bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Nano-encapsulation on Neonatal Porcine Islet-like Cell Clusters Using Polymersomes
Authors: Lee Sang Hoon , Kim Hyun-Ouk , Kang Jung-Taek
Published: March 2021

Researches proving methods for nano-encapsulation of neonatal porcine islet-like cell clusters (NPCCs) using polymersomes (PSomes) formed using polymers of polyethylene glycol-block-poly lactide. Herein, our studies present efficient nano-encapsulation procedure with minimal damage and loss of NPCCs.We used N-hydroxysuccinimide (NHS) on the N-terminal of PSomes to induce binding of amine groups in the extracellular matrix surrounding NPCCs. F-10 culture medium with bovine serum albumin was used in the nano-encapsulation procedure to minimize damage and loss of NPCCs. Finally, we induced cross-linking between bifunctional PSomes (NHS-/NH2-PSomes).
F-10 culture medium containing 0.25% BSA with pH of 7.3 minimized the damage and loss of NPCCs after nano-encapsulation as compared with using basic HBSS buffer (pH 8.0). Also, we induced the efficient nano-encapsulation through conjugation of PSomes using bifunctional PSomes (NHS-/NH2-PSomes).
An introduction to new robust linear and monotonic correlation coefficients
Authors: Tabatabai Mohammad , Bailey Stephanie , Bursac Zoran , Tabatabai Habib , Wilus Derek , Singh Karan P.
Published: March 2021

Background

The most common measure of association between two continuous variables is the Pearson correlation (Maronna et al. in Safari an OMC. Robust statistics, 2019. https://login.proxy.bib.uottawa.ca/login?url=https://learning.oreilly.com/library/view/-/9781119214687/?ar&orpq&email=^u). When outliers are present, Pearson does not accurately measure association and robust measures are needed. This article introduces three new robust measures of correlation: Taba (T), TabWil (TW), and TabWil rank (TWR). The correlation estimators T and TW measure a linear association between two continuous or ordinal variables; whereas TWR measures a monotonic association. The robustness of these proposed measures in comparison with Pearson (P), Spearman (S), Quadrant (Q), Median (M), and Minimum Covariance Determinant (MCD) are examined through simulation. Taba distance is used to analyze genes, and statistical tests were used to identify those genes most significantly associated with Williams Syndrome (WS).

Results

Based on the root mean square error (RMSE) and bias, the three proposed correlation measures are highly competitive when compared to classical measures such as P and S as well as robust measures such as Q, M, and MCD. Our findings indicate TBL2 was the most significant gene among patients diagnosed with WS and had the most significant reduction in gene expression level when compared with control (P value = 6.37E-05).

Conclusions

Overall, when the distribution is bivariate Log-Normal or bivariate Weibull, TWR performs best in terms of bias and T performs best with respect to RMSE. Under the Normal distribution, MCD performs well with respect to bias and RMSE; but TW, TWR, T, S, and P correlations were in close proximity. The identification of TBL2 may serve as a diagnostic tool for WS patients. A Taba R package has been developed and is available for use to perform all necessary computations for the proposed methods.
Bacterial community structure alterations within the colorectal cancer gut microbiome
Authors: Loftus Mark , Hassouneh Sayf Al-Deen , Yooseph Shibu
Published: March 2021

Background

Colorectal cancer is a leading cause of cancer-related deaths worldwide. The human gut microbiome has become an active area of research for understanding the initiation, progression, and treatment of colorectal cancer. Despite multiple studies having found significant alterations in the carriage of specific bacteria within the gut microbiome of colorectal cancer patients, no single bacterium has been unequivocally connected to all cases. Whether alterations in species carriages are the cause or outcome of cancer formation is still unclear, but what is clear is that focus should be placed on understanding changes to the bacterial community structure within the cancer-associated gut microbiome.

Results

By applying a novel set of analyses on 252 previously published whole-genome shotgun sequenced fecal samples from healthy and late-stage colorectal cancer subjects, we identify taxonomic, functional, and structural changes within the cancer-associated human gut microbiome. Bacterial association networks constructed from these data exhibited widespread differences in the underlying bacterial community structure between healthy and colorectal cancer associated gut microbiomes. Within the cancer-associated ecosystem, bacterial species were found to form associations with other species that are taxonomically and functionally dissimilar to themselves, as well as form modules functionally geared towards potential changes in the tumor-associated ecosystem. Bacterial community profiling of these samples revealed a significant increase in species diversity within the cancer-associated gut microbiome, and an elevated relative abundance of species classified as originating from the oral microbiome including, but not limited to,Fusobacterium nucleatum,Peptostreptococcus stomatis,Gemella morbillorum, andParvimonas micra. Differential abundance analyses of community functional capabilities revealed an elevation in functions linked to virulence factors and peptide degradation, and a reduction in functions involved in amino-acid biosynthesis within the colorectal cancer gut microbiome.

