bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and strategies to successful tuberculosis treatment in a high-burden tuberculosis setting: a qualitative study from the patient’s perspective
Authors: Pradipta Ivan S. , Idrus Lusiana R. , Probandari Ari , Lestari Bony W. , Diantini Ajeng , Alffenaar Jan-Willem C. , Hak Eelko
Published: October 2021

Background

Previously treated tuberculosis (TB) patients are a widely reported risk factor for multidrug-resistant tuberculosis. Identifying patients’ problems during treatment is necessary to control TB, especially in a high-burden setting. We therefore explored barriers to successful TB treatment from the patients’ perspective, aiming to identify potential patient-centred care strategies to improve TB treatment outcome in Indonesia.

Methods

A qualitative study was conducted in a province of Indonesia with high TB prevalence. Participants from various backgrounds (i.e., TB patients, physicians, nurses, pharmacists, TB activist, TB programmers at the district and primary care levels) were subject to in-depth interviews and focus group discussions (FGDs). All interviews and FGDs were transcribed verbatim from audio and visual recordings and the respective transcriptions were used for data analysis. Barriers were constructed by interpreting the codes’ pattern and co-occurrence. The information’s trustworthiness and credibility were established using information saturation, participant validation and triangulation approaches. Data were inductively analysed using the Atlas.ti 8.4 software and reported following the COREQ 32-items.

Results

We interviewed 63 of the 66 pre-defined participants and identified 15 barriers. The barriers were classified into three themes, i.e., socio-demography and economy; knowledge and perception and TB treatment. Since the barriers can be interrelated, we determined five main barriers across all barrier themes, i.e., lack of TB knowledge, stigmatisation, long distance to the health facility, adverse drug reaction and loss of household income.

Conclusion

The main treatment barriers can be considered to strengthen patient-centred care for TB patients in Indonesia. A multi-component approach including TB patients, healthcare providers, broad community and policy makers is required to improve TB treatment success.
Uses of equipoise in discussions of the ethics of randomized controlled trials of COVID-19 therapies
Authors: Nix Hayden P. , Weijer Charles
Published: October 2021

Background

Early in the COVID-19 pandemic, the urgent need to discover effective therapies for COVID-19 prompted questions about the ethical problem of randomization along with its widely accepted solution: equipoise. In this scoping review, uses of equipoise in discussions of randomized controlled trials (RCT) of COVID-19 therapies are evaluated to answer three questions. First, how has equipoise been applied to COVID-19 research? Second, has equipoise been employed accurately? And third, do concerns about equipoise pose a barrier to the ethical conduct of COVID-19 RCTs?

Methods

Google Scholar and Pubmed were searched for articles containing substantial discussion about equipoise and COVID-19 RCTs. 347 article titles were screened, 91 full text articles were assessed, and 48 articles were included. Uses of equipoise were analyzed and abstracted into seven categories.

Results and discussion

Approximately two-thirds of articles (33/48 articles) used equipoise in a way that is consistent with the concept. They invoked equipoise to support (1) RCTs of specific therapies, (2) RCTs in general, and (3) the early termination of RCTs after achieving the primary outcome. Approximately one-third of articles (15/48 articles) used equipoise in a manner that is inconsistent with the concept. These articles argued that physician preference, widespread use of unproven therapies, patient preference, or expectation of therapeutic benefit may undermine equipoise and render RCTs unethical. In each case, the purported ethical problem can be resolved by correcting the use of equipoise.

Conclusions

Our findings highlight the continued relevance of equipoise as it supports the conduct of well-conceived RCTs and provides moral guidance to physicians and researchers as they search for effective therapies for COVID-19.
Improving mental health care transitions through information capture during admission to inpatient mental health services: a quality improvement study
Authors: Tyler Natasha , Wright Nicola , Gregoriou Kyriakos , Waring Justin
Published: October 2021

Background

Many interventions aim to improve the transition from ward to community at the time of discharge, with varying success. Guidelines suggest that discharge planning should begin at admission, but in reality this is ideal rather than standard practice. We aimed to develop a novel information capture tool during admission that facilitates and accelerates discharge.

Methods

A quality improvement study to develop, implement and evaluate a novel tool that improves information capture upon admission to acute mental health wards within a single English National Health Service (NHS) trust. We developed the tool by synthesising existing evidence and working with multi-agency and multi-disciplinary professionals in two co-design workshops. During implementation the tool was piloted on three wards. Ethnographic observations (145 h) and interviews (45) were used to evaluate the implementation of the tool across the three wards. Thematic synthesis was used to consolidate the findings.

Results

The tool developed considerably as the process evolved. The finished product is a list of 10 information categories that should be captured from external agencies upon admission to hospital to facilitate discharge planning to community settings. Reported advantages of the tool were: (1) facilitating confidence in junior staff to legitimately question the suitability of a patient for an acute ward (2) collecting and storing essential information in a single accessible place that can be used throughout the care pathway and (3) collecting information from the services/agencies to which patients will eventually be discharged.

