bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent advances of non-coding RNAs in ovarian cancer prognosis and therapeutics
Authors: Chen Mengyu , Lei Ningjing , Tian Wanjia , Li Yong , Chang Lei
Published: August 2022

Ovarian cancer (OC) is the third most common gynecological malignancy with the highest mortality worldwide. OC is usually diagnosed at an advanced stage, and the standard treatment is surgery combined with platinum or paclitaxel chemotherapy. However, chemoresistance inevitably appears coupled with the easy recurrence and poor prognosis. Thus, early diagnosis, predicting prognosis, and reducing chemoresistance are of great significance for controlling the progression and improving treatment effects of OC. Recently, much insight has been gained into the non-coding RNA (ncRNA) that is employed for RNAs but does not encode a protein, and many types of ncRNAs have been characterized including long-chain non-coding RNAs, microRNAs, and circular RNAs. Accumulating evidence indicates these ncRNAs play very active roles in OC progression and metastasis. In this review, we briefly discuss the ncRNAs as biomarkers for OC prognosis. We focus on the recent advances of ncRNAs as therapeutic targets in preventing OC metastasis, chemoresistance, immune escape, and metabolism. The novel strategies for ncRNAs-targeted therapy are also exploited for improving the survival of OC patients.
Nab-paclitaxel plus S-1 versus oxaliplatin plus S-1 as first-line treatment in advanced gastric cancer: results of a multicenter, randomized, phase III trial (GAPSO study)
Authors: Dai Yu-Hong , Yu Xiong-Jie , Xu Hui-Ting , Zhuang Liang , Zhang Ming-Sheng , Zou Yan-Mei , Fu Qiang , Qiu Hong , Yuan Xiang-Lin
Published: August 2022

Background:

This study aimed to investigate the superiority of nab-paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC).

Methods:

In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS ( nab-paclitaxel 260 mg/m2 on day 1 or 130 mg/m2 on days 1 and 8; oral S-1 40–60 mg twice daily for 14 days) or SOX (130 mg/m2 oxaliplatin on day 1; oral S-1 40–60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety.

Results:

Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39–32.87]. The median PFS was 9.03 months (95% CI, 6.50–11.56) in the AS group and 5.07 months (95% CI, 4.33–5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37–0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group.

Conclusion:

Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities.

Trial registration:

Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.
Low-dose apatinib combined with neoadjuvant chemotherapy in the treatment of early-stage triple-negative breast cancer (LANCET): a single-center, single-arm, phase II trial
Authors: Yang Ciqiu , Zhang Junsheng , Zhang Yi , Ji Fei , Chen Yitian , Zhu Teng , Zhang Liulu , Gao Hongfei , Yang Mei , Li Jieqing , Cheng Minyi , Wang Kun
Published: August 2022

Background:

Antiangiogenic therapy combined with chemotherapy could improve pathological complete response (pCR) for breast cancer. Apatinib is an oral tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor 2. We assessed the efficacy and safety of apatinib combined with standard neoadjuvant chemotherapy in patients with triple-negative breast cancer (TNBC).

Materials and methods:

This single-arm, phase II study enrolled patients aged 18–70 years with previously untreated stage IIA-IIIB TNBC. Patients received oral apatinib at a dose of 250 mg once daily and intravenously docetaxel every 3 weeks for four cycles, followed by epirubicin plus cyclophosphamide every 3 weeks for four cycles. The primary endpoint was the pCR rate in the breast and lymph nodes. Secondary endpoints included objective response rate, event-free survival (EFS), overall survival (OS), and safety.

Results:

In all, 31 patients were enrolled, and the median follow-up time was 22.9 months (range: 10.1–41.6 months). The pCRs in both breast and lymph nodes were achieved in 17 [54.8%; 95% confidence interval (CI): 36.0–72.7] of 31 patients. Objective responses were achieved in 29 patients (93.5%; 95% CI: 78.6–99.2), and disease control was achieved in 31 patients (100%; 95% CI: 88.8–100.0). The 2-year EFS and 2-year OS were 90.9% and 94.4%, respectively. The five most common treatment-related adverse events were fatigue (51%), hypertension (41%), anorexia (39%), hand–foot syndrome (35%), and diarrhea (32%). Few grade 3 or more adverse events were observed.

Conclusion:

The combination of apatinib with docetaxel followed by epirubicin plus cyclophosphamide showed excellent efficacy and manageable toxicities; and further randomized controlled phase III trials are warranted.

Trial registration:

This trial was registered with ClinicalTrials.gov (NCT03243838) on 5 August 2017.
Who Are We If We Do Not Know Who Our Leader Is? Perceptions of Leaders’ Prototypicality Affects Followers’ Self-Prototypicality and Uncertainty
Authors: Kuljian Olivia R. , Hohman Zachary P. , Gaffney Amber M.
Published: August 2022