Conclusions

We utilize whole-genome shotgun sequenced fecal samples provided from a large cohort of late-stage colorectal cancer and healthy subjects to identify a number of potentially important taxonomic, functional, and structural alterations occurring within the colorectal cancer associated gut microbiome. Our analyses indicate that the cancer-associated ecosystem influences bacterial partner selection in the native microbiota, and we highlight specific oral bacteria and their associations as potentially relevant towards aiding tumor progression.
Psoriasis as risk factor for non-ischemic dilated cardiomyopathy: a population-based cross-sectional study
Authors: Alshami Abbas , Alfraji Nasam , Douedi Steven , Patel Swapnil , Hossain Mohammad , Alpert Deborah , Calderon Dawn
Published: March 2021

Background

Psoriasis is a chronic inflammatory skin condition commonly associated with psoriatic arthritis, malignancy, diabetes, inflammatory bowel disease, and cardiovascular disease. Several reports and studies have reported an association between psoriasis and non-ischemic dilated cardiomyopathy (NIDCM). We aim to study the relationship between psoriasis and non-ischemic dilated cardiomyopathy in a large population-based study.

Methods

We utilized the Healthcare Cost and Utilization Project National Inpatient Sample 2017 database, which represents a 20% sample of all payer hospitalizations in the United States. We investigated hospitalizations for patients aged 18 years old or older with diagnoses of any type of psoriasis and non-ischemic dilated cardiomyopathy. Psoriasis, cardiomyopathy, and other comorbidities were identified through their international classification of diseases, 10th revision codes recorded in the discharge record for each hospitalization.

Results

Of a total of 6,084,184 all-cause admissions, 0.5% were admissions for patients with psoriasis (n = 32,807). Of the patients with and without psoriasis who had non-ischemic dilated cardiomyopathy, after adjusting for age, sex, race, diabetes mellitus, hypertension, alcohol abuse, cocaine abuse, arrhythmias, and obesity in a multivariate analysis, the presence of psoriasis was not significantly associated with non-ischemic dilated cardiomyopathy.

Conclusion

Psoriasis is a chronic autoimmune disorder which carries a higher cardiovascular events and more prevalent traditional atherosclerotic risk factors in comparison to the general population. However, association with non-ischemic cardiomyopathy or NIDCM in particular has not been studied sufficiently. Our study, being one of the first larger studies to assess this correlation, indicated no relationship between psoriasis and non-ischemic dilated cardiomyopathy.
Expression of tricellular tight junction proteins and the paracellular macromolecule barrier are recovered in remission of ulcerative colitis
Authors: Hu Jia-Chen E. , Weiß Franziska , Bojarski Christian , Branchi Federica , Schulzke Jörg-Dieter , Fromm Michael , Krug Susanne M.
Published: March 2021

Background

Ulcerative colitis (UC) has a relapsing and remitting pattern, wherein the underlying mechanisms of the relapse might involve an enhanced uptake of luminal antigens which stimulate the immune response. The tricellular tight junction protein, tricellulin, takes charge of preventing paracellular passage of macromolecules. It is characterized by downregulated expression in active UC and its correct localization is regulated by angulins. We thus analyzed the tricellulin and angulin expression as well as intestinal barrier function and aimed to determine the role of tricellulin in the mechanisms of relapse.

Methods

Colon biopsies were collected from controls and UC patients who underwent colonoscopy at the central endoscopy department of Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin. Remission of UC was defined basing on the clinical appearance and a normal Mayo endoscopic subscore. Intestinal barrier function was evaluated by electrophysiological and paracellular flux measurements on biopsies mounted in Ussing chambers.

Results

The downregulated tricellulin expression in active UC was recovered in remission UC to control values. Likewise, angulins were in remission UC at the same levels as in controls. Also, the epithelial resistance which was decreased in active UC was restored in remission to the same range as in controls, along with the unaltered paracellular permeabilities for fluorescein and FITC-dextran 4 kDa.

Conclusions

In remission of UC, tricellulin expression level as well as intestinal barrier functions were restored to normal, after they were impaired in active UC. This points toward a re-sealing of the impaired tricellular paracellular pathway and abated uptake of antigens to normal rates in remission of UC.
Sex differences in dietary consumption and its association with frailty among middle-aged and older Australians: a 10-year longitudinal survey
Authors: Xu Xiaoyue , Inglis Sally C , Parker Deborah
Published: March 2021

Background

Nutritional status has been considered as a key factor in preventing the development of the frailty syndrome. However, sex-specific dietary consumption transition over time and how it impacts of frailty status are unclear.

Method

We assessed 113,039 adults (aged 50 years and over) from the 45 and Up Study who had completed both baseline (2006–2009) and follow-up (2012–2015) surveys. Dietary consumption was assessed by a short food frequency questionnaire. Frailty was identified by the FRAIL scale. Multinomial regression models were used to examine the association between a long-term dietary consumption and frailty, stratified by sex.

Results

Of a total of 113,039 participants, females had a higher percentage of pre-frailty and frailty than males (pre-frailty: 35.5% for female and 30.1% for male; frailty: 4.86% for female and 3.56% for male). As age increased, males had significant decreases in overall dietary risk scores, while females had significant increases in overall dietary risk scores. Males and females with a long-term consumption of adequate fruits, high grains or had a variety of foods were related to a low risk of frailty. Females with a long-term consumption of adequate vegetables or high lean meats and poultry were related to a low risk of frailty. Females with an unhealthy diet at both surveys [Relative Risk Ratio (RRR) = 1.32, 95% CI: 1.18; 1.49], and those with unhealthy diet at either surveys (RRR = 1.28, 95% CI: 1.12; 1.47, RRR = 1.19, 95% CI: 1.04; 1.37) had a higher risk of frailty compared to those had a long-term healthy diet. No association were found between overall dietary risk and frailty for males.

