bluuebunny/crossref_metadata_2025 huggingface dataset:
Calculation of Minimally Clinically Important Difference in VAS, SF-36, and LSA Scores for Hallux Rigidus Correction Via MTP Fusion
Authors: Manz Wesley J. , Lunati Matthew , Greenshields Joel , Zaldumbide Joel A. , Kadakia Rishin J. , Coleman Michelle M. , Bariteau Jason T.
Published: January 2022

Category:

Bunion; Midfoot/Forefoot; Other

Introduction/Purpose:

Hallux rigidus is a mobility limiting disease commonly seen in elderly patient populations. Correction via metatarsophalangeal (MTP) fusion has been shown to be a safe and effective means of treatment in these populations relative to younger cohorts. An increasingly important measure of surgical efficacy is the establishment of patient-reported outcomes for achieving meaningful change through a procedure. Calculation of a minimally clinically important difference (MCID) has been established to illuminate these thresholds. The objective of this study was to calculate MCID thresholds for visual analogue pain (VAS), Short Form 26 Health survey (SF-36), and LifeSpace Mobility Assessment (LSA) following first MTP fusion.

Methods:

A prospective study of all patients undergoing MTP fusion between August 1, 2015 and July 1, 2018 by a single surgeon was conducted following IRB approval. A total of 143 patients were included in the study. Demographics and surgical data were collected from review of the electronic medical record. Patient reported VAS, SF-36, and LSA scores were collected at routine 6- month and 12-month follow-up clinic appointments, as well as preoperatively. This study utilized a distribution-based approach for calculation of MCID for each of the patient reported outcomes. The MCID was defined as 0.5 times the standard deviation of the pre-operative score, 95% bootstrap confidence intervals were creating using the bias corrected and accelerated method.

Results:

The average age of patients undergoing first MTP fusion was 63.4 years (SD 10.6). Patient demographics were recorded, 25.9% of patients were current or former smokers, 60.8% had clinically managed hypertension, 9.8% had diabetes, and 31.5% carried a diagnosis of osteoarthritis. The average patient had 1.9 (SD 1.1) toes operated on during the procedure, including their MTP fusion. Mean tourniquet time was 65.6 (SD 24.8) minutes and mean operative time was 89.9 (SD 31.4) minutes. Mean (SD): VAS, 4.7 (2.8); LSA, 86.4 (35.1); SF-36 physical component score, 63.00 (19.9); SF-36 component score, 77.4 (19.8). MCID: VAS, 1.4 (95% CI 1.3 to 1.5); LSA, 17.6 (95% CI 14.4 to 21.4); SF-36 physical component score, 9.9 (95% CI 9.1 to 11.0); SF-36 mental component score, 9.8 (95% CI 8.7 to 11.4).

Conclusion:

This study identifies the MCID for VAS, SF-36, and LSA following first MTP fusion. The MCID of VAS reveals minimal improvements in pain (>1.5) are clinically significant. Both SF-36 physical and mental component scores reveal narrow 10- point differences have clinically significant changes. In contrast, LSA appears to have a relatively wide MCID value for patients undergoing first MTP fusion, highlighting the need for a large increase in mobility for significant improvement.
Efficacy of 3T MRI vs Diagnostic Arthroscopy for the Diagnosis of Osteochondral Lesions of the Talus in Patients Undergoing Brostrom Repair for Lateral Ankle Instability
Authors: Stauch Chris M. , Koroneos Zachary , Ptasinski Anna , Martinazzi Brandon , Bifano Shawn M. , Aynardi Michael C.
Published: January 2022

Category:

Ankle; Arthroscopy

Introduction/Purpose:

Osteochondral lesions of the talus (OLT) are commonly seen in patients with lateral ankle instability. If left undiagnosed, OLTs can lead to significant ankle pain and progressive osteoarthritis. While arthroscopy has long been the gold standard for the diagnosis of OLTs, MRI is a useful imaging modality for pre-operative evaluation and surgical planning in patients undergoing surgery for lateral ankle instability. The purpose of this study was to evaluate the diagnostic accuracy of 3T MRI for the diagnoses of OLTs in patients undergoing a Broström Gould procedure for lateral ankle instability.

Methods:

Following institutional review board approval, a database was obtained for all patients from 2/11/2015 to 1/21/2019 who underwent a Broström Gould procedure for lateral ankle instability in addition to diagnostic arthroscopy of the tibiotalar joint. Additionally, patients required a pre-operative 3T MRI for inclusion in the study. Patients who underwent the Broström Gould procedure but did not have a diagnostic arthroscopy or did not have a pre-operative MRI were excluded from the study. The average time from MRI to surgery was 3.5 months. Patient charts were then reviewed to determine the proportion of MRIs that correctly identified the presence or absence of OLTs compared to diagnostic arthroscopy.

Results:

A total of 80 patients were included for analysis with an average age of 38.1 +- 14.3 years. 46 (57.5%) patients were female and 34 (42.5%) were male. A total of 39 patients (48.8%) were identified to have an OLT on arthroscopy. Of these 39 patients, 28 patients (71.8%) were correctly identified by the pre-operative 3T MRI as having an OLT and 11 patients (28.2%) had MRIs that failed to identify an OLT. 41 patients had an arthroscopy that was negative for OLTs. Of these 41 patients, MRI correctly diagnosed 40 patients (97.6%) as not having an OLT and misdiagnosed 1 patient as a false positive (2.4%).