Leaders define group identities and people turn to leaders to understand their groups in a broader social context and their own places within them. When a leader loses status, people may become uncertain of the group identity and where they stand in relation to that group’s values and idealistic attributes. We predicted that Republicans would view President Trump as less prototypical of the party from pre- to postelection, which would negatively predict their own fit within the party and, in turn, positively predict self-uncertainty. We tested these predictions with two different studies conducted before and after the 2020 American Presidential election (total N = 762). Postelection, Republicans had reduced perceptions of their leader’s prototypicality compared with Democrats, which related to reduced self-prototypicality perceptions and increased uncertainty. Postelection, the losing leader’s identity as an ideal group member is questioned, which may affect how followers view their own prototypical status, prompting uncertainty.
Suspecting Foul Play When It Is Objectively There: The Association of Political Orientation With General and Partisan Conspiracy Beliefs as a Function of Corruption Levels
Authors: Alper Sinan , Imhoff Roland
Published: August 2022

Recent research has showed that people with right-wing political orientations and political extremists are more likely to harbor conspiracy beliefs. Utilizing a multisite data set (23 countries, N > 20,000), we show that corruption moderates how political orientation predicts conspiracy beliefs. We found that (1) the difference between left- and right-wingers in terms of adopting a conspiracy mind-set is attenuated in countries with high corruption; and (2) left-wingers are more likely to believe left-wing conspiracy theories, and right-wingers are more likely to believe right-wing conspiracy theories in high corruption countries. Including quadratic effects of political orientation yielded the same results. We argue that this is because corruption increases perceived plausibility of conspiracies, and everyone across the political spectrum becomes similarly likely to adopt a conspiracy mentality. This heightened suspicion, however, is reflected on partisan conspiracy theories differently for left- and right-wingers, depending on their different understandings of outgroup.
A case of monoclonal gammopathy of undetermined significance and minimal change disease complicated by bilateral pulmonary emboli
Authors: Neerukonda Thanuja , Witt Alexandra , Tan Arsen , Farooqi Bilal , Chaudhary Yasna , Kovacs Christina , Silva Luis
Published: August 2022

Nephrotic syndrome and monoclonal gammopathy of undetermined significance are thought to be associated with venous thromboembolism. However, the association is thought to be weak and is often ignored by clinicians. We present a rare case of sudden-onset bilateral pulmonary emboli with lower extremity deep vein thrombosis in a patient diagnosed with both minimal change disease and immunoglobulin M (IgM) kappa monoclonal gammopathy of undetermined significance. No previous report has been published describing venous thromboembolism in a patient with plasma cell dyscrasia and minimal change disease. This case establishes the importance of considering a diagnostic workup for both disorders in patients with venous thromboembolism. Furthermore, venous thromboembolism risk in patients with both of these diseases is significant. Benefits of prophylactic anticoagulation in these patients are still controversial.
Goal-directed upper limb movement patterns and hand grip forces in multiple sclerosis
Authors: Kanzler Christoph M , Sylvester Ramona , Gassert Roger , Kool Jan , Lambercy Olivier , Gonzenbach Roman
Published: August 2022

Background

Upper limb disability in persons with Multiple Sclerosis (pwMS) leads to increased dependence on caregivers. To better understand upper limb disability, observer-based or time-based clinical assessments have been applied. However, these only poorly capture the behavioural aspects underlying goal-directed task performance.

Objective

We aimed to document alterations in goal-directed upper limb movement patterns and hand grip forces in a cohort of pwMS (n = 123) with mild to moderate upper limb impairments.

Methods

We relied on the Virtual Peg Insertion Test (VPIT), a technology-aided assessment with a goal-directed pick-and-place task providing a set of validated digital health metrics.

Results

All metrics indicated significant differences to an able-bodied reference sample (p < 0.001), with smoothness, speed, and grip force control during object manipulation being most affected in pwMS. Such abnormalities negatively influenced the time to complete the goal-directed task (p < 0.001, R2 = 0.77), thereby showing their functional relevance. Lastly, abnormalities in movement patterns and grip force control were consistently found even in pwMS with clinically normal gross dexterity and grip strength.

Conclusion

This work provides a systematic documentation on goal-directed upper limb movement patterns and hand grip forces in pwMS, ultimately paving the way for an early detection of MS sign using digital health metrics.
“Across Time and Space, I Am Together with Many, Many Others”: Digital Writing and Temporality on Chinese Social Media
Authors: Zhou Feifei , Zhou Xiyin
Published: August 2022

Current scholarship tends to see temporality as a problem or challenge to be overcome in communication on social media (as in “context collapse” and “time collapse”). Drawing on in-depth interviews of Chinese users of a digital writing function (bullet comments) on a major video-sharing platform, we aim to expand current research and deepen understandings of temporality and digital writing. We offer a broader, more positive conceptualization of time on social media by highlighting an alternative set of time-related practices and experiences, mediated by bullet comments. Following recent studies of individuals’ making and experiencing of time in media-saturated societies, our article investigates Chinese social media users’ diverse time-sensitive practices and multi-dimensional temporal experiences. We outline their creative practices from the bottom up, which make use of the distinct technological design of bullet comments. Four interrelated themes in their temporal experiences are analyzed and the similarities and differences with the Deleuzian concept of “crystal of time” explained. Overall, we demonstrate the semiotic power of digital writing in facilitating new meaning-making practices, producing multi-layered mediated temporalities, and affording multisensory, enriching, bonding experiences. The significance and implications of this study for future studies are discussed, in view of the expansion of bullet comments to Chinese mainstream, commercial platforms.
Natural language processing to identify case factors in child protection court proceedings
Authors: Coulthard Beth , Taylor Brian J
Published: August 2022

