hisatomo , Kawamura Takuji , Yabuuchi Yohei , Mizuguchi Yasuhiko , Ikematsu Hiroaki , Yokoi Chizu , Hattori Santa , Ohno Kazuya , Yoshizawa Yashiro , Fukuzawa Masakatsu , Tsuji Yosuke , Konishi Jun , Yamamura Takeshi , Osawa Satoshi , Oka Shiro , Hikichi Takuto , Togashi Kazutomo , Hirasawa Kingo , Uraoka Toshio , Takeuchi Yoji , Chiba Hideyuki , Komeda Yoriaki , Doyama Hisashi , Oba Mari S. , Saito Yutaka
Published: February 2024

Background

Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate.

Methods

This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study.

Discussion

This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors.

Trial registration

Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.
Exploring the association between unintended pregnancies and unmet contraceptive needs among Ugandan women of reproductive age: an analysis of the 2016 Uganda demographic and health survey
Authors: Asrat Daniel , Copas Andrew , Olubukola Adesina
Published: February 2024

Background

Unintended pregnancy and unmet contraceptive needs pose significant public health challenges, particularly in developing nations, where they contribute to maternal health risks. While previous research has explored determinants of unintended pregnancies, there remains a gap in understanding the association between unplanned pregnancies and unmet contraceptive needs among Ugandan women of reproductive age. This study aimed to assess unmet contraceptive needs and their correlation with unintended pregnancies and other factors in Uganda, utilizing a nationally representative sample.

Methods

Data was extracted from the 2016 Uganda Demographic Health Survey (UDHS), a cross-sectional survey conducted in the latter half of 2016. The study encompassed 18,506 women aged 15–49 with a history of at least one prior pregnancy. The primary outcome variable was the planning status of the most recent pregnancy, while the principal independent variable was unmet contraceptive need. Additional variables were controlled in the analysis. Data analysis was performed using STATA version 17, involving descriptive analysis, cross-tabulation, chi-square testing, and logistic regression. Statistical significance was set at p < 0.05.

Results

A substantial proportion of women reported unintended pregnancies (44.5%), with approximately 21.09% experiencing an unmet need for contraception. In the adjusted model, women with unmet contraceptive needs had 3.97 times higher odds of unintended pregnancy (95% CI = 3.61–4.37) compared to those with met contraceptive needs. Significant factors linked to unintended pregnancies included women's age, place of residence, household wealth status, decision-making authority regarding contraceptive use, educational attainment, husband's occupation, and educational level.

Conclusion

This study revealed that both the rate of unintended pregnancies and unmet contraceptive needs in Uganda exceeded the global average, warranting urgent policy attention. Addressing unmet contraceptive needs emerges as a potential strategy to curtail unintended pregnancies. Further qualitative research may be necessary to elucidate the sociocultural and behavioral determinants of unwanted pregnancies, facilitating context-specific interventions.
Relative predictive value of sociodemographic factors for chronic diseases among All of Us participants: a descriptive analysis
Authors: Kunnath Ansley J. , Sack Daniel E. , Wilkins Consuelo H.
Published: February 2024

Background

Although sociodemographic characteristics are associated with health disparities, the relative predictive value of different social and demographic factors remains largely unknown. This study aimed to describe the sociodemographic characteristics of All of Us participants and evaluate the predictive value of each factor for chronic diseases associated with high morbidity and mortality.

Methods

We performed a cross-sectional analysis using de-identified survey data from the All of Us Research Program, which has collected social, demographic, and health information from adults living in the United States since May 2018. Sociodemographic data included self-reported age, sex, gender, sexual orientation, race/ethnicity, income, education, health insurance, primary care provider (PCP) status, and health literacy scores. We analyzed the self-reported prevalence of hypertension, coronary artery disease, any cancer, skin cancer, lung disease, diabetes, obesity, and chronic kidney disease. Finally, we assessed the relative importance of each sociodemographic factor for predicting each chronic disease using the adequacy index for each predictor from logistic regression.

