bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of two different semi-automated homogenization techniques in microbiological diagnosis of periprosthetic joint infection: disperser vs. bead milling method
Authors: Rieber Heime , Frontzek Andre , Heinrich Stephanie , Barden Bertram , Kortstegge Thomas , Dienstknecht Thomas , Breil-Wirth Andreas , Herwig Mathias , Jerosch Jörg , Pinkernell Ralf , Ulatowski Martin
Published: October 2022

Background

In microbiological diagnosis of periprosthetic joint infection (PJI) there is no consensus regarding the most suitable and optimal number of specimens to be cultured or the most effective technique of tissue processing. This comparative study analysed the accuracy of two semi-automated homogenization methods with special focus on the volume and exact origin of each sample.

Methods

We investigated a total of 722 periprosthetic tissue samples. PJI was defined according to the new scoring system for preoperative and intraoperative criteria. We compared the performance of our routinely used single tissue processing by disposable high-frequency disperser with the bead milling method.

Results

Eighty patients were included. Among forty classified PJIs, 34 patients yielded positive culture results. In 23 cases (68%) exact concordant results were generated with both techniques. However, in seven cases (20%) processing by the disperser and in four cases (12%) by bead milling provided additional positive samples, but without significant difference since the major definition criteria were met in all cases. The percentage of positive results was influenced by the volume and origin of the tissue samples. Results for small tissue samples tended to be better using the bead milling method. This might lead to improved preoperative arthroscopic diagnosis, as the volume of biopsies is generally limited. Six patients had negative results due to previous antimicrobial therapy. Forty other patients were classified as aseptic failures. Neither procedure resulted in any contamination.

Conclusion

Both methods enable reliable processing of tissue samples for diagnosis of PJI and are suitable for routine use.
Comparison of transvaginal cervical cerclage versus laparoscopic abdominal cervical cerclage in cervical insufficiency: a retrospective study from a single centre
Authors: Huang Guiqiong , Deng Chunyan , Liao Hua , Hu Qing , Yu Haiyan , Wang Xiaodong
Published: October 2022

Background

Cervical cerclage has been proposed as an effective treatment for cervical insufficiency, but there has been controversy regarding the surgical options of cervical cerclage in singleton and twin pregnancies. This study aimed to compare the pregnancy outcomes between transvaginal cervical cerclage (TVC) and laparoscopic abdominal cervical cerclage (LAC) in patients with cervical insufficiency. We also aimed to evaluate the efficacy and safety, and provide more evidence to support the application of cervical cerclage in twin pregnancies.

Methods

A retrospective study was carried out from January 2015 to December 2021. The primary outcomes were the incidence of spontaneous preterm birth (sPTB) < 24 weeks, < 28, < 32, < 34 weeks, and < 37weeks, gestational age at delivery, and the incidence of admission for threatened abortion or preterm birth after cervical cerclage. The secondary outcomes included admission to the Neonatal Intensive Care Unit, adverse neonatal outcomes and neonatal death. We also analysed the pregnancy outcomes of twin pregnancies after cervical cerclage.

Results

A total of 289 patients were identified as eligible for inclusion. The LAC group (n = 56) had a very low incidence of sPTB ˂ 34 weeks, and it was associated with a significant decrease in sPTB < 28 weeks, ˂32 weeks, ˂34 and < 37 weeks, and admission to the hospital during pregnancy for threatened abortion or preterm birth after cervical cerclage (0 vs.27%; 1.8% vs. 40.3%; 7.1% vs. 46.8%; 14% vs. 63.5%, 8.9% vs. 62.2%, respectively; P < 0.001), and high in gestational age at delivery compared with the TVC group (n = 233) (38.3 weeks vs.34.4 weeks,P < 0.001). Neonatal outcomes in the LAC group were significantly better than those in the TVC group. The mean gestational age at delivery was 34.3 ± 1.8 weeks, with a total foetal survival rate of 100% without serious neonatal complications in twin pregnancies with LAC.

Conclusion

In patients with cervical insufficiency, LAC appears to have better pregnancy outcomes than TVC. For some patients, LAC is a recommended option and may be selected as the first choice. Even in twin pregnancies, cervical cerclage can improve pregnancy outcomes with a longer latency period, especially in the LAC group.
Cost-effectiveness of Tele-delivered behavioral activation by Lay counselors for homebound older adults with depression
Authors: Chen Guoqing John , Kunik Mark E. , Marti C. Nathan , Choi Namkee G.
Published: October 2022

Background:

Low-income homebound older adults have limited access to psychosocial treatments because of their homebound state and geriatric mental health workforce shortages. Little is known about cost effectiveness of lay-counselor-delivered, videoconferenced, short-term behavioral activation on this study population. The objective of this study was to assess the cost-effectiveness of lay-counselor-delivered, videoconferenced, short-term behavioral activation (Tele-BA) compared to clinician-delivered, videoconferenced problem-solving therapy (Tele-PST) and telephone support calls (attention control; AC) for low-income homebound older adults.

