bluuebunny/crossref_metadata_2025 huggingface dataset:
CHANGE IN URGENCY STATUS AMONG ULCERATIVE COLITIS PATIENTS: UNDERSTANDING THE IMPACT OF TREATMENT CHANGES FROM THE COREVITAS INFLAMMATORY BOWEL DISEASE REGISTRY
Authors: Wolf Douglas , Naegeli April , Moore Page , Janak Judson , Crabtree Margaux , Shan Mingyang , Hunter Theresa , Sontag Angelina , Cross Raymond
Published: January 2022

BACKGROUND

Stooling urgency (also known as urgency to defecate) is one of the most common symptoms among Ulcerative Colitis (UC) patients (pts). Understanding factors associated with changes in urgency status, such as the association between timing of treatment changes and subsequent onset or resolution of urgency symptoms, are essential in addressing unmet pts needs. Our aim was to explore treatment frequency and persistence among UC pts stratified by a change in urgency status from enrollment to the 6-month follow-up (6M) visit.

METHODS

Participants included UC pts in the CorEvitas Inflammatory Bowel Disease Registry between 5/3/17-9/1/20. Stooling urgency was defined as no urgency or urgency using the categories, none and hurry/immediate, from the Simple Clinical Colitis Activity Index (SCCAI). Urgency status groups were formed by urgency at enrollment and the 6M visit: no persistent urgency (NPU), i.e., no urgency at both visits; change from urgency to no urgency (UN); change from no urgency to urgency (NU); and persistent urgency at both visits (PU). Chi-square tests were conducted to compare treatment use and change between urgency status groups (NPU=reference group). Kaplan Meier curves and log-rank tests were used to assess time to first treatment change between urgency status groups.

RESULTS

The urgency status groups (n=400) included: 44% NPU (n=175), 21% UN (n=86), 14% NU (n=56), and 21% PU (n=83). A higher proportion of UN (47%, p=0.03) and PU (51%, p=0.01) pts received two or more treatments compared to NPU (33%) pts. Compared to NPU pts, pts in all three groups, UN (52% vs. 27%, p< 0.001), NU (45% vs. 27%, p=0.02), and PU (53% vs. 27%, p< 0.001) were more likely to change treatment between enrollment and the 6M visit. Similarly, a higher proportion of pts on a biologic at enrollment, UN (24% vs. 11%, p=0.01), NU (23% vs. 11%, p=0.03), and PU (35% vs 11%, p< 0.001), changed treatment between enrollment and the 6M visit vs. NPU pts. The time to first treatment change was shorter for all other urgency status groups when compared to NPU pts (log-rank tests, all p<0.02) (Figure 1). Among pts without urgency at enrollment, the time to first treatment change was shorter for NU vs. NPU pts (p=0.01) whereas it was similar for pts with urgency at enrollment, UN vs. PU pts (p=0.93) (Figure 1).

CONCLUSION

Among UC pts in a real-world setting, there were significant differences in change of treatment and time to treatment change between pts who experienced urgency either at their enrollment visit, 6M, or both, compared to those without urgency. Urgency at any time point is a symptom of great concern to UC pts, is a sign of inadequate therapy, and often is an indication to switch treatment therapy.
PATIENTS’ PERSPECTIVES, EXPERIENCES, AND CONCERNS WITH CROHN’S PERIANAL FISTULAE: INSIGHTS FROM SOCIAL MEDIA PLATFORMS
Authors: Khalil Carine , van Deen Welmoed , Dupuy Taylor , Syal Gaurav , Arnold Corey , Cazzetta Susan , Nazarey Pradeep , Spiegel Brennan
Published: January 2022

INTRODUCTION

Crohn’s perianal fistulae (CPF) impact the physical, emotional, and social wellbeing of patients. Despite the high biopsychosocial burden of CPF, limited data exist regarding how patients navigate challenges associated with this complication of CD and how they perceive treatments. Social media offers a rich opportunity to gain an in-depth understanding of the impact of CPF on patients’ daily lives outside of controlled environments. In this study, we used social media to examine patients’ experiences and concerns with CPF and assess its impact on their behavior and overall wellbeing.

METHODS

We used a mixed-method approach to examine 119,986 publicly available posts related to CPF from 10 US CD forums between 1/1/10-1/1/20. We randomly selected 700 posts for qualitative analysis using an inductive thematic approach. A latent Dirichlet allocation probabilistic topic model was applied to explore themes in an unsupervised manner within the collection of the 119,986 posts. Fifty topics were generated and manually reviewed to identify themes, which were compared to the themes identified in the qualitative data analysis.