Conclusion:

In patients undergoing Broström Gould procedures with diagnostic arthroscopy for osteochondral lesions of the talus, 3T MRI demonstrates a sensitivity of 71.8% and a specificity of 97.8%. Thus, pre-operative MRI can be a useful imaging modality to assess for OLTs prior to surgery and should prompt surgeons to perform an arthroscopy with subsequent treatment of the OLT. However, a negative MRI does not rule out the possibility of an OLT being present due to a relatively high false- negative rate.
Mindfulness Practices for Children and Adolescents Receiving Cancer Therapies
Authors: Murphy Shelley , Donma Ani Jamyang , Kohut Sara Ahola , Weisbaum Elli , Chan Jacqueline H. , Plenert Erin , Tomlinson Deborah
Published: January 2022

Background: Mindfulness is our innate capacity to pay full, conscious, and compassionate attention to something in the moment. It is also a skill that can be strengthened by mental practice. More recently, mindfulness-based interventions (MBIs) are identified within clinical practice guidelines as an intervention in the treatment of certain symptoms for children with cancer. However, there is little guidance available on the practice of using MBIs in the pediatric oncology population. The aim of this paper is to provide an overview of mindfulness, highlights symptoms where mindfulness practices may be of benefit, identifies trauma-sensitive considerations, and provides examples of MBIs that may be considered in the context of pediatric oncology. Methods: Collaboration of expert opinion, which included The Mindfulness Project Team, has enabled this collective informative paper. Results: Mindfulness has been recommended to help with the symptom of fatigue in children with cancer. Emotional symptoms such as anxiety, sadness, and anger may also benefit from the use of MBIs. Ideal MBIs for this population may include mindful movement, mindfulness of the senses, mindfulness of breath, mindfulness of emotions, and the body scan. These approaches can easily be adapted according to the age of the child. Many approaches have been administered with minimal training, with very few requiring a facilitator. However, hospitals have started to incorporate mindfulness experts within their care provision. Conclusion: Future research should continue to investigate the use of MBI programs for children with cancer.
Reiki Therapy for Very Young Hospitalized Children Receiving Palliative Care
Authors: Thrane Susan E. , Williams Elisha , Grossoehme Daniel H. , Friebert Sarah
Published: January 2022

Background: Approximately half of children receiving palliative care are under age five; however, there are a few studies exploring palliative care interventions for this population. The purpose of this study was to evaluate the effects of Reiki on pain, stress, heart, and respiratory rates, oxygenation, and quality of life (QoL) in hospitalized young children receiving palliative care services. Methods: In this single-group pilot study, hospitalized children receiving palliative care who were aged 1–5 years received two Reiki sessions per week for 3 weeks. Physiologic measures were assessed pre/post each session, and parent report measures of pain and QOL were collected at baseline, 3 weeks, and 6 weeks. The parent rating of Reiki's perceived efficacy and their own symptoms were also measured. Results: Sixteen families consented. Children had a mean age of 26 months and included nine boys and seven girls. Results were not significant but there were medium-to-large clinical effect sizes for children's QoL, stress, oxygenation, heart, and respiratory rates. Parents’ physical and mental health scores decreased over time. Children exhibited signs of relaxation such as quiet sleep post-Reiki versus active awake pre-Reiki session. Conclusion: Reiki is a noninvasive relaxing therapy that is useful for hospitalized young children receiving palliative care. The children reacted positively in both action and outcome measures. Multisite studies with larger sample sizes are needed to be able to generate enough scientific evidence to fully recommend Reiki as an adjunct for pain management.
Introduction to a How I Treat series on managing complications in patients with lymphoid cancer
Authors: Sehn Laurie H.
Published: January 2022

Edited by Associate Editor Laurie Sehn, this How I Treat series features 5 state-of-the-art advisory pieces on how experts tackle recurring medical problems that may arise in the context of successful treatment for patients with lymphoid malignancies. Using case-based scenarios, the authors lay out recommendations for diagnosis, prevention, and treatment, providing clinicians with practical advice on how to optimize care for these patients, including through prevention.
Triadimefon in aquatic environments: occurrence, fate, toxicity, and ecological risk
Authors: Hou Lin , Jin Xiaowei , Liu Na , Luo Ying , Yan Zhenfei , Chen Miao , Liu Yang , Xie Huiyu , Giesy John P. , Wu Fengchang , Xu Jian
Published: January 2022

Background

As a triazole fungicide, triadimefon is widely used around the world. The ubiquitous occurrence of triadimefon in aquatic environments and potential adverse effects on aquatic organisms have resulted in global concerns. In this review, the current state of knowledge on occurrence, environmental behavior, and toxic effects are presented and used to conduct an assessment of risks posed by current concentrations of triadimefon in aquatic environments.

Results

The key findings from this review are that: (1) triadimefon occurred widely in surface waters, with high rates of detection; (2) abiotic degradation of triadimefon was affected by many factors. Stereoselectivity was found during biotic degradation and metabolism of triadimefon. Different enantiomers can cause various adverse effects, which complicates the assessment and requires enantiomers-specific considerations; (3) triadimefon exposure can affect organisms by causing multiple toxic effects on the thyroid, reproductive system, liver, nervous system as well as carcinogenicity and teratogenicity, and it can also act synergistically with other pesticides. Long-term, low-dose effects were considered to be the main characteristics of toxic effects of triadimefon; (4) results of the risk assessment based on probabilistic relationships represented by joint probability curves (JPCs) indicated that risk of triadimefon was classified as low risk.

