bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromatin lncRNA Platr10 controls stem cell pluripotency by coordinating an intrachromosomal regulatory network
Authors: Du Zhonghua , Wen Xue , Wang Yichen , Jia Lin , Zhang Shilin , Liu Yudi , Zhou Lei , Li Hui , Yang Wang , Wang Cong , Chen Jingcheng , Hao Yajing , Salgado Figueroa Daniela , Chen Huiling , Li Dan , Chen Naifei , Celik Ilkay , Zhu Yanbo , Yan Zi , Fu Changhao , Liu Shanshan , Jiao Benzheng , Wang Zhuo , Zhang Hui , Gülsoy Günhan , Luo Jianjun , Qin Baoming , Gao Sujun , Kapranov Philipp , Esteban Miguel A. , Zhang Songling , Li Wei , Ay Ferhat , Chen Runsheng , Hoffman Andrew R. , Cui Jiuwei , Hu Ji-Fan
Published: August 2021

Background

A specific 3-dimensional intrachromosomal architecture of core stem cell factor genes is required to reprogram a somatic cell into pluripotency. As little is known about the epigenetic readers that orchestrate this architectural remodeling, we used a novel chromatin RNA in situ reverse transcription sequencing (CRIST-seq) approach to profile long noncoding RNAs (lncRNAs) in theOct4promoter.

Results

We identifyPlatr10as anOct4-Sox2binding lncRNA that is activated in somatic cell reprogramming.Platr10is essential for the maintenance of pluripotency, and lack of this lncRNA causes stem cells to exit from pluripotency. In fibroblasts, ectopically expressedPlatr10functions in trans to activate core stem cell factor genes and enhance pluripotent reprogramming. Using RNA reverse transcription-associated trap sequencing (RAT-seq), we show thatPlatr10interacts with multiple pluripotency-associated genes, includingOct4,Sox2,Klf4, andc-Myc, which have been extensively used to reprogram somatic cells. Mechanistically, we demonstrate thatPlatr10helps orchestrate intrachromosomal promoter-enhancer looping and recruits TET1, the enzyme that actively induces DNA demethylation for the initiation of pluripotency. We further show thatPlatr10contains anOct4binding element that interacts with theOct4promoter and a TET1-binding element that recruits TET1. Mutation of either of these two elements abolishesPlatr10activity.

Conclusion

These data suggest thatPlatr10functions as a novel chromatin RNA molecule to control pluripotencyin transby modulating chromatin architecture and regulating DNA methylation in the core stem cell factor network.
Effects of autonomic nervous system activation on endothelial function in response to acute exercise in hypertensive individuals: study protocol for a randomized double-blind study
Authors: Waclawovsky Gustavo , Boll Liliana Fortini Cavalheiro , Neto Salvador Gomes , Irigoyen Maria Claudia Costa , Lehnen Alexandre M.
Published: August 2021

Background

Arterial hypertension has a direct association with endothelial dysfunction and major cardiovascular events. There is evidence showing the benefits of aerobic exercise on flow-mediated dilation (FMD) in hypertensive individuals but little is known about the effect of autonomic nervous system (ANS) activation on FMD of the brachial artery in response to different types of exercise in this specific population. This study aims to examine the effects of ANS activation on FMD of the brachial artery in response to exercise in hypertensive individuals following a session of different types of exercise including aerobic exercise (AE), resistance exercise (RE), or combined exercise (CE).

Methods

Thirty-nine hypertensive volunteers aged 35 to 55 years will be randomly assigned to two exercise sessions: AE (40 min on a cycle ergometer at 60% of HR reserve), RE (4 lower limb sets with 12 repetitions at 60% 1-RM for 40 min), or CE (RE for 20 min + AE for 20 min). Each exercise group will be randomized to receive either an α1-adrenergic blocker (doxazosin 0.05 mg/kg−1) or placebo. Ultrasound measurement of FMD is performed 10 min before and 10, 40, and 70 min after exercise. ANS activation is monitored using a Finometer and measurements are taken during 10 min before each FMD assessment. Arterial stiffness is assessed by pulse wave velocity (PWV) analysis using a Complior device.

Discussion

We expect to demonstrate the effect of ANS activation on FMD of the brachial artery in hypertensive individuals in response to different types of exercise. This study may give some insight on how to improve exercise prescription for hypertension management.

Trial registration

https://clinicaltrials.gov and ID "NCT04371757". Registered on May 1, 2020.
Real-time interactive digital healthcare system for post-operative breast cancer patients: study protocol for a randomized controlled trial
Authors: Park Hae-Yeon , Nam Kyung Eun , Lim Jae-Young , Yeo Seung Mi , In Lee Jong , Hwang Ji Hye
Published: August 2021

Background

After receiving breast cancer surgery or reconstruction, shoulder dysfunctions including weakness, post-operative pain, shoulder joint instability, and limited range of motion (ROM) often occur. Due to limited ROM, patients may suffer difficulty in activities of daily living, and quality of life may be reduced. The objective of this study is to compare the effects on shoulder ROM of a real-time interactive digital healthcare system and brochure-based home rehabilitation program in post-operative breast cancer patients.