RESULTS

We distinguished 4 main themes and several subthemes that were also identified in the qualitative thematic analysis. In 38% of the posts, patients used social media to seek peer-support and information about CPF symptoms, treatments, diet, experimental therapies, natural remedies, and patients’ apprehension regarding treatments. Moreover, 30% of the posts focused on discussions surrounding the biopsychosocial burden of CPF. Patients reported pain and constant discomfort, psychological effects including stress symptoms, distress, and fear, as well as social impact on work and intimate relationships. In 21% of the posts users discussed challenges associated with CPF treatments including financial challenges, unsuccessful procedures/treatments, recurrence of CPF post-treatment, and lack of information on CPF treatments. Lastly, 15% of the posts involved patients’ experiences with medications and surgeries such as efficacy of treatments, side effects experienced and complications. While the quantitative analysis revealed an additional subtheme related to financial challenges and local and topical care, the qualitative analysis revealed an additional subtheme related to patients’ apprehension to undergo treatments (Figure 1).

DISCUSSION

Social media analysis reveals a dynamic range of themes governing patients’ perspectives and experiences with CPF. The use of a mixed-methods approach generated complementary insights regarding patients’ need for information about CPF, the biopsychosocial burden of CPF, the different encountered challenges with treatment and the difficulty to navigate among available management options. These results highlight a gap in patient educational needs for CPF.
SEXUAL DYSFUNCTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Kaniewska Magdalena , Lewandowski Konrad , Szydlarska Dorota , Rydzewska Grazyna
Published: January 2022

INTRODUCTION

Inflammatory bowel disease (IBD) is likely to have an impact on sexual function because of its symptoms like diarrhea, fatigue and abdominal pain. The impact of the disease on sexuality and intimacy is one of the main concerns of IBD patients but there is still limited data on sexual (SD) and erectile dysfunction (ED) and its determinants in IBD.

AIM OF THE STUDY

This study aimed to evaluate sexual function and search for predictors of sexual dysfunction among patients with IBD during biological treatment.

METHODS

This was a prospective, one center study enrolled a cohort of 135 patients with Crohn’s disease (CD) and ulcerative colitis (UC) treated with biological treatment on the basis of the same inclusion criteria (CDAI>300 for CD, Total Mayo score>6 for CU). All IBD patients were invited to fill an anonymous validated questionnaire on their sexual function: Female Sexual Function Index (FSFI) or International Index of Erectile Function-5 (IIEF-5) and one question about how bowel problem limited sexual activity during the last 2 weeks from Inflammatory Bowel Disease Questionnaire (IBDQ).

RESULTS

Both groups of patients (CD and CU) considered for sexual function were treated with anti -TNF alfa agents. GKS were more frequent among females (24/68, 35%) than males (12/67, 18%), p = 0.037. Comorbidities index was also higher in females (31/68, 46% vs. 17/67, 25%), p = 0.023. In the entire study group SD occurred in 43,7% of patients, in comparable value of men and women (p =0,536). We didn’t demonstrate a relationship between the duration of IBD, taken drugs (GKS, immunosuppressants) and calprotectin levels and the results of the FSFI and IIEF-5 questionnaires. Self-assessment of limitation by disease (IBDQ) was significantly worse for females, than for men p < 0.001. There was a significant correlation between self-assessment of limitation by disease and IIEF-5 (p<0.001) and FSFI (p<0.001) scores in CU and CD patients.

CONCLUSIONS

According to our study SD and ED were mainly associated with psychological factors, the severity of the disease had no effect on them. The type of medication used to treat the underlying disease has no impact on the development of sexual dysfunction.
BIOLOGIC PRECISION DOSING IS NOW AVAILABLE AT THE BEDSIDE FOR CHILDREN AND ADULTS WITH INFLAMMATORY BOWEL DISEASE RECEIVING INFLIXIMAB
Authors: Minar Phillip , Samuels Abigail , Mizuno Tomoyuki , Menke Frank , Vogt Aaron , Punt Nieko , Vinks Alexander
Published: January 2022

INTRODUCTION

There is significant variability in infliximab (IFX) pharmacokinetics (PK) in children and adults with multiple population PK models developed and several covariates identified to better predict drug clearance. Fortunately, therapeutic drug monitoring (TDM) is widely available and can be used to simplify model-informed precision dosing. However, empiric (“trial and error”) dose intensifications following TDM to achieve targeted levels can delay obtaining an optimal drug exposure and is a risk for super-therapeutic levels. In this study, we highlight the formal processes to create a clinical decision support tool (CDST) for IFX and assess the physician usability of the novel CDST.