Conclusion

Triadimefon occurred widely in surface waters, with high rates of detection, while the concentration data of triadimefon in surface water is insufficient. Researches about toxic effects and mechanisms of triadimefon on invertebrate are needed. Meanwhile, researches about toxic effects and environmental exposure of chiral monomers are also required. Due to its reproductive toxicity, triadimefon might result in adverse effects on the population level or even on the ecosystem level. Risk assessments for pesticides that cause long-term and low-dose effects on aquatic organisms such as triadimefon need to consider higher-level ecological risk.
Optimizing left ventricular-arterial coupling during the initial resuscitation in septic shock – a pilot prospective randomized study
Authors: Zhou Xiaoyang , Zhang Yiqin , Pan Jianneng , Wang Yang , Wang Hua , Xu Zhaojun , Chen Bixin , Hu Caibao
Published: January 2022

Background

Left ventricular-arterial coupling (VAC), defined as the ratio of effective arterial elastance (Ea) to left ventricular end-systolic elastance (Ees), has been extensively described as a key determinant of cardiovascular work efficacy. Previous studies indicated that left ventricular-arterial uncoupling was associated with worse tissue perfusion and increased mortality in shock patients. Therefore, this study aims to investigate whether a resuscitation algorithm based on optimizing left VAC during the initial resuscitation can improve prognosis in patients with septic shock.

Methods

This pilot study was conducted in an intensive care unit (ICU) of a tertiary teaching hospital in China. A total of 83 septic shock patients with left ventricular-arterial uncoupling (i.e., the Ea/Ees ratio ≥ 1.36) were randomly assigned to receive usual care (usual care group, n = 42) or an algorithm-based resuscitation that attempt to reduce the Ea/Ees ratio to 1 within the first 6 h after randomization (VAC-optimized group, n = 41). The left VAC was evaluated by transthoracic echocardiography every 2 h during the study period. The primary endpoint was 28-days mortality. The secondary endpoints included lactate clearance rate, length of ICU stay, and duration of invasive mechanical ventilation (IMV).

Results

Eighty-two patients (98.8%) completed the study and were included in the final analysis. The Ea/Ees ratio was reduced in both groups, and the decrease in Ea/Ees ratio in the VAC-optimized group was significantly greater than that in the usual care group [median (interquartile range), 0.39 (0.26, 0.45) vs. 0.1 (0.06, 0.22); P < 0.001]. Compared with the usual care group, the VAC-optimized group likely exhibited the potential to reduce the 28-days mortality (33% vs. 50%; log-rank hazard ratio = 0.526, 95% confidence interval: 0.268 to 1.033). Moreover, the VAC-optimized group had a higher lactate clearance rate than the usual care group [27.7 (11.9, 45.7) % vs. 18.3 (− 5.7, 32.1) %; P = 0.038]. No significant difference was observed in terms of the length of ICU stay or duration of IMV.

Conclusions

During the initial resuscitation of septic shock, optimizing left ventricular-arterial coupling was associated with improved lactate clearance, while likely having a beneficial effect on prognosis.

Trial registration

Chinese Clinical Trial Registry,
ChiCTR1900024031. Registered 23 June 2019 - Retrospectively registered.
Did you hear about HIV self-testing? HIV self-testing awareness after community-based HIVST distribution in rural Zimbabwe
Authors: Rotsaert Anke , Sibanda Euphemia , Hatzold Karin , Johnson Cheryl , Corbett Elizabeth , Neuman Melissa , Cowan Frances
Published: January 2022

Background

Several trials of community-based HIV self-testing (HIVST) provide evidence on the acceptability and feasibility of campaign-style distribution to reach first-time testers, men and adolescents. However, we do not know how many remain unaware of HIVST after distribution campaigns, and who these individuals are. Here we look at factors associated with never having heard of HIVST after community-based campaign-style HIVST distribution in rural Zimbabwe between September 2016 and July 2017.

Methods

Analysis of representative population-based trial survey data collected from 7146 individuals following community-based HIVST distribution to households was conducted. Factors associated with having never heard of HIVST were determined using multivariable mixed-effects logistic regression adjusted for clustered design.

Results

Among survey participants, 1308 (18.3%) self-reported having never heard of HIVST. Individuals who were between 20 and 60 years old {20–29 years: [aOR = 0.74, 95% CI (0.58–0.95)], 30–39 years: [aOR = 0.56, 95% CI (0.42–0.74)], 40–49 years: [aOR = 0.50, 95% CI (0.36–0.68)], 50–59 years [aOR = 0.58, 95% CI (0.42–0.82)]}, who had attained at least ordinary level education [aOR = 0.51, 95% CI (0.34–0.76)], and who had an HIV test before [aOR = 0.30, 95% CI (0.25–0.37)] were less likely to have never heard of HIVST compared with individuals who were between 16 and 19 years old, who had a lower educational level and who had never tested for HIV before, respectively. In addition, non-household heads or household head representatives [aOR = 1.21, 95% CI (1.01–1.45)] were more likely to report never having heard of HIVST compared to household head and representatives.

Conclusions

Around one fifth of survey participants remain unaware of HIVST even after an intensive community-based door-to-door HIVST distribution. Of note, those least likely to have heard of self-testing were younger, less educated and less likely to have tested previously. Household heads appear to play an important role in granting or denying access to self-testing to other household members during door-to-door distribution. Differentiated distribution models are needed to ensure access to all.