Methods

This study is a prospective, multi-center, assessor-blinded randomized controlled trial. The study aims to recruit 100 breast cancer patients exhibiting limited shoulder ROM after undergoing axillary lymph node dissection or breast reconstruction following mastectomy. Patients will be randomly assigned to two groups for 8 weeks of rehabilitation: a digital healthcare system rehabilitation (intervention) group and a brochure-based rehabilitation (control) group. The primary outcome is the change in ROM of the affected shoulder between baseline and 12 weeks after enrollment. Secondary outcomes include pain in the affected shoulder, as measured using a numerical rating scale, functional outcomes (QuickDASH scores), and quality of life (FACT-B and EQ-5D-5L scores), all of which will be measured on enrollment and 4, 8, and 12 weeks thereafter.

Discussion

This study will compare the effectiveness of a newly developed, augmented reality-based real-time interactive digital healthcare system with that of brochure-based home rehabilitation for improving the shoulder ROM, pain, functional outcomes, and quality of life of post-operative breast cancer patients.

Trial registration

ClinicalTrials.govNCT04316156. Registered on 20 March 2020.
Multi-omics of the esophageal microenvironment identifies signatures associated with progression of Barrett’s esophagus
Authors: Deshpande Nandan P. , Riordan Stephen M. , Gorman Claire J. , Nielsen Shaun , Russell Tonia L. , Correa-Ospina Carolina , Fernando Bentotage S. M. , Waters Shafagh A. , Castaño-Rodríguez Natalia , Man Si Ming , Tedla Nicodemus , Wilkins Marc R. , Kaakoush Nadeem O.
Published: August 2021

Background

The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relationships between the esophageal microbiome and the host.

Methods

Here, we examine the esophageal microenvironment in gastro-esophageal reflux disease and metaplasia using multi-omics strategies targeting the microbiome and host transcriptome, followed by targeted culture, comparative genomics, and host-microbial interaction studies of bacterial signatures of interest.

Results

Profiling of the host transcriptome from esophageal mucosal biopsies revealed profound changes during metaplasia. Importantly, five biomarkers showed consistent longitudinal changes with disease progression from reflux disease to metaplasia. We showed for the first time that the esophageal microbiome is distinct from the salivary microbiome and the enrichment ofCampylobacterspecies as a consistent signature in disease across two independent cohorts. Shape fitting and matrix correlation identified associations between the microbiome and host transcriptome profiles, with a novel co-exclusion relationship found betweenCampylobacterand napsin B aspartic peptidase. Targeted culture ofCampylobacterspecies from the same cohort revealed a subset of isolates to have a higher capacity to survive within primary human macrophages. Comparative genomic analyses showed these isolates could be differentiated by specific genomic features, one of which was validated to be associated with intracellular fitness. Screening for theseCampylobacterstrain-specific signatures in shotgun metagenomics data from another cohort showed an increase in prevalence with disease progression. Comparative transcriptomic analyses of primary esophageal epithelial cells exposed to theCampylobacterisolates revealed expression changes within those infected with strains with high intracellular fitness that could explain the increased likelihood of disease progression.

Conclusions

We provide a comprehensive assessment of the esophageal microenvironment, identifying bacterial strain-specific signatures with high relevance to progression of metaplasia.
S100A8/A9 is not essential for the development of inflammation and joint pathology in interleukin-1 receptor antagonist knockout mice
Authors: Di Ceglie Irene , van Lent Peter L. E. M. , Geven Edwin J. W. , Koenders Marije I. , Blom Arjen B. , Vogl Thomas , Roth Johannes , van den Bosch Martijn H. J.
Published: August 2021

Background

Excessive osteoclast activity, which is strongly stimulated by pro-inflammatory mediators, results in bone and cartilage degeneration as central features of many arthritides. Levels of the alarmin S100A8/A9 and interleukin (IL)-1β are both increased in arthritis patients and correlate with disease activity and progression of tissue erosion. We previously presented S100A8/A9 as a good biomarker for joint inflammation and arthritis pathology under circumstances of high IL-1 signaling in mice that lack the gene encoding IL-1 receptor antagonist (Il1rn−/− mice). Here, we investigated whether S100A8/A9 is also actively involved in the development of joint inflammation and both cartilage and bone pathology under these conditions by comparing Il1rn−/− mice with mice that have an additional deficiency for S100a9 (Il1rn−/−XS100a9−/−).

Methods

Il1rn−/−XS100a9−/− on a BALB/c background were obtained by crossing S100a9−/− mice and Il1rn−/− mice. Arthritis incidence and severity were macroscopically scored. Myeloid cell populations in the bone marrow and spleen were determined using flow cytometry. In vitro osteoclastogenesis of bone marrow cells was evaluated with TRAP staining. Microscopic joint inflammation, cartilage degeneration, and bone destruction were evaluated using histology of ankle joints of 12- and 20-week-old mice.

Results

Macroscopically scored arthritis severity was comparable between Il1rn−/− and Il1rn−/−XS100a9−/− mice. Inflammation, cartilage erosion, and bone erosion were clearly present in 12-week-old mice of both strains lacking Il1rn−/−, but not significantly different between Il1rn−/−XS100a9−/− and Il1rn−/−. Moreover, we observed that the numbers of neutrophils and monocytes were increased by the absence of Il1rn, which was affected by the absence of S100a9 only in the spleen but not in the bone marrow. In line with our other findings, the absence of S100a9 did not affect the osteoclastogenic potential of osteoclast precursors in the absence of Il1rn. Finally, in agreement with the findings in early arthritis development in 12-week-old mice, cartilage and bone erosion in 20-week-old mice was significantly higher in both Il1rn−/− strains, but the additional absence of S100a9 did not further affect tissue pathology.