METHODS

The development team included a PK software consultant, pharmacologists, pediatric gastroenterologists, nurses, software architects, and a human factor engineering firm (Pomiet, Dayton, OH). CDST development occurred in 4 distinct phases (sprints). Design sprints started with structured interviews with key stakeholders and finished with the creation of CDST wireframes (prototypes). Physician usability was assessed with the System Usability Scale (SUS)1 at 3 timepoints.

RESULTS

CDST design sprints included in-person interviews with 11 unique health care providers (8 physicians) over 26 sessions. During Phase I, clinicians noted current practices and systems to dose optimize biologics are “cumbersome” and “not user-friendly” as key patient data to make informed decisions are in disparate locations within the electronic medical record (EMR). From Phase I to Phase IV, the design team used the wireframes for user feedback, made changes and developed the final CDST, RoadMABTM. Next, information services (IS) personnel integrated the CDST within the EMR. Patient data extraction occurs with a Fast Healthcare Interoperability Resources (FHIR) launch and produces an embedded browser within EMR. Additionally, our team created a standalone replica of the EMR CDST that is secured by Microsoft Azure and hosted by Amazon Web Services. Our precision dosing CDST is supported by PK software that incorporates past IFX administrations and laboratory results (covariates and drug concentrations), conducts Bayesian PK estimation using the selected population PK model and displays the past and predicted concentration-time profiles (Figure 1A). In order to simplify precision dosing during IFX induction, we also created the New Start Wizard within RoadMABTM. Finally, The SUS was administered at three timepoints with a minimum of 2 new physicians at each session. Physician clinical experience is presented in Table1. By the completion of RoadMABTM, the final mean (SD) SUS was 86.5/100 (15.2, Figure 1B).

CONCLUSION

Our team has created a usable CDST for IFX that is now integrated within the EMR and available as a web portal for bedside (point-of-care) precision dosing.
BIOLOGICAL THERAPY AND POST-OPERATIVE OUTCOMES IN CROHN’S DISEASE PATIENTS UNDERGOING REPEAT ILEOCOLIC RESECTION
Authors: Horesh Nir , Freund Michael , Garoufalia Zoe , Gefen Rachel , Zhang David , Smith Timothy , Wexner Steven
Published: January 2022

OBJECTIVES

To assess the surgical outcome in Crohn’s disease (CD) patients undergoing repeat ileocolic resection treated with biologic therapy prior to the surgical intervention.

METHODS

A retrospective analysis of a prospective database including all CD patients who underwent repeat ileocolic resection between 2011 and 2021 was conducted. Patients were divided into two groups: patients treated with biologic therapy prior to surgery and controls. Clinical, peri and post-operative data was extracted from medical records and analyzed.

RESULTS

Sixty three patients underwent repeat ileocolic resection for CD. Thirty-two patients (50.8%) were male and the mean age was 52 (range 23-82) years. The most common indication for repeat ileocolic resection was anastomotic stricture in 56 patients (88.9%). The mean time from the index ileocolic resection to the repeat surgery was 14.5 (range 1-53) years. Twenty-seven patients (42.8%) were treated with biologic therapy prior to repeat surgical intervention. No demographic differences were found between the biologic therapy group and the control group including patients’ gender (p=0.12), age (p=0.69), median American Society of Anesthesiologists (ASA) score (p=0.56) and body mass index (BMI) (p=0.17). In addition, no differences were found in mean time from the index ileocolic resection (p=0.69), indication for surgery (p=0.22) and pre-operative albumin (p=0.39). Thirty-eight patients (60.3%) underwent repeat ileocolic resection using a laparoscopic approach, with a mean operative time of 225 (range 121-386) minutes. In 19 patients (30.1%) a fistula was identified, while an abscess was seen and drained intra-operatively in 5 patients (7.9%). Overall, the post-operative complication rate was 44.5% (28 patients) and the mean length of stay was 5.7 days. Post-operative complications were found to be more common in the non-biologic therapy group compared to the biologic therapy group (55.6% vs 29.7%, respectively; p=0.04). Conversion rate from a laparoscopic to an open approach was slightly higher in the biologic therapy group compared to the biologic therapy group (40% vs 26.1%, respectively; p=0.36) although it did not amount to a statistical significance. Operative time (226 vs. 225 minutes; p=0.92), mean length of stay (5.1 vs. 6.1 days; p=0.18) and readmission rate (16.6% vs. 11.1%; p=0.72) were similar between the two groups. Multivariate analysis of risk factors for post-operative complications showed that only prior biologic treatment was correlated with a lower risk (HR -0.28, CI 95% -0.5596 to -0.01898; p = 0.03).