Trial registration PACTR, PACTR201607001701788. Registered 29 June 2016, https://pactr.samrc.ac.za/ PACTR201607001701788
Age-adjusted Charlson comorbidity index in recurrent glioblastoma: a new prognostic factor?
Authors: Barz Melanie , Bette Stefanie , Janssen Insa , Aftahy A. Kaywan , Huber Thomas , Liesche-Starnecker Friederike , Ryang Yu-Mi , Wiestler Benedikt , Combs Stephanie E. , Meyer Bernhard , Gempt Jens
Published: January 2022

Background

For recurrent glioblastoma (GB) patients, several therapy options have been established over the last years such as more aggressive surgery, re-irradiation or chemotherapy. Age and the Karnofsky Performance Status Scale (KPSS) are used to make decisions for these patients as these are established as prognostic factors in the initial diagnosis of GB. This study’s aim was to evaluate preoperative patient comorbidities by using the age-adjusted Charlson Comorbidity Index (ACCI) as a prognostic factor for recurrent GB patients.

Methods

In this retrospective analysis we could include 123 patients with surgery for primary recurrence of GB from January 2007 until December 2016 (43 females, 80 males, mean age 57 years (range 21–80 years)). Preoperative age, sex, ACCI, KPSS and adjuvant treatment regimes were recorded for each patient. Extent of resection (EOR) was recorded as a complete/incomplete resection of the contrast-enhancing tumor part.

Results

Median overall survival (OS) was 9.0 months (95% CI 7.1–10.9 months) after first re-resection. Preoperative KPSS > 80% (P < 0.001) and EOR (P = 0.013) were associated with significantly improved survival in univariate analysis. Including these factors in multivariate analysis, preoperative KPSS < 80 (HR 2.002 [95% CI: 1.246–3.216], P = 0.004) and EOR are the only significant prognostic factor (HR 1.611 [95% CI: 1.036–2.505], P = 0.034). ACCI was not shown as a prognostic factor in univariate and multivariate analyses.

Conclusion

For patients with surgery for recurrent glioblastoma, the ACCI does not add further information about patient’s prognosis besides the well-established KPSS and extent of resection.
Effect of a pediatric fruit and vegetable prescription program on child dietary patterns, food security, and weight status: a study protocol
Authors: Saxe-Custack Amy , Todem David , Anthony James C. , Kerver Jean M. , LaChance Jenny , Hanna-Attisha Mona
Published: January 2022

Background

Although nutrients in fruits and vegetables are necessary for proper development and disease prevention, most US children consume fewer servings than recommended. Prescriptions for fruits and vegetables, written by physicians to exchange for fresh produce, address access and affordability challenges while emphasizing the vital role of diet in health promotion and disease prevention. Michigan’s first fruit and vegetable prescription program (FVPP) exclusively for children was introduced in 2016 at one large pediatric clinic in Flint and expanded to a second clinic in 2018. The program provides one $15 prescription for fresh produce to all pediatric patients at every office visit. Prescriptions are redeemable at a year-round farmers’ market or a local mobile market. The current study will assess the impact of this FVPP on diet, food security, and weight status of youth.

Methods

Demographically similar pediatric patient groups with varying levels of exposure to the FVPP at baseline will be compared: high exposure (> 24 months), moderate exposure (12–24 months), and no previous exposure. Data collection will focus on youth ages 8–16 years. A total of 700 caregiver-child dyads (one caregiver and one child per household) will be enrolled in the study, with approximately 200 dyads at clinic 1 (high exposure); 200 dyads at clinic 2 (moderate exposure), and 300 dyads at clinic 3 (no previous exposure). Children with no previous exposure will be introduced to the FVPP, and changes in diet, food security, and weight status will be tracked over two years. Specific aims are to (1) compare baseline diet, food security, and weight status between pediatric patients with varying levels of exposure to the FVPP; (2) measure changes in diet, food security, and weight status before and after never-before-exposed children are introduced to the FVPP; and (3) compare mean 12- and 24-month follow-up measures of diet, food security, and weight status in the initial no exposure group to baseline measures in the high exposure group.

Discussion

Completion of study aims will provide evidence for the effectiveness of pediatric FVPPs and insights regarding the duration and intensity of exposure necessary to influence change.

Trial registration

The study was registered through clinicaltrials.gov [ID: NCT04767282] on February 23, 2021.
Does an endocrinology subspecialty residency rotation enhance resident endocrine clinical knowledge?
Authors: Miller-Chang Yeng M. , Gauer Jacqueline L. , Butler Logan , Olson Andrew P.J. , Shrestha Rupendra T. , Redmon J. Bruce
Published: January 2022

Background

Internal Medicine (IM) programs offer elective subspecialty rotations in which residents may enroll to supplement the experience and knowledge obtained during general inpatient and outpatient rotations. Objective evidence that these rotations provide enhanced subspecialty specific knowledge is lacking. The purpose of this study was to determine whether exposure to an endocrinology subspecialty rotation enhanced a resident’s endocrinology-specific knowledge beyond that otherwise acquired during IM residency.