Methods:

We performed a cost-effectiveness analysis based on data from a recently completed, 3-group (Tele-BA, Tele-PST, and AC) randomized controlled trial with 277 participants aged 50+. We measured total costs of (1) intervention and (2) outpatient care, ED visits, and inpatient care using the Cornell Services Index. The effectiveness outcome was quality-adjusted life-years (QALY). We used EuroQol’s EQ-5D-5L to assess each participant’s health-related quality of life (HRQoL) at baseline and at 12, 24, and 36 weeks. The end-point measure of cost-effectiveness was the incremental cost-effectiveness ratio (ICER) of (1) Tele-BA versus AC, (2) Tele-PST versus AC, and (3) Tele-BA versus Tele-PST.

Results:

Relative to AC, both Tele-BA and Tele-PST are cost-saving treatment options. The ICERs for both Tele-BA and Tele-PST were well below $50,000, the lower-bound threshold for cost-effectiveness. Relative to AC, both Tele-PST, Tele-BA are cost-saving treatment options (i.e. lower costs and more QALYs).

Conclusion:

Costs of tele- and lay-counselor-delivered depression treatment are modest and cost effective relative to providing telephone support. Though our results show that Tele-BA may not be cost effective relative to Tele-PST, a clinician-delivered psychotherapy, when a low bound ICER threshold of $50,000 would be used, lay counselors can fill the professional geriatric mental health workforce shortage gap and Tele-BA by lay counselors can improve homebound older adults’ access to evidence-and skills-based, cost effective depression care.

Trial registration:

ClinicalTrials.gov identifier: NCT02600754 (11/09/2015).
Regional differences and temporal trend analysis of Hepatitis B in Brazil
Authors: Grandi Giuliano , Lopez Luis Fernandez , Burattini Marcelo Nascimento
Published: October 2022

Background

Burden disease related to chronic HBV infection is increasing worldwide. Monitoring Hepatitis B occurrence is difficult due to intrinsic characteristics of the infection, nonetheless analyzing this information improves strategic planning towards reducing the burden related to chronic infection. In this line of thought, this study aims to analyze national and regional epidemiology of Hepatitis B and it’s temporal trends based on Brazilian reported cases.

Methods

Data obtained from the Brazilian National Notifiable Disease Reporting System (SINAN) from 2007 to 2018 were classified by infection status with an original classification algorithm, had their temporal trends analyzed by Joinpoint regression model and were correlated with gender, age and region.

Results

Of the 487,180 hepatitis B cases notified to SINAN, 97.65% had it infection status correctly classified by the new algorithm. Hepatitis B detection rate, gender and age-distribution were different among Brazilian regions. Overall, detection rates remained stable from 2007 to 2018, achieving their maximal value (56.1 cases per 100,000 inhabitants) in North region. However, there were different temporal trends related to different hepatitis B status and age. Women mean age at notification were always inferior to those of men and the difference was higher in Central-West, North and Northeast regions.

Conclusion

Hepatitis B affects heterogeneously different populations throughout Brazilian territory. The differences shown in its temporal trends, regional, gender and age-related distribution helps the planning and evaluation of control measures in Brazil.
Importance of oxidative stress in the evaluation of acute pulmonary embolism severity
Authors: Sagcan Gülseren , Konukoglu Dildar , Uzun Hafize , Arseven Orhan , Okumus Gulfer , Cuhadaroglu Caglar
Published: October 2022

Background

Pulmonary embolism (PE) is a common and potentially life-threatening disorder. Our study was aimed to investigate whether oxidative stress markers can be used as clinical markers in the evaluation of acute PE (APE) severity.

Methods

47 patients with objectively documented diagnosis of APE were recorded. Of these patients, 14 had low-risk PE, 16 had moderate-risk PE, and 17 had high-risk PE. 21 healthy subjects were also enrolled in this study. Ischemia-modified albumin (IMA), prooxidants-antioxidants balance (PAB), advanced protein oxidation products (AOPPs), and ferric reducing antioxidant power (FRAP) were measured as oxidative stress parameters to evaluate the role of oxidative stress.

Results

In the low-risk and moderate-risk APE groups, AOPPs and PAB levels were significantly higher and FRAP levels were significantly lower than those in the control group. AOPPs and IMA levels in the patients with high-risk PE were significantly higher than those in both the low-risk and moderate-risk APE patients. There was a significant correlation between levels of AOPPs and the levels of both IMA (r: 0.462, p < 0.001) and PAB (r:0.378, p < 0.005). Serum FRAP levels were negatively correlated with PAB (r:− 0.683, p < 0.001) and AOPPs levels (r:− 0,384, p < 0.001). There was also a significant positive correlation between the serum IMA and PAB levels.