CONCLUSION

In our series, patients treated with biologic therapy for CD who underwent repeat ileocolic resection had fewer post-operative complications.
WITHDRAWN: EFFICACY, SAFETY, AND TOLERABILITY OF OMILANCOR IN A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF PATIENTS WITH ULCERATIVE COLITIS
Authors: Leber Andrew , Hontecillas Raquel , Tubau-Juni Nuria , Lichtiger Simon , Bassaganya-Riera Josep
Published: January 2022

BACKGROUND

Omilancor is an oral, once-daily, gut-restricted, small molecule, first-in-class therapeutic for Crohn’s disease (CD) and ulcerative colitis (UC) that targets the novel LANCL2 pathway. Through LANCL2 activation, omilancor increases the suppressive capacity of regulatory immune cells, including regulatory CD4+ T cells (Tregs), locally within the intestinal mucosa. In a Phase I study in normal healthy volunteers no changes in AEs or trends in safety laboratory trends were observed up to daily oral doses of 7500 mg/day.

METHODS

In a Phase 2, proof of concept, double blind, parallel-group study, adult patients with Mayo Clinic scores (MCS) of 4 – 10 and endoscopic subscores of 2 or more were randomly assigned to groups given omilancor 440 mg QD (n=66), omilancor 880 mg QD (n=66) or placebo (n=66) for 12 weeks. The primary endpoint was clinical remission after 12 weeks as defined by rectal bleeding (RB) equal to 0, stool frequency (SF) equal to 0 or 1 and endoscopic appearance (MES) equal to 0 or 1. A modified intent to treat (mITT) population was defined by patients with RB > 0, histological activity and elevated fecal calprotectin (FCP) at baseline. Secondary endpoints included histological remission as defined by a Geboes score < 3.1 with absence of neutrophils in the lamina propria, endoscopic remission as defined by a MES < 2, normalization of FCP and pharmacokinetics (PK) of omilancor in stool, tissue and plasma.

RESULTS

Oral omilancor was well tolerated with no trends in AE profile observed and most AEs of mild severity and no dose-limiting toxicities. In the mITT population, clinical remission was induced in 30.4% of omilancor treated patients relative to 3.7% of patients given placebo (Δ = 26.7, p = 0.01), thereby meeting the primary endpoint. Endoscopic remission was induced in 41.7% of patients treated with omilancor relative to 18.6% of patients given placebo (Δ = 23.1, p = 0.07). Histological remission was induced in 41.7% of patients treated with omilancor relative to 22.2% of patients given placebo (Δ = 19.5, p = 0.14). In patients with elevated baseline FCP, normalization occurred in 43.8% of the omilancor 880 mg group and 40.6% of the omilancor 440 mg group relative to 21.4% of the placebo group after 2 weeks (p = 0.048). PK analysis validated a gut-restricted profile with stable drug levels in stool over the 12-week treatment period and penetration into colonic biopsy tissue with limited systemic exposure. Reduction of patient reported outcomes occurred during the OLE with nearly 90% of patients reaching SF ≤ 1 and RB = 0 after 36 weeks of open-label treatment.

CONCLUSIONS

Once a day oral dosing with omilancor was well-tolerated and induced clinical remission in a Phase II mild to moderate UC population. A Phase II study in CD and a Phase III program in UC (PACIFY) were initiated in 2021 and are currently recruiting.
Distribution of Triatoma dimidiata sensu lato (Reduviidae: Triatominae) and Risk Factors Associated with Household Invasion in Northern Belize, Central America
Authors: Caranci Angela T , Grieco John P , Achee Nicole L , Hoel David F , Bautista Kim , King Russell , Stewart V Ann , Murphy Jittawadee , Masuoka Penny , Olsen Cara H
Published: January 2022

To date, Triatoma dimidiata sensu lato [Reduviidae: Triatominae (Latreille 1811)] remains the sole vector species associated with Chagas disease transmission reported from Belize. Human infection data are limited for Belize and the disease transmission dynamics have not been thoroughly investigated, yet the likelihood of autochthonous transmission is supported by the widespread collection of infected vectors from within local households. Here, we report updated infection rates of the vector population and infestation rates for villages in north and central Belize. Overall, 275 households were enrolled in an ongoing vector surveillance program. Of the 41 insects collected, 25 were PCR positive for T. cruzi, indicating an infection rate as high as 60%. To further characterize the epidemiological risk of human–vector contact, determinants of household invasion were modeled. Local households were surveyed and characterized with respect to over 25 key factors that may be associated with household infestation by T. dimidiata s.l. While final models were not strongly predictive with respect to the risk factors that were surveyed, likely due to the low number of collection observations, the presence of domestic/peri-domestic dogs, nearby light sources, and household structure materials could be the focus of continued risk assessments. In northern Belize, this vector survey lends support to T. dimidiata s.l. inhabiting sylvatic settings as opposed to the classical paradigm of domiciliated vector populations. This designation has strong implications for the local level of human exposure risk which can help guide vector surveillance and control resources.
Recognizing Moyamoya Disease in a Soldier With Recurrent Cerebrovascular Symptoms
Authors: Jeong Paul S
Published: January 2022