Methods

Data were collected on internal medicine resident scores on the American College of Physicians Internal Medicine In-Training Examinations (IM-ITE) for calendar years 2012 through 2018 along with enrollment data as to whether residents had completed an endocrinology subspecialty rotation prior to sitting for a given IM-ITE. Three hundred and six internal medicine residents in the University of Minnesota Internal Medicine residency program with 664 scores total on the IM-ITE for calendar years 2012 through 2018. Percentage of correct answers on the overall and endocrine subspecialty content areas on the IM-ITE for each exam were determined and the association between prior exposure to an endocrinology subspecialty rotation and percentage of correct answers in the endocrinology content area was analyzed using generalized linear mixed-effects models.

Results

Two hundred and thirty-three residents (76%) completed an endocrinology subspecialty rotation at some point during their residency; 121 (40%) residents had at least one IM-ITE both before and after exposure to an endocrine subspecialty rotation. Exposure to an endocrinology subspecialty rotation exhibited a positive association with the expected IM-ITE percent correct on the endocrinology content area (5.5% predicted absolute increase). Advancing year of residency was associated with a predicted increase in overall IM-ITE score but did not improve the predictive model for endocrine subspecialty score.

Conclusions

Completion of an endocrinology subspecialty elective was associated with an increase in resident endocrine specific knowledge as assessed by the IM-ITE. These findings support the value of subspecialty rotations in enhancing a resident’s subspecialty specific medical knowledge.
Magnitude of mortality and its associated factors among Burn victim children admitted to South Gondar zone government hospitals, Ethiopia, from 2015 to 2019
Authors: Tiruneh Chalie Marew , Belachew Amare , Mulatu Sileshi , Emiru Tigabu Desie , Tibebu Nigusie Selomon , Abate Moges Wubneh , Nigat Adane Birhanu , Belete Amsalu , Walle Belete Gelaw
Published: January 2022

Abstracts

Background

Burn is one of the leading causes of preventable death and disability every year in low and middle-income countries, which mainly affects those aged less than 15 years. Death from burn injuries carries the most significant losses, which often have grave consequences for the countries. Even though data from different settings are necessary to tackle it, pieces of evidence in this area are limited. Thus, this study was aimed to answer the question, what is the Magnitude of Mortality? And what are the factors associated with mortality among burn victim children admitted to South Gondar Zone Government Hospitals, Ethiopia, from 2015 to 2019?

Methods

Institutional-based cross-sectional study design was used to study 348 hospitalized burn victim pediatrics’, from 2015 to 2019. A simple random sampling method was used. Data were exported from Epidata to SPSS version 23 for analysis. Significant of the variables were declared when ap-value is < 0.05.

Result

The mortality rate of burn victim children in this study was 8.5% (95% CI = 5.5–11.4). Medical insurance none users burn victim children were more likely (AOR 3.700; 95% CI =1.2–11.5) to die as compared with medical insurance users, burn victim children with malnutrition were more risk (AOR 3.9; 95% CI = 1.3–12.2) of mortality as compared with well-nourished child. Moreover, electrical (AOR 7.7; 95% CI = 1.8–32.5.2) and flame burn (AOR 3.3; 95% CI = 1.2–9.0), total body surface area greater than 20% of burn were more likely (AOR 4.6; 95% CI 1.8–11.8) to die compared to less than 20% burn area and burn victim children admitted with poor clinical condition at admission were four times (AOR 4.1, 95% CI = 1.3–12.0) of mortality compared to a good clinical condition.

Conclusion

The mortality among burn victim children was higher than most of the studies conducted all over the world. Medical insurance none users, being malnourished, burned by electrical and flame burn, having total body surface area burnt greater than 20%, and having poor clinical condition at addition were significantly associated with mortality of burn victim pediatrics. Therefore, timely identification and monitoring of burn injury should be necessary to prevent mortality of burn victim pediatrics.
Statistics or biology: the zero-inflation controversy about scRNA-seq data
Authors: Jiang Ruochen , Sun Tianyi , Song Dongyuan , Li Jingyi Jessica
Published: January 2022

Researchers view vast zeros in single-cell RNA-seq data differently: some regard zeros as biological signals representing no or low gene expression, while others regard zeros as missing data to be corrected. To help address the controversy, here we discuss the sources of biological and non-biological zeros; introduce five mechanisms of adding non-biological zeros in computational benchmarking; evaluate the impacts of non-biological zeros on data analysis; benchmark three input data types: observed counts, imputed counts, and binarized counts; discuss the open questions regarding non-biological zeros; and advocate the importance of transparent analysis.
Immune profiles and DNA methylation alterations related with non-muscle-invasive bladder cancer outcomes
Authors: Chen Ji-Qing , Salas Lucas A. , Wiencke John K. , Koestler Devin C. , Molinaro Annette M. , Andrew Angeline S. , Seigne John D. , Karagas Margaret R. , Kelsey Karl T. , Christensen Brock C.
Published: January 2022

Background

Non-muscle-invasive bladder cancer (NMIBC) patients receive frequent monitoring because ≥ 70% will have recurrent disease. However, screening is invasive, expensive, and associated with significant morbidity making bladder cancer the most expensive cancer to treat per capita. There is an urgent need to expand the understanding of markers related to recurrence and survival outcomes of NMIBC.