Conclusion

S100A8/A9 deficiency does not significantly affect inflammation and joint destruction in mice with high IL1β signaling suggesting that S100A8/A9 is not essential for the development of arthritis under these conditions.
Diabetes self-care practices and resilience in the Brazilian COVID-19 pandemic: results of a web survey: DIABETESvid
Authors: Binhardi Bárbara Aparecida , de Souza Teixeira Carla Regina , de Almeida-Pititto Bianca , Barbosa-Junior Francisco , Franco Laercio Joel , de Melo Karla Fabiana Santana , Malerbi Domingos Augusto Cherino , de Oliveira Rinaldo Eduardo Machado
Published: August 2021

Background

The world guidance on the measures of social distancing for prevention of COVID-19 has changed the daily habits of great part of the population, and this could influence the care and resilience with diabetes during situations of adversity. This study aimed at assessing the characteristics of diabetic individuals and self-care practices and resilience with diabetes in the context of the COVID-19 pandemic in Brazil.

Methods

This is a cross-sectional web survey study carried out among adults with diabetes, in which a structured 43-item questionnaire was conducted on the REDCap plataform, including the Diabetes Self-Care Activities Questionnaire and Connor-Davidson Resilience Scale, to measure socio-demographic and clinical characteristics. The web survey was disseminated through the main social media and data were collected from September 1st to October 19th, 2020. Data analysis was performed according to type of diabetes mellitus (DM) and at a significance level of 5% (p < 0.05).

Results

Of the 1633 participants, 67.5% were women, 43.2% aged between 35 and 59 years old, 68.0% lived in the south-eastern region of Brazil, 57.1% had a high education level, 49% reported to have DM1 and 140 participants reported to have had COVID-19. Diabetes care mostly involved the use of medications (93%), whereas the least used ones were physical activity (24.6%) and examination of the shoes (35.7%). About 40% of the participants reported to be followed up by telemedicine, 61.5% monitored the glycaemic levels, 61.2% followed a healthy diet and 43.4% left home only to go to the supermarket and drugstore. The mean resilience was 25.4 (SD = 7.7).

Conclusions

In Brazil, individuals with diabetes followed social distancing and maintained their medication treatment for DM. However, practice of physical activity and foot examination was little followed by the participants, who also had a low level of resilience. These findings showed the importance of patient follow-up in the healthcare services, meaning that telemedicine should be improved and support provided for adaptation in view of the therapeutic setbacks.
Multiple schwannomas of the facial nerve mimicking cervical lymphoma: a case report
Authors: Kühn Jan Philipp , Wagner Mathias , Bozzato Alessandro , Linxweiler Maximilian
Published: August 2021

Background

In this report, we describe the first case in literature of a patient with multiple schwannomas of the marginal mandibular branch of the facial nerve.

Case presentation

A Caucasian patient presented with a sudden onset of left lower facial nerve palsy House–Brackmann score III for 1 month. Computed tomography imaging was performed to exclude a cerebral event and revealed multiple tumors within the left parotid gland. Duplex ultrasound and magnetic resonance imaging scans delineated multiple, hypoechoic tumors, round in shape and well defined without a hilar structure along the left mandible. For histological verification, a left-side partial parotidectomy and extirpation of an intraparotideal node was performed with use of a nerve-integrity monitor. Histomorphological analysis of the resected tissue revealed a benign schwannoma. Facial nerve function remained unchanged since the operation. The size of the nonresected tumors is currently monitored regularly by ultrasonography. Fibromatosis has been excluded.

Conclusions

If multiple tumors occur in the parotid gland and the angle of the jaw, schwannomas need to be considered as a differential diagnosis. To plan the right diagnostic surgical intervention and prevent nerve damage, a thorough ultrasound examination is essential in preoperative diagnostic work-up for any suspicious lesion of the parotid gland and jaw region.
Acute pharmacogenetic dystonic reactions in a family with the CYP2D6 *41 allele: a case report
Authors: Wong Darice Y. , Fogel Brent L.
Published: August 2021

Background

Dystonia is a known neurological complication of certain medications; however, the mechanism behind such effects is often undetermined. Similarly, the clinical pharmacogenomic effects associated with various alleles of the cytochrome P450 family of proteins, and their role in acute dystonic reactions, are also presently unknown.

Case presentation

We describe a woman presenting with acute dystonic reactions to ondansetron, prochlorperazine, and metoclopramide followed by persistent focal dystonia. A similar family history was reported in her siblings and her father to prochlorperazine, drugs all metabolized by the cytochrome P450 2D6 (CYP2D6) enzyme. Pharmacogenomic testing indicated the patient was heterozygous for the intermediate metabolizer *41 allele (CYP2D6 2988G>A, NM_000106.6:c.985+39G>A, rs28371725). Her father was homozygous for this CYP2D6 *41 allele, and consequently, her siblings were obligate carriers.