Results

Among the 372,050 participants in this analysis, the median age was 53 years, 59.8% reported female sex, and the most common racial/ethnic categories were White (54.0%), Black (19.9%), and Hispanic/Latino (16.7%). Participants who identified as Asian, Middle Eastern/North African, and White were the most likely to report annual incomes greater than $200,000, advanced degrees, and employer or union insurance, while participants who identified as Black, Hispanic, and Native Hawaiian/Pacific Islander were the most likely to report annual incomes less than $10,000, less than a high school education, and Medicaid insurance. We found that age was most predictive of hypertension, coronary artery disease, any cancer, skin cancer, diabetes, obesity, and chronic kidney disease. Insurance type was most predictive of lung disease. Notably, no two health conditions had the same order of importance for sociodemographic factors.

Conclusions

Age was the best predictor for the assessed chronic diseases, but the relative predictive value of income, education, health insurance, PCP status, race/ethnicity, and sexual orientation was highly variable across health conditions. Identifying the sociodemographic groups with the largest disparities in a specific disease can guide future interventions to promote health equity.
Communities catalyzing change with data to mitigate an invisible menace, traffic-related air pollution
Authors: Sprague Martinez Linda , Ginzburg Shir Lerman , Ron Sharon , Brinkerhoff Cristina Araujo , Haque Samiya , England Sophia Angali , Khimani Kynza , Zamore Wig , Reisner Ellin , Lowe Lydia , Brugge Doug
Published: February 2024

Objectives

To identify strategies and tactics communities use to translate research into environmental health action.

Methods

We employed a qualitative case study design to explore public health action conducted by residents, organizers, and public health planners in two Massachusetts communities as part of a community based participatory (CBPR) research study. Data sources included key informant interviews (n = 24), reports and direct observation of research and community meetings (n = 10) and project meeting minutes from 2016–2021. Data were coded deductively drawing on the community organizing and implementation frameworks.

Results

In Boston Chinatown, partners drew broad participation from community-based organizations, residents, and municipal leaders, which resulted in air pollution mitigation efforts being embedded in the master planning process. In Somerville, partners focused on change at multiple levels, developer behavior, and separate from the funded research, local legislative efforts, and litigation.

Conclusions

CBPR affords communities the ability to environmental health efforts in a way that is locally meaningful, leveraging their respective strengths. External facilitation can support the continuity and sustainment of community led CBPR efforts.
Incidence and risk factors of stress urinary incontinence after laparoscopic hysterectomy
Authors: Qian XiaoHong , Ren DongFang , Gu liJuan , Ye Cong
Published: February 2024

Objective

To observe the long-term effects of total hysterectomy on urinary function, evaluate the effects of preoperative nutritional status, urinary occult infection, and surgical factors on the induction of postoperative stress urinary incontinence (SUI), and explore the incidence and risk factors of SUI.

Study design

From January 2017 to December 2017, 164 patients with benign non-prolapsing diseases who underwent a laparoscopic total hysterectomy in the First People's Hospital of Taicang were selected as the analysis objects. The International Incontinence Standard Questionnaire for Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and Pelvic Floor Impact Questionnaire-short version 20 (PFDI-20) were used for telephone follow-up to subjectively assess the urinary function of patients, collect their medical records, and statistically analyze the number of postoperative SUI cases. Logistic multivariate analysis was used to analyze the influencing factors of postoperative female SUI, presented as adjusted odds ratios with 95% confidence intervals.

Results

Only 97 out of 164 patients completed the ICIQ-FLUTS and PFDI-20 questionnaires. Among these participants, 28 patients (28.86%) were diagnosed with SUI (study group), while 69 patients (71.13%) were classified as women without SUI (control group). The age, menopause, parity ≥ 2 times, Body mass index (BMI) ≥ 28 kg/m2, neonatal weight ≥ 4000 g, history of chronic cough, preoperative hemoglobin ≤ 100 g/L, preoperative urine bacteria ≥ 100u/L, preoperative uterine volume ≥ 90 cm3, intraoperative blood loss, and operation time of the study group were compared with those of the control group. The differences were statistically significant (P < 0.05). Further Logistic multivariate analysis showed that menopause, preoperative hemoglobin ≤ 100 g/L, preoperative urine bacteria ≥ 100u/L, uterine volume ≥ 90 cm3, history of chronic cough, BMI ≥ 28 kg/m2 were risk factors for postoperative SUI in patients undergoing hysterectomy (P < 0.05).