Conclusions

We clearly demonstrated that reactive oxygen species formation is significantly enhanced in APE. IMA and AOPPs may be used as clinical markers in the evaluation of APE severity in clinical practice. However, further studies with larger patient populations and longer follow-up periods are required to confirm the mechanisms underlying these findings.
Postoperative proximal junctional kyphosis correlated with thoracic inlet angle in Lenke 5c adolescent idiopathic scoliosis patients following posterior surgery
Authors: Hu Bowen , Wang Linnan , Song Yueming , Yang Xi , Liu Limin , Zhou Chunguang
Published: October 2022

Background

Proximal junctional kyphosis is a common complication after posterior fusion in patients with adolescent idiopathic scoliosis and is correlated with postoperative changes of thoracic kyphosis. In lenke 5c patients, higher postoperative LL and spontaneous change of TK may produce an effect on final PJK. However, no studies has been performed to evaluate the correlation of PJK with thoracocervical parameters in patients with AIS.

Methods

Data from 98 patients who underwent posterior fusion for Lenke 5C AIS with 2 years of follow-up were retrospectively reviewed. Patients in the extended fusion group underwent fusion at levels higher than upper-end vertebra + 2 (n = 38), and those in the thoracolumbar/lumbar (TL/L) fusion group underwent fusion at UEV + 2 or lower (n = 60).

Results

During an average follow-up of 38.1 months, 23 of 98 patients developed PJK. The extended fusion group had a higher incidence of PJK than the TL/L fusion group (14/38 vs. 9/60, respectively; P = 0.01) and a significantly greater decrease in thoracic kyphosis than the TL/L group (P < 0.01). Patients with PJK had a significantly larger preoperative thoracic inlet angle (TIA) than those without PJK (P < 0.01). Multivariate analysis showed that a greater preoperative TIA and extended fusion were associated with PJK. The Scoliosis Research Society 22-item questionnaire score did not significantly differ between the PJK and non-PJK groups.

Conclusions

The preoperative TIA could be a predictor of PJK. Among patients with Lenke 5C AIS, those with a TIA of > 71° are more likely to develop PJK. Additionally, extended fusion in patients with Lenke 5C may increase the risk of PJK.
Effect of contamination of bulk-fill flowable resin composite with different contaminants during packing on its surface microhardness and compressive strength: in vitro study
Authors: Aidaros Nawal Hassan , Abdou Ahmed
Published: October 2022

Background

Proper isolation and restoration of class V subgingival cavities are technique sensitive, thus the resin composite restoration is liable to contamination. This in vitro study was conducted to evaluate the surface microhardness and compressive strength of bulk-fill flowable resin composite after being contaminated during its packing.

Methods

Resin composite discs were prepared using split mold. The contaminated specimens were allocated into four groups (n = 20) according to the contaminant used: hemostatic agent (Group 1), alcohol (Group 2), artificial saliva (Group 3) and powdered gloves (Group 4). The non-contaminated specimens (n = 20) were used as control group. The surface microhardness and compressive strength of each group were tested 1-day post-photocuring (n = 5) and 1 month post-photocuring (n = 5). Values were presented as mean, standard deviation values and confidence intervals.

Results

The surface microhardness of all groups didn’t show a significant difference for different tested groups except for alcohol which showed a significant reduction on surface microhardness compared to control at 1 day post-photocuring (p = 0.001). The highest compressive strength mean values at 1 day and 1 month post-photocuring were recorded in control groups (110.42 MPa and 172.87 MPa respectively), followed by alcohol groups, then hemostatic agent groups, followed by artificial saliva with the least value recorded in powdered gloves groups (56.71 MPa and 49.5 MPa respectively).

Conclusions

Contamination of bulk-fill flowable resin composite with hemostatic agent, alcohol, artificial saliva, or powdered gloves during its packing decreased its compressive strength after 1 month post-photocuring rather than affecting its surface microhardness.
Perception of pediatric residents from a tertiary hospital in the city of México regarding their training during the COVID-19 pandemic
Authors: Bracho Blanchet Eduardo , Klünder Klünder Miguel , Morales José Antonio Orozco , De Titto Carolina Hill , Montiel Diana Avila
Published: October 2022

Backgrounds

On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic, which changed the residents’ teaching and learning process. The purpose of this study was to determine residents’ satisfaction and impressions on their training during the pandemic in a tertiary pediatric hospital.

Methods

This was a descriptive cross-sectional study. An online survey was designed to determine residents’ demographic and personal characteristics, as well as their perception about the theoretical and practical training, as well as about their emotional situation. The analysis separated medical students from surgical students in order to identify any differences existing between these groups, for which χ2 was calculated.

Results

Overall, 148 of 171 residents (86.5%) responded to the questionnaire; 75% belonged to the medical specialty and 25% to the surgical specialty. Statistically significant differences were found in terms of those training aspects they were concerned about during the pandemic (p < 0.001) and about the difficulties associated with online learning (p = 0.001). Differences were also found regarding their satisfaction toward the time needed to complete their thesis (p = 0.059) and activities outside the hospital (p = 0.029). Regarding their degree of satisfaction in general, most medical specialty students felt slightly satisfied (43.2%) and surgical specialty students felt mostly neutral (37.8%). Regarding their feelings about their mental health, statistically significant differences were found between both groups (p = 0.038) although both groups reported the same percentage of overall dissatisfaction (2.7%) in this area.