Conclusion

Males and females changed their dietary consumption as they age. These changes affect its association with frailty, particularly for females. Sex-specific dietary advice in prevention of frailty needs to be further developed.
Experience using mTOR inhibitors for subependymal giant cell astrocytoma in tuberous sclerosis complex at a single facility
Authors: Tomoto Kyoichi , Fujimoto Ayataka , Inenaga Chikanori , Okanishi Tohru , Imai Shin , Ogai Masaaki , Fukunaga Akiko , Nakamura Hidenori , Sato Keishiro , Obana Akira , Masui Takayuki , Arai Yoshifumi , Enoki Hideo
Published: March 2021

Background

Subependymal giant cell astrocytoma (SEGA) is occasionally seen in tuberous sclerosis complex (TSC). Two main options are currently available for treating SEGA: surgical resection or pharmacotherapy using mammalian target of rapamycin inhibitors (mTORi). We hypothesized that opportunities for surgical resection of SEGA would have reduced with the advent of mTORi.

Methods

We retrospectively reviewed the charts of patients treated between August 1979 and July 2020, divided into a pre-mTORi era group (Pre-group) of patients treated before November 2012, and a post-mTORi era group (Post-group) comprising patients treated from November 2012, when mTORi became available in Japan for SEGA. We compared groups in terms of treatment with surgery or mTORi. We also reviewed SEGA size, rate of acute hydrocephalus, recurrence of SEGA, malignant transformation and adverse effects of mTORi.

Results

In total, 120 patients with TSC visited our facility, including 24 patients with SEGA. Surgical resection was significantly more frequent in the Pre-group (6 of 7 patients, 86 %) than in the Post-group (2 of 17 patients, 12 %; p = 0.001). Acute hydrocephalus was seen in 1 patient (4 %), and no patients showed malignant transformation of SEGA. The group treated using mTORi showed significantly smaller SEGA compared with the group treated under a wait-and-see policy (p = 0.012). Adverse effects of pharmacotherapy were identified in seven (64 %; 6 oral ulcers, 1 irregular menstruation) of the 11 patients receiving mTORi.

Conclusions

The Post-group underwent surgery significantly less often than the Pre-group. Since the treatment option to use mTORi in the treatment of SEGA in TSC became available, opportunities for surgical resection have decreased in our facility.
Understanding the relationship between the 32-item motor function measure and daily activities from an individual with spinal muscular atrophy and their caregivers’ perspective: a two-part study
Authors: Duong Tina , Braid Jessica , Staunton Hannah , Barriere Aurelie , Petridis Fani , Reithinger Johannes , Cruz Rosangel , Jarecki Jill , De Lemus Mencia , Gusset Nicole , Broekgaarden Ria , Randhawa Sharan , Flynn Jessica , Arbuckle Rob , Reif Sonia , Yang Lida , De Martini Angela , Vuillerot Carole
Published: March 2021

Background

The 32-item Motor Function Measure (MFM32) is a clinician-reported outcome measure used to assess the functional abilities of individuals with neuromuscular diseases, including those with spinal muscular atrophy (SMA). This two-part study explored the relationship between the functional abilities assessed in the MFM32 and activities of daily living (ADLs) from the perspective of individuals with Type 2 and Type 3 (non-ambulant and ambulant) SMA and their caregivers through qualitative interviews and a quantitative online survey.

Methods

In-depth, semi-structured, qualitative interviews were conducted with individuals with SMA and caregivers from the US. Subsequently, a quantitative online survey was completed by individuals with SMA or their caregivers from France, Germany, Italy, Poland, Spain, Canada, the United States (US) and the UK. In both parts of the study, participants were asked to describe the ADLs considered to be related to the functional abilities assessed in the MFM32. Results from the qualitative interviews informed the content of the quantitative online survey.

Results

Qualitative interviews were conducted with 15 adult participants, and 217 participants completed the quantitative online survey. From the qualitative interviews, all of the functional abilities assessed in the patient-friendly MFM32 were deemed as related to one or more ADL. The specific ADLs that participants considered related to the patient-friendly MFM32 items could be grouped into 10 key ADL domains: dressing, mobility/transferring, self-care, self-feeding, reaching, picking up and holding objects, physical activity, writing and technology use, social contact/engagement, toileting and performing work/school activities. These results were confirmed by the quantitative online survey whereby the ADLs reported to be related to each patient-friendly MFM32 item were consistent and could be grouped into the same 10 ADL domains.

Conclusion

This study provides in-depth evidence from the patient/caregiver perspective supporting the relevance of the patient-friendly MFM32 items to the ADLs of individuals with Type 2 and Type 3 SMA.
Radiation-irritated skin and hyperpigmentation may impact the quality of life of breast cancer patients after whole breast radiotherapy
Authors: Chu Chin-Nan , Hu Kai-Chieh , Wu Rick Sai-Chuen , Bau Da-Tian
Published: March 2021

Background

This study aimed to investigate skin condition, quality of life, and psychological impact of breast cancer patients after radiation therapy. We designed and administered a questionnaire to breast cancer survivors for better understanding the skin sequelae after radiation therapy.