Moyamoya is a rare and progressive cerebrovascular disease involving collateral small vessel formation associated with intracranial artery narrowing. It is a disease that frequently presents with stroke and transient ischemic attacks and has potential to affect our active duty service members and their families with its bimodal age of onset of 10 and 40. This case report describes a soldier with moyamoya whose diagnosis was unrecognized for over a year after seeing multiple medical providers regarding his symptoms. The goal of this case report is to raise vigilance for this disease as it can cause significant morbidity and mortality with mental decline, recurrent strokes, and death without timely surgery.
The SENSOR System: Using Standardized Data Entry and Dashboards for Review of Scientific Studies Using the Clinical Applications of Psychedelics as an Illustration
Authors: Kamal Latifah , Godsell Major Pauline , Mulligan Bryce , Eberspaecher Stefan , Myint Danny , Besemann LCol Markus , Minerbi Amir , Gupta Gaurav
Published: January 2022

Introduction

Literature reviews are useful tools for communicating the breadth of scientific discovery for a given topic. Irrespective of the nature of the review, data should be communicated in effective, easy to understand ways. In trying to address these limitations of traditional scientific reviews, we propose using dynamic data driven displays that have been used in multiple other industries to improve communication and decision making. Given the recent interest in the clinical applications of psychedelics for various mental health issues, we chose to test the SENSOR System (Standardized Data Entry and Dashboards for Review of Scientific Studies) as an alternative for an existing review article.

Methods

To validate the SENSOR System, an existing review with a topical, heterogenous, and growing set of studies was selected. In this case we chose the Wheeler et al. review on psychedelics in clinical practice where articles had already been preselected and reviewed. Detailed discussion of this review and the cited papers preceded designing the content and shared links for a Google Form for data intake, Google Drive for article access, and Google Sheets linked to the form intake data.

Results

A total of 46 study entries were made by 2 team members, including 3 articles published since the review to demonstrate the ease of updating the system Various representations of the Google Forms intake data in the SENSOR System dashboard are presented.

Discussion

Visual representation of review studies using a dashboard proved feasible and advantageous for numerous reasons. As the technology and guidelines for these systems evolve there is an opportunity to standardize reporting, centralize legacy datasets, streamline the submission process, improve collaboration between researchers, measure relative contribution of participating authors, and improve patient involvement. For the use case of clinical applications of psychedelics, limitations of conveying data accurately includes heterogeneity of study design, dosing, indications, and outcome measures.

Conclusion

Creation of a system for standardized data entry and dashboards for reviews of scientific studies is a feasible alternative and/or adjunct to the dissemination of summaries through traditional scientific review. There are numerous proposed advantages of the flexible, dynamic, and graphical display that requires further validation.
Thyroid hormone axis and anthropometric recovery of children/adolescents with overweight/obesity: a scoping review
Authors: Urrea Carlos Ramos , Pedroso Amanda Paula , Thomazini Fernanda , do Carmo Andreia Cristina Feitosa , Telles Mônica Marques , Sawaya Ana Lydia , Pinho Franco Maria do Carmo , Ribeiro Eliane Beraldi
Published: January 2022

Thyroid hormones play multiple physiological effects essential for the maintenance of basal metabolic rate (BMR), adaptive thermogenesis, fat metabolism, and appetite. The links between obesity and the hormones of the thyroid axis, i.e., triiodothyronine (T3), thyroxine (T4), thyrotropin-releasing hormone (TRH), and thyrotropin (TSH), are still controversial, especially when considering children and adolescents. This population has high rates of overweight and obesity and several treatment approaches, including nutritional, psychological, and physical exercise interventions have been used. Understanding the importance of the hormones of the thyroid axis in the recovery from overweight and obesity may help directing measures to the maintenance of a healthy body composition. The present scoping review was carried out to analyze studies evaluating these hormonal levels throughout interventions directed at treating overweight and obesity in children and adolescents. The main purpose was to ascertain whether the hormones levels vary during weight loss. We selected for analysis 16 studies published between 1999 and 2019. Most of the studies showed that the changes in body composition parameters in response to the multidisciplinary interventions correlated positively with free T3 (fT3)/ total T3 (TT3)/TSH. With respect to free T4 (fT4)/ total T4 (TT4), the most common finding was of unchanged levels and hence, no significant association with weight loss. Importantly, the response to the intervention has even been found to not be affected by fT4 supplementation. Further studies are necessary to elucidate the relevance of the variations in hormone levels to the establishment of overweight/obesity and to the recovery from these conditions in children/adolescents.
Elevated COVID-19 Case Rates of Government Employees, District of Columbia, 2020-22
Authors: Hua Xinyi , Yin Jingjing , Fung Isaac C. H.
Published: January 2022