Conclusions

The metabolism of ondansetron, metoclopramide, or prochlorperazine in patients with the *41 CYP2D6 allele has not been studied. In this family, clinical evidence implicates the *41 CYP2D6 allele as causing extrapyramidal adverse pharmacologic reactions. Patients with a family history of medication-induced dystonia involving these medications should be considered for pharmacogenomic testing, and patients carrying the *41 CYP2D6 allele should consider reduction or avoidance of CYP2D6-mediated medications to minimize the potential risk of adverse extrapyramidal effects.
cGMP-grade human iPSC-derived retinal photoreceptor precursor cells rescue cone photoreceptor damage in non-human primates
Authors: Lingam Swathi , Liu Zengping , Yang Binxia , Wong Wendy , Parikh Bhav Harshad , Ong Jun Yi , Goh Debbie , Wong Daniel Soo Lin , Tan Queenie Shu Woon , Tan Gavin S. W. , Holder Graham E. , Regha Kakkad , Barathi Veluchamy Amutha , Hunziker Walter , Lingam Gopal , Zeng Xianmin , Su Xinyi
Published: August 2021

Background

Retinal regenerative therapies hold great promise for the treatment of inherited retinal degenerations (IRDs). Studies in preclinical lower mammal models of IRDs have suggested visual improvement following retinal photoreceptor precursors transplantation, but there is limited evidence on the ability of these transplants to rescue retinal damage in higher mammals. The purpose of this study was to evaluate the therapeutic potential of photoreceptor precursors derived from clinically compliant induced pluripotent stem cells (iPSCs).

Methods

Photoreceptor precursors were sub-retinally transplanted into non-human primates (Macaca fascicularis). The cells were transplanted both in naïve and cobalt chloride-induced retinal degeneration models who had been receiving systemic immunosuppression for one week prior to the procedure. Optical coherence tomography, fundus autofluorescence imaging, electroretinography, ex vivo histology and immunofluorescence staining were used to evaluate retinal structure, function and survival of transplanted cells.

Results

There were no adverse effects of iPSC-derived photoreceptor precursors on retinal structure or function in naïve NHP models, indicating good biocompatibility. In addition, photoreceptor precursors injected into cobalt chloride-induced retinal degeneration NHP models demonstrated an ability both to survive and to mature into cone photoreceptors at 3 months post-transplant. Optical coherence tomography showed restoration of retinal ellipsoid zone post-transplantation.

Conclusions

These findings demonstrate the safety and therapeutic potential of clinically compliant iPSC-derived photoreceptor precursors as a cell replacement source for future clinical trials.
Effective asymmetric preparation of (R)-1-[3-(trifluoromethyl)phenyl]ethanol with recombinant E. coli whole cells in an aqueous Tween-20/natural deep eutectic solvent solution
Authors: Zhuang Wenjin , Liu Hanyu , Zhang Ying , He Junyao , Wang Pu
Published: August 2021

(R)-1-[3-(Trifluoromethyl)phenyl]ethanol ((R)-MTF-PEL) is an important chiral building block for the synthesis of a neuroprotective compound, (R)-3-(1-(3-(trifluoromethyl)phenyl)ethoxy)azetidine-1-carboxamide. In this work, an effective whole-cell-catalyzed biotransformation was developed to produce (R)-MTF-PEL, and its productivity was increased by medium engineering strategy. The recombinant E. coli BL21(DE3)-pET28a(+)-LXCAR-S154Y variant affording carbonyl reductase was adopted for the reduction of 3'-(trifluoromethyl)acetophenone to (R)-MTF-PEL with enantiomeric excess (ee) > 99.9%. The addition of 0.6% Tween-20 (w/v) boosted the bioreduction, because the substrate concentration was increased by 4.0-fold than that in the neat buffer solution. The biocatalytic efficiency was further enhanced by introducing choline chloride: lysine (ChCl:Lys, molar ratio of 1:1) in the reaction medium, because the product yield reached 91.5% under 200 mM substrate concentration in the established Tween-20/ChCl:Lys-containing system, which is the highest ever reported for (R)-MTF-PEL production. The optimal reduction conditions were as follows: 4% (w/v) ChCl:Lys, 12.6 g (DCW)/L recombinant E. coli cells, pH 7.0, 30 ℃ and 200 rpm, reaction for 18 h. The combined strategy of surfactant and NADES has great potential in the biocatalytic process and the synthesis of chiral alcohols.
A nonlinear fractional Rayleigh–Stokes equation under nonlocal integral conditions
Authors: Luc Nguyen Hoang , Long Le Dinh , Van Ho Thi Kim , Nguyen Van Thinh
Published: August 2021

In this paper, we study the fractional nonlinear Rayleigh–Stokes equation under nonlocal integral conditions, and the existence and uniqueness of the mild solution to our problem are considered. The ill-posedness of the mild solution to the problem recovering the initial value is also investigated. To tackle the ill-posedness, a regularized solution is constructed by the Fourier truncation method, and the convergence rate to the exact solution of this method is demonstrated.
Dietary phytochemicals as a promising nutritional strategy for sarcopenia: a systematic review and meta-analysis of randomized controlled trials
Authors: Jeong Hye Yun , Kwon Oran
Published: August 2021

The decline in skeletal muscle mass and strength, also called sarcopenia, accelerates with age, leading to negative health outcomes and poor quality of life. Diet is important to promote health and plays a key role in muscle aging. Plant-based foods have recently received attention as sources of phytochemical components to attenuate loss of muscle mass and strength in older adults. This systematic review and meta-analysis evaluated the benefits of botanical extracts and their phytochemical compounds for muscle health in older adults. Randomized controlled trials were identified via systematic searches of four electronic databases (PubMed, Cochrane Library, Web of Science, and KoreaMed) up to June 2021 and were quality assessed. The results of muscle strength, mass, and physical performance were pooled using a random-effects model. Fourteen studies involving 528 subjects aged between 50 and 80 years met the inclusion criteria. Dietary phytochemicals significantly increased handgrip strength [0.90 kg; 95% confidence interval (CI) 0.26–1.53,p =  0.01] and physical performance (timed up-and-go test: − 0.5 s, 2.73 times; 95% CI − 0.84 to − 0.15,p <  0.01; 30-s chair stand test: 95% CI 0.88–4.59,p <  0.01; 6-min walk test: 29.36 m; 95% CI 14.58–44.13,p <  0.0001) but had no effect on improvement in muscle mass. Publication bias evaluated by funnel plots and Egger’s regression test demonstrated no evidence of substantial publication bias (p >  0.05). The findings of this systematic review and meta-analysis suggest that phytochemicals are a potential nutritional strategy to improve muscle health in older adults.
Cutaneous microbial biofilm formation as an underlying cause of red scrotum syndrome
Authors: Perry Theodore W.
Published: August 2021

