bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased intramuscular adipose tissue of the quadriceps at admission is more strongly related to activities of daily living recovery at discharge compared to muscle mass loss in older patients with aspiration pneumonia
Authors: Akazawa Naoki , Funai Keita , Hino Toshikazu , Tsuji Ryota , Tamura Wataru , Tamura Kimiyuki , Hioka Akemi , Moriyama Hideki
Published: January 2024

Background

Recent studies reported that an increase in intramuscular adipose tissue of the quadriceps in older patients negatively affects the recovery of activities of daily living (ADL) more than the loss of muscle mass. However, whether intramuscular adipose tissue of the quadriceps in older patients with aspiration pneumonia is related to ADL recovery remains unclear. This study aimed to determine the relationship between intramuscular adipose tissue of the quadriceps and ADL recovery in older patients with aspiration pneumonia.

Methods

Thirty-nine older inpatients who were diagnosed with aspiration pneumonia participated in this prospective study. The main outcome of this study was ADL at discharge. ADL were assessed using the Barthel Index (BI). The intramuscular adipose tissue and muscle mass of the quadriceps were evaluated at admission using echo intensity and muscle thickness observed on ultrasound images. A multiple linear regression analysis was performed to confirm whether the quadriceps echo intensity was related to the BI score at discharge, even after adjusting for confounding factors.

Results

The medians [interquartile range] of the BI score at admission and discharge were 15.0 [0.0–35.0] and 20.0 [5.0–55.0], respectively. The BI score at discharge was significantly higher than that at admission (p = 0.002). The quadriceps echo intensity (β =  − 0.374; p = 0.036) and BI score at admission (β = 0.601; p < 0.001) were independently and significantly related to the BI score at discharge (R2 = 0.718; f2 = 2.546; statistical power = 1.000). In contrast, the quadriceps thickness (β =  − 0.216; p = 0.318) was not independently and significantly related to the BI score at discharge.

Conclusions

Increased intramuscular adipose tissue of the quadriceps at admission is more strongly and negatively related to ADL recovery at discharge than the loss of muscle mass among older patients with aspiration pneumonia. Interventions targeting the intramuscular adipose tissue of the quadriceps may improve ADL among these patients.
Stakeholder needs assessment for developing ageing in place solutions – a qualitative study
Authors: Kastl Andrea , Rauner Yvonne Nadine , Mayer-Huber Sandra , Oestreich Claudia , Benstetter Franz , Fettke Ulrike
Published: January 2024

Background

Ageing in place is a common desire among older adults and people in need of care. Accessible housing and ambient assisted living (AAL) technologies can help to live independently at home. However, they cannot replace the human support network of informal caregivers, healthcare professionals and social workers. The needs of these stakeholders should be considered and analysed in order to develop user-friendly and acceptable (digital) solutions for ageing in place while supporting human support networks in fulfilling their roles. This paper presents the first step for a comprehensive multi-level needs analysis within the framework of an user-centered design thinking approach.

Methods

Guideline-based interviews were conducted with healthcare professionals, social workers and an informal caregiver to collect data about the needs of older adults as well as people in need of care, and their human support networks.

Results

The call for more information that is easier to find is a common desire of the three groups. There is agreement on system-based communication and orientation problems, the existence of physical and psychological stress exacerbated by a lack of human resources, the desire for personalised care, the need to feel safe and supported in emergencies, and the need for advice and help with administrative tasks. Overall, the needs of one group are closely linked to those of the other.

Conclusion

Stakeholder selection and diversity are decisive for findings about ageing in place. The overlaps between the stakeholders’ needs offer chances and challenges at the same time for the development of user-friendly, acceptable (digital) solutions and products that support ageing in place.
Emergence and spread of SARS-CoV-2 variants of concern in Canada: a retrospective analysis from clinical and wastewater data
Authors: Champredon David , Becker Devan , Peterson Shelley W. , Mejia Edgard , Hizon Nikho , Schertzer Andrea , Djebli Mohamed , Oloye Femi F. , Xie Yuwei , Asadi Mohsen , Cantin Jenna , Pu Xia , Osunla Charles A. , Brinkmann Markus , McPhedran Kerry N. , Servos Mark R. , Giesy John P. , Mangat Chand
Published: January 2024

Background

The spread of SARS-CoV-2 has been studied at unprecedented levels worldwide. In jurisdictions where molecular analysis was performed on large scales, the emergence and competition of numerous SARS-CoV-2lineages have been observed in near real-time. Lineage identification, traditionally performed from clinical samples, can also be determined by sampling wastewater from sewersheds serving populations of interest. Variants of concern (VOCs) and SARS-CoV-2 lineages associated with increased transmissibility and/or severity are of particular interest.

Method

Here, we consider clinical and wastewater data sources to assess the emergence and spread of VOCs in Canada retrospectively.

Results

We show that, overall, wastewater-based VOC identification provides similar insights to the surveillance based on clinical samples. Based on clinical data, we observed synchrony in VOC introduction as well as similar emergence speeds across most Canadian provinces despite the large geographical size of the country and differences in provincial public health measures.