Conclusions

Hysterectomy for benign non-prolapse diseases has a long-term potential impact on the urinary system of patients, and the risk of postoperative SUI increases. The main risk factors of SUI are parity, menopausal status, obesity, preoperative nutritional status, and occult infection of the urinary system.
Hospital readiness for the provision of care to critically ill patients in Tanzania– an in-depth cross-sectional study
Authors: Khalid Karima , Schell Carl Otto , Oliwa Jacquie , English Mike , Onyango Onesmus , Mcknight Jacob , Mkumbo Elibariki , Awadh Khamis , Maiba John , Baker Tim
Published: February 2024

Background

Critical illness is a state of ill health with vital organ dysfunction, a high risk of imminent death if care is not provided and potential for reversibility. The burden of critical illness is high, especially in low- and middle-income countries. Critical care can be provided as Essential Emergency and Critical Care (EECC)– the effective, low-cost, basic care that all critically ill patients should receive in all parts of all hospitals in the world– and advanced critical care– complex, resource-intensive care usually provided in an intensive care unit. The required resources may be available in the hospital and yet not be ready in the wards for immediate use for critically ill patients. The ward readiness of these resources, although harder to evaluate, is likely more important than their availability in the hospital. This study aimed to assess the ward readiness for EECC and the hospital availability of resources for EECC and for advanced critical care in hospitals in Tanzania.

Methods

An in-depth, cross-sectional study was conducted in five purposively selected hospitals by visiting all wards to collect data on all the required 66 EECC and 161 advanced critical care resources. We defined hospital-availability as a resource present in the hospital and ward-readiness as a resource available, functioning, and present in the right place, time and amounts for critically ill patient care in the wards. Data were analyzed to calculate availability and readiness scores as proportions of the resources that were available at hospital level, and ready at ward level respectively.

Results

Availability of EECC resources in hospitals was 84% and readiness in the wards was 56%. District hospitals had lower readiness scores (less than 50%) than regional and tertiary hospitals. Equipment readiness was highest (65%) while that of guidelines lowest (3%). Availability of advanced critical care resources was 31%.

Conclusion

Hospitals in Tanzania lack readiness for the provision of EECC– the low-cost, life-saving care for critically ill patients. The resources for EECC were available in hospitals, but were not ready for the immediate needs of critically ill patients in the wards. To provide effective EECC to all patients, improvements are needed around the essential, low-cost resources in hospital wards that are essential for decreasing preventable deaths.
Diagnostic and progression biomarkers in cerebrospinal fluid of Alzheimer’s disease patients
Authors: Chatanaka Miyo K. , Prassas Ioannis , Diamandis Eleftherios P.
Published: February 2024

In this commentary, we address a paper published by Johnson et al. by assessing the robustness of their method to discover diagnostic biomarkers in Alzheimer’s disease (AD). In addition, we examine how these newly discovered and previously discovered biomarkers, can play a role in assisting patients with AD and those at risk for developing AD, with an emphasis on the translational hurdles that accompany such discoveries.
Comparison of long-term radial artery occlusion via distal vs. conventional transradial access (CONDITION): a randomized controlled trial
Authors: Chen Tao , Li Lamei , Li Feng , Lu Wei , Shi Ganwei , Li Wenhua , Yang Anni , Huang Hui , Xiao Jianqiang , Zhang Qiuwei , Gu Jun , Xue Sheliang , Zhang Liuyan , Li Li , Xu Lingxia , Ji Rongrong , Wang Haibo , Cai Gaojun
Published: February 2024

Background

The distal transradial access (dTRA) has become an attractive and alternative access to the conventional transradial access (TRA) for cardiovascular interventional diagnosis and/or treatment. There was a lack of randomized clinical trials to evaluate the effect of the dTRA on the long-term radial artery occlusion (RAO).