The rate ratios of COVID-19 cases among 5 District of Columbia departments’ personnel with reference to D.C. residents were found greater than one from March 2020 to early January 2022, suggesting higher case rates for emergency responders and frontline personnel than for general population. Vaccination is highly recommended.

Article summary line

Government employees from five D.C. departments, especially fire fighters and police officers, experienced higher COVID-19 case rates than D.C. residents.
Outcomes of the Advanced Visualization In Corneal Surgery Evaluation (ADVISE) trial; a non-inferiority randomized control trial to evaluate the use of intraoperative OCT during Descemet membrane endothelial keratoplasty
Authors: Muijzer Marc B , Delbeke H. , Dickman M.M. , Nuijts R.M.M.A. , Noordmans H.J. , Imhof S.M. , Wisse Robert P L
Published: January 2022

Purpose

To evaluate if an intraoperative OCT (iOCT) optimized surgical protocol without prolonged overpressure is non-inferior to a standard protocol during Descemet membrane endothelial keratoplasty (DMEK).

Design

A multicenter international prospective non-inferiority randomized control trial

Subjects

Sixty-five pseudophakic eyes of 65 patients with corneal endothelial dysfunction resulting from Fuchs endothelial corneal dystrophy were enrolled in 3 corneal centers in The Netherlands and Belgium.

Methods

The study was powered to include 63 patients scheduled for routine DMEK. Subjects were randomized to the control arm (n=33) without iOCT-use and raising the intraocular pressure above normal physiological limits for 8 minutes (i.e., overpressure) or the intervention arm (n=32) with OCT-guidance to assess graft orientation and adherence while refraining from prolonged raising the intraocular pressure. The RD and 95% confidence intervals (95% CI) were calculated from a logistic regression model using 1,000 bootstrap samples. Secondary outcomes included the incidence of graft detachment, surgeon-reported iOCT-aided surgical decision making, surgical time, endothelial cell density (ECD), and corrected distance visual acuity (CDVA).

Main Outcome Measures

The primary outcome was the incidence of postoperative surgery-related adverse events, defined as rebubbling, graft failure, and iatrogenic acute glaucoma. The non-inferiority margin was set at a risk difference (RD) of 10%.

Results

In the control group, 13 adverse events were recorded in 10 subjects compared to 13 adverse events in 12 subjects in the intervention group. The mean unadjusted RD measured 0.38% (95%CI: - 9.64–10.64) and the RD adjusted for study site measured -0.32% (95%CI: -10.29–9.84). No significant differences in ECD and CDVA were found between the two groups 3 and 6 months postoperatively. Surgeons reported that iOCT aided surgical decision-making in 40% of cases. Surgical- and graft unfolding time were, respectively, 13% and 27% shorter in the iOCT-group.

Conclusions

iOCT-guided DMEK surgery with refraining from prolonged over-pressuring was non-inferior compared to conventional treatment. Surgery times were reduced considerably, and surgeons reported the iOCT aided surgical decision-making in 40% of cases. Refraining from prolonged overpressure did not affect postoperative ECD or CDVA.
Protocol for a Systematic Review to validate or not, the philosophic explanation under the mechanism of action of the Tension Band Wiring to estabilizase an Olecranon fracture
Authors: Barcia Sergio , Boretto Jorge
Published: January 2022

Olecranon fractures in young people are commonly treated surgically. When a transverse pattern is presented the most used method to fix the fracture is the Tension Band Wiring. The AO Foundation proposed a theory for the mechanism of action of this device. It could transform the tensile forces on the posterior side into compression forces on the joint side during flexion of the elbow. Our objective is to systematically review the available literature in order to confirm or not this hypothesis.

We will include biomedical research studies evaluating Tension Band Wiring function. We are planning to search on Medline, Embase and other sources including grey literature. The studies will be selected and the data extracted. Results will include a descriptive analysis and a meta-analysis to compare the observed compression force before and after the flexion of the elbow.