Conclusion

The COVID-19 pandemic has brought significant challenges to medical education systems. Lack of practice in decision-making and maneuver execution are concerns for residents and may affect their future professional performance.
Design and implementation of an online admissions interview for selection to nursing and midwifery programmes: a partnership approach
Authors: Traynor Marian , Dunleavy Stephanie , McIlfatrick Sonja , Fitzsimons Donna , Stevenson Michael , McEvoy Roisin , Mulvenna Caroline
Published: October 2022

Background

The recent surge in applications to nursing in the United Kingdom together with the shift towards providing virtual interviews through the use of video platforms has provided an opportunity to review selection methodologies to meet a new set of challenges. However there remains the requirement to use selection methods which are evidence-based valid and reliable even under these new challenges.

Method

This paper reports an evaluation study of applicants to nursing and midwifery and reports on how to plan and use online interviews for in excess of 3000 applicants to two schools of nursing in Northern Ireland. Data is reported from Participants, Assessors and Administrators who were asked to complete an online evaluation using Microsoft Forms.

Results

A total of 1559 participants completed the questionnaire. The majority were aged 17–20. The findings provide evidence to support the validity and reliability of the online interview process. Importantly the paper reports on the design and implementation of a fully remote online interview process that involved a collaboration with two schools of nursing without compromising the rigour of the admissions process. The paper provides practical, quantitative, and qualitative reasons for concluding that the online remote selection process generated reliable data to support its use in the selection of candidates to nursing and midwifery.

Conclusion

There are significant challenges in moving to online interviews and the paper discusses the challenges and reflects on some of the broader issues associated with selection to nursing and midwifery. The aim of the paper is to provide a platform for discussion amongst other nursing schools who might be considering major changes to their admissions processes.
Health literacy, health outcomes and community health worker utilization: a cohort study in HIV primary care
Authors: Freibott Christina E. , Sprague Martinez Linda S. , Rajabiun Serena , Drainoni Mari-Lynn
Published: October 2022

Background

People with HIV (PWH) have complex needs, and those with limited health literacy consistently have poorer HIV-related knowledge and health outcomes. One strategy to facilitate better outcomes for PWH is the inclusion of community health workers (CHWs) into care teams. This cohort study examines the effect of health literacy on clinical outcomes and utilization of CHW services among PWH enrolled in a CHW intervention. The secondary aim is to characterize most common purposes of CHW encounters.

Methods

PWH (n = 209) enrolled in a CHW intervention with completed 6-month follow-up evaluation visits were included. Health literacy level was measured at baseline with the BRIEF tool and categorized into inadequate, marginal, and adequate health literacy. Adjusted logistic regressions assessed the effect of health literacy on viral load suppression, HIV primary care visits at 6-month follow-up, CHW utilization and purpose of CHW encounter. Purpose of CHW encounters included logistical support, accompany to appointment, transportation coordination, concrete services, coaching, and emotional support. Linear regression assessed the association between purpose of CHW encounters and CHW utilization.

Results

Individuals with inadequate health literacy were more likely to receive coaching from CHWs (p = 0.029), and individuals with marginal health literacy were more likely to have an HIV primary care visit at 6 months (p = 0.044). Individuals receiving transportation coordination, concrete services, coaching, and emotional support had more total CHW encounters.

Conclusions

Purpose of encounter was highly correlated with frequency of CHW encounters, while health literacy status was not. This suggests individuals receiving these services require more assistance from CHWs, regardless of health literacy level. Training CHWs to conduct comprehensive social needs assessment and screening for risk factors at the initial visit with clients can identify resources and guide CHW service delivery as part of the care team.
Flourishing together: research protocol for developing methods to better include disabled people’s knowledge in health policy development
Authors: Martin Rachelle A. , Baker Angelo P. , Smiler Kirsten , Middleton Lesley , Hay-Smith Jean , Kayes Nicola , Grace Catherine , Apiata Te Ao Marama , Nunnerley Joanne L. , Brown Anna E.
Published: October 2022

Background

To positively impact the social determinants of health, disabled people need to contribute to policy planning and programme development. However, they report barriers to engaging meaningfully in consultation processes. Additionally, their recommendations may not be articulated in ways that policy planners can readily use. This gap contributes to health outcome inequities. Participatory co-production methods have the potential to improve policy responsiveness. This research will use innovative methods to generate tools for co-producing knowledge in health-related policy areas, empowering disabled people to articulate experience, expertise and insights promoting equitable health policy and programme development within Aotearoa New Zealand. To develop these methods, as an exemplar, we will partner with both tāngata whaikaha Māori and disabled people to co-produce policy recommendations around housing and home (kāinga)—developing a nuanced understanding of the contexts in which disabled people can access and maintain kāinga meeting their needs and aspirations.