Conclusion

In particular, it took approximately four months for VOC Alpha and Delta to contribute to half of the incidence. In contrast, VOC Omicron achieved the same contribution in less than one month. This study provides significant benchmarks to enhance planning for future VOCs, and to some extent for future pandemics caused by other pathogens, by quantifying the rate of SARS-CoV-2 VOCs invasion in Canada.
Respiratory sarcopenia screening in dialysis patients: cross-sectional and multicentre study protocol
Authors: Andrade Francini Porcher , Borges Sheila , da Silva Filho César Alencar , Martins Taís Ferreira , Benvenutti Heloíse , de Freitas Júlia de Melo Cardoso , Thomé Fernando Saldanha , Karohl Cristina , Souza Gabriela Correa , Cipriano Graziella França Bernardelli , Rovedder Paula Maria Eidt
Published: January 2024

Background

Respiratory sarcopenia is characterized by the weakness of respiratory muscles associated with sarcopenia due to aging or systemic diseases such as chronic kidney disease (CKD). Patients with CKD undergoing dialysis are particularly susceptible to respiratory muscle weakness caused by factors such as fluid overload and electrolyte imbalance. This weakness not only affects ventilation but also impairs oxygen uptake and delivery to muscle tissue, potentially leading to severe sarcopenia. Thus, the objective of this study is to conduct a respiratory sarcopenia screening in patients with CKD undergoing haemodialysis (HD) and peritoneal dialysis (PD).

Methods

This is an observational, cross-sectional and multicentre study conducted between March 2023 and March 2025. The study was approved by the Research Ethics Committee at two centres. Sarcopenia diagnosis is determined based on low handgrip strength and amount of appendicular skeletal muscle mass, assessed through bioelectrical impedance analysis. Respiratory sarcopenia is diagnosed in patients with sarcopenia who have low inspiratory muscle strength, evaluated through a manovacuometry test. The severity of sarcopenia and respiratory sarcopenia is defined, respectively, by low physical performance (measured using the Short Physical Performance Battery and Timed-Up and Go test) and pulmonary performance (measured through spirometry). Thus, this study will include 81 patients undergoing dialysis (41 on HD and 40 on PD) from three participating centres.

Discussion

The literature has been focused on respiratory function in CKD; however, the relationship with sarcopenia remains understudied. We believe that, similar to appendicular skeleton muscles, the axial skeleton muscles are also likely to weaken with the presence of chronic disease, such as CKD.
Development of a new staining protocol for the Kleihauer–Betke test to facilitate the reading of difficult cases
Authors: Serban Adrian , Tholance Yannick , Aanei Carmen , Campos Lydia , Iobagiu Cristina
Published: January 2024

Background

The Kleihauer–Betke (KB) test allows the detection of fetal red blood cells (containing fetal hemoglobin, HbF) in the maternal blood to identify and quantify potential fetal-maternal hemorrhages. In certain cases, detecting fetal red blood cells with conventional staining is difficult. False-positive results or overestimation of the quantity of fetal red blood cells may occur in cases of maternal hemoglobinopathy. In this study, we developed a new staining protocol to facilitate the reading of difficult smears and improve the precision of the quantification of fetal red blood cells; we also analyzed the performance of this new method. This study assessed blood samples with and without hemoglobin abnormalities, which present difficulties when interpreting the KB test.

Methods

The new staining formula is based on an improved elution technique and the use of a different stain instead of hematoxylin. To test this staining method, 16 samples from patients with abnormal hemoglobin electrophoresis and 14 samples from patients with normal hemoglobin electrophoresis were analyzed using the KB test with the classical staining method and the new staining method. In addition, a second series was prepared using the same samples spiked with fetal red blood cells from newborn blood, to compare the accuracy of the two methods in identifying fetal red blood cells.

Results

In the 60 slides analyzed with both staining methods, we found that the new technique improved the accuracy from 78 to 85%; lowered the coefficient of variation between the operators, which decreased from 20.7% to 12.7%; increased the specificity in our population from 56 to 70%; and decreased the number of false-positive cases by 30%.

Conclusions

We successfully developed a new staining technique that facilitates the reading of difficult slides and improves the specificity of the detection of fetal red blood cells. This technique is recommended as a secondary method to use before sending the sample for additional exploration.
Topographic and surgical risk factors for high postoperative residual astigmatism after small incision lenticule extraction in patients with different degrees of myopia: a retrospective cohort study
Authors: Lee Chia-Yi , Shen Jen-Hsiang , Chao Chen-Cheng , Lian Ie-Bin , Huang Jing-Yang , Yang Shun-Fa , Chang Chao-Kai
Published: January 2024

Background

To evaluate the possible topographic and surgical risk factors for high postoperative residual astigmatism in patients who undergo small-incision lenticule extraction (SMILE) surgery and have different myopia degrees.

Methods

A retrospective cohort study was conducted, and patients who underwent SMILE surgery were enrolled. A total of 80 and 150 eyes from 40 to 75 individuals, respectively, were selected as the low myopia and high myopia groups. The demographic data, visual acuity, refraction, topographic parameters and surgical settings were recorded. Multiple linear regression with interaction tests were performed to survey the risk factors for high postoperative residual astigmatism in each group.

Results

Five (6.25%) and 9 (6.00%) eyes presented with high postoperative residual astigmatism in the low myopia and high myopia groups, respectively, but these differences were not significant (P = 0.569). A steep corneal curvature was correlated with a greater risk of high postoperative residual astigmatism in the low myopia group (P = 0.015), while a higher degree of cycloplegic cylinder power, steeper corneal curvature, greater topographic cylinder power, smaller optic zone and longer incision length were associated with a high rate of postoperative residual astigmatism in the high myopia group (all P < 0.05). In addition, the interaction effects of cycloplegic and topographic cylinder power and longer incision length on the incidence of high postoperative residual astigmatism development were more evident in the high myopia group than in the low myopia group (all P < 0.05).