Background

Red scrotum syndrome is typically described as well-demarcated erythema of the anterior scrotum accompanied by persistent itching and burning. It is chronic and difficult to treat and contributes to significant psychological distress and reduction in quality of life. The medical literature surrounding the condition is sparse, with the prevalence likely under-recognized and the pathophysiology remaining poorly understood. Formation of a cutaneous microbial biofilm has not been proposed as an underlying etiology. Microbial biofilms can form whenever microorganisms are suspended in fluid on a surface for a prolonged time and are becoming increasingly recognized as important contributors to medical disease (e.g., chronic wounds).

Case presentation

A 26-year-old man abruptly developed well-demarcated erythema of the bilateral scrotum after vaginal secretions were left covering the scrotum overnight. For 14 months, the patient experienced daily scrotal itching and burning while seeking care from multiple physicians and attempting numerous failed therapies. He eventually obtained complete symptomatic relief with the twice daily application of 0.8% menthol powder. Findings in support of a cutaneous microbial biofilm as the underlying etiology include: (1) the condition began following a typical scenario that would facilitate biofilm formation; (2) the demarcation of erythema precisely follows the scrotal hairline, suggesting that hair follicles acted as scaffolding during biofilm formation; (3) despite resolution of symptoms, the scrotal erythema has persisted, unchanged in boundary 15 years after the condition began; and (4) the erythematous skin demonstrates prolonged retention of gentian violet dye in comparison with adjacent unaffected skin, suggesting the presence of dye-avid material on the skin surface.

Conclusion

The probability that microorganisms, under proper conditions, can form biofilm on intact skin is poorly recognized. This case presents a compelling argument for a cutaneous microbial biofilm as the underlying cause of red scrotum syndrome in one patient, and a review of similarities with other reported cases suggests the same etiology is likely responsible for a significant portion of the total disease burden. This etiology may also be a significant contributor to the disease burden of vulvodynia, a condition with many similarities to red scrotum syndrome.
Rural sustainability and food choice: the effect of territorial characteristics on the consumers’ preferences for organic lentils
Authors: Paffarini Chiara , Torquati Biancamaria , Tempesta Tiziano , Venanzi Sonia , Vecchiato Daniel
Published: August 2021

The importance of pulse cultivation and consumption is recognized by the scientific community in terms of human nutrition, food security, biodiversity and a valid substitute for animal protein. In some marginal areas, pulse cultivation represents also a protection against the abandonment of agricultural land, the preservation of traditional landscape and the maintenance of natural environments, besides contributing to the safeguard of traditional gastronomy and culture.

This study explores how some characteristics connected with rural sustainability, like the preservation of the traditional rural landscape, production area in a Natura 2000 Site of Community Importance (SCI) and EU quality labels (PDO and PGI), might influence organic consumers’ choice of lentils. Data were collected in the Umbria region (Italy) in 2014 by interviewing 213 consumers’ members of Organic Solidarity Purchase Groups (O-SPGs). The Discrete Choice Experiment methodology was used, and three different models (Multinomial Logit Model (MNL), Mixed Logit Model (RPL) and Endogenous Attribute Attendance (EAA)) were applied to verify the reliability of the estimates. Attribute non-attendance (ANA) behaviour was taken into account. Results reveal that the presence of ANA had an impact on both the relative importance of the estimated attributes and the magnitude of the estimated mean WTP. Therefore, this study suggests that WTP mean estimates should be considered with caution for marketing purposes if ANA is not considered. Looking at pulses, the results help to understand the importance in monetary terms of the relationship between lentil choice and rural sustainability.
Ecological and behavioural risk factors of scrub typhus in central Vietnam: a case-control study
Authors: Tran Hanh Thi Duc , Hattendorf Jan , Do Hung Manh , Hoang Thanh Tien , Hoang Hang Thi Hai , Lam Hoa Ngoc , Huynh Mai Kim , Vu Lan Thi Hoang , Zinsstag Jakob , Paris Daniel Henry , Schelling Esther
Published: August 2021

Background

The risk factors for scrub typhus in Vietnam remain unknown. Scrub typhus caused byOrientia tsutsugamushioften presents as an undifferentiated febrile illness and remains under appreciated due to the limited availability of diagnostic tests. This tropical rickettsial illness is increasingly recognized as an important cause of non-malaria acute undifferentiated fever in Asia. This study aimed to investigate behavioural and ecological related risk factors of scrub typhus to prevent this potentially life-threatening disease in Vietnam.

Methods

We conducted a clinical hospital-based active surveillance study, and a retrospective residence-enrolment date-age-matched case–control study in Khanh Hoa province, Vietnam, from August 2018 to March 2020. Clinical examinations, polymerase chain reaction and enzyme-linked immunosorbent assay IgM tests were applied to define cases and controls. All enrolled participants filled out a questionnaire including demographic socio-economic status, personal behaviors/protective equipment, habitat connections, land use, and possible exposure to the vector. Multivariable conditional logistic regression was used to define the scrub typhus associated risk factors.