Methods

Participatory co-production methods with disabled people, embedded within a realist methodological approach, will develop theories on how best to co-produce and effectively articulate knowledge to address equitable health-related policy and programme development—considering what works for whom under what conditions. Theory-building workshops (Phase 1) and qualitative surveys (Phase 2) will explore contexts and resources (i.e., at individual, social and environmental levels) supporting them to access and maintain kāinga that best meets their needs and aspirations. In Phase 3, a realist review with embedded co-production workshops will synthesise evidence and co-produce knowledge from published literature and non-published reports. Finally, in Phase 4, co-produced knowledge from all phases will be synthesised to develop two key research outputs: housing policy recommendations and innovative co-production methods and tools empowering disabled people to create, synthesise and articulate knowledge to planners of health-related policy.

Discussion

This research will develop participatory co-production methods and tools to support future creation, synthesis and articulation of the knowledge and experiences of disabled people, contributing to policies that positively impact their social determinants of health.
The economic cost of bovine trypanosomosis in pastoral and ago pastoral communities surrounding Murchision Falls National park, Buliisa district, Uganda
Authors: Kizza Daniel , Ocaido Michael , Mugisha Anthony , Azuba Rose , Nalubwama Sylvia , Nalule Sarah , Onyuth Howard , Musinguzi Simon Peter , Waiswa Charles
Published: October 2022

Background:

Animal diseases that are endemic like tsetse transmitted trypanosomosis cause the continuous expenditure of financial resources of livestock farmers and loss of productivity of livestock. Estimating the cost of controlling animal trypanosomosis can provide evidence for priority setting and targeting cost-effective control strategies.

Methodology:

A cross-sectional survey to estimate the economic cost of bovine trypanosomosis was conducted in cattle-keeping communities living around Murchision falls National Park, in Buliisa district Uganda. Data was collected on herd structure, the cost of treatment and control, prevalence of morbidity and mortality rates due to trypanosomosis, and salvage sales losses in cattle herds in the last year.

Results:

In this study, 55.4% (n = 87) of the households reported their cattle had been affected by trypanosomosis during the previous last year. There was a high economic cost of trypanosomosis (USD 653) per household in cattle-keeping communities in Buliisa district of which 83% and 9% were due to mortality and milk loss respectively/ High mortality loss was due to low investment in treatment. The study showed that prophylactic treatment 3 times a year of the whole herd of cattle using Samorin ® (Isometamidium chloride) at a cost of USD 110 could drastically reduce cattle mortality loss due to trypanosomosis due to trypanosomosis with a return on investment of USD 540 annually per herd. This could be coupled with strategic restricted insecticide spraying of cattle with deltamethrin products.

Conclusion:

The results show a high economic cost of trypanosomosis in cattle-keeping communities in Buliisa district, with cattle mortality contributing the largest proportion of the economic cost. The high mortality loss was due to low investment in treatment of sick cattle.
Tumor microenvironment: barrier or opportunity towards effective cancer therapy
Authors: Tiwari Aadhya , Trivedi Rakesh , Lin Shiaw-Yih
Published: October 2022

Tumor microenvironment (TME) is a specialized ecosystem of host components, designed by tumor cells for successful development and metastasis of tumor. With the advent of 3D culture and advanced bioinformatic methodologies, it is now possible to study TME’s individual components and their interplay at higher resolution. Deeper understanding of the immune cell’s diversity, stromal constituents, repertoire profiling, neoantigen prediction of TMEs has provided the opportunity to explore the spatial and temporal regulation of immune therapeutic interventions. The variation of TME composition among patients plays an important role in determining responders and non-responders towards cancer immunotherapy. Therefore, there could be a possibility of reprogramming of TME components to overcome the widely prevailing issue of immunotherapeutic resistance. The focus of the present review is to understand the complexity of TME and comprehending future perspective of its components as potential therapeutic targets. The later part of the review describes the sophisticated 3D models emerging as valuable means to study TME components and an extensive account of advanced bioinformatic tools to profile TME components and predict neoantigens. Overall, this review provides a comprehensive account of the current knowledge available to target TME.
Quarantining: a mentally distressful but physically comfortable experience in South Korea
Authors: Kwon Hye-Young , Kim Yongjoo , Lee Seung-Young , Kim Chang-Bo
Published: October 2022

Objective

Quarantine is the first response to the COVID-19 pandemic. Restricting daily life can cause several problems. This study aimed to measure the impact of the COVID-19 quarantine on health-related quality of life (HRQoL) by comparing to the pre-pandemic.

Methods

HRQoL during COVID-19 quarantine was surveyed online using EQ-5D index and matched to that of the pre-pandemic-extracted from nationwide representative data of the Korea Community Health Survey- with propensity scores. A beta regression for the EQ-5D scores and a logistic analysis for individual dimensions of the EQ-5D index were performed to measure the impact of the COVID-19 quarantine on health utility.