Social work case files hold rich detail about the lives and needs of vulnerable groups. Traditional case-reading studies to gain generalisable knowledge are resource-intensive, however, and sample sizes thereby limited. The advent of ‘big data’ technology, and vast repositories of centrally stored electronic records offer social work researchers novel alternatives, including data linkage and predictive risk modelling using administrative data. Free-text documents, however – including assessments, reports, and case chronologies – remain a largely untapped resource. This paper describes how 5000 social work court statements held by the Child and Family Court Advisory Support Service in England (Cafcass) were analysed using natural language processing (NLP) based on simple rules and mathematical principles. Thirteen factors relating to harm and risk to children involved in care proceedings in England were identified by automated computer techniques, and almost 90% agreement with professional readers achieved when the factors were clear-cut. The study represents an innovative approach for social work research on complex social problems. In conclusion, the paper discusses learning points; practical implications; future research avenues; and the technical and ethical challenges of NLP.
Redo-ALCAPA Repair With Left Subclavian Artery-to-Left Main Coronary Bypass for Left Coronary Atresia
Authors: Malankar Dhananjay P. , Mali Shivaji , Dhake Shyam , Soni Bharat , Kandavel Dinesh , Mhatre Amit , Bind Dilip , Bhargava Rajat , Raj Jinil , Sheth Ronak , Garekar Swati
Published: August 2022

Different surgical techniques have been described for the primary repair of anomalous left coronary artery arising from the pulmonary artery (ALCAPA); however, very few techniques are described for management of coronary artery occlusion following ALCAPA repair. We present a case of a 7-year-old girl with left main coronary atresia status-post left coronary button transfer for ALCAPA in infancy. She underwent redo-sternotomy and left subclavian artery-to-left main coronary artery bypass plus mitral valve repair and had an uneventful postoperative course.
How Representative of the Protest Movement Against Police Violence Are Opportunistic People Looking to Commit Crime?: Racial Differences in Public Opinion
Authors: Cho Ahram , Cooper Maisha N. , Updegrove Alexander H. , Luo Fei
Published: August 2022

The largest protests in U.S. history occurred during summer 2020. Despite being overwhelmingly peaceful, some property damage, looting, and violence transpired. This study used Wave 68 of the American Trends Panel, collected by the Pew Research Center 10 days after Minneapolis police murdered George Floyd, to test whether: (1) Black people are less likely than white people to oppose Black Lives Matter (BLM); (2) compared to white people, Black people perceive individuals who use protests as a pretext for committing crime to comprise a smaller proportion of the overall protest movement; and (3) opposition to BLM mediates some or all of the relationship between race and perceptions of the degree to which people who use protests as a pretext to commit crime comprise the overall protest movement. Results from generalized ordered logistic regression analyses confirmed that, compared to white people, Black people were less likely to oppose BLM and perceived the summer 2020 protest movement to have contained fewer opportunistic individuals looking to commit crime. Pathway analysis results showed that BLM opposition fully mediated the relationship between race and how much of the overall protest movement participants thought consisted of individuals using protests to commit crime.
A Rare Culprit of Methemoglobinemia
Authors: Fadah Kahtan , Rivera Miguel , Lingireddy Ajay , Kalas M. Ammar , Ghafouri Reshad S. , Deoker Abhizith
Published: August 2022

Methemoglobinemia is a rare cause of hypoxia and can be a diagnostic challenge early in the disease course. The incidence of medication-induced methemoglobinemia is more common than congenital-related methemoglobinemia. The most common cause of methemoglobinemia is exposure to household detergents, illicit drugs, or medications with nitrate or sulfonamide chemical groups. The 2 main medications accounting for up to 45% of medication-induced cases are dapsone and benzocaine. We report a case of hypoxia and diarrhea with an arterial blood gas (ABG) showing methemoglobinemia at 26%. Infectious and autoimmune workup were negative. Methemoglobinemia level returned to normal level within 2 weeks of hydrochlorothiazide discontinuation, suggesting medication-induced methemoglobinemia at appropriate hypertension dosage. In this case, there was an acute rise in methemoglobin levels following initiation of an hydrochlorothiazide-losartan combination, which improved following the discontinuation of hydrochlorothiazide. Extensive workup ruled out cytochrome b5 reductase (Cb5R) and Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which raised the suspicion of hydrochlorothiazide-induced methemoglobinemia, as it is part of the sulfa drug family.
Increased Risk of ACL Injury for Female but Not Male Soccer Players on Artificial Turf Versus Natural Grass: A Systematic Review and Meta-Analysis
Authors: Xiao Michelle , Lemos Jacie L. , Hwang Calvin E. , Sherman Seth L. , Safran Marc R. , Abrams Geoffrey D.
Published: August 2022

Background:

Both natural grass (NG) and artificial turf (AT) are popular playing surfaces for soccer. Biomechanical studies have found increased frictional forces on AT that may lead to anterior cruciate ligament (ACL) injury. The increased risk of ACL injury during soccer in female participants may amplify this effect.

Purpose:

To systematically review the literature for studies comparing ACL injury risk in soccer players on AT versus NG and to specifically determine whether there were differences in injury risk in male versus female players when considering the playing surface.

Study Design:

Systematic review; Level of evidence, 3.