Conclusions

Improving the quality of information at admission has the potential to facilitate and accelerate discharge. The novel tool provides a framework for capturing this information that can be incorporated into existing information systems. However, the introduction of the tool exacerbated complex, fragile distributed team dynamics, highlighting the importance of sociocultural context in information flow transitional interventions within distributed teams.
Monocyte as a prognostic marker in patients with idiopathic pulmonary fibrosis
Authors: Zhu Shiping
Published: October 2021

This letter raised some concerns about the study by Karampitsakos et al. in a recent issue of Respiratory Research.
Respiratory function declines in children with asthma associated with chemical species of fine particulate matter (PM2.5) in Nagasaki, Japan
Authors: Kim Yoonhee , Park Eun Ha , Ng Chris Fook Sheng , Chung Yeonseung , Hashimoto Kunio , Tashiro Kasumi , Hasunuma Hideki , Doi Masataka , Tamura Kei , Moriuchi Hiroyuki , Nishiwaki Yuji , Kim Hwajin , Yi Seung-Muk , Kim Ho , Hashizume Masahiro
Published: October 2021

Background

The differential effects of PM2.5 fractions on children’s lung function remain inconclusive. This study aimed to examine whether lung function in asthmatic children was associated with increased PM2.5 fractions in urban areas in Nagasaki prefecture, Japan, where the air pollution level is relatively low but influenced by transboundary air pollution.

Methods

We conducted a multiyear panel study of 73 asthmatic children (boys, 60.3%; mean age, 8.2 years) spanning spring 2014–2016 in two cities. We collected self-measured peak expiratory flow (PEF) twice a day and daily time-series data for PM2.5 total mass and its chemical species. We fitted a linear mixed effects model to examine short-term associations between PEF and PM2.5, adjusting for individual and time-varying confounders. A generalized linear mixed effects model was also used to estimate the association for worsening asthma defined by severe PEF decline. Back-trajectory and cluster analyses were used to investigate the long-range transboundary PM2.5 in the study areas.

Results

We found that morning PEFs were adversely associated with higher levels of sulfate (− 1.61 L/min; 95% CI: − 3.07, − 0.15) in Nagasaki city and organic carbon (OC) (− 1.02 L/min; 95% CI: − 1.94, − 0.09) in Isahaya city, per interquartile range (IQR) increase at lag1. In addition, we observed consistent findings for worsening asthma, with higher odds of severe PEF decline in the morning for sulfate (odds ratio (OR) = 2.31; 95% CI: 1.12, 4.77) and ammonium (OR = 1.73; 95% CI: 1.06, 2.84) in Nagasaki city and OC (OR = 1.51; 95% CI: 1.06, 2.15) in Isahaya city, per IQR increase at lag1. The significant chemical species were higher on days that could be largely attributed to the path of Northeast China origin (for sulfate and ammonium) or both the same path and local sources (for OC) than by other clusters.

Conclusions

This study provides evidence of the differential effects of PM2.5 fractions on lung function among asthmatic children in urban areas, where the Japanese national standards of air quality have been nearly met. Continuous efforts to promote mitigation actions and public awareness of hazardous transboundary air pollution are needed to protect susceptible children with asthma.
A case of ectopic pancreas of the stomach accompanied by intraductal papillary mucinous neoplasm with GNAS mutation
Authors: Nambu Naoko , Yamasaki Takashi , Nakagomi Nami , Kumamoto Tsutomu , Nakamura Tatsuro , Tamura Akio , Tomita Toshihiko , Miwa Hiroto , Shinohara Hisashi , Hirota Seiichi
Published: October 2021

Background

Ectopic pancreas is basically a benign disease and is not always necessary to be removed. However, all types of neoplasms occurring in the normal pancreas such as ductal adenocarcinomas and intraductal papillary mucinous neoplasms (IPMNs) may develop even within ectopic pancreas. We recently encountered an extremely rare case of ectopic pancreas in the gastric antrum associated with IPMN possessing a GNAS mutation.

Case presentation

A 71-year-old Japanese woman complained of epigastric pain. Computed tomography and upper gastrointestinal endoscopy showed an intramural cystic mass in the antrum of the stomach. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy did not give a definitive diagnosis, and the patient underwent resection of the lesion. Histology of the resected specimen showed that the gastric intramural lesion was ectopic pancreas. Moreover, the lesion contained dilated duct components with tubulo-villous epithelial proliferation consistent with pancreatic IPMN. Since the covering epithelial cells had highly atypical nuclei, the lesion was diagnosed as IPMN with high grade dysplasia. Immunohistochemistry showed that the IPMN component showed to be MUC2-, MUC5AC-, and CDX2-positive but MUC1- and MUC6-negative. Mutational analyses using genomic DNA revealed that the IPMN component had a mutation of GNAS at exon 8 (Arg201Cys).

Conclusion

We finally diagnosed this case as gastric ectopic pancreas accompanied by intestinal type IPMN with high grade dysplasia possessing GNAS mutation. Although there were 17 cases of ectopic pancreas with IPMN including 6 cases of gastric ones reported in the English literature, this is the first case of ectopic pancreas with IPMN which was proved to have GNAS mutation. Intimate preoperative examinations including imaging analyses and EUS-FNA biopsy/cytology are recommended to decide whether the lesion has to be resected or not even if they are not effective for getting the right diagnosis.
RSV: perspectives to strengthen the need for protection in all infants
Authors: Navarro Alonso Jose Antonio , Bont Louis J. , Bozzola Elena , Herting Egbert , Lega Federico , Mader Silke , Nunes Marta C. , Ramilo Octavio , Valiotis George , Olivier Catherine Weil , Yates Ann , Faust Saul N.
Published: October 2021