Methods

This was a prospective, randomized controlled study. The primary endpoint was the incidence of long-term RAO at 3 months after discharge. The secondary endpoints included the successful puncture rate, puncture time, and other access-related complications.

Results

The incidence of long-term RAO was 0.8% (3/361) for dTRA and 3.3% (12/365) for TRA (risk ratio = 0.25, 95% confidence interval = 0.07–0.88,P = 0.02). The incidence of RAO at 24 h was significantly lower in the dTRA group than in the TRA group (2.5% vs. 6.7%,P < 0.01). The puncture success rate (96.0% vs. 98.5%,P = 0.03) and single puncture attempt (70.9% vs. 83.9%,P < 0.01) were significantly lower in the dTRA group than in the TRA group. However, the number of puncture attempts and puncture time were higher in the dTRA group. The dTRA group had a lower incidence of bleeding than the TRA group (1.5% vs. 6.0%,P < 0.01). There was no difference in the success rate of the procedure, total fluoroscopy time, or incidence of other access-related complications between the two groups. In the per-protocol analysis, the incidence of mEASY type ≥ II haematoma was significantly lower in the dTRA group, which was consistent with that in the as-treated analysis.

Conclusions

The dTRA significantly reduced the incidence of long-term RAO, bleeding or haematoma.

Trial registration

ClinicalTrials.gov identifer: NCT05253820.
Association of musculoskeletal involvement with lung function and mortality in patients with idiopathic pulmonary fibrosis
Authors: Sridhar Meenakshi , Bodduluri Sandeep , O’Hare Lanier , Blumhoff Scott , Acosta Lara Maria del Pilar , de Andrade Joao A. , Kim Young-Il , Luckhardt Tracy , McDonald MerryLynn , Kulkarni Tejaswini
Published: February 2024

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF. In this study, 70 patients with IPF underwent assessment of body composition, lung function, 6-min walk distance (6MWD) testing, hand grip strength, quality of life (QoL) assessment by St. George’s Respiratory questionnaire (SGRQ) and frailty assessment using the SHARE-FI tool. FFMI was calculated using pectoralis muscle cross-sectional area (PM-CSA) on CT chest images and the lowest quartile defined reduced muscle mass. Sarcopenia was defined as low FFMI and handgrip strength. Regression analyses were conducted to determine predictive value of frailty, low FFMI and sarcopenia on clinical outcomes. The Cox proportional hazards model was used to analyze the impact of FFMI and frailty score on survival. The mean age was 70 years with moderate impairment in lung function (mean ppFVC 68.5%, ppDLCO 45.6%). Baseline forced vital capacity (p < 0.001), diffusion capacity of lung for carbon monoxide (p =  < 0.01), 6WMD (p < 0.05) were significantly lower in frail patients compared to non-frail patients. BMI was found to closely correlate with FFMI (r = 0.79, p < 0.001), but not with frailty score (r = − 0.2, p = 0.07). Frailty was a significant predictor of FVC, DLCO, 6MWD, SGRQ scores when adjusted for age and gender. Muscle mass and sarcopenia were significant predictors of FVC, DLCO, but not 6MWD or QoL scores. Multivariate cox-proportional hazards ratio model adjusting for age and gender showed that frailty was significantly associated with increased mortality (HR = 2.6, 95% CI 1.1–6.1). Low FFMI (HR = 1.3, 95% CI 0.6–2.8), and sarcopenia (HR = 2.1, 95% CI 0.8–5.3), though associated with a trend to increased mortality, were not statistically significant. Frailty is associated with lower lung function and higher mortality in patients with IPF. Longitudinal evaluations are necessary to further determine the associations between low FFMI, sarcopenia and frailty with outcomes in IPF.
What are the common downstream molecular events between alcoholic and nonalcoholic fatty liver?
Authors: Tarantino Giovanni , Citro Vincenzo
Published: February 2024