Methods:

A systematic review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Three databases were searched for studies with evidence level 1 to 3 that compared the incidence of ACL injuries on AT versus NG in soccer players. Data recorded included study characteristics, sex, competition level, exposure setting (games or practices), turf type, and ACL injury information. Study methodological quality was analyzed using the methodological index for non-randomized studies (MINORS) score, and incidence rate ratios (IRRs) were calculated.

Results:

Included were 7 articles (3 studying professional soccer, 3 collegiate soccer, 1 youth-level soccer; 4 male cohorts, 2 female cohorts, and 1 male and female cohort; mean MINORS score, 20 ± 0.8). Pooled ACL injury IRRs demonstrated no significant differences in overall ACL injury risk when playing soccer on AT compared with NG (IRR = 0.57 [95% CI, 0.21-1.53]; P = .31). A significantly increased risk of ACL injury in games played on AT compared with NG was detected for female (IRR = 1.18 [95% CI, 1.05-1.31]; P = .004) but not for male players (IRR = 1.18 [95% CI, 0.97-1.42]; P = .09). Subgroup analyses showed no significant differences in injury risk for games (IRR = 1.07 [95% CI, 0.97-1.18]; P = .20) or practices (IRR = 0.21 [95% CI, 0.04-1.23]; P = .09).

Conclusion:

Findings indicated that female soccer players had a significantly higher risk of ACL injury when playing games on AT versus NG, whereas no significant difference was seen in male players. No differences were found for the combined male/female cohort or for soccer games or training sessions played on AT compared with NG.
Midterm Outcomes After Revision Posterior Cruciate Ligament Reconstruction With a Single-Bundle Transtibial Autograft
Authors: Chen Yi-Jou , Yang Cheng-Pang , Ho Chin-Shan , Weng Chun-Jui , Chen Alvin Chao-Yu , Hsu Wei-Hsiu , Hsu Kuo-Yao , Chan Yi-Sheng
Published: August 2022

Background:

There is a lack of consensus regarding the optimal technique for revision posterior cruciate ligament (PCL) reconstruction.

Purpose:

To evaluate midterm outcomes after revision PCL reconstruction using a single-bundle transtibial autograft.

Study Design:

Case series; Level of evidence, 4.

Methods:

We reviewed 17 patients who underwent revision PCL reconstruction performed in our medical center by a single surgeon from 2003 to 2016. The cohort included 12 male and 5 female patients with a mean age of 31.3 years (range, 17-48 years). All of the patients underwent single-bundle transtibial reconstruction using the same surgical technique and were reviewed at a minimum of 4 years postoperatively. Preoperative and postoperative posterior stress radiography was performed. The preoperative tibial slope and tibiofemoral angle were also measured. Preoperative and postoperative functional outcomes were evaluated using the International Knee Documentation Committee (IKDC) subjective and objective scores as well as the Lysholm score.

Results:

The most common factor that contributed to the failure of primary surgery was misplaced tunnels, especially on the femoral side. There were 2 patients who had grade 2 laxity preoperatively, and 15 patients had grade 3 laxity preoperatively. At the latest follow-up, all 17 patients had grade 1 laxity. On posterior stress radiography, posterior displacement improved from 10.8 ± 2.1 mm preoperatively to 2.9 ± 1.1 mm at the latest follow-up ( P < .001). The IKDC subjective score improved from 34.9 ± 6.8 preoperatively to 75.3 ± 15.7 postoperatively ( P < .001), and the Lysholm score improved from 38.1 ± 10.0 preoperatively to 88.5 ± 7.6 postoperatively ( P < .001). All patients reached the minimal clinically important difference (MCID) for the Lysholm score, and 94% reached the MCID for the IKDC subjective score, with 65% reaching the Patient Acceptable Symptom State.

Conclusion:

According to the findings of this study, arthroscopic revision PCL reconstruction with a single-bundle transtibial autograft offered satisfactory outcomes at midterm follow-up.
High Rate of Radiographic Union at the Fibular Osteotomy Site With No Complications After an Acute Oblique Osteotomy and Ligation Procedure to Shorten the Fibula in High Tibial Osteotomy
Authors: Ueda Daisuke , Yasuda Kazunori , Kaibara Takuma , Yabuuchi Koji , Yamaguchi Jun , Onodera Jun , Iwasaki Norimasa , Yagi Tomonori , Kondo Eiji
Published: August 2022

Background:

A fibular shortening osteotomy is needed to perform lateral closing-wedge high tibial osteotomy (LCW-HTO). To achieve this shortening, we have recently developed an acute oblique osteotomy and ligation (AO/L) procedure for the center of the fibular shaft, based on the AO procedure.

Purpose:

To compare the 2-year follow-up outcomes between the AO/L procedure and the AO procedure.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

A prospective comparative cohort study was conducted involving 83 patients (83 knees) who underwent shortening osteotomy of the fibula in LCW-HTO between April 2017 and March 2019. The first consecutive 41 knees (AO group) underwent fibular osteotomy with the AO procedure. The remaining 42 knees (AO/L group) underwent fibular osteotomy with the AO/L procedure. All of the patients were evaluated for at least 2 years postoperatively via clinical and radiological assessments. To determine the time needed for complete union at the osteotomy site, we evaluated the radiographs using a radiographic union score for tibial fractures, which was modified for fibular osteotomy. Comparison of outcomes between the 2 groups was performed using the Student t test for continuous variables and the Mann-Whitney U test or Fisher exact test for discrete variables.