Respiratory syncytial virus (RSV)—the most common viral cause of bronchiolitis—is a significant cause of serious illness among young children between the ages of 0–5 years and is especially concerning in the first year of life. Globally, RSV is a common cause of childhood acute lower respiratory illness (ALRI) and a major cause of hospital admissions in young children and infants and represents a substantial burden for health-care systems. This burden is strongly felt as there are currently no effective preventative options that are available for all infants. However, a renaissance in RSV prevention strategies is unfolding, with several new prophylactic options such as monoclonal antibodies and maternal vaccinations that are soon to be available. A key concern is that health decision makers and systems may not be ready to take full advantage of forthcoming technological innovations. A multi-stakeholder approach is necessary to bridge data gaps to fully utilise upcoming options. Knowledge must be made available at multiple levels to ensure that parents and doctors are aware of preventative options, but also to ensure that stakeholders and policymakers are given the necessary information to best advise implementation strategies.
Revisiting kinorhynch segmentation: variation of segmental patterns in the nervous system of three aberrant species
Authors: Herranz Maria , Park Taeseo , Di Domenico Maikon , Leander Brian S. , Sørensen Martin V. , Worsaae Katrine
Published: October 2021

Background

Kinorhynch segmentation differs from the patterns found in Chordata, Arthropoda and Annelida which have coeloms and circulatory systems. Due to these differences and their obsolete status as ‘Aschelminthes’, the microscopic kinorhynchs are often not acknowledged as segmented bilaterians. Yet, morphological studies have shown a conserved segmental arrangement of ectodermal and mesodermal organ systems with spatial correspondence along the anterior-posterior axis. However, a few aberrant kinorhynch lineages present a worm-like body plan with thin cuticle and less distinct segmentation, and thus their study may aid to shed new light on the evolution of segmental patterns within Kinorhyncha.

Results

Here we found the nervous system in the aberrantCateria styxandFranciscideres kalenesosto be clearly segmental, and similar to those of non-aberrant kinorhynchs; hereby not mirroring their otherwise aberrant and posteriorly shifted myoanatomy. InZelinkaderes yong, however, the segmental arrangement of the nervous system is also shifted posteriorly and misaligned with respect to the cuticular segmentation.

Conclusions

The morphological disparity together with the distant phylogenetic positions ofF. kalenesos,C. styxandZ. yongsupport a convergent origin of aberrant appearances and segmental mismatches within Kinorhyncha.
Novel alterations in IFT172 and KIFAP3 may induce basal cell carcinoma
Authors: Onodera Shoko , Morita Nana , Nakamura Yuriko , Takahashi Shinichi , Hashimoto Kazuhiko , Nomura Takeshi , Katakura Akira , Kosaki Kenjiro , Azuma Toshifumi
Published: October 2021

Background

Basal cell carcinoma (BCC) is the most commonly occurring neoplasm in patients with Gorlin syndrome. It is widely accepted that multiple basal cell carcinomas simultaneously develop in middle-aged patients with this syndrome. However, the presence of driver genes other than thePTCH1in Gorlin syndrome has not been explored. This study aimed to identify common gene mutations other thanPTCH1in simultaneously occurring basal cell carcinomas in patients with Gorlin syndrome via exome sequencing analysis.

Methods

Next-generation sequencing analysis was performed using four basal cell carcinoma samples, one dental keratinocyte sample, and two epidermoid cyst samples, which were surgically resected from one patient with Gorlin syndrome on the same day.

Results

Overall, 282 somatic mutations were identified in the neoplasms. No additional somatic mutations inPTCH1,PTCH2,TP53, andSMOwere identified. However, enrichment analysis showed that multiple genes, such asIFT172andKIFAP3,could regulate ciliary functions important for Hedgehog signaling.

Conclusion

The development of BCCs in patients with Gorlin syndrome may be triggered by mutations that cause substantial dysfunction of cilia.
The Youth Aware of Mental Health program in Australian Secondary Schools: 3- and 6-month outcomes
Authors: McGillivray Lauren , Shand Fiona , Calear Alison L. , Batterham Philip J. , Rheinberger Demee , Chen Nicola A. , Burnett Alexander , Torok Michelle
Published: October 2021

Objective

The evidence base for suicide prevention programs in Australian schools is limited. The aim of this study was to examine the impact of a universal, mental health promotion and suicide prevention program—Youth Aware of Mental Health (YAM)—on suicidal ideation, mental health, and help-seeking in Australian secondary school students from baseline to post-intervention and 6-month follow up.

Methods

Using a single-arm design, the YAM program was delivered to Year 9 students (13–16 years) in secondary schools located within four regions across New South Wales, Australia. A structured self-report questionnaire using validated scales was administered at each time point. Linear mixed-effects modelling was used to examine differences in suicidal ideation scores across time, while accounting for random effects of individual schools.

Results

Suicidal ideation reduced significantly from baseline to post, and from baseline to follow-up (p < 0.001). Depression severity declined (p < 0.001) and help-seeking intentions increased (p < 0.001) at post-intervention and 6- months following the intervention period. No suicide deaths were reported for any study participants.

Conclusion

The current findings provide preliminary evidence that the YAM program is a promising preventive intervention for Australian schools, particularly for reducing suicidal ideation, depression and increasing help-seeking intentions in young people. The implementation of YAM in a large number of schools across New South Wales demonstrates the feasibility, and acceptability by schools, of implementing this program at scale.