Results

The overall scores of the EQ-5D index were significantly higher in the group under quarantine during the COVID-19 pandemic (0.971 SD 0.064) than those before the pandemic (0.964 SD 0.079, Diff. 0.007 SD 0.101, p = 0.043). The beta regression for the overall scores of EQ-5D revealed that quarantining during the COVID-19 pandemic increased by 52.7% compared to normal life before the outbreak(p = 0.045). Specifically, “Depression/Anxiety” deteriorated significantly during quarantining (OR = 0.62, 95% CI:0.48–0.80). However, “Pain/Discomfort” and “Mobility” significantly improved (OR = 5.37, 95% CI:3.71–7.78 and OR = 2.05, 95% CI:1.11–3.80, respectively).

Conclusion

Although the world is facing a challenging moment that it has never been through before, mandatory quarantine has served as an experience that provided mental distress but physical comfort in the Korean context.
Literature review of imaging, pathological diagnosis, and outcomes of metachronous lung and pancreatic metastasis of cecal cancer
Authors: Wu Xiang , Zhou Shuping , Zhou Xinhua , Xu Xiao , Wang Luoluo , Ruan Yi , Lu Jun , Li Haili , Xu Hongfeng , Ma Xinyi , Li Hong
Published: October 2022

Background

Pancreatic metastasis from colorectal cancer is extremely rare. Here, we report a case of colorectal cancer with lung and pancreatic metastasis and analyze the histopathology, immunohistochemistry, and next-generation sequencing (NGS) to generate a differential diagnosis and treatment of metastatic colon cancer.

Case presentation

AC1

A 78-year-old man was admitted because of a recently elevated carcinoembryonic antigen. This patient had undergone laparoscopic right hemicolectomy for cecal cancer IIA (T3N0M0) 5 years before admission, and thoracoscopic left upper lung wedge resection for primary colon cancer lung metastasis 2 years before admission. At that time, the patient was thought to have pancreatic metastasis from colon cancer. He underwent laparoscopic distal pancreatectomy (combined with splenectomy). Postoperative pathology revealed colon cancer metastasis. We performed NGS on tumor samples at three loci and found colon cancer's most common oncogenic driver genes (KRAS, APC, and TP53). One month after surgery, the patient was given capecitabine for six cycles of chemotherapy. At present, no high adverse reactions have been reported.

Discussion

For patients with pancreatic space-occupying, such as a previous history of colorectal cancer, and recent carcinoembryonic antigen elevation, we should highly suspect pancreatic metastatic colorectal cancer. NGS is an essential auxiliary for identifying metastatic tumors. Surgery combined with postoperative chemotherapy is an effective treatment.
Surgical explantation of quaternate transcatheter aortic valve replacement bioprostheses: a case report
Authors: Liang Mengya , Jian Bohao , Chen Guangxian , Wu Zhongkai
Published: October 2022

Background

Transcatheter aortic valve replacement (TAVR) is a growing less invasive surrogate for high-risk patients with aortic valve disease. Although the number of TAVR procedures is growing rapidly, TAVR prosthesis surgical explantation are rare procedures but increasing in frequency.

Case presentation

We herein presented a case of 68-year-old male who underwent quaternate TAVR bioprostheses implantation. Three months later, his symptoms deteriorated due to aggravated paravalvular leakage and severe mitral regurgitation. A challenging surgical explantation procedure was therefore performed. During the surgery, lethal penetrations of aortic wall due to migration of these devices were found and four bioprostheses were integrally explanted. The native calcified aortic leaflet was removed and replaced with a 23 mm. The impaired segment of ascending aorta was replaced with a Dacron graft afterwards.

Conclusions

In summary, we presented a surgical case of explantation of four TAVR Bioprostheses, which is so far the maximum number of surgical-explant devices ever reported. This extreme individual case aggregates our technical experiences with this unique category of patients and raise the concern of the best initial valve strategy for relatively younger patients with severe aortic valve stenosis.
Monitoring antimicrobial usage in companion animals: exploring the use of the Danish VetStat database
Authors: Glavind Anne-Sofie , Kruse Amanda Brinch , Nielsen Liza Rosenbaum , Stege Helle
Published: October 2022

Background

In the Danish Veterinary Statistics Program, VetStat, sales data on medicinal products prescribed for veterinary consumption is collected. The Danish Food and Veterinary Administration (DVFA) manages the database and each purchase contains detailed product-specific information linked with a species-specific ID. National surveillance systems are also implemented or being developed in the other European Union Member States. By 2029, all Member States are required to report data on antimicrobial usage for companion animals to the European Medicines Agency. This study aimed to assess the challenges encountered when using the VetStat database to quantify antimicrobial use in Danish companion animals. Raw VetStat data were propagated by the DVFA and originated from veterinary practitioners and Danish pharmacies.

Results

Comprehensive estimates of antimicrobial use in Danish companion animals were not readily available due to database construct. Antimicrobials sold for use in companion animals (linked to a companion animal ID) comprised a large number of products licensed solely for horses or livestock, while data assigned a replacement code encompassed both topical and peroral antimicrobials licensed for companion animals. Additionally, antimicrobials sold from pharmacies to veterinary practitioners presented the biggest challenge in data retrieval and validation. Treatment data are only transferred to VetStat through the billing systems when Danish veterinarians are treating livestock, but not companion animals. Information on products sold for in-house use in companion animals is only available from pharmacy records without a species-specific ID. As a result, parenteral antimicrobials with multi-species authorization utilized by small animal veterinary practitioners are not accounted for in the overall estimate for companion animals.