Results:

Around the fibular osteotomy site, no perioperative complications were found in either group. The radiographic union score was significantly higher in the AO/L group than in the AO group ( P < .0001 at 2, 3, and 6 months; P = .0290 at 12 and 24 months). The union rate at the fibular osteotomy site was significantly higher in the AO/L group (97.6%) than in the AO group (82.9%) at 12 months ( P = .0290).

Conclusion:

The AO/L procedure significantly accelerated the formation of bridging callus at the fibular osteotomy site and provided a significantly higher union rate compared with the AO procedure. Both AO/L and AO procedures were free from perioperative complications. These results suggest that the AO/L procedure is clinically useful as an osteotomy procedure to shorten the fibula in LCW-HTO.
Patient Satisfaction Among the OPD Attendees at a Secondary Care Hospital in Northern India
Authors: Kaur Ravneet , Kant Shashi , Goel Akhil Dhanesh , Sharma Nitika
Published: August 2022

Patient satisfaction reflects the quality and effectiveness of healthcare. Healthcare services have become more patient-centric in today’s era as patients are viewed as active consumers of healthcare services rather than passive recipients. Measuring patient satisfaction level has become an objective criterion for defining the effectiveness of these services. Feedback from patients makes healthcare services more responsive to the expectations of patients. We conducted a cross-sectional study among 200 OPD attendees of a secondary-care hospital to assess the level of satisfaction. A 5-point Likert scale was used to record the responses. For overall satisfaction with the OPD services, most common responses were “good” or “very-good”, with mean (SD) score of 3.8 (0.77). Majority of the patients were satisfied with facilities such as drinking water and toilets, and with consultation time provided by the doctors. The patients were not satisfied with the time taken at the registration window and behavior of other hospital employees. This highlights the importance of reorientation training on communication and interpersonal skills for all categories of healthcare staff.
Image segmentation and separation of spectrally similar dyes in fluorescence microscopy by dynamic mode decomposition of photobleaching kinetics
Authors: Wüstner Daniel
Published: August 2022

Background

Image segmentation in fluorescence microscopy is often based on spectral separation of fluorescent probes (color-based segmentation) or on significant intensity differences in individual image regions (intensity-based segmentation). These approaches fail, if dye fluorescence shows large spectral overlap with other employed probes or with strong cellular autofluorescence.

Results

Here, a novel model-free approach is presented which determines bleaching characteristics based on dynamic mode decomposition (DMD) and uses the inferred photobleaching kinetics to distinguish different probes or dye molecules from autofluorescence. DMD is a data-driven computational method for detecting and quantifying dynamic events in complex spatiotemporal data. Here, DMD is first used on synthetic image data and thereafter used to determine photobleaching characteristics of a fluorescent sterol probe, dehydroergosterol (DHE), compared to that of cellular autofluorescence in the nematode Caenorhabditis elegans. It is shown that decomposition of those dynamic modes allows for separating probe from autofluorescence without invoking a particular model for the bleaching process. In a second application, DMD of dye-specific photobleaching is used to separate two green-fluorescent dyes, an NBD-tagged sphingolipid and Alexa488-transferrin, thereby assigning them to different cellular compartments.

Conclusions

Data-based decomposition of dynamic modes can be employed to analyze spatially varying photobleaching of fluorescent probes in cells and tissues for spatial and temporal image segmentation, discrimination of probe from autofluorescence and image denoising. The new method should find wide application in analysis of dynamic fluorescence imaging data.
ProbeTools: designing hybridization probes for targeted genomic sequencing of diverse and hypervariable viral taxa
Authors: Kuchinski Kevin S. , Duan Jun , Himsworth Chelsea , Hsiao William , Prystajecky Natalie A.
Published: August 2022

Background

Sequencing viruses in many specimens is hindered by excessive background material from hosts, microbiota, and environmental organisms. Consequently, enrichment of target genomic material is necessary for practical high-throughput viral genome sequencing. Hybridization probes are widely used for enrichment in many fields, but their application to viral sequencing faces a major obstacle: it is difficult to design panels of probe oligo sequences that broadly target many viral taxa due to their rapid evolution, extensive diversity, and genetic hypervariability. To address this challenge, we created ProbeTools, a package of bioinformatic tools for generating effective viral capture panels, and for assessing coverage of target sequences by probe panel designs in silico. In this study, we validated ProbeTools by designing a panel of 3600 probes for subtyping the hypervariable haemagglutinin (HA) and neuraminidase (NA) genome segments of avian-origin influenza A viruses (AIVs). Using in silico assessment of AIV reference sequences and in vitro capture on egg-cultured viral isolates, we demonstrated effective performance by our custom AIV panel and ProbeTools’ suitability for challenging viral probe design applications.

Results

Based on ProbeTool’s in silico analysis, our panel provided broadly inclusive coverage of 14,772 HA and 11,967 NA reference sequences. For each reference sequence, we calculated the percentage of nucleotide positions covered by our panel in silico; 90% of HA and NA references sequences had at least 90.8 and 95.1% of their nucleotide positions covered respectively. We also observed effective in vitro capture on a representative collection of 23 egg-cultured AIVs that included isolates from wild birds, poultry, and humans and representatives from all HA and NA subtypes. Forty-two of forty-six HA and NA segments had over 98.3% of their nucleotide positions significantly enriched by our custom panel. These in vitro results were further used to validate ProbeTools’ in silico coverage assessment algorithm; 89.2% of in silico predictions were concordant with in vitro results.