Trial registration:ANZCTR, ACTRN12619000338167. Registered 5 March 2019—Retrospectively registered,http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376989&isReview=true.
Innovative clinical trial design and delivery: a phase 3 COVID-19 post-exposure prophylaxis study in skilled nursing and assisted living facilities (BLAZE-2)
Authors: Knorr Jack , Tuttle Jay L. , Sabo Janelle A. , East Dawn H. , Price Karen L. , Shen Lei
Published: October 2021

The efficient community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the current pandemic of coronavirus disease-2019 (COVID-19), which in severe and critical cases results in progressive pulmonary infection, complicated by respiratory failure, with a high prevalence of acute respiratory distress syndrome. Of all age groups, older adults have the greatest risk of severe COVID-19 and the associated complications. Globally, there are many reports of the rapid spread of COVID-19 among residents of skilled nursing facilities, with high associated rates of morbidity and mortality. With over 1.3 million residents in nursing home care in the USA, there is an urgent need for therapeutic strategies to prevent COVID-19 in these populations.

Lilly, in collaboration with the National Institute of Allergy and Infectious Diseases, conducted the BLAZE-2 trial to evaluate the efficacy and safety of the monoclonal antibody bamlanivimab (LY3819253) in preventing SARS-CoV-2 infection and COVID-19, defined as symptomatic infection, in skilled nursing and assisted living facilities. It is a phase 3 randomized, double-blind, placebo-controlled trial, where participants were randomized to bamlanivimab (4200 mg) or placebo and then followed up for 24 weeks. Conducting a trial in the midst of a pandemic in these facilities poses several challenges, including a vulnerable elderly population, travel restrictions, supply chain interruptions, and defining the target population. The operational challenges were addressed by the innovative use of mobile research units which are customized, equipped, and staffed to support BLAZE-2 randomization and participant dosing within the skilled nursing and assisted living facilities. Herein, we describe the design of the study, the analytics behind facility selection, and an innovative operational model.
Impact of systemic lupus erythematosus on the 5-year survival of critically ill septic patients
Authors: Chen Hsin-Hua , Chen Hsian-Min , Chen Yi-Ming , Chen Yi-Hsing , Lin Ching-Heng , Chao Wen-Cheng
Published: October 2021

Background

Infectious disease is an increasing threat to patients with systemic lupus erythematosus (SLE); however, the long-term outcome in critically ill septic patients with SLE remains unclear, and we aimed to address the impact of SLE on 5-year survival in critically ill septic patients.

Methods

We used the 2003–2017 nationwide data with 825,556 patients with sepsis in Taiwan. We identified lupus cases with sepsis that required admission to the intensive care unit and mechanical ventilation and selected controls matched (1:4) for age, sex, and index-year. Conditional logistic regression analysis was used to determine risk factors for mortality risk and shown as odds ratios (HRs) with 95% confidence intervals (CIs).

Results

A total of 513 SLE-sepsis patients and 2052 matched non-SLE septic individuals were enrolled. The mortality rate was higher in the SLE group (38.5 per 100,000 person-year) than that in the non-SLE group (13.7 per 100,000 person-year), with an IRR of 2.8 (95% CI, 2.5–3.2). We found that SLE was independently associated with a high mortality rate after adjusting relevant variables (HR 1.47, 95% CI 1.27–1.77). In addition to SLE, a higher age (HR 1.02, 95% CI 1.02–1.02), more comorbidities, and receiving prednisolone equivalent dose higher than 5 mg/day (HR 1.55, 95% CI 1.27–1.90), methotrexate (HR 2.19, 95% CI 1.61–2.99), and immunosuppressants (HR 1.45, 95% CI 1.22–1.74) were also independent risks for mortality.

Conclusions

We identified that SLE affects the long-term mortality in critically ill septic patients, and more studies are warranted for the underlying mechanism.
Noninvasive assessment of kidney dysfunction in children by using blood oxygenation level-dependent MRI and intravoxel incoherent motion diffusion-weighted imaging
Authors: Liang Ping , Chen Yaxian , Li ShiChao , Xu Chuou , Yuan Guanjie , Hu Daoyu , Kamel Ihab , Zhang Yu , Li Zhen
Published: October 2021

Objectives

To explore whether multiparametric approach including blood oxygenation level-dependent MRI (BOLD-MRI) and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can be applied in the assessment of renal function in children with chronic kidney disease (CKD).

Materials and methods

This prospective study included 74 children (CKD stage 1–3, 51; CKD stage 4–5, 12; healthy volunteers, 11) for renal MRI examinations including coronal T2WI, axial T1WI and T2WI, BOLD-MRI, and DWI sequences. We measured the renal cortex and medulla T2*, ADC, Dt, Dp, and fp values on BOLD and DWI images. Appropriate statistical methods were applied for comparing MRI-derived parameters among the three groups and calculating the correlation coefficients between MRI-derived parameters and clinical data. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of MRI-derived parameters.

Results

There were significant differences in cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt among the three groups. Cortex T2*, ADC, Dt, fp and medulla T2*, ADC, Dt had a trend: CKD stage 4–5 < CKD stage 1–3 < healthy volunteers. Cortex and medulla T2*, ADC, Dt were significantly correlated with eGFR, serum creatinine (Scr), cystatin C. In addition, cortex T2* and eGFR showed the highest correlation coefficient (r = 0.824, p < 0.001). Cortex Dt and medulla T2* were optimal parameters for differentiating healthy volunteers and CKD stage 1–3 or CKD stage 4–5 and CKD stage 1–3, respectively.