Liver fat storage, also called hepatic steatosis, is increasingly common and represents a very frequent diagnosis in the medical field. Excess fat is not without consequences. In fact, hepatic steatosis contributes to the progression toward liver fibrosis. There are two main types of fatty liver disease, alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Although AFLD and NAFLD are similar in their initial morphological features, both conditions involve the same evolutive forms. Moreover, there are various common mechanisms underlying both diseases, including alcoholic liver disease and NAFLD, which are commonalities. In this Review, the authors explore similar downstream signaling events involved in the onset and progression of the two entities but not completely different entities, predominantly focusing on the gut microbiome. Downstream molecular events, such as the roles of sirtuins, cytokeratins, adipokines and others, should be considered. Finally, to complete the feature, some new tendencies in the therapeutic approach are presented.
PRMT1 in human neoplasm: cancer biology and potential therapeutic target
Authors: Shen Shiquan , Zhou Honglong , Xiao Zongyu , Zhan Shaofen , Tuo Yonghua , Chen Danmin , Pang Xiao , Wang Yezhong , Wang Ji
Published: February 2024

Protein arginine methyltransferase 1 (PRMT1), the predominant type I protein arginine methyltransferase, plays a crucial role in normal biological functions by catalyzing the methylation of arginine side chains, specifically monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), within proteins. Recent investigations have unveiled an association between dysregulated PRMT1 expression and the initiation and progression of tumors, significantly impacting patient prognosis, attributed to PRMT1’s involvement in regulating various facets of tumor cell biology, including DNA damage repair, transcriptional and translational regulation, as well as signal transduction. In this review, we present an overview of recent advancements in PRMT1 research across different tumor types, with a specific focus on its contributions to tumor cell proliferation, metastasis, invasion, and drug resistance. Additionally, we expound on the dynamic functions of PRMT1 during distinct stages of cancer progression, elucidating its unique regulatory mechanisms within the same signaling pathway and distinguishing between its promotive and inhibitory effects. Importantly, we sought to provide a comprehensive summary and analysis of recent research progress on PRMT1 in tumors, contributing to a deeper understanding of its role in tumorigenesis, development, and potential treatment strategies.
Development and validation of the coffee task: a novel functional assessment for prosthetic grip selection
Authors: Lee Christina , Vaskov Alex K. , Davis Alicia J. , Kartes Jordan M. , Gates Deanna H.
Published: February 2024

Background

Lack of standardized assessments that explicitly quantify performance during prosthetic grip selection poses difficulty determining whether efforts to improve the design of multi-grip hands and their control approaches are successful. In this study, we developed and validated a novel assessment of multi-grip prosthetic performance: The Coffee Task.

Methods

Individuals without limb loss completed the Box and Block Test and two versions of the Coffee Task – Continuous and Segmented - with a myoelectric prosthetic emulator. On different days, participants selected prosthetic grips using pattern recognition and trigger control. Outcomes of the Continuous and Segmented Coffee Task were completion time and number of errors, respectively. Two independent raters assessed outcomes of the Coffee Task using video recordings to determine inter-rater reliability. Known-group validity was assessed by comparing outcomes with the emulator to those with an intact limb. Convergent validity was assessed through the correlation of the Coffee Task outcomes and those of the Box and Blocks Test. Responsiveness to changes with practice and control approach were assessed using the standardized response mean (SRM).

Results

Inter-rater reliability was high for both versions of the Coffee Task (Intra-class coefficient > 0.981). Coffee Task outcomes were moderately correlated with the Box and Blocks outcomes (|r| ≥ 0.412, p ≤ 0.007). Participants completed the Coffee Task faster with their intact limb than with the emulator (p < 0.001). Both versions of the Coffee Task were responsive to changes with training (SRM ≥ 0.81) but not control approach (SRM ≤ 0.12).