Our findings will be discussed having in mind the potentially clinical implications of results.
Human influenza virus infection elicits distinct patterns of monocyte and dendritic cell mobilization in blood and the nasopharynx
Authors: Vangeti S. , Falck-Jones S. , Yu M. , Österberg B. , Liu S. , Asghar M. , Sondén K. , Albert J. , Johansson N. , Färnert A. , Smed-Sörensen A.
Published: January 2022

During respiratory viral infections, the precise roles of monocytes and dendritic cells (DCs) in the nasopharynx in limiting infection and influencing disease severity are incompletely described. We studied circulating and nasopharyngeal monocytes and DCs in healthy individuals and in patients with mild respiratory infections (primarily influenza A virus, IAV). As compared to healthy controls (HCs), patients with acute IAV infection displayed reduced DC but increased intermediate monocytes frequencies in blood, and an accumulation of most monocyte and DC subsets in the nasopharynx. IAV patients had more mature monocytes and DCs in the nasopharynx, and higher levels of TNFα, IL-6 and IFNα in plasma and the nasopharynx. In blood, monocytes, the most frequent cellular source of TNFα during IAV infection, remained responsive to additional stimulation with TLR7/8L. Immune responses in older patients skewed towards increased monocytes rather than DCs suggesting a contributory role for monocytes in disease severity. In patients with other respiratory virus infections, we observed changes in monocyte and DC frequencies in the nasopharynx distinct from IAV patients, while differences in blood were more similar across patient groups. Together, our findings demonstrate tissue-specific and pathogen-specific patterns of monocyte and DC function during human respiratory viral infections and highlight the importance of comparative investigations in blood and the nasopharynx.
BOS1 is a positive regulator of wounding induced cell death and plant susceptibility to Botrytis
Authors: Cui Fuqiang , Li Xiaoxiao , Wu Wenwu , Luo Wenbo , Wu Ying , Brosché Mikael , Overmyer Kirk
Published: January 2022

Programmed cell death (PCD) is required for many aspects of plant biology, including stress responses, immunity, and plant development including root and flower development. Our understanding of PCD regulation is incomplete, especially concerning regulators involved in multiple divergent processes. The botrytis-suscetible1 (bos1) mutant is one of the genotypes most susceptible to Botrytis cinerea (Botrytis) and has revealed the role of BOS1 in cell death propagation during plant responses to wounding. The bos1-1 allele harbours a T-DNA located in the 5’UTR upstream from the start codon that results in elevated BOS1 transcript levels. Here, we resequenced the bos1-1 genome and found a MAS promoter at the ends of the T-DNAs. Expression of the BOS1 gene under control of the MAS promoter conferred the characteristic bos1-1 Botrytis- sensitivity and wounding phenotypes in wildtype plants. We used Crispr-Cas9 to create new bos1 alleles that disrupt exons. These lines lacked the typical bos1-1 wounding and Botrytis phenotypes, but exhibited reduced fertility, as previously observed in other bos1 T-DNA alleles. With multiple overexpression lines of BOS1, we demonstrate that BOS1 is involved in regulation of cell death propagation in a dosage dependent manner. Our data support that bos1-1 is a gain-of-function mutant and that BOS1 acts as a positive regulator of wounding and Botrytis-induced PCD. Taken together these finding suggest that BOS1 function in both fertility and Botrytis response could be unified under cell death control.
Associations between maternal iron supplementation in pregnancy and offspring growth and cardiometabolic risk outcomes in infancy and childhood
Authors: Petry Clive J. , Olga Laurentya , Hughes Ieuan A. , Ong Ken K.
Published: January 2022

It was previously observed that maternal iron supplementation in pregnancy was associated with increased offspring size and adiposity at birth, possibly mediated through increased risk of gestational diabetes. In this study we explored associations of maternal iron supplementation in pregnancy with postnatal offspring growth in infancy and indices of cardiometabolic disease risk factors such as glucose tolerance, insulin sensitivity and blood pressure in mid-childhood (at ∼9.5 years of age) in the Cambridge Baby Growth Study. In infancy adiposity-promoting associations with maternal iron supplementation in pregnancy were evident at 3 months of age (e.g. mean difference in skinfold thickness: β=+0.15 mm, p=0.02, in n=341 whose mothers supplemented versus 222 that did not; waist circumference: β=+0.7 cm, p=0.04, in n=159 and 78, respectively) but differences lessened after this time (e.g. 3-12 month change in mean difference in skinfold thickness: β=-0.2 mm, p=0.03, in n=272 and 178, respectively). At ∼9.5 years of age associations with maternal iron supplementation in pregnancy were not evident for markers of growth, glucose tolerance, insulin sensitivity or secretion. However, children whose mothers supplemented with iron in pregnancy had lower mean arterial blood pressures (β=-1.0 mmHg, p=0.03, in n=119 and 78, respectively). These results suggest that most of the associations of maternal iron supplementation in pregnancy on growth and adiposity evident at birth disappear during infancy, but there may be some evidence of long-term nutritional programming evident later in childhood.
The economic burden of low back pain in KwaZulu-Natal, South Africa: a prevalence-based cost-of-illness analysis from the healthcare provider’s perspective
Authors: Kahere Morris , Ngcamphalala Cebisile , Östensson Ellinor , Ginindza Themba
Published: January 2022

Background

Globally, low back pain (LBP) is associated with high economic costs due to healthcare expenditure and production loss. There is lack of evidence regarding this in low-and-middle-income-countries (LMICs), including South Africa. Thus, the study aimed to determine the economic burden of LBP from the providers perspective.