Conclusions

BOLD-MRI and IVIM-DWI might be used as a feasible method for noninvasive assessment of renal function in children with CKD.
The brainstem in multiple sclerosis: MR identification of tracts and nuclei damage
Authors: Nguyen Thien Huong , Vaussy Alexis , Le Gaudu Violette , Aboab Jennifer , Espinoza Sophie , Curajos Irina , Heron Emmanuel , Habas Christophe
Published: October 2021

Objective

To evaluate the 3D Fast Gray Acquisition T1 Inversion Recovery (FGATIR) sequence for MRI identification of brainstem tracts and nuclei damage in multiple sclerosis (MS) patients.

Methods

From april to december 2020, 10 healthy volunteers and 50 patients with remitted-relapsing MS (58% female, mean age 36) underwent MR imaging in the Neuro-imaging department of the C.H.N.O. des Quinze-Vingts, Paris, France. MRI was achieved on a 3 T system (MAGNETOM Skyra) using a 64-channel coil. 3D FGATIR sequence was first performed on healthy volunteers to classify macroscopically identifiable brainstem structures. Then, FGATIR was assessed in MS patients to locate brainstem lesions detected with Proton Density/T2w (PD/T2w) sequence.

Results

In healthy volunteers, FGATIR allowed a precise visualization of tracts and nuclei according to their myelin density. Including FGATIR in MR follow-up of MS patients helped to identify structures frequently involved in the inflammatory process. Most damaged tracts were the superior cerebellar peduncle and the transverse fibers of the pons. Most frequently affected nuclei were the vestibular nuclei, the trigeminal tract, the facial nerve and the solitary tract.

Conclusion

Combination of FGATIR and PD/T2w sequences opened prospects to define MS elective injury in brainstem tracts and nuclei, with particular lesion features suggesting variations of the inflammatory process within brainstem structures. In a further study, hypersignal quantification and microstructure information should be evaluated using relaxometry and diffusion tractography. Technical improvements would bring novel parameters to train an artificial neural network for accurate automated labeling of MS lesions within the brainstem.
Red blood cells and their releasates compromise bone marrow-derived human mesenchymal stem/stromal cell survival in vitro
Authors: Dregalla Ryan Christopher , Herrera Jessica Ann , Donner Edward Jeffery
Published: October 2021

Purpose

The use of bone marrow aspirate (BMA) and bone marrow aspirate concentrate (BMC) in the treatment of inflammatory orthopedic conditions has become a common practice. The therapeutic effect of BMA/BMC is thought to revolve primarily around the mesenchymal stem/stromal cell (MSC) population residing within the nucleated cell fraction. MSCs have the unique ability to respond to site of injury via the secretion of immunomodulating factors, resolving inflammation in diseased joints. Recently, the importance of hematocrit (HCT) in BMC has been debated, as the potential impact on MSC function is unknown. In the present study, we investigate MSC health over a short time-course following exposure to a range of HCT and red blood cell releasate (RBCrel) conditions.

Methods

Bone marrow-derived human MSCs in early passage were grown under conditions of 0%, 2.5%, 5%, 10%, 20% and 40% HCT and RBCrel conditions for 3 days. At each day, the percentage of viable, apoptotic and necrotic MSCs was determined via flow cytometry. Relative viable MSC counts in each condition was determined to account for dynamic changes in overall MSC densities over the time-course. Statistical analysis was performed using a one-way ANOVA comparing test conditions to the control followed by a Dunnett’s multiple comparison test.

Results

Significant reductions in viable MSCs concurrent with an increase in necrotic MSCs in high HCT and RBCrel conditions was observed within 24 h. At each successive timepoint, the percent and relative number of viable MSCs were reduced, becoming significant in multiple HCT and RBCrel conditions by Day 3. Necrosis appears to be the initial mode of MSC death following exposure to HCT and RBCrel, followed by apoptosis in surviving MSC fractions.

Conclusion

Various levels of HCT and RBCrel severely compromise MSC health within 3 days and HCT should be controlled in the preparation of BMC products. Further, HCT of BMCs should be routinely recorded and tracked with patient outcomes along with routine metrics (e.g. nucleated cell counts, fibroblast-colony forming units). Differences in HCT may account for the inconsistencies in the efficacy of BMC reported when treating orthopedic conditions.
Induced pluripotent stem cells can improve thrombolytic effect of low-dose rt-PA after acute carotid thrombosis in rat
Authors: Hsieh Hsi-Lung , Liang Ching-Chung , Lu Cheng-You , Yang Jen-Tsung , Chung Chiu-Yen , Ko Yu-Shien , Lee Tsong-Hai
Published: October 2021

Background

Intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) is the standard treatment for acute ischemic stroke. Standard-dose rt-PA (0.9 mg/kg) is known to achieve good recanalization but carries a high bleeding risk. Lower dose of rt-PA has less bleeding risk but carries a high re-occlusion rate. We investigate if induced pluripotent stem cells (iPSCs) can improve the thrombolytic effect of low-dose rt-PA (0.45 mg/kg).