Methods and results

We used the Illumina HumanMethylationEPIC array to measure peripheral blood DNA methylation profiles of NMIBC patients (N = 603) enrolled in a population-based cohort study in New Hampshire and applied cell type deconvolution to estimate immune cell-type proportions. Using Cox proportional hazard models, we identified that increasing CD4T and CD8T cell proportions were associated with a statistically significant decreased hazard of tumor recurrence or death (CD4T: HR = 0.98, 95% CI = 0.97–1.00; CD8T: HR = 0.97, 95% CI = 0.95–1.00), whereas increasing monocyte proportion and methylation-derived neutrophil-to-lymphocyte ratio (mdNLR) were associated with the increased hazard of tumor recurrence or death (monocyte: HR = 1.04, 95% CI = 1.00–1.07; mdNLR: HR = 1.12, 95% CI = 1.04–1.20). Then, using an epigenome-wide association study (EWAS) approach adjusting for age, sex, smoking status, BCG treatment status, and immune cell profiles, we identified 2528 CpGs associated with the hazard of tumor recurrence or death (P < 0.005). Among these CpGs, the 1572 were associated with an increased hazard and were significantly enriched in open sea regions; the 956 remaining CpGs were associated with a decreased hazard and were significantly enriched in enhancer regions and DNase hypersensitive sites.

Conclusions

Our results expand on the knowledge of immune profiles and methylation alteration associated with NMIBC outcomes and represent a first step toward the development of DNA methylation-based biomarkers of tumor recurrence.
Parsing heterogeneity within dementia with Lewy bodies using clustering of biological, clinical, and demographic data
Authors: Abdelnour Carla , Ferreira Daniel , van de Beek Marleen , Cedres Nira , Oppedal Ketil , Cavallin Lena , Blanc Frédéric , Bousiges Olivier , Wahlund Lars-Olof , Pilotto Andrea , Padovani Alessandro , Boada Mercè , Pagonabarraga Javier , Kulisevsky Jaime , Aarsland Dag , Lemstra Afina W. , Westman Eric
Published: January 2022

Background

Dementia with Lewy bodies (DLB) includes various core clinical features that result in different phenotypes. In addition, Alzheimer’s disease (AD) and cerebrovascular pathologies are common in DLB. All this increases the heterogeneity within DLB and hampers clinical diagnosis. We addressed this heterogeneity by investigating subgroups of patients with similar biological, clinical, and demographic features.

Methods

We studied 107 extensively phenotyped DLB patients from the European DLB consortium. Factorial analysis of mixed data (FAMD) was used to identify dimensions in the data, based on sex, age, years of education, disease duration, Mini-Mental State Examination (MMSE), cerebrospinal fluid (CSF) levels of AD biomarkers, core features of DLB, and regional brain atrophy. Subsequently, hierarchical clustering analysis was used to subgroup individuals based on the FAMD dimensions.

Results

We identified 3 dimensions using FAMD that explained 38% of the variance. Subsequent hierarchical clustering identified 4 clusters. Cluster 1 was characterized by amyloid-β and cerebrovascular pathologies, medial temporal atrophy, and cognitive fluctuations. Cluster 2 had posterior atrophy and showed the lowest frequency of visual hallucinations and cognitive fluctuations and the worst cognitive performance. Cluster 3 had the highest frequency of tau pathology, showed posterior atrophy, and had a low frequency of parkinsonism. Cluster 4 had virtually normal AD biomarkers, the least regional brain atrophy and cerebrovascular pathology, and the highest MMSE scores.

Conclusions

This study demonstrates that there are subgroups of DLB patients with different biological, clinical, and demographic characteristics. These findings may have implications in the diagnosis and prognosis of DLB, as well as in the treatment response in clinical trials.
Transcriptome-scale spatial gene expression in rat arcuate nucleus during puberty
Authors: Zhou Shasha , Zang Shaolian , Hu Yanping , Shen Yifen , Li Hua , Chen Wenlian , Li Pin , Shen Yihang
Published: January 2022

Background

A variety of neurons in hypothalamus undergo a complicated regulation on transcription activity of multiple genes for hypothalamic–pituitary–gonadal axis activation during pubertal development. Identification of puberty-associated cell composition and characterization of the unique transcriptional signatures across different cells are beneficial to isolation of specific neurons and advanced understanding of their functions.

Methods

The hypothalamus of female Sprague–Dawley rats in postnatal day-25, 35 and 45 were used to define the dynamic spatial atlas of gene expression in the arcuate nucleus (ARC) by 10× Genomics Visium platform. A surface protein expressed selectively by kisspeptin neurons was used to sort neurons by flow cytometric assay in vitro. The transcriptome of the isolated cells was examined using Smart sequencing.

Results

Four subclusters of neurons with similar gene expression signatures in ARC were identified. Only one subcluster showed the robust expression of Kiss1, which could be isolated by a unique membrane surface biomarker Solute carrier family 18 member A3 (SLC18A3). Moreover, genes in different subclusters presenting three expression modules distinctly functioned in each pubertal stage. Different types of cells representing distinct functions on glial or neuron differentiation, hormone secretion as well as estradiol response precisely affect and coordinate with each other, resulting in a complicated regulatory network for hypothalamic–pituitary–gonadal axis initiation and modulation.

Conclusion

Our data revealed a comprehensive transcriptomic overview of ARC within different pubertal stages, which could serve as a valuable resource for the study of puberty and sexual development disorders.
Has Latin America achieved universal health coverage yet? Lessons from four countries
Authors: Gilardino Ramiro E. , Valanzasca Pilar , Rifkin Susan B.
Published: January 2022

Background

Seven years after the commitment to United Nations’ call for Universal Health Coverage, healthcare services in Argentina, Brazil, Colombia, Mexico are generally accessible and affordable; but they still struggle to meet population health demands and address the rising health care costs. We aim to describe measures taken by these four countries to commit by Universal Health Coverage, addressing their barriers and challenges.