Conclusions

The Coffee Task is reliable, has good known-group and convergent validity, and is responsive to changes due to practice. Future work should assess whether the Coffee Task is feasible and reliable for people with upper limb loss who use multi-grip prostheses.
Clinical and genetic characterization of 47 Chinese pediatric patients with Pitt–Hopkins syndrome: a retrospective study
Authors: Zhao Tingting , Wu Shengnan , Shen Yiping , Leng Jing , Genchev Georgi Z. , Lu Hui , Feng Jincai
Published: February 2024

Background

Pitt–Hopkins syndrome (PTHS) is a neurodevelopmental disorder that remains underdiagnosed and its clinical presentations and mutation profiles in a diverse population are yet to be evaluated. This retrospective study aims to investigate the clinical and genetic characteristics of Chinese patients with PTHS.

Methods

The clinical, biochemical, genetic, therapeutic, and follow-up data of 47 pediatric patients diagnosed with PTHS between 2018 and 2021 were retrospectively analyzed.

Results

The Chinese PTHS patients presented with specific facial features and exhibited global developmental delay of wide severity range. The locus heterogeneity of the TCF4 gene in the patients was highlighted, emphasizing the significance of genetic studies for accurate diagnosis, albeit no significant correlations between genotype and phenotype were observed in this cohort. The study also reports the outcomes of patients who underwent therapeutic interventions, such as ketogenic diets and biomedical interventions.

Conclusions

The findings of this retrospective analysis expand the phenotypic and molecular spectra of PTHS patients. The study underscores the need for a long-term prospective follow-up study to assess potential therapeutic interventions.
DNA hypomethylation promotes the expression of CASPASE-4 which exacerbates inflammation and amyloid-β deposition in Alzheimer’s disease
Authors: Daily Kylene P. , Badr Asmaa , Eltobgy Mostafa , Estfanous Shady , Whitham Owen , Tan Michelle H. , Carafice Cierra , Krause Kathrin , McNamara Andrew , Hamilton Kaitlin , Houle Samuel , Gupta Spandan , Gupta Gauruv A. , Madhu Shruthi , Fitzgerald Julie , Saadey Abbey A. , Laster Brooke , Yan Pearlly , Webb Amy , Zhang Xiaoli , Pietrzak Maciej , Kokiko-Cochran Olga N. , Ghoneim Hazem E. , Amer Amal O.
Published: February 2024

Alzheimer’s disease (AD) is the sixth leading cause of death in the USA. It is established that neuroinflammation contributes to the synaptic loss, neuronal death, and symptomatic decline of AD patients. Accumulating evidence suggests a critical role for microglia, innate immune phagocytes of the brain. For instance, microglia release pro-inflammatory products such as IL-1β which is highly implicated in AD pathobiology. The mechanisms underlying the transition of microglia to proinflammatory promoters of AD remain largely unknown. To address this gap, we performed reduced representation bisulfite sequencing (RRBS) to profile global DNA methylation changes in human AD brains compared to no disease controls. We identified differential DNA methylation of CASPASE-4 (CASP4), which when expressed promotes the generation of IL-1β and is predominantly expressed in immune cells. DNA upstream of the CASP4 transcription start site was hypomethylated in human AD brains, which was correlated with increased expression of CASP4. Furthermore, microglia from a mouse model of AD (5xFAD) express increased levels of CASP4 compared to wild-type (WT) mice. To study the role of CASP4 in AD, we developed a novel mouse model of AD lacking the mouse ortholog of CASP4 and CASP11, which is encoded by mouse Caspase-4 (5xFAD/Casp4−/−). The expression of CASP11 was associated with increased accumulation of pathologic protein aggregate amyloid-β (Aβ) and increased microglial production of IL-1β in 5xFAD mice. Utilizing RNA-sequencing, we determined that CASP11 promotes unique transcriptomic phenotypes in 5xFAD mouse brains, including alterations of neuroinflammatory and chemokine signaling pathways. Notably, in vitro, CASP11 promoted generation of IL-1β from macrophages in response to cytosolic Aβ through cleavage of downstream effector Gasdermin D (GSDMD). Therefore, here we unravel the role for CASP11 and GSDMD in the generation of IL-1β in response to Aβ and the progression of pathologic inflammation in AD. Overall, our results demonstrate that overexpression of CASP4 due to differential DNA methylation in AD microglia contributes to the progression of AD pathobiology. Thus, we identify CASP4 as a potential target for immunotherapies for the treatment and prevention of AD.
Prevalence of asthma in people with type 1 diabetes mellitus: a scoping review
Authors: Kamei Júlia Marchatto , Maués Raissa Dias , de Oliveira Silva Gabriel , Machado Alessandra Helena , Hoshino Erika Megumi , Bacchiega Fabiana Menezes , Sena Laís Mota Furtado , Negrato Carlos Antonio
Published: February 2024