Conclusions

Owing to the database structure and requirements for data entry, antimicrobial use in companion animals is an approximation. The actual consumption may be significantly higher than what is currently calculated from the database, as the majority of parenteral products are not included. Consumption data can be measured more accurately provided treatment data from veterinary practitioners in small or mixed practices are transferred to the database through the billing system. This would equal the legal requirements for Danish veterinary practitioners treating livestock.
Synthesis and characterization of growth factor free nanoengineered bioactive scaffolds for bone tissue engineering
Authors: Abedi Fatemeh , Moghaddam Sevil Vaghefi , Ghandforoushan Parisa , Aghazadeh Marziyeh , Ebadi Hafez , Davaran Soodabeh
Published: October 2022

Background

To address the obstacles that come with orthopedic surgery for biological graft tissues, including immune rejections, bacterial infections, and weak osseointegration, bioactive nanocomposites have been used as an alternative for bone grafting since they can mimic the biological and mechanical properties of the native bone. Among them, PCL-PEG-PCL (PCEC) copolymer has gained much attention for bone tissue engineering as a result of its biocompatibility and ability for osteogenesis.

Methods

Here, we designed a growth factor-free nanoengineered scaffold based on the incorporation of Fe3O4 and hydroxyapatite (HA) nanoparticles into the PCL-PEG-PCL/Gelatin (PCEC/Gel) nanocomposite. We characterized different formulations of nanocomposite scaffolds in terms of physicochemical properties. Also, the mechanical property and specific surface area of the prepared scaffolds, as well as their feasibility for human dental pulp stem cells (hDPSCs) adhesion were assessed.

Results

The results of in vitro cell culture study revealed that the PCEC/Gel Fe3O4&HA scaffold could promote osteogenesis in comparison with the bare scaffold, which confirmed the positive effect of the Fe3O4 and HA nanoparticles in the osteogenic differentiation of hDPSCs.

Conclusion

The incorporation of Fe3O4 and HA with PCEC/gelatin could enhance osteogenic differentiation of hDPSCs for possible substitution of bone grafting tissue.

Graphical Abstract
The synthetic lethality of targeting cell cycle checkpoints and PARPs in cancer treatment
Authors: Li Shuangying , Wang Liangliang , Wang Yuanyuan , Zhang Changyi , Hong Zhenya , Han Zhiqiang
Published: October 2022

Continuous cell division is a hallmark of cancer, and the underlying mechanism is tumor genomics instability. Cell cycle checkpoints are critical for enabling an orderly cell cycle and maintaining genome stability during cell division. Based on their distinct functions in cell cycle control, cell cycle checkpoints are classified into two groups: DNA damage checkpoints and DNA replication stress checkpoints. The DNA damage checkpoints (ATM-CHK2-p53) primarily monitor genetic errors and arrest cell cycle progression to facilitate DNA repair. Unfortunately, genes involved in DNA damage checkpoints are frequently mutated in human malignancies. In contrast, genes associated with DNA replication stress checkpoints (ATR-CHK1-WEE1) are rarely mutated in tumors, and cancer cells are highly dependent on these genes to prevent replication catastrophe and secure genome integrity. At present, poly (ADP-ribose) polymerase inhibitors (PARPi) operate through “synthetic lethality” mechanism with mutant DNA repair pathways genes in cancer cells. However, an increasing number of patients are acquiring PARP inhibitor resistance after prolonged treatment. Recent work suggests that a combination therapy of targeting cell cycle checkpoints and PARPs act synergistically to increase the number of DNA errors, compromise the DNA repair machinery, and disrupt the cell cycle, thereby increasing the death rate of cancer cells with DNA repair deficiency or PARP inhibitor resistance. We highlight a combinational strategy involving PARP inhibitors and inhibition of two major cell cycle checkpoint pathways, ATM-CHK2-TP53 and ATR-CHK1-WEE1. The biological functions, resistance mechanisms against PARP inhibitors, advances in preclinical research, and clinical trials are also reviewed.
Normalization and de-noising of single-cell Hi-C data with BandNorm and scVI-3D
Authors: Zheng Ye , Shen Siqi , Keleş Sündüz
Published: October 2022

Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, and a deep generative modeling framework, scVI-3D, to account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in a time and memory efficient manner for cell-type separation, identification of interacting loci, and recovery of cell-type relationships, while scVI-3D exhibits advantages for rare cell types and under high sparsity scenarios. Application of BandNorm coupled with gene-associating domain analysis reveals scRNA-seq validated sub-cell type identification.
Evaluation of cell-cell interaction methods by integrating single-cell RNA sequencing data with spatial information
Authors: Liu Zhaoyang , Sun Dongqing , Wang Chenfei
Published: October 2022

Background

Cell-cell interactions are important for information exchange between different cells, which are the fundamental basis of many biological processes. Recent advances in single-cell RNA sequencing (scRNA-seq) enable the characterization of cell-cell interactions using computational methods. However, it is hard to evaluate these methods since no ground truth is provided. Spatial transcriptomics (ST) data profiles the relative position of different cells. We propose that the spatial distance suggests the interaction tendency of different cell types, thus could be used for evaluating cell-cell interaction tools.