Results

We identified 44 confirmed cases and matched them with 152 controls. Among cases and controls, the largest age group was the 41–50 years old and males accounted for 61.4% and 42.8%, respectively. There were similarities in demographic characteristics between the two groups, with the exception of occupation. Several factors were significantly associated with acquisition of scrub typhus, including sitting/laying directly on household floor [adjustedOR(aOR) = 4.9, 95%CI:1.6–15.1,P = 0.006], household with poor sanitation/conditions (aOR = 7.9, 95%CI:1.9–32.9,P = 0.005), workplace environment with risk (aOR = 3.0, 95%CI:1.2–7.6,P = 0.020), always observing mice around home (aOR = 3.7, 95%CI:1.4–9.9,P = 0.008), and use of personal protective equipment in the field (aOR = 0.4, 95%CI:0.1–1.1,P = 0.076).

Conclusions

Ecological and household hygiene-related factors were more associated with scrub typhus infection, than individual-level exposure activities in the hyper-endemic area. These findings support local education and allow people to protect themselves from scrub typhus, especially in areas with limitations in diagnostic capacity.

Graphical abstract
Piloting I-SLEEP: a patient-centered education and empowerment intervention to improve patients’ in-hospital sleep
Authors: Mason Noah R. , Orlov Nicola M. , Anderson Samantha , Byron Maxx , Mozer Christine , Arora Vineet M.
Published: August 2021

Background

Sleep disturbances in hospitalized patients are linked to poor recovery. In preparation for a future randomized controlled trial, this pilot study evaluated the feasibility and acceptability of a multi-component intervention (I-SLEEP) that educates and empowers inpatients to advocate for fewer nighttime disruptions in order to improve sleep during periods of hospitalization.

Methods

Eligible inpatients received I-SLEEP, which included an educational video, brochure, sleep kit, and three questions patients can ask their team to reduce nighttime disruptions. Following I-SLEEP, inpatients were surveyed on the primary feasibility outcomes of satisfaction with and use of I-SLEEP components. Inpatients were also surveyed regarding empowerment and understanding of intervention materials. Patient charts were reviewed to collect data on nighttime (11 PM–7 AM) vital sign and blood draws disruptions.

Results

Ninety percent (n= 26/29) of patients were satisfied with the brochure and 87% (n= 27/31) with the video. Nearly all (95%,n= 36/37) patients felt empowered to ask their providers to minimize nighttime disruptions and 68% (n= 26/37) intended to alter sleep habits post-discharge. Forty-nine percent (n= 18/37) of patients asked an I-SLEEP question. Patients who asked an I-SLEEP question were significantly more likely to experience nights with fewer disruptions due to nighttime vitals (19% vs. 2.1%,p= 0.008).

Conclusion

This pilot study found that I-SLEEP was well-accepted and enabled hospitalized patients to advocate for less disrupted sleep. Educating patients to advocate for reducing nighttime disruptions may be a patient-centered, low-cost strategy to improve patients’ care and in-hospital experience. These results suggest that I-SLEEP is ready to be evaluated against routine care in a future randomized controlled trial.

Trial registration

ClinicalTrials.GovNCT04151251.
Clinical utility of fetal echocardiography: an Egyptian center experience
Authors: Al-Fahham Marwa Moustapha , Gad Nada Ayman , Ramy Ahmed Ramy Mohamed , Habeeb Nevin Mamdouh
Published: August 2021

Background

The impact of early diagnosis of fetal cardiac abnormalities on the postnatal outcome has been controversial in literature. We aimed to evaluate the role of fetal echocardiography (FE) as a diagnostic tool for early detection and proper management of fetal cardiac abnormalities, study the indications of referral and detect the perinatal outcome in our institution.

Results

This is a cross-sectional observational and descriptive study that included one hundred and one singleton pregnant women (101 fetuses) who were referred for FE over a period of one year. Indications for referral and perinatal risk factors were documented. FE and postnatal transthoracic echocardiography were done. Fetal cardiac abnormalities were detected in 46.5% of cases. Congenital heart defects (CHDs) in 34.6%, fetal arrythmias in 9.9%, cardiomyopathy in 2.9% and cardiac mass (Rhabdomyoma) in 1% (combined structural and rhythm abnormalities were observed in two fetuses). Of the CHDs, complex heart lesions were diagnosed in 57.1%, common atrioventricular canal in 28.6% and conotrunchal anomalies in 14.3%. Of the ten cases with fetal arrythmias, five fetuses had tachyarrhythmias, four had ectopics and one fetus had congenital heart block in association with maternal lupus. The indications for referral were abnormal obstetric ultrasound (52.5%), maternal medical illnesses (23.8%), multiple neonatal deaths (13.9%) and positive family history of CHD (10.9%). The number of fetuses with cardiac abnormalities was significantly higher than those without cardiac abnormalities in mothers not exposed to perinatal risk factors (p = 0.009) and was statistically lower in mothers exposed to perinatal risk factors (p = 0.005). FE showed 100% accuracy in diagnosing complex lesions, common atrio-ventricular canals, cono-truncal anomalies, cardiac masses and fetal arrhythmias. It missed two cases of tiny muscular ventricular septal defects and one case of aortic coarctation. Cases of fetal supraventricular tachycardia were successfully treated in-utero.