Methods

This study performed an anonymous online survey. Invitation join was posted in Facebook groups for Breast Cancer. Content of the questionnaire included basic information and a three-point scale on the degree of skin dryness, sweating, hotness sensation, itchy sensation, presence of pigment deposition, history of severe skin disorder, psychological impact, and quality of life after radiotherapy. Categorical variables were summarized using counts and percentages, and then Mantel–Haenszel chi-square tests, multiple correspondence analysis, Wald chi-square statistics, and logistic regression analyses were performed; P < 0.05 was considered statistically significant.

Results

In total, 421 breast cancer survivors completed the questionnaire. Among them, 331 (78.62%) reported rarely sweating; 340 (80.76%) reported dry skin; 184 (43.71%) reported itchy skin in addition to dry skin; 336 (79.81%) had severe or mild skin color deposition; and 76 (18.05%) had eczema or contact dermatitis. Dry skin problems were caused by absent sweating and skin dryness in the irradiated skin area, post-RT severe skin disorders, and skin color deposition. Compared with patients sweating normally in the radiation field, patients with absent sweating and hotness sensation in the radiation field had a higher risk of depression.

Conclusions

This study showed that breast cancer patients after whole breast radiotherapy may experience skin dryness, hypersensitivity and hyper pigmentation in the irradiated skin area. These “radiation-irritated skin” lesions may induce depressive psychological status and impact the quality of life in breast cancer patients after whole breast radiotherapy.
Comprehensive analysis of immune-related prognostic genes in the tumour microenvironment of hepatocellular carcinoma
Authors: Gao Weike , Li Luan , Han Xinyin , Liu Siyao , Li Chengzhen , Yu Guanying , Zhang Lei , Zhang Dongsheng , Liu Caiyun , Meng Erhong , Hong Shuai , Wang Dongliang , Guo Peiming , Shi Guangjun
Published: March 2021

Background

The mortality rate of hepatocellular carcinoma (HCC) remains high worldwide despite surgery and chemotherapy. Immunotherapy is a promising treatment for the rapidly expanding HCC spectrum. Therefore, it is necessary to further explore the immune-related characteristics of the tumour microenvironment (TME), which plays a vital role in tumour initiation and progression.

Methods

In this research, 866 immune-related differentially expressed genes (DEGs) were identified by integrating the DEGs of samples from The Cancer Genome Atlas (TCGA)-HCC dataset and the immune-related genes from databases (InnateDB; ImmPort). Afterwards, 144 candidate prognostic genes were defined through weighted gene co-expression network analysis (WGCNA).

Results

Seven immune-related prognostic DEGs were identified using the L1-penalized least absolute shrinkage and selection operator (LASSO) Cox proportional hazards (PH) model, and the ImmuneRiskScore model was constructed on this basis. The prognostic index of the ImmuneRiskScore model was then validated in the relevant dataset. Patients were divided into high- and low-risk groups according to the ImmuneRiskScore. Differences in the immune cell infiltration of patients with different ImmuneRiskScore values were clarified, and the correlation of immune cell infiltration with immunotherapy biomarkers was further explored.

Conclusion

The ImmuneRiskScore of HCC could be a prognostic marker and can reflect the immune characteristics of the TME. Furthermore, it provides a potential biomarker for predicting the response to immunotherapy in HCC patients.
The EPICURE study: a pilot prospective cohort study of heterogeneous and massive data integration in metastatic breast cancer patients
Authors: Colombié Mathilde , Jézéquel Pascal , Rubeaux Mathieu , Frenel Jean-Sébastien , Bigot Frédéric , Seegers Valérie , Campone Mario
Published: March 2021

Background

Breast cancer is the most common cancer in women and the first cancer concerning mortality. Metastatic breast cancer remains a disease with a poor prognosis and about 30% of women diagnosed with an early stage will have a secondary progression. Metastatic breast cancer is an incurable disease despite significant therapeutic advances in both supportive cares and targeted specific therapies. In the management of a metastatic patient, each clinician follows a highly complex and strictly personal decision making process. It is based on a number of objective and subjective parameters which guides therapeutic choice in the most individualized or adapted manner.

Methods/design

The main objective is to integrate massive and heterogeneous data concerning the patient’s environment, personal and familial history, clinical and biological data, imaging, histological results (with multi-omics data), and microbiota analysis. These characteristics are multiple and in dynamic interaction overtime. With the help of mathematical units with biological competences and scientific collaborations, our project is to improve the comprehension of treatment response, based on health clinical and molecular heterogeneous big data investigation.

Discussion

Our project is to prove feasibility of creation of a clinico-biological database prospectively by collecting epidemiological, socio-economic, clinical, biological, pathological, multi-omic data and to identify characteristics related to the overall survival status before treatment and within 15 years after treatment start from a cohort of 300 patients with a metastatic breast cancer treated in the institution.

Trial registration

ClinicalTrials.gov identifier (NCT number): NCT03958136. Registration 21st of May, 2019; retrospectively registered.
An analysis of COVID-19 clusters in India
Authors: Sengupta Pooja , Ganguli Bhaswati , SenRoy Sugata , Chatterjee Aditya
Published: March 2021

Background

In this study we cluster the districts of India in terms of the spread of COVID-19 and related variables such as population density and the number of specialty hospitals. Simulation using a compartment model is used to provide insight into differences in response to public health interventions. Two case studies of interest from Nizamuddin and Dharavi provide contrasting pictures of the success in curbing spread.