Conclusions

A steep corneal curvature correlates with a high risk of high postoperative residual astigmatism after SMILE surgery, and a higher degree of cycloplegic and topographic cylinder and longer incision are associated with high postoperative residual astigmatism in individuals with high myopia.
Identification of biomarker candidates for exfoliative glaucoma from autoimmunity profiling
Authors: Potter Ryan , Ayala Marcelo , Tilevik Andreas
Published: January 2024

Background

Exfoliative glaucoma (XFG) is a subtype of open-angle glaucoma characterized by distinctive extracellular fibrils and a yet unknown pathogenesis potentially involving immune-related factors. The aim of this exploratory study was to identify biomarkers for XFG using data from autoimmunity profiling performed on blood samples from a Scandinavian cohort of patients.

Methods

Autoantibody screening was analyzed against 258 different protein fragments in blood samples taken from 30 patients diagnosed with XFG and 30 healthy donors. The 258 protein fragments were selected based on a preliminary study performed on 3072 randomly selected antigens and antigens associated with the eye. The “limma” package was used to perform moderated t-tests on the proteomic data to identify differentially expressed reactivity between the groups.

Results

Multiple associated genes were highlighted as possible biomarker candidates including FUT2, CDH5, and the LOX family genes. Using seven variables, our binary logistic regression model was able to classify the cases from the controls with an AUC of 0.85, and our reduced model using only one variable corresponding to the FUT2 gene provided an AUC of 0.75, based on LOOCV. Furthermore, over-representation gene analysis was performed to identify pathways that were associated with antigens differentially bound to self-antibodies. This highlighted the enrichment of pathways related to collagen fibril formation and the regulatory molecules mir-3176 and mir-876-5p.

Conclusions

This study suggests several potential biomarkers that may be useful in developing further models of the pathology of XFG. In particular, CDH5, FUT2, and the LOX family seem to have a relationship which merits additional exploration.
The efficacy of sleep lifestyle interventions for the management of overweight or obesity in children: a systematic review and meta-analysis
Authors: Liu Ruyu , Figueroa Roger , Brink Heidi Vanden , Vorland Colby J. , Auckburally Sameera , Johnson Lynn , Garay Jessica , Brown Tamara , Simon Stacey , Ells Louisa
Published: January 2024

Background

Childhood obesity remains a significant public health concern. Sleep duration and quality among children and youth are suboptimal worldwide. Accumulating evidence suggests an association between inadequate sleep and obesity risk, yet it is unclear whether this relationship is causal. This systematic review examines the efficacy of sleep interventions alone or as a part of lifestyle interventions for the management of overweight or obesity among children and adolescents.

Methods

A keyword/reference search was performed twice, in January 2021 and May 2022 in MEDLINE/PubMed, EMBASE/Ovid, PsycINFO/EBSCO, The Cochrane Library, Web of Science Core Collection/Web of Science, SciELO/Web of Science, and CINAHL/EBSCO. Study eligibility criteria included youth with overweight or obesity between 5 and 17, were RCTs or quasi-randomized, and focused on the treatment of overweight and obesity with a sleep behavior intervention component. Risk of bias was assessed using the Cochrane Risk of Bias assessment tool (RoB2). A Meta-analysis was conducted to estimate the effect of interventions with a sleep component on BMI. The study protocol was registered in PROSPERO (CRD42021233329).

Results

A total of 8 studies (2 quasi-experiments, 6 RCTs) met inclusion criteria and accounted for 2,231 participants across 7 countries. Only one study design isolated the effect of sleep in the intervention and reported statistically significant decreases in weight and waist circumference compared to control, though we rated it at high risk of bias. Our meta-analysis showed no significant overall effect on children’s BMI as a result of participation in an intervention with a sleep component (Cohen’s d = 0.18, 95% CI= -0.04, 0.40, Z = 1.56, P = .11), though caution is warranted due to substantial heterogeneity observed across studies (Tau2 = 0.08; X2 = 23.05, df = 7; I2 = 83.73%).

Conclusions

There were mixed results on the effect of sleep interventions across included studies on BMI, other weight-related outcomes, diet, physical activity, and sleep. Except for one study at low risk of bias, three were rated as ‘some concerns’ and four ‘high risk of bias’. Findings from this study highlight the need for additional RCTs isolating sleep as a component, focusing on children and adolescents living with overweight and obesity.
Health-related fitness in medical students: a curricular intervention in Bogota, Colombia
Authors: Paez Diana C. , Cortés-Corrales Sebastián , Jimenez-Mora Mario A. , Gutiérrez Agustín , Arango-Paternina Carlos M. , Duperly John
Published: January 2024

Objective

To evaluate the impact of a curricular intervention to promote health-related fitness (HRF) among medical students in Bogota, Colombia.

Method

The study was conducted between May 2014 and December 2015 as part of the medical physiology course, in which 208 medical students were enrolled.The curricular intervention included two lectures on physical activity (PA) and student-led group presentations on the physiological effects of exercise on human physiology. An academic incentive (10% of final grade) was given to students who reported and documented regular PA practice during the semester. This study assessed students’ HRF variables, perceptions of the curriculum intervention, and PA practices using quantitative and qualitative approaches.