Methods

Single irradiation with 6 mW/cm2 light-emitting diode (LED) for 4 h at rat common carotid artery was used as thrombosis model according to our previous report. Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and interleukin 1 beta (IL-1 beta) were used as the inflammatory markers for artery endothelial injury. Angiopoietin-2 (AP-2), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were examined in artery wall and iPSCs culture. Animal ultrasound was used to evaluate the stenosis degree of common carotid artery before and at 2 h, 24 h, 4 days and 7 days after LED irradiation.

Results

After LED irradiation alone, there was a persistent occlusion from 2 h to 7 days. Standard-dose rt-PA alone could recanalize the occluded artery from 24 h to 7 days to stenotic degree ≤ 50%. Low-dose rt-PA or 1 × 106 mouse iPSCs alone could not recanalize the occluded arteries from 2 h to 7 days. Combination use of low-dose rt-PA plus 1 × 106 mouse iPSCs caused better recanalization from 24 h to 7 days. ET-1, ICAM-1 and IL-1 beta were strongly expressed after LED irradiation but reduced after iPSCs treatment. AP-2, BDNF and VEGF were rarely induced after LED irradiation but strongly expressed after iPSCs treatment. In vitro study showed iPSCs could express AP-2, BDNF and VEGF.

Conclusion

The adjuvant use of iPSCs may help improving the thrombolytic effect of low-dose rt-PA by suppressing inflammatory factors and inducing angiogenic trophic factors. Stem cells could be a potential regimen in acute thrombolytic therapy to improve recanalization and reduce complications.
Genomic signatures of host adaptation in group B Salmonella enterica ST416/ST417 from harbour porpoises
Authors: Sandholt Arnar K. S. , Neimanis Aleksija , Roos Anna , Eriksson Jenny , Söderlund Robert
Published: October 2021

A type of monophasic group B Salmonella enterica with the antigenic formula 4,12:a:- (“Fulica-like”) has been described as associated with harbour porpoises (Phocoena phocoena), most frequently recovered from lung samples. In the present study, lung tissue samples from 47 porpoises found along the Swedish coast or as bycatch in fishing nets were analysed, two of which were positive for S. enterica. Pneumonia due to the infection was considered the likely cause of death for one of the two animals. The recovered isolates were whole genome sequenced and found to belong to sequence type (ST) 416 and to be closely related to ST416/ST417 porpoise isolates from UK waters as determined by core-genome MLST. Serovars Bispebjerg, Fulica and Abortusequi were identified as distantly related to the porpoise isolates, but no close relatives from other host species were found. All ST416/417 isolates had extensive loss of function mutations in key Salmonella pathogenicity islands, but carried accessory genetic elements associated with extraintestinal infection such as iron uptake systems. Gene ontology and pathway analysis revealed reduced secondary metabolic capabilities and loss of function in terms of signalling and response to environmental cues, consistent with adaptation for the extraintestinal niche. A classification system based on machine learning identified ST416/417 as more invasive than classical gastrointestinal serovars. Genome analysis results are thus consistent with ST416/417 as a host-adapted and extraintestinal clonal population of S. enterica, which while found in porpoises without associated pathology can also cause severe opportunistic infections.
Head-mounted accelerometry accurately detects prey capture in California sea lions
Authors: Cole Mason R. , Zeligs Jenifer A. , Skrovan Stefani , McDonald Birgitte I.
Published: October 2021

Detecting when and where animals feed is key to understanding their ecophysiology, but our ability to collect these data in marine mammals remains limited. Here, we test a tag-based accelerometry method to detect prey capture in California sea lions. From synchronized underwater video and acceleration data of two trained sea lions, we isolated a combined acceleration and Jerk pattern that reliably indicated prey capture in training datasets. We observed a stereotyped feeding motion in underwater video that included (1) mouth opening while approaching prey; (2) head deceleration to allow initial suction or prey engulfment, and (3) jaw closure. This motion (1–3) was repeated if a prey item was not initially engulfed. This stereotyped feeding motion informed a signal pattern phrase that accurately detected feeding in a training dataset. This phrase required (1) an initial heave-axis Jerk signal surpassing a threshold based on sampling rate; (2) an estimated dynamic surge-axis deceleration signal surpassing −0.7 g beginning within 0.2 s of the initial Jerk signal; and (3) an estimated dynamic surge-axis acceleration signal surpassing 1.0 g within 0.5 s of the beginning of the prior deceleration signal. We built an automated detector in MATLAB to identify and quantify these patterns. Blind tests of this detector on non-training datasets found high true-positive detection rates (91%–100%) with acceleration sampled at 50–333 Hz and low false-positive detection rates (0%–4.8%) at all sampling rates (16–333 Hz). At 32 Hz and below, true-positive detection rates decreased due to attenuation of signal detail. A detector optimized for an adult female was also accurate at 32–100 Hz when tested on an adult male’s data, suggesting the potential future use of a generalized detector in wild subjects. When tested on the same data, a published triaxial Jerk method produced high true-positive detection rates (91–100%) and low-to-moderate false-positive detection rates (15–43%) at ≥ 32 Hz. Using our detector, larger prey elicited longer prey capture duration in both animals at almost all sampling rates 32 Hz or faster. We conclude that this method can accurately detect feeding and estimate relative prey length in California sea lions.
Days to visit an offshore island: effect of weather conditions on arrival fuel load and potential flight range for common blackbirds Turdus merula migrating over the North Sea
Authors: Kelsey Natalie A. , Hüppop Ommo , Bairlein Franz
Published: October 2021

Background

Crossing open water instead of following the coast(line) is one way for landbirds to continue migration. However, depending on prevailing weather and the birds’ physiological conditions, it is also a risky choice. To date, the question remains as to which interplay between environmental and physiological conditions force landbirds to stop on remote islands. We hypothesise that unfavourable winds affect lean birds with low energy resources, while poor visibility affects all birds regardless of their fuel loads.