Background

According to the Th1/Th2 paradigm, the expansion of Th1-type clones in individuals with type 1 diabetes results in reduced Th2-type clones, preventing the development of atopic diseases and vice versa. However, there is no consensus regarding the direct or inverse relationship between autoimmune and atopic diseases.

Objective

The aim of this scoping review was to examine the knowledge gap about the possibility of coexistence of asthma and type 1 diabetes and determine the prevalence of this association.

Methods

A scoping review was conducted, following the proposal of the Joanna Briggs Institute. The Population, Concept, and Context strategy was used to formulate the guiding question. The proposed question was: “What is the prevalence of asthma in people with T1DM?” After excluding duplicate articles, analyzing titles and abstracts, and excluding articles that did not answer the guiding question, 17 articles remained and were included in this review.

Results

Most of the articles selected conformed to the Th1/Th2 hypothesis, as the prevalence of asthma was lower in individuals with T1DM. However, similar or higher prevalence of asthma was found between cases and controls in few articles.

Conclusion

The prevalence of asthma in people with T1DM ranged from 1.7% to 23.1%. Maybe the mechanisms that characterizes the Th1/Th2 paradigm aren’t as simple as just the interaction of certain cytokines, since Th1-mediated autoimmune diseases and Th2- mediated atopy can coexist.
Contrast-enhanced mammography BI-RADS: a case-based approach to radiology reporting
Authors: Nicosia Luca , Battaglia Ottavia , Venturini Massimo , Fontana Federico , Minenna Manuela , Pesenti Aurora , Budascu Diana , Pesapane Filippo , Bozzini Anna Carla , Pizzamiglio Maria , Meneghetti Lorenza , Latronico Antuono , Signorelli Giulia , Mariano Luciano , Cassano Enrico
Published: February 2024

Contrast-enhanced mammography (CEM) is a relatively recent diagnostic technique increasingly being utilized in clinical practice. Until recently, there was a lack of standardized reporting for CEM findings. However, this has changed with the publication of a supplement in the Breast Imaging Reporting and Data System (BI-RADS). A comprehensive understanding of CEM is essential for further enhancing its role in both screening and managing patients with breast malignancies. CEM can also be beneficial for problem-solving, improving the management of uncertain breast findings. Practitioners in this field should become more cognizant of how and when to employ this technique and interpret the various CEM findings. This paper aims to outline the key findings in the updated version of the BI-RADS specifically dedicated to CEM. Additionally, it will present some clinical cases commonly encountered in clinical practice.

Critical relevance statement Standardized reporting and a thorough understanding of CEM findings are pivotal for advancing the role of CEM in screening and managing breast cancer patients. This standardization contributes significantly to integrating CEM as an essential component of daily clinical practice.

Key points • A complete knowledge and understanding of the findings outlined in the new BI-RADS CEM are necessary for accurate reporting.

• BI-RADS CEM supplement is intuitive and practical to use.

• Standardization of the CEM findings enables more accurate patient management.