Results

55% of the students were female, with a mean age of 19.5 years. Body fat, estimated maximum oxygen consumption (VO2max), handgrip, and sit-up strength showed statistically significant improvements at the end of the intervention. Students reported that PA practice was positively influenced by the curriculum intervention, particularly the academic incentive and the HRF tests. Students reported a wide variety of PA practices, which were mainly done with friends, classmates, or family members. Lack of time was the main reported barrier to PA practice.

Conclusion

The curricular intervention was effective in improving HRF and promoting PA. It remains to be investigated whether these gains are sustained over time.
Lung ultrasound score and in-hospital mortality of adults with acute respiratory distress syndrome: a meta-analysis
Authors: Wang Dandan , Qi Yun
Published: January 2024

Background

Lung ultrasound (LUS) score could quantitatively reflect the lung aeration, which has been well applied in critically ill patients. The aim of the systematic review and meta-analysis was to evaluate the association between LUS score at admission and the risk of in-hospital mortality of adults with acute respiratory distress syndrome (ARDS).

Methods

Toachieve the objective of this meta-analysis, we conducted a thorough search of PubMed, Embase, Cochrane Library, and the Web of Science to identify relevant observational studies with longitudinal follow-up. We employed random-effects models to combine the outcomes, considering the potential influence of heterogeneity.

Results

Thirteen cohort studies with 1,022 hospitalized patients with ARDS were included. Among them, 343 patients (33.6%) died during hospitalization. The pooled results suggested that the LUS score at admission was higher in non-survivors as compared to survivors (standardized mean difference = 0.73, 95% confidence interval [CI]: 0.55 to 0.91, p < 0.001; I2 = 25%). Moreover, a high LUS score at admission was associated with a higher risk of in-hospital mortality of patients with ARDS (risk ratio: 1.44, 95% CI: 1.14 to 1.81, p = 0.002; I2 = 46%). Subgroup analyses showed consistent results in studies with LUS score analyzed with 12 or 16 lung regions, and in studies reporting mortality during ICU or within 1-month hospitalization.

Conclusion

Our findings suggest that a high LUS score at admission may be associated with a high risk of in-hospital mortality of patients with ARDS.
Analysis of the correlation between serum Klotho and FeNO: a cross-sectional study from NHANES (2007–2012)
Authors: Mao Haiyan , Xie Zhenye , Huang Shanshan , Shen Xingkai , Jin Shaofeng , Lin Tong , Yang Zhouxin
Published: January 2024

Background

Klotho is an anti-aging protein that has multiple functions and may play a key role in the pathogenesis and progression of chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD). Fractional Exhaled Nitric Oxide (FeNO) is a non-invasive and novel biomarker that has the advantages of being simple, fast and reproducible. It can effectively assess the degree of airway inflammation in diseases such as asthma and COPD. Despite these insights, the relationship between serum Klotho levels and FeNO has not been explored yet.

Methods

Leveraging data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012, we investigated the correlation between FeNO and serum Klotho levels. This association was scrutinized both as continuous variables and within quartile distributions, utilizing the Kruskal-Wallis H test. The correlation between the two variables was assessed through Spearman rank analysis. Employing survey weight-adjusted linear regression models, we gauged the strength of these associations.

Results

This study included 6,527 participants with a median FeNO level of 14.5 parts per billion (ppb). We found that FeNO levels varied significantly across different quartiles of Klotho protein (H = 7.985, P = 0.046). We also found a significant positive correlation between serum Klotho levels and FeNO levels in the whole population (Spearman’s rho = 0.029, P = 0.019). This correlation remained significant after adjusting for covariates such as age, gender, lung function, smoking status, alcohol use, BMI, cardiovascular disease (including hypertension, heart failure, coronary heart disease, and myocardial infarction), diabetes, inflammatory markers, serum vitamin D level and BUN (P < 0.05 for all). Furthermore, this correlation was stronger at the high (K3) and super high (K4) levels of Klotho than at the low (K1) and medium (K2) levels (β = 1.979 ppb and β = 1.993 ppb for K3 and K4 vs. K1, respectively; 95% CI: 0.497 ~ 2.953 and 95% CI: 0.129 ~ 2.827, respectively; P = 0.007 and P = 0.032, respectively). The β coefficient for serum Klotho was 0.002 ppb/pg/ml.

Conclusions

Our study illuminates a positive correlation between serum Klotho levels and FeNO. Further study is needed to verify the causality of this association and elucidate the underlying mechanisms.
Mānuka oil based ECMT-154 versus vehicle control for the topical treatment of eczema: study protocol for a randomised controlled trial in community pharmacies in Aotearoa New Zealand
Authors: Shortt Gabrielle , Shortt Nicholas , Bird Georgina , Kerse Kyley , Lieffering Nico , Martin Alexander , Eathorne Allie , Black Bianca , Kim Bob , Rademaker Marius , Reiche Louise , Paa Selwyn Te , Harding Suki , Armour Mike , Semprini Alex
Published: January 2024

Background

Eczema is a chronic, relapsing skin condition commonly managed by emollients and topical corticosteroids. Prevalence of use and demand for effective botanical therapies for eczema is high worldwide, however, clinical evidence of benefit is limited for many currently available botanical treatment options. Robustly-designed and adequately powered randomised controlled trials (RCTs) are essential to determine evidence of clinical benefit. This protocol describes an RCT that aims to investigate whether a mānuka oil based emollient cream, containing 2% ECMT-154, is a safe and effective topical treatment for moderate to severe eczema.