Results

We benchmark 16 cell-cell interaction methods by integrating scRNA-seq with ST data. We characterize cell-cell interactions into short-range and long-range interactions using spatial distance distributions between ligands and receptors. Based on this classification, we define the distance enrichment score and apply an evaluation workflow to 16 cell-cell interaction tools using 15 simulated and 5 real scRNA-seq and ST datasets. We also compare the consistency of the results from single tools with the commonly identified interactions. Our results suggest that the interactions predicted by different tools are highly dynamic, and the statistical-based methods show overall better performance than network-based methods and ST-based methods.

Conclusions

Our study presents a comprehensive evaluation of cell-cell interaction tools for scRNA-seq. CellChat, CellPhoneDB, NicheNet, and ICELLNET show overall better performance than other tools in terms of consistency with spatial tendency and software scalability. We recommend using results from at least two methods to ensure the accuracy of identified interactions. We have packaged the benchmark workflow with detailed documentation at GitHub (https://github.com/wanglabtongji/CCI).
Evolutionary dynamics of pseudoautosomal region 1 in humans and great apes
Authors: Bergman Juraj , Schierup Mikkel Heide
Published: October 2022

Background

The pseudoautosomal region 1 (PAR1) is a 2.7 Mb telomeric region of human sex chromosomes. PAR1 has a crucial role in ensuring proper segregation of sex chromosomes during male meiosis, exposing it to extreme recombination and mutation processes. We investigate PAR1 evolution using population genomic datasets of extant humans, eight populations of great apes, and two archaic human genome sequences.

Results

We find that PAR1 is fast evolving and closer to evolutionary nucleotide equilibrium than autosomal telomeres. We detect a difference between substitution patterns and extant diversity in PAR1, mainly driven by the conflict between strong mutation and recombination-associated fixation bias at CpG sites. We detect excess C-to-G mutations in PAR1 of all great apes, specific to the mutagenic effect of male recombination. Despite recent evidence for Y chromosome introgression from humans into Neanderthals, we find that the Neanderthal PAR1 retained similarity to the Denisovan sequence. We find differences between substitution spectra of these archaics suggesting rapid evolution of PAR1 in recent hominin history. Frequency analysis of alleles segregating in females and males provided no evidence for recent sexual antagonism in this region. We study repeat content and double-strand break hotspot regions in PAR1 and find that they may play roles in ensuring the obligate X-Y recombination event during male meiosis.

Conclusions

Our study provides an unprecedented quantification of population genetic forces governing PAR1 biology across extant and extinct hominids. PAR1 evolutionary dynamics are predominantly governed by recombination processes with a strong impact on mutation patterns across all species.
Local CpG density affects the trajectory and variance of age-associated DNA methylation changes
Authors: Higham Jonathan , Kerr Lyndsay , Zhang Qian , Walker Rosie M. , Harris Sarah E. , Howard David M. , Hawkins Emma L. , Sandu Anca-Larisa , Steele J. Douglas , Waiter Gordon D. , Murray Alison D. , Evans Kathryn L. , McIntosh Andrew M. , Visscher Peter M. , Deary Ian J. , Cox Simon R. , Sproul Duncan
Published: October 2022

Background

DNA methylation is an epigenetic mark associated with the repression of gene promoters. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Altered rates of aging inferred from these clocks are observed in human disease. However, the molecular mechanisms underpinning age-associated DNA methylation changes remain unknown. Local DNA sequence can program steady-state DNA methylation levels, but how it influences age-associated methylation changes is unknown.

Results

We analyze longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs. We show that changes in methylation with age occur at 182,760 loci largely independently of variation in cell type proportions. These changes are especially apparent at 8322 low CpG density loci. Using SNP data from the same individuals, we demonstrate that methylation trajectories are affected by local sequence polymorphisms at 1487 low CpG density loci. More generally, we find that low CpG density regions are particularly prone to change and do so variably between individuals in people aged over 65. This differs from the behavior of these regions in younger individuals where they predominantly lose methylation.

Conclusions

Our results, which we reproduce in two independent groups of individuals, demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.
Global early replication disrupts gene expression and chromatin conformation in a single cell cycle
Authors: Santos Miguel M. , Johnson Mark C. , Fiedler Lukáš , Zegerman Philip
Published: October 2022

Background

The early embryonic divisions of many organisms, including fish, flies, and frogs, are characterized by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear.

Results

Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of the majority of origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly implicating origin firing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape.

Conclusions

Together, these data provide new insight into the role of the temporal control of origin firing during S-phase for coordinating replication, gene expression, and chromatin establishment as occurs in the early embryo.