Methods

A cluster analysis of the worst affected districts in India provides insight about the similarities between them. The effects of public health interventions in flattening the curve in their respective states is studied using the individual contact SEIQHRF model, a stochastic individual compartment model which simulates disease prevalence in the susceptible, infected, recovered and fatal compartments.

Results

The clustering of hotspot districts provide homogeneous groups that can be discriminated in terms of number of cases and related covariates. The cluster analysis reveal that the distribution of number of COVID-19 hospitals in the districts does not correlate with the distribution of confirmed COVID-19 cases. From the SEIQHRF model for Nizamuddin we observe in the second phase the number of infected individuals had seen a multitudinous increase in the states where Nizamuddin attendees returned, increasing the risk of the disease spread. However, the simulations reveal that implementing administrative interventions, flatten the curve. In Dharavi, through tracing, tracking, testing and treating, massive breakout of COVID-19 was brought under control.

Conclusions

The cluster analysis performed on the districts reveal homogeneous groups of districts that can be ranked based on the burden placed on the healthcare system in terms of number of confirmed cases, population density and number of hospitals dedicated to COVID-19 treatment. The study rounds up with two important case studies on Nizamuddin basti and Dharavi to illustrate the growth curve of COVID-19 in two very densely populated regions in India. In the case of Nizamuddin, the study showed that there was a manifold increase in the risk of infection. In contrast it is seen that there was a rapid decline in the number of cases in Dharavi within a span of about one month.
Socio-economic consequences of mental distress: quantifying the impact of self-reported mental distress on the days of incapacity to work and medical costs in a two-year period: a longitudinal study in Germany
Authors: Müller Gerhard , Bombana Manuela , Heinzel-Gutenbrenner Monika , Kleindienst Nikolaus , Bohus Martin , Lyssenko Lisa , Vonderlin Ruben
Published: March 2021

Background

Mental disorders are related to high individual suffering and significant socio-economic burdens. However, it remains unclear to what extent self-reported mental distress is related to individuals’ days of incapacity to work and their medical costs. This study aims to investigate the impact of self-reported mental distress for specific and non-specific days of incapacity to work and specific and non-specific medical costs over a two-year span.

Method

Within a longitudinal research design, 2287 study participants’ mental distress was assessed using the Hospital Anxiety and Depression Scale (HADS). HADS scores were included as predictors in generalized linear models with a Tweedie distribution with log link function to predict participants’ days of incapacity to work and medical costs retrieved from their health insurance routine data during the following two-year period.

Results

Current mental distress was found to be significantly related to the number of specific days absent from work and medical costs. Compared to participants classified as no cases by the HADS (2.6 days), severe case participants showed 27.3-times as many specific days of incapacity to work in the first year (72 days) and 10.3-times as many days in the second year (44 days), and resulted in 11.4-times more medical costs in the first year (2272 EUR) and 6.2-times more in the second year (1319 EUR). The relationship of mental distress to non-specific days of incapacity to work and non-specific medical costs was also significant, but mainly driven from specific absent days and specific medical costs. Our results also indicate that the prevalence of presenteeism is considerably high: 42% of individuals continued to go to work despite severe mental distress.

Conclusions

Our results show that self-reported mental distress, assessed by the HADS, is highly related to the days of incapacity to work and medical costs in the two-year period. Reducing mental distress by improving preventive structures for at-risk populations and increasing access to evidence-based treatments for individuals with mental disorders might, therefore, pay for itself and could help to reduce public costs.
Perimenopausal women show modulation of excitatory and inhibitory neuromuscular mechanisms
Authors: Pesonen Heidi , Laakkonen Eija K. , Hautasaari Pekka , Aukee Pauliina , Kovanen Vuokko , Sipilä Sarianna , Finni Taija , Tarkka Ina M.
Published: March 2021

Background

Menopausal transition exposes women to an early decline in muscle force and motor function. Changes in muscle quality and function, especially in lower limbs, are crucial, as they expose individuals to increased risk of falls. To elucidate some of the related neuromuscular mechanisms, we investigated cortical inhibition and peripheral muscle twitch force potentiation in women during the early and late stages of perimenopause.

Methods

Participants were 63 women aged 48–55 years categorized as early (EP, n = 25) or late (LP, n = 38) perimenopausal according to serum follicle-stimulating hormone (FSH) levels and menstrual diaries. EP women had an irregular menstrual cycle and FSH < 25 IU/L, while LP women had an irregular cycle and > 25 IU/L. We examined motor evoked potential (MEP) and silent period (SP) elicited by transcranial magnetic stimulation (TMS), in the tibialis anterior muscle at 20%, 40%, and 60% of maximal voluntary contraction (MVC) levels, and twitch force potentiation in plantar flexors.

Results

EP group showed a longer SP duration in 40% MVC condition and larger motor evoked potential amplitude in 20% MVC condition compared to the LP group. No group difference was detected in twitch force potentiation; however, it correlated negatively with FSH levels. Other factors, such as age, height, body mass index, or physical activity did not explain group differences.