Methods

This multicentre, single-blind, parallel-group, randomised controlled trial aims to recruit 118 participants from community pharmacies in Aotearoa New Zealand. Participants will be randomised 1:1 to receive topical cream with 2% ECMT-154 or vehicle control, and will apply assigned treatment twice daily to affected areas for six weeks. The primary outcome is improvement in subjective symptoms, assessed by change in POEM score. Secondary outcomes include change in objective symptoms assessed by SCORAD (part B), PO-SCORAD, DLQI, and treatment acceptability assessed by TSQM II and NRS.

Discussion

Recruitment through community pharmacies commenced in January 2022 and follow up will be completed by mid-2023. This study aims to collect acceptability and efficacy data of mānuka oil based ECMT-154 for the treatment of eczema. If efficacy is demonstrated, this topical may provide an option for a novel emollient treatment. The community-based design of the trial is anticipated to provide a generalisable result.

Ethics and dissemination

Ethics approval was obtained from Central Health and Disability Ethics Committee (reference: 2021 EXP 11490). Findings of the study will be disseminated to study participants, published in peer-reviewed journal and presented at scientific conferences.

Trial registration

Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621001096842. Registered on August 18, 2021 (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=382412&isReview=true).

Protocol version

2.1 (Dated 18/05/2022).
Using simulation to introduce students and healthcare professionals to losses experienced by older adults: a pre-post analysis
Authors: Prete Donna , Tamburri Linda , Rolston Nicole , Sturgill Marc , Bridgeman Mary
Published: January 2024

Background

To introduce students and healthcare professionals to losses experienced by older adults and instill compassion among interprofessional learners, an interactive narrative simulation activity was developed and incorporated in clinical staff orientation and student professional course work. Narrative simulation allows learners to incorporate skills of examination, exploration, sharing, and reflection applied to simulated losses and lived experience of the older adult to promote empathy and understanding.

Methods

A pre-post analysis was conducted to evaluate changes in self-reported empathy scores among nurses, pharmacists, student nurses and student pharmacists using the 20-item Jefferson Scale of Empathy©, Health Professional and Health Professional Student versions. The instrument was administered prior to and after narrative simulation participation.

Results

A total of 152 students and 107 health care professionals completed both assessments. Median (interquartile range, IQR) post-simulation scores were significantly higher among nursing professionals [118.5 (112.25, 126.75) versus 126 (117, 132); P < 0.001; effect size 0.81] and nursing students [116 (107, 121) versus 119 (109, 126); P < 0.001; effect size 0.28], as well as pharmacy students [111 (101, 117) versus 116 (107.5, 125); P < 0.001; effect size 0.47]. Although a moderate effect size of 0.7 was observed for pharmacy professionals, there was no difference between pre- and post-activity empathy scores [117 (98, 137) versus 116 (101, 137); P = 0.16] for pharmacists participating in the narrative simulation exercise.

Conclusions

A statistically significant change in self-reported levels of empathy, particularly for nurses, nursing students, and pharmacy students, was observed; results of this activity did not suggest a change in pharmacist self-reported empathy levels. This activity could be implemented by educators seeking to increase awareness of losses experienced by the older adult.
Psychosocial interventions for people with amyotrophic lateral sclerosis and motor neuron disease and their caregivers: a scoping review
Authors: Oh Juyeon , An Jiwon , Park Kyongok , Park Youngok
Published: January 2024

Background

As amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) is a fatal progressive neurodegenerative disorder, patients experience severe impairments, with patients and family caregivers facing emotional distress and exhaustion. Several psychosocial interventions are aimed at providing tailored support for ALS/MND patients and caregivers. The aim of this study was to conduct a scoping review and present a comprehensive overview of psychosocial interventions designed for individuals and families affected by ALS/MND, while also pinpointing research gaps.

Methods

This scoping review utilized Arksey and O'Malley's methodological framework to investigate psychosocial interventions designed for individuals with ALS/MND and their families. The study adhered to the PRISMA-ScR checklist for reporting.

Results

A total of 27 articles describing 25 interventions met the inclusion criteria. The predominant interventions observed in the research encompassed education-related strategies, closely followed by behavior therapy, counseling, social support interventions, and psychotherapy interventions. Across the majority of the studies, findings indicated promising feasibility and acceptability of these interventions. Notably, a significant proportion of quantitative investigations yielded one or more statistically significant effects, while qualitative studies consistently reported favorable outcomes, including enhancements in well-being and heightened awareness of individual circumstances.

Conclusions

Given the progressive and debilitating nature of this condition, coupled with the absence of a cure, the adoption of a psychosocial approach can prove beneficial for both ALS/MND patients and their families. However, high-quality RCTs with a large sample size are recommended to examine and confirm the effectiveness.
The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges
Authors: Taracena-Agarwal M. L. , Hixson B. , Nandakumar S. , Girard-Mejia A. P. , Chen R. Y. , Huot L. , Padilla N. , Buchon N.
Published: January 2024

Background

Hematophagous mosquitoes transmit many pathogens that cause human diseases. Pathogen acquisition and transmission occur when female mosquitoes blood feed to acquire nutrients for reproduction. The midgut epithelium of mosquitoes serves as the point of entry for transmissible viruses and parasites.