Methods

To test this hypothesis, we caught 1312 common blackbirdsTurdus merulastopping over on Helgoland during autumn and spring migration. Arrival fuel load was measured using quantitative magnetic resonance technology. Weather parameters (wind and relative humidity as a proxy for visibility) were interpolated for the night before arrival. Further, we calculated whether caught individuals would have successfully crossed the North Sea instead of landing on Helgoland, depending on wind conditions.

Results

Both wind and relative humidity the night before arrival were correlated with arrival fuel load. After nights with strong headwinds, birds caught the following day were mostly lean, most of which would not have managed to cross the sea if they had not stopped on Helgoland. In contrast, fat birds that could have successfully travelled on were caught mainly after nights with high relative humidity (≥ 80%). Furthermore, the rate of presumably successful flights was lower due to wind: although only 9% of all blackbirds captured on Helgoland had insufficient fuel loads to allow safe onward migration in still air, real wind conditions would have prevented 30% of birds from successfully crossing the sea during autumn and 21% during spring migration.

Conclusions

We were able to decipher how physiological condition, wind and relative humidity partially force blackbirds to stop on a remote island. Adverse winds tend to affect lean birds with low energy resources, while poor visibility can affect blackbirds, regardless of whether the arrival fuel load was sufficient for onward flight. Our findings will help to understand different migratory strategies and explain further questions like migration timing.
Deep learning reveals disease-specific signatures of white matter pathology in tauopathies
Authors: Vega Anthony R. , Chkheidze Rati , Jarmale Vipul , Shang Ping , Foong Chan , Diamond Marc I. , White Charles L. , Rajaram Satwik
Published: October 2021

Although pathology of tauopathies is characterized by abnormal tau protein aggregation in both gray and white matter regions of the brain, neuropathological investigations have generally focused on abnormalities in the cerebral cortex because the canonical aggregates that form the diagnostic criteria for these disorders predominate there. This corticocentric focus tends to deemphasize the relevance of the more complex white matter pathologies, which remain less well characterized and understood. We took a data-driven machine-learning approach to identify novel disease-specific morphologic signatures of white matter aggregates in three tauopathies: Alzheimer disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). We developed automated approaches using whole slide images of tau immunostained sections from 49 human autopsy brains (16 AD,13 CBD, 20 PSP) to identify cortex/white matter regions and individual tau aggregates, and compared tau-aggregate morphology across these diseases. Tau burden in the gray and white matter for individual subjects strongly correlated in a highly disease-specific fashion. We discovered previously unrecognized tau morphologies for AD, CBD and PSP that may be of importance in disease classification. Intriguingly, our models classified diseases equally well based on either white or gray matter tau staining. Our results suggest that tau pathology in white matter is informative, disease-specific, and linked to gray matter pathology. Machine learning has the potential to reveal latent information in histologic images that may represent previously unrecognized patterns of neuropathology, and additional studies of tau pathology in white matter could improve diagnostic accuracy.
Trench and drilling investigation of the Median Tectonic Line in Shikoku, southwest Japan: implications for fault geometry
Authors: Miyawaki Masahiro , Sakaguchi Arito
Published: October 2021

The Median Tectonic Line (MTL) is a thousand-kilometer-long fault that extends across southwest Japan. Near the Nyugawa region of Shikoku, the MTL comprises (i) a low-angle inactive terrane boundary fault (the MTLTB) that divides the Jurassic and Cretaceous geological terranes, and (ii) a subparallel high-angle active fault zone (the MTLAFZ; Kawakami Fault). To better understand the relationship between the MTLTB and MTLAFZ fault traces, we exposed a ten-meter-long trench of approximately 2-m depth across the Kawakami Fault. We also drilled and cored five boreholes with lengths 80‒330 m along a 100 m transect to understand the cross-cutting relationship between the MTL faults and to determine the fault plane geometries and their dipping values. The Kawakami Fault was found to be a high-angle (> 70°) active fault exposed at the surface; however, it represents a non-vertical or listric fault that converges to the low-angle MTLTB fault dipping to the north at 30°. The Kawakami Fault was originally formed as a reverse fault, and subsequent dextral strike–slip displacement occurred along the same fault plane. Although the MTLTB is poorly oriented with respect to the regional stress field, it is capable of rupturing owing to its significantly weak interface; the properties of local faulted rock material are expected to play an important role in determining slip behavior.
Quantitative analysis on photon numbers received per cell for triggering β-carotene accumulation in Dunaliella salina
Authors: Xi Yimei , Xue Song , Cao Xupeng , Chi Zhanyou , Wang Jinghan
Published: October 2021

Accumulation of β-carotene in Dunaliella salina is highly dependent on light exposure intensity and duration, but quantitative analysis on photon numbers received per cell for triggering β-carotene accumulation is not available so far. In this study, experiment results showed that significant β-carotene accumulation occurred after at least 8 h illumination at 400 µmol photons·m−2·s−1. To quantify the average number of photons received per cell, correlations of light attenuation with light path, biomass concentration, and β-carotene content were, respectively, established using both Lambert–Beer and Cornet models, and the latter provided better simulation. Using Cornet model, average number of photons received per cell (APRPC) was calculated and proposed as a parameter for β-carotene accumulation, and constant APRPC was maintained by adjusting average irradiance based on cell concentration and carotenoids content changes during the whole induction period. It was found that once APRPC reached 0.7 µmol photons cell−1, β-carotene accumulation was triggered, and it was saturated at 9.9 µmol photons cell−1. This study showed that APRPC can be used as an important parameter to precisely simulate and control β-carotene production by D. salina.