Conclusions

CHDs exist in fetuses with no underlying perinatal risk factors. FE can accurately diagnose most of the cardiac anomalies though few errors remain challenging (aortic coarctation). It also offers a good chance for successful early life-saving management of some types of fetal arrhythmia.
Joint seismic and petrophysical nonlinear inversion with Gaussian mixture-based adaptive regularization
Authors: Guo Qiang , Ba Jing , Fu Li-Yun , Luo Cong
Published: August 2021

The estimation of reservoir parameters from seismic observations is one of the main objectives in reservoir characterization. However, the forward model relating the petrophysical properties of rocks to observed seismic data is highly nonlinear, and solving the relevant inverse problem is a challenging task. We have developed a novel inversion method for jointly estimating the elastic and petrophysical parameters of rocks from prestack seismic data. We combine a full rock-physics model and the exact Zoeppritz equation as the forward model. To overcome the ill conditioning of the inverse problem and address the complex prior distribution of model parameters given lithofacies variations, we have developed a regularization term based on the prior Gaussian mixture model under a Bayesian framework. The objective function is optimized by the fast simulated annealing algorithm, during which the Gaussian mixture-based regularization terms are adaptively and iteratively adjusted by the maximum likelihood estimator, allowing the posterior distribution to be more consistent with the observed seismic data. The adaptive regularization method improves the accuracy of petrophysical parameters compared with sequential inversion and nonadaptive regularization methods, and the inversion result can be used for indicating gas-saturated areas when applied to field data.
Performance of Multiple-Batch Approaches to Pharmacokinetic Bioequivalence Testing for Orally Inhaled Drug Products with Batch-to-Batch Variability
Authors: Burmeister Getz Elise , Carroll Kevin J. , Christopher J. David , Morgan Beth , Haughie Scott , Cavecchi Alessandro , Wiggenhorn Christopher , Beresford Hayden , Strickland Helen , Lyapustina Svetlana
Published: August 2021

Batch-to-batch pharmacokinetic (PK) variability of orally inhaled drug products has been documented and can render single-batch PK bioequivalence (BE) studies unreliable; results from one batch may not be consistent with a repeated study using a different batch, yet the goal of PK BE is to deliver a product comparison that is interpretable beyond the specific batches used in the study. We characterized four multiple-batch PK BE approaches to improve outcome reliability without increasing the number of clinical study participants. Three approaches include multiple batches directly in the PK BE study with batch identity either excluded from the statistical model (“Superbatch”) or included as a fixed or random effect (“Fixed Batch Effect,” “Random Batch Effect”). A fourth approach uses a bio-predictive in vitro test to screen candidate batches, bringing the median batch of each product into the PK BE study (“Targeted Batch”). Three of these approaches (Fixed Batch Effect, Superbatch, Targeted Batch) continue the single-batch PK BE convention in which uncertainty in the Test/Reference ratio estimate due to batch sampling is omitted from the Test/Reference confidence interval. All three of these approaches provided higher power to correctly identify true bioequivalence than the standard single-batch approach with no increase in clinical burden. False equivalence (type I) error was inflated above the expected 5% level, but multiple batches controlled type I error better than a single batch. The Random Batch Effect approach restored 5% type I error, but had low power for small (e.g., <8) batch sample sizes using standard [0.8000, 1.2500] bioequivalence limits.
Diabetes and Outcomes Following Personalized Antiplatelet Therapy in Coronary Artery Disease Patients Who Have Undergone PCI
Authors: Zheng Ying-Ying , Wu Ting-Ting , Yang Yi , Hou Xian-Geng , Chen You , Ma Xiang , Ma Yi-Tong , Zhang Jin-Ying , Xie Xiang
Published: August 2021

Context

A personalized antiplatelet therapy guided by a novel platelet function testing (PFT), PL-12, is considered an optimized treatment strategy in stable coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, the safety and efficacy of any dual-antiplatelet therapy (DAPT) strategy may differ in relation to diabetes status.

Objective

The aim of this study was to compare the outcomes of PFT-guided personalized DAPT in stable CAD patients with and without diabetes mellitus.

Methods

The PATH-PCI trial randomly assigned 2285 stable CAD patients to either personalized antiplatelet therapy or standard antiplatelet treatment. We investigated the association and interaction of diabetes on clinical outcomes across 2 treatment groups.

Results

We did not find a significant difference between the personalized group and the standard group in net adverse clinical events in either diabetes patients (10.3% vs 13.4%, P = .224) or in the nondiabetic group (3.1% vs 5.0%, P = .064). In diabetes patients (n = 646, 28.3%), the overall ischemic event rates were significantly low (6.8% vs 11.3%, HR = 0.586, 95% CI, 0.344-0.999, P = .049) and the bleeding event rates did not differ between the 2 groups (3.5% vs 3.3%, HR = 1.066, 95% CI, 0.462-2.458, P = .882). Similarly, in nondiabetic patients, the overall ischemic event rates were significantly low (1.8% vs 4.2%, HR = 0.428, 95% CI, 0.233-0.758, P = .006) and the bleeding event rates did not differ between the 2 groups (1.6% vs 0.9%, HR = 1.802, 95% CI: 0.719-4.516, P = .209).