Results

We studied midgut epithelial dynamics in five major mosquito vector species by quantifying PH3-positive cells (indicative of mitotic proliferation), the incorporation of nucleotide analogs (indicative of DNA synthesis accompanying proliferation and/or endoreplication), and the ploidy (by flow cytometry) of cell populations in the posterior midgut epithelium of adult females. Our results show that the epithelial dynamics of post-emergence maturation and of mature sugar-fed guts were similar in members of the Aedes, Culex, and Anopheles genera. In the first three days post-emergence, ~ 20% of cells in the posterior midgut region of interest incorporated nucleotide analogs, concurrent with both proliferative activity and a broad shift toward higher ploidy. In mature mosquitoes maintained on sugar, an average of 3.5% of cells in the posterior midgut region of interest incorporated nucleotide analogs from five to eight days post-emergence, with a consistent presence of mitotic cells indicating constant cell turnover. Oral bacterial infection triggered a sharp increase in mitosis and nucleotide analog incorporation, suggesting that the mosquito midgut undergoes accelerated cellular turnover in response to damage. Finally, blood feeding resulted in an increase in cell proliferation, but the nature and intensity of the response varied by mosquito species and by blood source (human, bovine, avian or artificial). In An. gambiae, enterocytes appeared to reenter the cell cycle to increase ploidy after consuming blood from all sources except avian.

Conclusions

We saw that epithelial proliferation, differentiation, and endoreplication reshape the blood-fed gut to increase ploidy, possibly to facilitate increased metabolic activity. Our results highlight the plasticity of the midgut epithelium in mosquitoes’ physiological responses to distinct challenges.

Graphical Abstract
Genomic characterization and immunotherapy for microsatellite instability-high in cholangiocarcinoma
Authors: Yang Xu , Lian Baofeng , Zhang Nan , Long Junyu , Li Yiran , Xue Jingnan , Chen Xiangqi , Wang Yunchao , Wang Yanyu , Xun Ziyu , Piao Mingjian , Zhu Chenpei , Wang Shanshan , Sun Huishan , Song Zhijian , Lu Leilei , Dong Xiaowei , Wang Aodi , Liu Wenjin , Pan Jie , Hou Xiaorong , Guan Mei , Huo Li , Shi Jie , Zhang Haohai , Zhou Jinxue , Lu Zhenhui , Mao Yilei , Sang Xinting , Wu Liqun , Yang Xiaobo , Wang Kai , Zhao Haitao
Published: January 2024

Background

Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA.

Methods

We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA.

Results

Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P < 0.001) and more positive programmed death ligand 1 (PD-L1) expression (37.5% vs. 11.9%, P < 0.001) than those with an MSS status. Among patients receiving PD-1 inhibitor-based therapy, those with MSI-H had a longer median overall survival (OS, hazard ratio (HR) = 0.17, P = 0.001) and progression-free survival (PFS, HR = 0.14, P < 0.001) than patients with MSS. Integrating MSI-H and PD-L1 expression status (combined positive score ≥ 5) could distinguish the efficacy of immunotherapy.

Conclusions

MSI-H status was associated with a higher TMB value and more positive PD-L1 expression in CCA tumors. Moreover, in patients with advanced CCA who received PD-1 inhibitor-based immunotherapy, MSI-H and positive PD-L1 expression were associated with improved both OS and PFS.

Trial registration

This study was registered on ClinicalTrials.gov on 07/01/2017 (NCT03892577).
Whole genome sequencing in clinical practice
Authors: Bagger Frederik Otzen , Borgwardt Line , Jespersen Andreas Sand , Hansen Anna Reimer , Bertelsen Birgitte , Kodama Miyako , Nielsen Finn Cilius
Published: January 2024

Whole genome sequencing (WGS) is becoming the preferred method for molecular genetic diagnosis of rare and unknown diseases and for identification of actionable cancer drivers. Compared to other molecular genetic methods, WGS captures most genomic variation and eliminates the need for sequential genetic testing. Whereas, the laboratory requirements are similar to conventional molecular genetics, the amount of data is large and WGS requires a comprehensive computational and storage infrastructure in order to facilitate data processing within a clinically relevant timeframe. The output of a single WGS analyses is roughly 5 MIO variants and data interpretation involves specialized staff collaborating with the clinical specialists in order to provide standard of care reports. Although the field is continuously refining the standards for variant classification, there are still unresolved issues associated with the clinical application. The review provides an overview of WGS in clinical practice - describing the technology and current applications as well as challenges connected with data processing, interpretation and clinical reporting.
Integrated analysis identifies GABRB3 as a biomarker in prostate cancer
Authors: Chen Jun-Yan , Chang Chi-Fen , Huang Shu-Pin , Huang Chao-Yuan , Yu Chia-Cheng , Lin Victor C. , Geng Jiun-Hung , Li Chia-Yang , Lu Te-Ling , Bao Bo-Ying
Published: January 2024

Background

Treatment failure following androgen deprivation therapy (ADT) presents a significant challenge in the management of advanced prostate cancer. Thus, understanding the genetic factors influencing this process could facilitate the development of personalized treatments and innovative therapeutic strategies. The phosphoinositide 3-kinase (PI3K)/AKT signaling pathway plays a pivotal role in controlling cell growth and tumorigenesis. We hypothesized that genetic variants within this pathway may affect the clinical outcomes of patients undergoing ADT for prostate cancer.