Conclusions

Our preliminary results indicate subtle modulation in both TMS-induced inhibitory and excitatory mechanisms and twitch force potentiation in women already in the late perimenopausal stage. This suggests that the reduction of estrogens may have an accelerating role in the aging process of neuromuscular control.
Perception of the primary health care response capacity by patients with and without mental health problems, and health professionals: qualitative study
Authors: Rodríguez-Eguizabal Eva , Oliván-Blázquez Bárbara , Coronado-Vázquez Valle , Sánchez-Calavera Mª. Antonia , Gil-de-Goméz Mª. Josefa , Lafita-Mainz Sergio , Garcia-Roy África , Magallón-Botaya Rosa
Published: March 2021

Background

The objective of this study is to deepen our understanding of perceptions towards Primary Health Care Response Capacity by specifically using patients with and without mental disorders, as well as family doctors and a manager, in order to compare and endorse perspectives. For it, a qualitative study was performed. In-depth interviews were conducted with 28 patients with and without mental health disorders and focus groups were held with 21 professionals and a manager. An inductive thematic content analysis was performed in order to explore, develop and define the emergent categories of analysis.

Results

The fundamental domains for patients are dignity, communication, and rapid service. People with mental health problems also highlight the domain of confidentiality as relevant, while patients who do not have a mental health problem prioritize the domain of autonomy. Patients with mental health disorders report a greater number of negative experiences in relation to the domain of dignity. Patients do not consider their negative experiences to be a structural problem of the system. These findings are also endorsed by health care professionals.

Conclusions

It is necessary to take these results into account as responsive systems can improve service uptake, ensure adherence to treatment, and ultimately enhance patient welfare.
Loss of splicing factor IK impairs normal skeletal muscle development
Authors: Ka Hye In , Seo Hyemin , Choi Youngsook , Kim Joohee , Cho Mina , Choi Seok-Yong , Park Sujeong , Han Sora , An Jinsu , Chung Hak Suk , Yang Young , Kim Min Jung
Published: March 2021

Background

IK is a splicing factor that promotes spliceosome activation and contributes to pre-mRNA splicing. Although the molecular mechanism of IK has been previously reported in vitro, the physiological role of IK has not been fully understood in any animal model. Here, we generate an ik knock-out (KO) zebrafish using the CRISPR/Cas9 system to investigate the physiological roles of IK in vivo.

Results

The ik KO embryos display severe pleiotropic phenotypes, implying an essential role of IK in embryonic development in vertebrates. RNA-seq analysis reveals downregulation of genes involved in skeletal muscle differentiation in ik KO embryos, and there exist genes having improper pre-mRNA splicing among downregulated genes. The ik KO embryos display impaired neuromuscular junction (NMJ) and fast-twitch muscle development. Depletion of ik reduces myod1 expression and upregulates pax7a, preventing normal fast muscle development in a non-cell-autonomous manner. Moreover, when differentiation is induced in IK-depleted C2C12 myoblasts, myoblasts show a reduced ability to form myotubes. However, inhibition of IK does not influence either muscle cell proliferation or apoptosis in zebrafish and C2C12 cells.

Conclusion

This study provides that the splicing factor IK contributes to normal skeletal muscle development in vivo and myogenic differentiation in vitro.
Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak
Authors: Da Veiga Leal Silvania , Ward Daniel , Campino Susana , Benavente Ernest Diez , Ibrahim Amy , Claret Tânia , Isaías Varela , Monteiro Davidson , Clark Taane G. , Gonçalves Luzia , Valdez Tomas , da Luz Lima Mendonça Maria , Silveira Henrique , Nogueira Fatima
Published: March 2021

Background

Cape Verde is an archipelago located off the West African coast and is in a pre-elimination phase of malaria control. Since 2010, fewer than 20Plasmodium falciparummalaria cases have been reported annually, except in 2017, when an outbreak in Praia before the rainy season led to 423 autochthonous cases. It is important to understand the genetic diversity of circulatingP. falciparumto inform on drug resistance, potential transmission networks and sources of infection, including parasite importation.

Methods

Enrolled subjects involved malaria patients admitted to Dr Agostinho Neto Hospital at Praia city, Santiago island, Cape Verde, between July and October 2017. Neighbours and family members of enrolled cases were assessed for the presence of anti-P. falciparumantibodies. Sanger sequencing and real-time PCR was used to identify SNPs in genes associated with drug resistance (e.g.,pfdhfr, pfdhps, pfmdr1, pfk13, pfcrt), and whole genome sequencing data were generated to investigate the population structure ofP. falciparumparasites.

Results

The study analysed 190 parasite samples, 187 indigenous and 3 from imported infections. Malaria cases were distributed throughout Praia city. There were no cases of severe malaria and all patients had an adequate clinical and parasitological response after treatment. Anti-P. falciparumantibodies were not detected in the 137 neighbours and family members tested. No mutations were detected inpfdhps. The triple mutation S108N/N51I/C59R inpfdhfrand the chloroquine-resistant CVIET haplotype in thepfcrtgene were detected in almost all samples. Variations inpfk13were identified in only one sample (R645T, E668K). The haplotype NFD forpfmdr1was detected in the majority of samples (89.7%).