Conclusions

ProbeTools generated an effective panel for subtyping AIVs that can be deployed for genomic surveillance, outbreak prevention, and pandemic preparedness. Effective probe design against hypervariable AIV targets also validated ProbeTools’ design and coverage assessment algorithms, demonstrating their suitability for other challenging viral capture applications.
Correlation of CT-derived pectoralis muscle status and COVID-19 induced lung injury in elderly patients
Authors: Ying-hao Pei , Hai-dong Zhang , Yuan Fang , Yong-kang Liu , Sen Liang , Wei-long Xu , Yu-shan Yang , Jun-feng Zhu , Hai-qi Zhou , Hua Jiang
Published: August 2022

Objectives

To explore the association between CT-derived pectoralis muscle index (PMI) and COVID-19 induced lung injury.

Methods

We enrolled 116 elderly COVID-19 patients linked to the COVID-19 outbreak in Nanjing Lukou international airport. We extracted three sessions of their CT data, including one upon admission (T1), one during the first 2 weeks when lung injury peaked (T2) and one on day 14 ± 2 (T3). Lung injury was assessed by CT severity score (CTSS) and pulmonary opacity score (POS). Pneumonia evolution was evaluated by changes of CT scores at T2 from T1(Δ).

Results

The maximum CT scores in low PMI patients were higher than those of normal PMI patients, including CTSS1 (7, IQR 6–10 vs. 5, IQR 3–6, p < 0.001), CTSS2 (8, IQR 7–11 vs. 5, IQR 4–7, p < 0.001) and POS (2, IQR 1–2.5 vs. 1, IQR 1–2, p < 0.001). Comorbidity (OR = 6.15, p = 0.023) and the presence of low PMI (OR = 5.43, p = 0.001) were predictors of lung injury aggravation with ΔCTSS1 > 4. The presence of low PMI (OR = 5.98, p < 0.001) was the predictor of lung injury aggravation with ΔCTSS2 > 4. Meanwhile, presence of low PMI (OR = 2.82, p = 0.042) and incrementally increasing D-dimer (OR = 0.088, p = 0.024) were predictors of lung injury aggravation with ΔPOS = 2.

Conclusions

PMI can be easily assessed on chest CT images and can potentially be used as one of the markers to predict the severity of lung injury in elderly COVID-19 patients.
Impact of time in range during hospitalization on clinical outcomes in diabetic patients with toe amputation: a propensity score matching analysis
Authors: Li Su , Huang Ze-Xin , Lou Dong-hao , Jiang Ye-Yong , Zhao Sheng
Published: August 2022

Purpose

In recent years, time in range (TIR), defined as a percentage within a target time range, has attracted much attention. This study was aimed to investigate the short-term effects of Time in Rang on diabetic patients undergoing toe amputation in a more specific and complete manner.

Methods

A retrospective analysis on patients with diabetic foot ulcer (DFU) treated by toe amputation or foot amputation at the First Affiliated Hospital of Wenzhou Medical University between January 2015 and December 2019 were evaluated. A 1:1 match was conducted between the TIR < 70% group and the TIR ≥ 70% group using the nearest neighbor matching algorithm. Data were analyzed using Chi-squared, Fisher’s exact, and Mann–Whitney U tests.

Results

Compared with patients in the TIR ≥ 70% group, patients in the TIR < 70% had a higher rate of re-amputation, and a higher rate of postoperative infection. Multivariate analysis revealed that smoking, lower extremity arterial disease and TIR < 70% were risk factors for surgery of re-amputation. The results of subgroup analysis found that the TIR < 70% was associated with a greater risk of re-amputation in patients with HbA1c < 7.5%, lower extremity arterial disease, and non-smokers.

Conclusions

TIR can be used as a short-term glycemic control indicator in patients with DFUs and should be widely accepted in clinical practice. However, a future multicenter prospective study is needed to determine the relationship between TIR and toe re-amputation in diabetic foot patients.
Evaluation of bleaching agent effects on color and microhardness change of silver diamine fluoride-treated demineralized primary tooth enamel: An in vitro study
Authors: Rafiee Azade , Memarpour Mahtab , Benam Hadi
Published: August 2022

Background

The present study aimed to assess the impact of application of fluoridated- 10% carbamide peroxide (CP) with or without potassium iodide (KI) on silver diamine fluoride (SDF)-treated enamel surface in the primary teeth.

Methods

After stained-remineralized caries lesions (s-RCLs) creation, 96 teeth were randomly allocated to four experimental groups: Group 1:SDF-treated enamel followed by 8-h/day application of 10% CP for 2 weeks; Group 2: SDF-treated enamel followed by 15-min/day application of 10% CP for 3 weeks; Group 3: SDF + KI-treated enamel followed by 8-h/day application of 10% CP for 2 weeks; and Group 4: SDF + KI-treated enamel followed by 15-min/day application of 10% CP for 3 weeks. Enamel microhardness (EMH) test (n = 12) and spectrophotometric color assessment (n = 12) was performed at four stages: baseline (intact enamel), demineralized enamel, aged remineralized-stained enamel, and after final intervention. Sixteen samples were used for SEM evaluation. Data were analyzed with the paired t-test, one-way ANOVA, and Tukey’s post-hoc test (p < 0.05).