Methods

Scoping literature review, supplemented with targeted stakeholders survey.

Results

The four countries analysed achieved an overall index of essential coverage of 76–77%, and households out of pocket health expenditures fall below 25%. Services coverage was improved by expanding access to primary healthcare systems and coverage for non-communicable diseases, while provided community outreach by the increase in the number of skilled healthcare workers. New pharmaceutical support programs provided access to treatments for chronic conditions at zero cost, while high-costs drugs and cancer treatments were partially guaranteed. However, the countries lack with effective financial protection mechanisms, that continue to increase out of pocket expenditure as noted by lowest financial protection scores, and lack of effective financial mechanisms besides cash transfers.

Conclusions

Argentina, Brazil, Colombia, and Mexico have made progress towards UHC. Although, better financial protection is urgently required.
Geographic distribution and prevalence of human echinococcosis at the township level in the Tibet Autonomous Region
Authors: Wang Liying , Quzhen Gongsang , Qin Min , Liu Zehang , Pang Huasheng , Frutos Roger , Gavotte Laurent
Published: January 2022

Background

Echinococcosis, a zoonotic parasitic disease, is caused by larval stages of cestodes in the Echinococcus genus. Echinococcosis is highly prevalent in ten provinces/autonomous regions of western and northern China. In 2016, an epidemiological survey of Tibet Autonomous Region (TAR) revealed that the prevalence of human echinococcosis was 1.66%, which was much higher than the average prevalence in China (0.24%). Therefore, to improve on the current prevention and control measures, it is important to understand the prevalence and spatial distribution characteristics of human echinococcosis at the township level in TAR.

Methods

Data for echinococcosis cases in 2018 were obtained from the annual report system of echinococcosis of Tibet Center for Disease Control and Prevention. Diagnosis had been performed via B-ultrasonography. The epidemic status of echinococcosis in all townships in TAR was classified according to the relevant standards of population prevalence indices as defined in the national technical plan for echinococcosis control. Spatial scan statistics were performed to establish the geographical townships that were most at risk of echinococcosis.

Results

In 2018, a total of 16,009 echinococcosis cases, whose prevalence was 0.53%, were recorded in 74 endemic counties in TAR. Based on the order of the epidemic degree, all the 692 townships were classified from high to low degrees. Among them, 127 townships had prevalence rates ≥ 1%. The high prevalence of human echinococcosis in TAR, which is associated with a wide geographic distribution, is a medical concern. Approximately 94.65% of the villages and towns reported echinococcosis cases. According to spatial distribution analysis, the prevalence of human echinococcosis was found to be clustered, with the specific clustering areas being identified. The cystic echinococcosis primary cluster covered 88 townships, while that of alveolar echinococcosis’s covered 38 townships.

Conclusions

This study shows spatial distributions of echinococcosis with different epidemic degrees in 692 townships of TAR and high-risk cluster areas at the township level. Our findings indicate that strengthening the echinococcosis prevention and control strategies in TAR should directed at townships with a high prevalence and high-risk clustering areas.

Graphical Abstract
The role of wind in controlling the connectivity of blue mussels (Mytilus edulis L.) populations
Authors: Demmer Jonathan , Robins Peter , Malham Shelagh , Lewis Matthew , Owen Aaron , Jones Trevor , Neill Simon
Published: January 2022

Background

Larval connectivity between distinct benthic populations is essential for their persistence. Although connectivity is difficult to measure in situ, it can be predicted via models that simulate biophysical interactions between larval behaviour and ocean currents. The blue mussel (Mytilus Edulis L.) is widespread throughout the northern hemisphere and extensively commercialised worldwide. In the Irish Sea, this industry represents ~ 50% of Welsh shellfisheries, where cultivation is mainly based on wild spat. However, the main sources and amount of spat varied interannually (1100 tonnes harvest in 2014 against zero in 2018). The aim of this study is to characterise the structure and dynamics of the blue mussel metapopulation within the northern part of the Irish Sea.

Methods

We develop a Lagrangian particle tracking model, driven by a high-resolution (from 30 to 5000 m) validated unstructured coastal hydrodynamic model of the Irish Sea, to simulate spatial and temporal variability of larval dispersal and connectivity between distinct mussel populations and potential settlement areas.

Results

Our results showed that: (1) larvae positioned near the surface were strongly influenced by wind-driven currents suggesting that connectivity networks had the potential to span hundreds of kilometres; (2) in contrast, larvae positioned deeper in the water column were driven by tidal currents, producing intricate spatial patterns of connectivity between mussel beds over tens of kilometres that were consistent over time.