Graphical Abstract
Understanding how therapeutic exercise prescription changes outcomes important to patients with persistent non-specific low back pain: a realist review protocol
Authors: Wood Lianne , Booth Vicky , Dean Sarah , Foster Nadine E. , Hayden Jill A. , Booth Andrew
Published: February 2024

Introduction

Persistent low back pain (LBP) is the leading cause of disability worldwide, and therapeutic exercise is recommended as a first-line treatment in international guidelines. The effects of exercise on clinical outcomes of pain and physical function are small to moderate, despite broader impacts on cardiovascular systems, biological health, mood, and emotional well-being. Therapeutic exercise prescription is defined as exercise that is prescribed by a clinician for a health-related treatment. It is unknown how therapeutic exercise prescription creates effects on outcomes of importance. Realist reviews explore how underlying mechanisms (M) may be active in the context (C) of certain situations, settings, or populations to create an intended or unintended outcome (O). Our objective is to explore and understand the mechanisms by which therapeutic exercise prescription changes outcomes for people with persistent LBP.

Methods

We will develop initial programme theories based on preliminary data from a previous systematic review and consensus workshop. These theories will be modified with input from a steering group (experts), a stakeholder group (people with lived experience of exercise for persistent LBP and clinicians), and a scoping search of the published literature. An information specialist will design and undertake an iterative search strategy. These will be used to create CMO configurations, which will be refined and tested using the literature. The realist review will be reported following RAMESES guidance.

Discussion

Realist reviews are uncommon in LBP research to date, yet those offer an opportunity to contrast with traditional methods of randomised controlled trials and systematic reviews and provide additional information regarding the contexts and mechanisms that may trigger certain outcomes. This can aid our understanding of the contextual features that may influence exercise prescription, such as for whom they are most effective, in what setting, how they are implemented and why. This realist synthesis will enhance our understanding of therapeutic exercise prescription to improve adherence and engagement and ultimately will provide clinically relevant recommendations regarding exercise prescription for those with persistent LBP.

Systematic review registration

The review has been registered with PROSPERO (CRD42017072023).
Protein–protein interaction network-based integration of GWAS and functional data for blood pressure regulation analysis
Authors: Tsare Evridiki-Pandora G. , Klapa Maria I. , Moschonas Nicholas K.
Published: February 2024

Background

It is valuable to analyze the genome-wide association studies (GWAS) data for a complex disease phenotype in the context of the protein–protein interaction (PPI) network, as the related pathophysiology results from the function of interacting polyprotein pathways. The analysis may include the design and curation of a phenotype-specific GWAS meta-database incorporating genotypic and eQTL data linking to PPI and other biological datasets, and the development of systematic workflows for PPI network-based data integration toward protein and pathway prioritization. Here, we pursued this analysis for blood pressure (BP) regulation.

Methods

The relational scheme of the implemented in Microsoft SQL Server BP-GWAS meta-database enabled the combined storage of: GWAS data and attributes mined from GWAS Catalog and the literature, Ensembl-defined SNP-transcript associations, and GTEx eQTL data. The BP-protein interactome was reconstructed from the PICKLE PPI meta-database, extending the GWAS-deduced network with the shortest paths connecting all GWAS-proteins into one component. The shortest-path intermediates were considered as BP-related. For protein prioritization, we combined a new integrated GWAS-based scoring scheme with two network-based criteria: one considering the protein role in the reconstructed by shortest-path (RbSP) interactome and one novel promoting the common neighbors of GWAS-prioritized proteins. Prioritized proteins were ranked by the number of satisfied criteria.

Results

The meta-database includes 6687 variants linked with 1167 BP-associated protein-coding genes. The GWAS-deduced PPI network includes 1065 proteins, with 672 forming a connected component. The RbSP interactome contains 1443 additional, network-deduced proteins and indicated that essentially all BP-GWAS proteins are at most second neighbors. The prioritized BP-protein set was derived from the union of the most BP-significant by any of the GWAS-based or the network-based criteria. It included 335 proteins, with ~ 2/3 deduced from the BP PPI network extension and 126 prioritized by at least two criteria. ESR1 was the only protein satisfying all three criteria, followed in the top-10 by INSR, PTN11, CDK6, CSK, NOS3, SH2B3, ATP2B1, FES and FINC, satisfying two. Pathway analysis of the RbSP interactome revealed numerous bioprocesses, which are indeed functionally supported as BP-associated, extending our understanding about BP regulation.

Conclusions

The implemented workflow could be used for other multifactorial diseases.