Conclusion

The present study suggests that personalized antiplatelet therapy according to PFT can reduce ischemic events but not increase bleedings in stable CAD patients with or without diabetes who have undergone PCI.
Health of Immigrant Children: The Role of Immigrant Generation, Exogamous Family Setting, and Family Material and Social Resources
Authors: Loi Silvia , Pitkänen Joonas , Moustgaard Heta , Myrskylä Mikko , Martikainen Pekka
Published: August 2021

Although the children of first-generation immigrants tend to have better health than the native population, the health advantage of the children of immigrant families deteriorates over generations. It is, however, poorly understood where on the generational health assimilation spectrum children with one immigrant and one native parent (i.e., exogamous families) lie, to what extent family resources explain health assimilation, and whether the process of assimilation varies across health conditions. We seek to extend our understanding of the process of health assimilation by analyzing the physical and mental health of immigrant generations, assessing the role of exogamous family arrangements, and testing the contributions of family material and social resources to children's outcomes. We use register-based longitudinal data on all children residing in Finland, born in 1986–2000, and alive in 2000; these data are free of reporting bias and loss to follow-up. We estimate the risk of receiving inpatient and outpatient care for somatic conditions, psychopathological disorders, and injuries by immigrant generation status. Our results show evidence of a negative health assimilation process, with both first- and second-generation immigrant children having a higher prevalence of physical problems and particularly mental health problems than native children that is only partially explained by family resources. We find that the children of exogamous families are at especially high risk of developing psychopathological disorders. These results provide strong support for the hypothesis that children of exogamous families constitute a specific health risk group and that the impact on children's health of family social and material resources seems to be secondary to other unobserved factors.
Spinal Brucellosis: A Case Report and Review of the Literature
Authors: Rizkalla James M , Alhreish Khalid , Syed Ishaq Y
Published: August 2021

Introduction: The most common location of infection of brucellosis is the musculoskeletal system. It is estimated that the spine is involved in 2–54% of brucellosis infections, with the lumbar spine most commonly affected. We report an uncommon case of brucellar spondylodiscitis, in addition to the pathology, common presentation, and management of spinal brucellosis through additional literature review.
Case Report: A 65-year-old Hispanic male presented to an orthopedic spine surgeon with signs and symptoms concerning for metastatic disease to the spine. Investigation revealed that the patient had the rare diagnosis of brucellar spondylodiscitis. This only became apparent after detailed questioning of the patient’s history revealed his employment within a Mexican meat slaughterhouse and a regular consumer of unpasteurized Mexican cheeses.
Conclusion: Although uncommon, brucellosis spondylodiscitis should remain as a differential diagnosis in any patient who presents with back pain and fever. Detailed history taking and thorough physical examination remain vital in the work-up of brucellar spondylodiscitis. Understanding the pathology, radiographic findings, and necessary work-up are essential to properly treat this infection.
Keywords: Spine, Brucella, spinal brucellosis, infection, spondylodiscitis, discitis, abscess.
The Surgical Management of the Rare Neurogenic Myositis Ossificans of the Hip: A Report of 3 Cases
Authors: Hammad Yazan , Akiely Reem , Hajjaj Nada , Tahboub Farah , Al-Ajlouni Jihad
Published: August 2021

Introduction: Myositis ossificans (MO) is a benign non-neoplastic condition in which heterotopic bone formation occurs in soft tissues. Neurogenic MO is one variant of MO where the lesion is a result of neurological disorders, including brain and spinal cord injuries, especially when followed by immobility and spasticity. MO can also be a result of direct trauma or even genetic mutations.
Case Report: We present three cases of young men (16, 37, and 22-year-old) who developed MO of the hip joint following brain or spinal cord injuries. One of them had also sustained a direct trauma to the affected hip joint at the time of the accident. All three patients presented with inability to walk independently due to diminished range of motion at the affected joint. X-rays and computerized tomography (CT) scans with 3-dimentional (3D) reconstruction suggested the diagnosis of MO, but the serum alkaline phosphatase was within normal limits at the time of presentation. The first case had bilateral involvement with unmistakable separation between the heterotopic bone formation and the frank hip joints on CT. This patient underwent successful staged excision of the ossifications. The second patient had unilateral hip joint involvement with the absence of clear separation between the heterotopic bone formation and the hip joint, thus, underwent total hip replacement for the affected side as excision was not possible. The third patienthad unilateral hip joint involvement and underwent excision of the ossification with dynamic hip screw insertion after sustaining a stable intertrochanteric fracture intraoperatively. Postoperatively, all three patients received physiotherapy and oral indomethacin. Upon recovery, they were able to walk independently with a near-normal range of motion at the hip joint. There was no evidence of recurrence upon follow-up visits, and CT scans in patients I and II. Follow-ups for patient III were not possible as the patient died 1 month after surgery due t
Inadvertent Debridement of the Medial Patellofemoral Ligament Following Arthroscopic Knee Surgery for Infection: A Case Report
Authors: Jain Gunjar , Nag Hira Lal , Roy Amit
Published: August 2021

Introduction: Arthroscopic debridement of the knee is usually considered a safe procedure. There are no case reports of medial patellofemoral ligament (MPFL) injury leading to habitual dislocation of the patella following this procedure in the literature.
Case Presentation: A 35-year-old male presented with complaints of habitual dislocation of the left patella, which he noticed after multiple arthroscopic surgeries of the left knee performed elsewhere. He had a history of septic arthritis of the knee following anterior cruciate ligament reconstruction, for which he underwent arthroscopic debridement of the knee twice. After a detailed evaluation, we noticed MPFL medial patellofemoral ligament injury.
Conclusion: The MPFL medial patellofemoral ligament injury occurred as a result of extensive resection of the medial joint capsule while operating for septic arthritis. This rare grave surgical complication emphasizes the care one should take during arthroscopic debridement of the knee.
Keywords: Knee arthroscopy, complications, pyogenic arthritis, patella, dislocation.