Results

EMH values in all groups showed significant decrease after demineralization (all, p < 0.00001). All samples showed complete recovery of EMH values (%REMH) after SDF application compared to demineralization (%REMHSDF) (p = 0.971). Bleaching caused a slight decrease in %REMH for all groups. However, the differences were not statistically significant (p = 0.979). SEM findings revealed no changes in enamel porosity after bleaching. Bleaching application ameliorated the discoloration in all groups (all, p < 0.00001). All samples in Groups 2 and 4 had significantly lighter color after 21 days as compared to 14-day exposure to the bleaching material (both, p < 0.00001).

Conclusions

SDF application on demineralized primary tooth enamel completely recovered enamel microhardness. 10% carbamide peroxide effectively bleached SDF stain without causing significant decrease in EMH values. Color improvement was more evident with the use of KI immediately after SDF application. Both 15-min and 8-h application of fluoridated CP resulted in statistically similar color enhancement in primary teeth.
Ethical challenges experienced by prehospital emergency personnel: a practice-based model of analysis
Authors: Bruun Henriette , Milling Louise , Mikkelsen Søren , Huniche Lotte
Published: August 2022

Background

Ethical challenges constitute an inseparable part of daily decision-making processes in all areas of healthcare. In prehospital emergency medicine, decision-making commonly takes place in everyday life, under time pressure, with limited information about a patient and with few possibilities of consultation with colleagues. This paper explores the ethical challenges experienced by prehospital emergency personnel.

Methods

The study was grounded in the tradition of action research related to interventions in health care. Ethical challenges were explored in three focus groups, each attended by emergency medical technicians, paramedics, and prehospital anaesthesiologists. The participants, 15 in total, were recruited through an internal information network of the emergency services. Focus groups were audio-recorded and transcribed verbatim.

Results

The participants described ethical challenges arising when clinical guidelines, legal requirements, and clinicians’ professional and personal value systems conflicted and complicated decision-making processes. The challenges centred around treatment at the end of life, intoxicated and non-compliant patients, children as patients—and their guardians, and the collaboration with relatives in various capacities. Other challenges concerned guarding the safety of oneself, colleagues and bystanders, prioritising scarce resources, and staying loyal to colleagues with different value systems. Finally, challenges arose when summoned to situations where other professionals had failed to make a decision or take action when attending to patients whose legitimate needs were not met by the appropriate medical or social services, and when working alongside representatives of authorities with different roles, responsibilities and tasks.

Conclusion

From the perspective of the prehospital emergency personnel, ethical challenges arise in three interrelated contexts: when caring for patients, in the prehospital emergency unit, and during external collaboration. Value conflicts may be identified within these contexts as well as across them. A proposed model of analysis integrating the above contexts can assist in shedding light on ethical challenges and value conflicts in other health care settings. The model emphasises that ethical challenges are experienced from a particular professional perspective, in the context of the task at hand, and in a particular, the organisational setting that includes work schedules, medical guidelines, legal requirements, as well as professional and personal value systems.
On the universality of medical device regulations: the case of Benin
Authors: Maccaro A. , Piaggio D. , Leesurakarn S. , Husen N. , Sekalala S. , Rai S. , Pecchia L.
Published: August 2022

Background

Regulatory frameworks surrounding medical devices (MDs) and medical locations are of utter importance for safeguarding patients and users, and for granting a universal access to healthcare.

Currently, as the main existing regulatory frameworks are drafted by high-income countries, they pretend to be general and applicable globally, but fail to understand particular contexts, specifically those in low-resource settings (LRSs), resulting, therefore, inapplicable. In particular, LRSs present a varied situation, with legal transplants of guidelines from their previous colonial regimes. This apparently theoretical issue, is, effectively, a tangible and rising matter of concern, given the ever-increasing number of MD patent applications per year, as well as the appearance of low- and middle-income countries (LMICs) on the MD market itself.

This article will focus on the European Regulation on MDs 745/2017 and its applicability in LRSs, specifically presenting the case of Benin, a Sub-Saharan African country.

Methods

This work is based on a field study conducted in 2019 in Benin, which is particularly exemplar to show the complexity of the “legal transplantation” concept. A multidisciplinary approach, comprising the standard tools and methods of ethics, law, and biomedical engineering, was used to draft a heuristic hermeneutic framework, and to analyse related bioethical issues concerning Medical Device Regulations (MDRs) in LRSs, the role of Maintenance, and other sociological questions; as well as the rural population’s perception on MDs and health technologies, and the role of ethics in the hospitals of LRSs.

Results

The definition of these themes helped approach the local perspective and define the research questions. Downstream of the analysis of the Medical Devices Regulations, the Maintenance and other bioethical issues in Benin, the heuristic hermeneutic framework was created to guide a shift in the paradigm of law and regulation making, so as to make them more contextualised and inclusive, globally.