Conclusions

Polymorphisms inpfk13associated with artemisinin-based combination therapy (ACT) tolerance in Southeast Asia were not detected, but the majority of the tested samples carried thepfmdr1haplotype NFD and anti-malarial-associated mutations in the thepfcrtandpfdhfrgenes. The first whole genome sequencing (WGS) was performed for Cape Verdean parasites that showed that the samples cluster together, have a very high level of similarity and are close to other parasites populations from West Africa.
Private health care market shaping and changes in inequities in childhood diarrhoea treatment coverage: evidence from the analysis of baseline and endline surveys of an ORS and zinc scale-up program in Nigeria
Authors: Braimoh Tiwadayo , Danat Isaac , Abubakar Mohammed , Ajeroh Obinna , Stanley Melinda , Wiwa Owens , Prescott Marta Rose , Lam Felix
Published: March 2021

Background

Nearly 90,000 under-five children die from diarrhoea annually in Nigeria. Over 90% of the deaths can be prevented with oral rehydration salt (ORS) and zinc treatment but coverage nationally was less than 34% for ORS and 3% for zinc with wide inequities. A program was implemented in eight states to address critical barriers to the optimal functioning of the health care market to deliver these treatments. In this study, we examine changes in the inequities of coverage of ORS and zinc over the intervention period.

Methods

Baseline and endline household surveys were used to measure ORS and zinc coverage and household assets. Principal component analysis was used to construct wealth quintiles. We used multi-level logistic regression models to estimate predictive coverage of ORS and zinc by wealth and urbanicity at each survey period. Simple measures of disparity and concentration indices and curves were used to evaluate changes in ORS and zinc coverage inequities.

Results

At baseline, 28% (95% CI: 22–35%) of children with diarrhoea from the poorest wealth quintile received ORS compared to 50% (95% CI: 52–58%) from the richest. This inequality reduced at endline as ORS coverage increased by 21%-points (P <  0.001) for the poorest and 17%-points (P <  0.001) for the richest. Zinc coverage increased significantly for both quintiles at endline from an equally low baseline coverage level. Consistent with the findings of the pairwise comparison of the poorest and the richest, the summary measure of disparity across all wealth quintiles showed a narrowing of inequities from baseline to endline. Concentration curves shifted towards equality for both treatments, concentration indices declined from 0.1012 to 0.0480 for ORS and from 0.2640 to 0.0567 for zinc. Disparities in ORS and zinc coverage between rural and urban at both time points was insignificant except that the use of zinc in the rural at endline was significantly higher at 38% (95%CI: 35–41%) compared to 29% (95%CI, 25–33%) in the urban.

Conclusion

The results show a pro-rural improvement in coverage and a reduction in coverage inequities across wealth quintiles from baseline to endline. This gives an indication that initiatives focused on shaping healthcare market systems may be effective in reducing health coverage gaps without detracting from equity as a health policy objective.
Engineering of bioactive metal sulfide nanomaterials for cancer therapy
Authors: Fei Weidong , Zhang Meng , Fan Xiaoyu , Ye Yiqing , Zhao Mengdan , Zheng Caihong , Li Yangyang , Zheng Xiaoling
Published: March 2021

Metal sulfide nanomaterials (MeSNs) are a novel class of metal-containing nanomaterials composed of metal ions and sulfur compounds. During the past decade, scientists found that the MeSNs engineered by specific approaches not only had high biocompatibility but also exhibited unique physicochemical properties for cancer therapy, such as Fenton catalysis, light conversion, radiation enhancement, and immune activation. To clarify the development and promote the clinical transformation of MeSNs, the first section of this paper describes the appropriate fabrication approaches of MeSNs for medical science and analyzes the features and limitations of each approach. Secondly, we sort out the mechanisms of functional MeSNs in cancer therapy, including drug delivery, phototherapy, radiotherapy, chemodynamic therapy, gas therapy, and immunotherapy. It is worth noting that the intact MeSNs and the degradation products of MeSNs can exert different types of anti-tumor activities. Thus, MeSNs usually exhibit synergistic antitumor properties. Finally, future expectations and challenges of MeSNs in the research of translational medicine are spotlighted.
Persistent or permanent atrial fibrillation is associated with severe cardioembolic stroke in patients with non-valvular atrial fibrillation
Authors: Hagii Joji , Metoki Norifumi , Saito Shin , Shiroto Hiroshi , Sasaki Satoko , Takahashi Koki , Hitomi Hiroyasu , Baba Yoshiko , Yamada Natsumi , Seino Satoshi , Kamada Takaatsu , Uchizawa Takamitsu , Nakamura Taigen , Yasujima Minoru , Tomita Hirofumi
Published: March 2021

Background

Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke severity in patients with CE stroke divided by the type of AF.

Methods

Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between patients with PAF (n = 127) and PerAF (n = 231).

Results

Patients with PerAF were more likely to take oral anticoagulants (OACs) than those with PAF (37% vs. 13%, P <  0.0001), even though still underuse of OAC in both patients. Regarding stroke severity on admission, patients with PerAF exhibited a tendency toward a higher score on the National Institutes of Health Stroke Scale (NIHSS) compared with patients with PAF (12 [5–20] vs. 9 [4–18]; P = 0.12). Mortality and mRS score at discharge were higher in the PerAF than in the PAF group (13% vs. 4%; P = 0.005, and 3 [1–5] vs. 2 [1–4]; P = 0.01, respectively). Multivariate analyses confirmed that PerAF was a significant determinant of severe stroke (NIHSS score > 8) on admission (odds ratio [OR] to PAF = 1.80; 95% confidence interval [CI] 1.08–2.98; P = 0.02) and of an mRS score ≥ 3 at discharge (OR = 2.07; 95% CI 1.24–3.46; P = 0.006). Patients with PerAF had three times more internal carotid artery occlusion evaluated by magnetic resonance angiography, which indicated a more severe cerebral embolism compared with patients with PAF.