Graphic Abstract
Effect of Rearfoot Strikes on the Hip and Knee Rotational Kinetic Chain During the Early Phase of Cutting in Female Athletes
Authors: Ogasawara Issei , Shimokochi Yohei , Konda Shoji , Mae Tatsuo , Nakata Ken
Published: October 2021

Background

Biomechanical factors affecting horizontal-plane hip and knee kinetic chain and anterior cruciate ligament (ACL) injury risk during cutting maneuvers remain unclear. This study aimed to examine whether different foot strike patterns alter horizontal-plane hip and knee kinetics and kinematics during a cutting maneuver in female athletes and clarify the individual force contribution for producing high-risk hip and knee loadings. Twenty-five healthy female athletes performed a 60° cutting task with forefoot and rearfoot first strike conditions. Horizontal-plane hip and knee moment components, angles, and angular velocities were calculated using synchronized data of the marker positions on the body landmarks and ground reaction forces (GRFs) during the task. The one-dimensional statistical parametric mapping paired t test was used to identify the significant difference in kinetic and kinematic time-series data between foot strike conditions.

Results

In the rearfoot strike condition, large hip and knee internal rotation loadings were produced during the first 5% of stance due to the application of GRFs, causing a significantly larger hip internal rotation excursion than that of the forefoot strike condition. Dissimilarly, neither initial hip internal rotation displacement nor knee internal rotation GRF loadings were observed in the forefoot strike condition.

Conclusions

Rearfoot strike during cutting appears to increase noncontact ACL injury risk as the GRF tends to produce combined hip and knee internal rotation moments and the high-risk lower limb configuration. Conversely, forefoot strike during cutting appears to be an ACL-protective strategy that does not tend to produce the ACL-harmful joint loadings and lower extremity configurations. Thus, improving foot strike patterns during cutting should be incorporated in ACL injury prevention programs.
Effect of Whitlockite as a new bone substitute for bone formation in spinal fusion and ectopic ossification animal model
Authors: Jin Yuan-Zhe , Zheng Guang-Bin , Cho Minjoon , Lee Jae Hyup
Published: October 2021

Background

Bone substrates like hydroxyapatite and tricalcium phosphate have been widely used for promoting spinal fusion and reducing the complications caused by autograft. Whitlockite has been reported to promote better bone formation in rat calvaria models compare with them, but no study investigated its effect on spinal fusion yet. Also, the higher osteoinductivity of whitlockite raised concern of ectopic ossification, which was a complication of spinal fusion surgery that should be avoided.

Methods

In this study, we compared the osteoinductivity of whitlockite, hydroxyapatite, and tricalcium phosphate porous particles with SD rat spine posterolateral fusion model and investigated whether whitlockite could induce ectopic ossification with SD rat abdominal pouch model.

Results

The micro-CT result from the posterolateral fusion model showed whitlockite had slightly but significantly higher percent bone volume than tricalcium phosphate, though none of the materials formed successful fusion with surrounding bone tissue. The histology results showed the bone formed on the cortical surface of the transverse process but did not form a bridge between the processes. The result from the abdominal pouch model showed whitlockite did not induce ectopic bone formation.

Conclusion

Whitlockite had a potential of being a better bone substrate hydroxyapatite and tricalcium phosphate in spinal fusion with low risk of inducing ectopic ossification.
Tuberculosis amidst COVID-19 pandemic in India: unspoken challenges and the way forward
Authors: Bardhan Mainak , Hasan Mohammad Mehedi , Ray Ishita , Sarkar Anusua , Chahal Priyanka , Rackimuthu Sudhan , Essar Mohammad Yasir
Published: October 2021

India is home to the most significant number of tuberculosis (TB) cases around the globe. The COVID-19 crisis has deeply perturbed most of the essential TB services in India. Regulating TB is difficult in a densely populated country like India due to latent TB infection in millions of Indians, which can reactivate at any point in the future. Due to the ongoing pandemic, healthcare workers have been diverted to activities implemented for effective COVID-19 management, leaving a meager workforce to help deal with TB management. Integrating TB and COVID-19 to augment India’s health outreach is the need of the hour to diminish the effect of the COVID-19 crisis on TB. Increasing overall testing capacity, active screening, implementation of strategies for easy identification of TB hotspots, and ensuring uninterrupted drug supply for treatment through heedful planning of local and regional distribution and transportation will especially help cater to the vulnerable population who are at a high risk of suffering from adverse outcomes of TB. Lessons learnt in the battle against COVID-19 can most definitely help in providing insights to fulfill the goal of eliminating TB from India.