Conclusion

This article proposes a framework that will help policymakers take into account the particularism of each context, especially those of the most vulnerable countries, when drafting and issuing regulatory frameworks, promoting an ever-evolving model of universalism.
Dilemmas and deliberations in managing the care trajectory of elderly patients with complex health needs: a single-case study
Authors: Kumlin Marianne , Berg Geir Vegar , Kvigne Kari , Hellesø Ragnhild
Published: August 2022

Background

Today, the ageing population is larger than ever before, and people who are living longer with chronic illnesses and multimorbidity need support from multiple healthcare service levels. Similarly, healthcare systems are becoming increasingly specialised and fragmented. The World Health Organization has highlighted novel policies for developing integrated and person-centred services. However, patients, next of kin and health professionals face several challenges in managing healthcare during the care trajectory. Limited literature has addressed the challenges experienced by these groups. Therefore, this study aimed to identify the dilemmas and deliberations faced by patients, next of kin and health professionals during the care trajectory of elderly patients with complex healthcare needs.

Method

The study had a qualitative single-case design. The case was taken from a multi-case study exploring the care trajectory of elderly patients. The participants were the patient, their next of kin and the health professionals involved in the patient’s care trajectory. Data were obtained via observation and individual interviews conducted during the patient’s hospital stay and after the patient returned home.

Results

The dilemmas and deliberations in managing the care trajectory were divided into four main themes: the health professionals’ pursuit of appropriate and feasible healthcare services, the next of kin’s planning horizons, being the person left in limbo and reorganising the home for comprehensive healthcare.

Conclusion

The pursuit of a tailored and suitable healthcare service lead to a comprehensive mobilisation of and work by all actors involved. Having a comprehensive understanding of these conditions are of importance in developing an appropriate care trajectory for the elderly patient with complex need.
Localization of Salmonella and albumin-IL-2 to the tumor microenvironment augments anticancer T cell immunity
Authors: Kung Yu-Jui , Lam Brandon , Tseng Ssu-Hsueh , MacDonald Alana , Tu Hsin-Fang , Wang Suyang , Lin John , Tsai Ya Chea , Wu T. C. , Hung Chien-Fu
Published: August 2022

Background

For centuries, microbial-based agents have been investigated as a therapeutic modality for the treatment of cancer. In theory, these methods would be cheap to produce, broadly applicable in a wide array of cancer types, and could synergize with other cancer treatment strategies. We aimed to assess the efficacy of combining microbial-based therapy usingSalmonellaSL7207 with interleukin-2 (IL-2), a potent immunostimulatory agent, in the treatment of murine colon carcinoma.

Methods

Female BALB/c mice were implanted subcutaneously with CT26 tumors, a model of colon carcinoma. Mice bearing tumors were selected and administered Albumin-IL-2 (Alb-IL2), a fusion protein, for further analysis of anticancer effect.

Results

We demonstrated thatSalmonellaSL7207, a genetically modified strain ofSalmonella entericaserovar Typhimurium, preferentially accumulates in the tumor microenvironment, potentiating it to stimulate localized innate immunity. We delivered IL-2 as a fusion protein, Alb-IL2, which we demonstrate to have preferential accumulation properties, bringing it to the tumor and secondary lymphoid organs. Treatment of tumor-bearing mice withSalmonella + Alb-IL2 leads to superior tumor control and enhanced overall survival compared to controls. When assessing immunological factors contributing to our observed tumor control, significantly enhanced T cell population with superior effector function was observed in mice treated withSalmonella + Alb-IL2. We confirmed that these T cells were indispensable to the observed tumor control through antibody-mediated T cell depletion experiments.

Conclusions

These findings highlight the ability ofSalmonella + Alb-IL2 to serve as a novel therapeutic approach to induce T cell-mediated antitumor immunity and exert long-term tumor control in a murine model of cancer.
ZC3H4 regulates infiltrating monocytes, attenuating pulmonary fibrosis through IL-10
Authors: Liu Yaping , Zhang Xinxin , Wang Jing , Yang Fuhuang , Luo Wei , Huang Jie , Chen Mengling , Wang Sha , Li Caolong , Zhang Wei , Chao Jie
Published: August 2022

Silicosis is a pulmonary fibrosis-associated disease caused by the inhalation of large amounts of free silicon dioxide (SiO2) that mainly manifests as early inflammation and late pulmonary fibrosis. As macrophage precursors, monocytes accumulate in the lung during early inflammation, but their role in the development of silicosis is unclear. Single-cell sequencing (cell numbers = 25,002), Western blotting, quantitative real-time PCR, ELISA and cell functional experiments were used to explore the specific effects of monocytes on fibroblasts. The CRISPR/Cas9 system was used to specifically knock down ZC3H4, a novel member of the CCCH zinc finger protein family, and was combined with pharmacological methods to explore the mechanism by which ZC3H4 affects chemokine and cytokine secretion. The results indicated that (1) SiO2induced an infiltrating phenotype in monocytes; (2) infiltrating monocytes inhibited the activation, viability and migration of fibroblasts by regulating IL-10 but not IL-8; and (3) SiO2downregulated IL-10 via ZC3H4-induced autophagy. This study revealed that ZC3H4 regulated the secretion function of monocytes, which, in turn, inhibited fibroblast function in early inflammation through autophagy signaling, thereby reducing pulmonary fibrosis. These findings provide a new idea for the clinical treatment of silicosis.