Conclusions

Dispersal of mussel larvae in the tidally energetic Irish Sea during the April–May spawning season is potentially driven by wind-driven surface currents, as confirmed by fisherman observations of inter-annual variability in wild spat collection. These results have important implications for metapopulation dynamics within the context of climate change and sustainable shellfisheries management (i.e. gain and loss of populations and harvest areas according to wind conditions).
Ancient mural segmentation based on a deep separable convolution network
Authors: Cao Jianfang , Tian Xiaodong , Chen Zhiqiang , Rajamanickam Leelavathi , Jia Yiming
Published: January 2022

Traditional methods for ancient mural segmentation have drawbacks, including fuzzy target boundaries and low efficiency. Targeting these problems, this study proposes a pyramid scene parsing MobileNetV2 network (PSP-M) by fusing a deep separable convolution-based lightweight neural network with a multiscale image segmentation model. In this model, deep separable convolution-fused MobileNetV2, as the backbone network, is embedded in the image segmentation model, PSPNet. The pyramid scene parsing structure, particularly owned by the two models, is used to process the background features of images, which aims to reduce feature loss and to improve the efficiency of image feature extraction. In the meantime, atrous convolution is utilized to expand the perceptive field, aiming to ensure the integrity of image semantic information without changing the number of parameters. Compared with traditional image segmentation models, PSP-M increases the average training accuracy by 2%, increases the peak signal-to-noise ratio by 1–2 dB and improves the structural similarity index by 0.1–0.2.
Morphology, mating system and taxonomy of Volvox africanus (Volvocaceae, Chlorophyceae) from Thailand
Authors: Nozaki Hisayoshi , Mahakham Wuttipong , Heman Wirawan , Matsuzaki Ryo , Kawachi Masanobu
Published: January 2022

Background

The oogamous green algal genusVolvoxexhibits extensive diversity in mating systems, including heterothallism and homothallism with unisexual (male and/or female) and/or bisexual spheroids. Although four mating systems have been recognized worldwide in strains identified as “Volvox africanus”, most of these strains are extinct. However, we previously rediscovered two types of the four mating systems (heterothallic, and homothallic with male and bisexual spheroids within a clone) from an ancient Japanese lake, Lake Biwa.

Results

Here, we obtained strains exhibiting the third mating system (homothallic with unisexual male and female spheroids within a clone) from a freshwater area of Kalasin Province, Thailand. When sexual reproduction was induced in the present Thai strains, both male and female unisexual spheroids developed to form smooth-walled zygotes within a clonal culture. Phylogenetic analyses of the internal transcribed spacer region-2 of nuclear ribosomal DNA sequences from all four mating systems, including the extinct strains, resolved the third mating system is basal or paraphyletic within the homothallic clade.

Conclusions

The present morphological and molecular data of the Thai strains indicate that they belong to the homothallic speciesV. africanus. The phylogenetic results suggested that third mating system (homothallic with separate male and female sexual spheroids) may represent an initial evolutionary stage of transition from heterothallism to homothallism withinVolvox africanus. Further field collections in geologically stable intracontinental regions may be fruitful for studying diversity and taxonomy of the freshwater green algal genusVolvox.
The effect of educational game design process on students’ creativity
Authors: Bulut Derman , Samur Yavuz , Cömert Zeynep
Published: January 2022

In the 2020s, it is clear that children now spend most of their days in front of the screen. During screen time, playing games is one of the most important activities of children. However, technology is developing day by day and innovations are quickly becoming a natural part of life. Therefore, children now need to be creative people who produce innovation, rather than just consuming themselves with the digital content offered to them. For this reason, students need to improve their creative thinking skills. Also, they need guidance for producing with technology. Considering this circumstance, this research, which was aimed at 5th and 6th grade school students designed educational games in a blended learning environment, employed a single group pretest posttest experimental design research. At the beginning and end of the research, the creativity level of students was examined by using the Torrance Test of Creativity. The study tries to seek an answer to the following question: “How does the educational game designing process affect 5th and 6th grade students’ creative thinking development?”. As a result, it was determined that there was a statistically significant difference in the creative thinking skill scores of those who designed their own educational game. This result is tangible evidence that the game is not only a drill and practice activity but it also presents a creative thinking environment for students.
Structural equation modelling the relationship between anti-fungal prophylaxis and Pseudomonas bacteremia in ICU patients
Authors: Hurley James C.
Published: January 2022

Purpose

Animal models implicate candida colonization facilitating invasive bacterial infections. The clinical relevance of this microbial interaction remains undefined and difficult to study directly. Observations from studies of anti-septic, antibiotic, anti-fungal, and non-decontamination-based interventions to prevent ICU acquired infection collectively serve as a natural experiment.

Methods

Three candidate generalized structural equation models (GSEM), with Candida and Pseudomonas colonization as latent variables, were confronted with blood culture and respiratory tract isolate data derived from 464 groups from 279 studies including studies of combined antibiotic and antifungal exposures within selective digestive decontamination (SDD) interventions.

Results

Introducing an interaction term between Candida colonization and Pseudomonas colonization substantially improved GSEM model fit. Model derived coefficients for singular exposure to anti-septic agents (− 1.23; − 2.1 to − 0.32), amphotericin (− 1.78; − 2.79 to − 0.78) and topical antibiotic prophylaxis (TAP; + 1.02; + 0.11 to + 1.93) versus Candida colonization were similar in magnitude but contrary in direction. By contrast, the model-derived coefficients for singular exposure to TAP, as with anti-septic agents, versus Pseudomonas colonization were weaker or non-significant. Singular exposure to amphotericin would be predicted to more than halve candidemia and Pseudomonas bacteremia incidences versus literature benchmarks for absolute differences of approximately one percentage point or less.

Conclusion

GSEM modelling of published data supports the postulated interaction between Candida and Pseudomonas colonization towards promoting bacteremia among ICU patients. This would be difficult to detect without GSEM modelling. The model indicates that anti-fungal agents have greater impact in preventing Pseudomonas bacteremia than TAP, which has no impact.