Methods

We genotyped 399 single-nucleotide polymorphisms (SNPs) across 28 core PI3K/AKT pathway genes in a cohort of 630 patients with prostate cancer undergoing ADT. We assessed the potential association of the SNPs with patient survival. Functional analyses of the implicated genes were also performed to evaluate their effects on prostate cancer.

Results

After multivariate Cox regression analysis and multiple testing correction, GABRB3 rs12591845 exhibited the most significant association with both overall and cancer-specific survivals (P < 0.003). A comprehensive pooled analysis of 16 independent gene expression datasets revealed elevated expression of GABRB3 in prostate cancer tissues compared to that in normal tissues (P < 0.001). Furthermore, gene set enrichment analysis unveiled differential enrichment of pathways such as myogenesis, interferon γ and α responses, and the MYC proto-oncogene pathway in tumors with elevated GABRB3 expression, implying a role for GABRB3 in prostate cancer.

Conclusion

Our results suggest that rs12591845 could potentially serve as a valuable prognostic indicator for patients undergoing ADT. The potential role of GABRB3 in promoting prostate tumorigenesis is also highlighted.
Promising antibacterial efficacy of arenicin peptides against the emerging opportunistic pathogen Mycobacterium abscessus
Authors: Casanova Magali , Maresca Marc , Poncin Isabelle , Point Vanessa , Olleik Hamza , Boidin-Wichlacz Céline , Tasiemski Aurélie , Mabrouk Kamel , Cavalier Jean-François , Canaan Stéphane
Published: January 2024

Background

Mycobacterium abscessus, a fast-growing non-tuberculous mycobacterium, is an emerging opportunistic pathogen responsible for chronic bronchopulmonary infections in people with respiratory diseases such as cystic fibrosis (CF). Due to its intrinsic polyresistance to a wide range of antibiotics, most treatments for M. abscessus pulmonary infections are poorly effective. In this context, antimicrobial peptides (AMPs) active against bacterial strains and less prompt to cause resistance, represent a good alternative to conventional antibiotics. Herein, we evaluated the effect of three arenicin isoforms, possessing two or four Cysteines involved in one (Ar-1, Ar-2) or two disulfide bonds (Ar-3), on the in vitro growth of M. abscessus.

Methods

The respective disulfide-free AMPs, were built by replacing the Cysteines with alpha-amino-n-butyric acid (Abu) residue. We evaluated the efficiency of the eight arenicin derivatives through their antimicrobial activity against M. abscessus strains, their cytotoxicity towards human cell lines, and their hemolytic activity on human erythrocytes. The mechanism of action of the Ar-1 peptide was further investigated through membrane permeabilization assay, electron microscopy, lipid insertion assay via surface pressure measurement, and the induction of resistance assay.

Results

Our results demonstrated that Ar-1 was the safest peptide with no toxicity towards human cells and no hemolytic activity, and the most active against M. abscessus growth. Ar-1 acts by insertion into mycobacterial lipids, resulting in a rapid membranolytic effect that kills M. abscessus without induction of resistance.

Conclusion

Overall, the present study emphasized Ar-1 as a potential new alternative to conventional antibiotics in the treatment of CF-associated bacterial infection related to M. abscessus.
Elucidating the role of Pyroptosis in papillary thyroid cancer: prognostic, immunological, and therapeutic perspectives
Authors: Li Fang , Du Rui , Kou Jiedong , Li Jingting , Zhou Le , Zhang Daqi , Fu Yantao , Dionigi Gianlorenzo , Bertoli Simona , Sun Hui , Liang Nan
Published: January 2024

Background

Pyroptosis, an inflammatory form of programmed cell death, has been implicated in the pathogenesis and progression of several cancers. However, the significance of pyroptosis-related genes (PRGs) in papillary thyroid cancer (PTC) remains unclear.

Methods

Transcriptome and clinical data of PTC patients were obtained from The Cancer Genome Atlas. The expression patterns of PRGs were identified by consensus clustering. A prognostic model for predicting the thyroid cancer-free interval (TCFi) employed five machine learning methods. Enrichment and immune-related analyses were performed to elucidate the role of pyroptosis. The responses to radioactive iodine (RAI), immune checkpoint inhibitors (ICIs), molecular targeted therapy (MTT), and chemotherapy (CTx) were predicted based on pyroptosis-derived features. Additionally, the expression of prognostic PRGs was validated via six external datasets, 16 cell lines, and 20 pairs of clinical samples.

Results

PTC patients were classified into three PyroClusters, C1 exhibited BRFA-like tumors with the highest invasiveness and the worst prognosis, C2 presented RAS-like tumors, and C3 was characterized by gene fusion. Nine PRGs (CXCL8, GJA1, H2BC8, IFI27, PRDM1, PYCARD, SEZ6L2, SIGLEC15, TRAF6) were filtered out to construct a PyroScore prognostic model. A derived nomogram demonstrated superior predictive performance than four clinical staging systems. A strong correlation between pyroptosis and tumor immune microenvironment (TIME) remodeling was observed in mechanistic analyses. Patients with a high PyroScore exhibited “hot” tumor immunophenotypes and had a poorer prognosis but could benefit more from ICIs and CTx (such as paclitaxel). Patients with a low PyroScore were more sensitive to RAI and MTT (such as pazopanib and sorafenib).