Conclusions

We found underuse of OAC in high risk AF patients with CE stroke. PerAF is significantly associated with severe stroke on admission and an unfavorable functional outcome at discharge in Japanese patients with CE stroke.
Developing a Thai national critical care allocation guideline during the COVID-19 pandemic: a rapid review and stakeholder consultation
Authors: Marshall Aniqa Islam , Archer Rachel , Witthayapipopsakul Woranan , Sirison Kanchanok , Chotchoungchatchai Somtanuek , Sriakkpokin Pisit , Srisookwatana Orapan , Teerawattananon Yot , Tangcharoensathien Viroj
Published: March 2021

Background

At the height of the COVID-19 pandemic, Thailand had almost depleted its critical care resources, particularly intensive care unit (ICU) beds and ventilators. This prompted the necessity to develop a national guideline for resource allocation. This paper describes the development process of a national guideline for critical resource allocation in Thailand during the COVID-19 pandemic.

Methods

The guideline development process consisted of three steps: (1) rapid review of existing rationing guidelines and literature; (2) interviews of Thai clinicians experienced in caring for COVID-19 cases; and (3) multi-stakeholder consultations. At steps 1 and 2, data was synthesized and categorized using a thematic and content analysis approach, and this guided the formulation of the draft guideline. Within step 3, the draft Thai critical care allocation guideline was debated and finalized before entering the policy-decision stage.

Results

Three-order prioritization criteria consisting of (1) clinical prognosis using four tools (Charlson Comorbidity Index, Sequential Organ Failure Assessment, frailty assessment and cognitive impairment assessment), (2) number of life-years saved and (3) social usefulness were proposed by the research team based on literature reviews and interviews. At consultations, stakeholders rejected using life-years as a criterion due to potential age and gender discrimination, as well as social utility due to a concern it would foster public distrust, as this judgement can be arbitrary. It was agreed that the attending physician is required to be the decision-maker in the Thai medico-legal context, while a patient review committee would play an advisory role. Allocation decisions are to be documented for transparency, and no appealing mechanism is to be applied. This guideline will be triggered only when demand exceeds supply after the utmost efforts to mobilize surge capacity. Once implemented, it is applicable to all patients, COVID-19 and non-COVID-19, requiring critical care resources prior to ICU admission and during ICU stay.

Conclusions

The guideline development process for the allocation of critical care resources in the context of the COVID-19 outbreak in Thailand was informed by scientific evidence, medico-legal context, existing norms and societal values to reduce risk of public distrust given the sensitive nature of the issue and ethical dilemmas of the guiding principle, though it was conducted at record speed. Our lessons can provide an insight for the development of similar prioritization guidelines, especially in other low- and middle-income countries.
Clinical features of central nervous system involvement in patients with eosinophilic granulomatosis with polyangiitis: a retrospective cohort study in China
Authors: Liu Suying , Guo Ling , Fan Xiaoyuan , Zhang Zhaocui , Zhou Jiaxin , Tian Xinping , Li Mengtao , Zeng Xiaofeng , Wang Li , Zhang Fengchun
Published: March 2021

Background

Central nervous system (CNS) involvement is extremely rare in eosinophilic granulomatosis with polyangiitis (EGPA), but is associated with a poor prognosis in the five-factor score. This study aims to elucidate the clinical features and independently associated factors of EGPA with CNS involvement.

Results

CNS involvement was observed in 17.3% (19/110) of EGPA patients from Peking Union Medical College Hospital between 2007 and 2019. We retrospectively reviewed their clinical data and analyzed the independently associated factors. Their mean age was 51.7 ± 11.56 years with no male/female predominance. Ischemic lesions were the most common manifestations, accounting for 63.2% of the 19 cases, followed by posterior reversible encephalopathy syndrome (36.8%), spinal cord involvement (15.8%), medulla oblongata involvement (15.8%), and intracranial hemorrhages (15.8%). Compared to the control group, patients with CNS involvement were of older age (51.7 ± 11.56 vs. 43.7 ± 13.78 years, p = 0.019) and had a higher ratio in the digestive tract involvement (52.6% vs. 28.6%, p = 0.042). Further multivariate analysis revealed that age, disease duration, and fever were the potential independent risk factors for CNS involvement of EGPA. Glucocorticoids combined with cyclophosphamide were the strategic therapy (94.7%). Intrathecal injections of dexamethasone and methotrexate were administered to 21.1% of the patients. Although seven patients relapsed during glucocorticoid reduction, seventeen patients finally achieved clinical remission. One patient died of acute intracerebral hemorrhage within one month, and another died of gastrointestinal perforation. Outcomes and cumulative survival show no significant differences between the two groups.

Conclusions

CNS involvement is uncommon in EGPA with various manifestations, and ischemic lesions are the most frequent. Age, disease duration, and fever are independent factors associated with CNS involvement in EGPA. The therapy of glucocorticoids combined with cyclophosphamide and intrathecal injections yields favorable responses. Acute intracranial hemorrhage and gastrointestinal perforation may be the principal causes of death.