Conclusions

PyroScore model can effectively predict TCFi in patients with PTC. Dysregulated expression of PRGs is associated with the TIME modeling. Pyroptosis features have potential significance for developing novel therapeutic strategies for PTC patients.
Molecular surveillance of Kelch 13 polymorphisms in Plasmodium falciparum isolates from Kenya and Ethiopia
Authors: Jeang Brook , Zhong Daibin , Lee Ming-Chieh , Atieli Harrysone , Yewhalaw Delenasaw , Yan Guiyun
Published: January 2024

Background

Timely molecular surveillance of Plasmodium falciparum kelch 13 (k13) gene mutations is essential for monitoring the emergence and stemming the spread of artemisinin resistance. Widespread artemisinin resistance, as observed in Southeast Asia, would reverse significant gains that have been made against the malaria burden in Africa. The purpose of this study was to assess the prevalence of k13 polymorphisms in western Kenya and Ethiopia at sites representing varying transmission intensities between 2018 and 2022.

Methods

Dried blood spot samples collected through ongoing passive surveillance and malaria epidemiological studies, respectively, were investigated. The k13 gene was genotyped in P. falciparum isolates with high parasitaemia: 775 isolates from four sites in western Kenya (Homa Bay, Kakamega, Kisii, and Kombewa) and 319 isolates from five sites across Ethiopia (Arjo, Awash, Gambella, Dire Dawa, and Semera). DNA sequence variation and neutrality were analysed within each study site where mutant alleles were detected.

Results

Sixteen Kelch13 haplotypes were detected in this study. Prevalence of nonsynonymous k13 mutations was low in both western Kenya (25/783, 3.19%) and Ethiopia (5/319, 1.57%) across the study period. Two WHO-validated mutations were detected: A675V in three isolates from Kenya and R622I in four isolates from Ethiopia. Seventeen samples from Kenya carried synonymous mutations (2.17%). No synonymous mutations were detected in Ethiopia. Genetic variation analyses and tests of neutrality further suggest an excess of low frequency polymorphisms in each study site. Fu and Li’s F test statistic in Semera was 0.48 (P > 0.05), suggesting potential population selection of R622I, which appeared at a relatively high frequency (3/22, 13.04%).

Conclusions

This study presents an updated report on the low frequency of k13 mutations in western Kenya and Ethiopia. The WHO-validated R622I mutation, which has previously only been reported along the north-west border of Ethiopia, appeared in four isolates collected from eastern Ethiopia. The rapid expansion of R622I across Ethiopia signals the need for enhanced monitoring of the spread of drug-resistant P. falciparum parasites in East Africa. Although ACT remains currently efficacious in the study areas, continued surveillance is necessary to detect early indicators of artemisinin partial resistance.
Correlations between genetically predicted lipid-lowering drug targets and inflammatory bowel disease
Authors: Huang Kuiyuan , Huang Shenan , Xiong Ming
Published: January 2024

Background

Millions of individuals globally suffer from Inflammatory bowel diseases (IBDs). There is a dearth of large population-based investigations on lipid metabolism and IBDs, and it is unclear whether lipid-lowering drugs target IBDs causally. Consequently, the aim of this study was to investigate the effects of lipid-lowering medication targets on the occurrence and progression of IBDs.

Methods

Among the more than 400,000 participants in the UK Biobank cohort and the more than 170,000 participants in the Global Lipids Genetics Consortium, a total of nine genes linked to lipid-lowering drug targets were obtained (ABCG5/ABCG8, APOB, APOC3, LDLR, LPL, HMGCR, NPC1L1, PCSK9, and PPARA). IBD data were acquired from de Lange et al. (patients/sample size of IBDs: 25042/59957; ulcerative colitis (UC): 12366/45,975; Crohn's disease (CD): 12194/40,266) and the FinnGen cohort (patients/total sample size of IBDs: 4420/176,899; CD: 1520/171,906; UC: 3325/173,711). All four datasets were cross-combined for validation via Mendelian randomization analysis, and potential mediating factors were explored via mediation analysis.

Results

Genetically proxied APOC3 inhibition was related to increased IBD risk (odds ratio (95% confidence interval): 0.87 (0.80–0.95); P < 0.01) and UC risk (0.83 (0.73–0.94); P < 0.01). IBD and CD risk were reduced by genetic mimicry of LDLR and LPL enhancements, respectively (odds ratioLDLR: 1.18 (1.03–1.36); P = 0.018; odds ratioCD: 1.26 (1.11–1.43); P = 2.60E-04). Genetically proxied HMGCR inhibition was associated with increased CD risk (0.68 (0.50–0.94); P = 0.018). These findings were confirmed through Mendelian analysis of the cross-combination of four separate datasets. APOC3-mediated triglyceride levels may contribute to IBDs partly through mediated triglycerides, Clostridium sensu stricto 1, Clostridiaceae 1, or the Lachnospiraceae FCS020 group. LDLR enhancement may contribute to IBDs partly through increasing Lactobacillaceae.

Conclusion

Vigilance is required to prevent adverse effects on IBDs (UC) for patients receiving volanesorsen (an antisense oligonucleotide targeting ApoC3 mRNA) and adverse effects on CD for statin users. LPL and LDLR show promise as candidate drug targets for CD and IBD, respectively, with mechanisms that are potentially independent of their lipid-lowering effects.