Methods

We used a retrospective prevalence-based cost-of-illness methodology to estimate the direct medical cost of LBP. Direct medical costs constituted costs associated with healthcare utilisation in inpatient care, outpatient care, investigations, consultations, and cost of auxiliary devices. We used diagnostic-specific data obtained from hospital clinical reports. All identifiable direct medical costs were estimated using a top-down approach for costs associated with healthcare and a bottom-up approach for costs associated with inpatient and outpatient care.

Results

The prevalence of CLBP was 24.3% (95% CI: 23.5 – 25.1). The total annual average direct medical costs associated with LBP was US$5.4 million. Acute LBP and CLBP contributed 17% (US$0.92 million) and 83% (US$4.48 million) of the total annual average direct medical cost, respectively. The per patient total annual average direct medical cost for acute LBP and CLBP were US$99.43 and US$1,516.67, respectively. The total average cost of medication per patient for acute and CLBP were US$82.53 and US$320.31, respectively. Overall, the outpatient care costs contributed the largest share (38.9%, US$2.10 million) of the total average direct medical cost, 54.9% (US$1.15 million) of which was attributed to NSAIDs and only 10% (US$0.21 million) of the total outpatient cost was due to rehabilitation. The total average cost of diagnostic investigations was estimated at US$831,595.40, which formed 15.4% of the average total cost.

Conclusion

The economic burden of LBP is high in South Africa. Majority of costs were attributed to CLBP. Action should be taken to develop culturally validated cost-effective prevention measures to mitigate the burden of LBP.
Single-Cell Transcriptomic Analyses of Tumor Ecosystems and Spatial Architectures in Human Small Cell Lung Cancer
Authors: Ouyang Huiling , Chen Jian , Xu Chaoliang , He Cong , Sheng Luoyan , Wang Jing , Pan Deshen , Lin Jun , Augert Arnaud , Zhu Yuming , Jia Deshui
Published: January 2022

Small cell lung cancer (SCLC) is a highly heterogenous disease characterized by aggressive phenotypes and poor prognosis. In order to dissect the cellular components and their spatial distribution in SCLC ecosystems, here we performed single-cell RNA sequencing and spatial transcriptomics analyses of 12 resected human primary SCLCs. Our analysis revealed extensive heterogeneity of both tumor and non-tumor cells, and a predominant immunosuppressive microenvironment. Importantly, multiple hybrid tumor cell states were unmasked, including hybrid SCLC and lung adenocarcinoma cells as well as hybrid tumor and immune cells, indicating high phenotypic plasticity of tumor cells. Moreover, we revealed the cellular origin and evolution of these hybrid tumor cells, and critical roles of tumor-stromal cellular crosstalk in driving the development of hybrid cells. In conclusion, this study deepens our understanding of human SCLC ecosystems and provides rationales to target the hybrid tumor cells and immunosuppressive microenvironment for SCLC therapies.
Combined multiple transcriptional repression mechanisms generate ultrasensitivity and oscillations
Authors: Jeong Eui Min , Song Yun Min , Kim Jae Kyoung
Published: January 2022

Transcriptional repression can occur via various mechanisms, such as blocking, sequestration, and displacement. For instance, the repressors can hold the activators to prevent binding with DNA or can bind to the DNA-bound activators to block their transcriptional activity. Although the transcription can be completely suppressed with a single mechanism, multiple repression mechanisms are utilized together to inhibit transcriptional activators in many systems, such as circadian clocks and NF-κB oscillators. This raises the question of what advantages arise if seemingly redundant repression mechanisms are combined. Here, by deriving equations describing the multiple repression mechanisms, we find that their combination can synergistically generate a sharply ultrasensitive transcription response and thus strong oscillations. This rationalizes why the multiple repression mechanisms are used together in various biological oscillators. The critical role of such combined transcriptional repression for strong oscillations is further supported by our analysis of formerly identified mutations disrupting the transcriptional repression of the mammalian circadian clock. The hitherto unrecognized source of the ultrasensitivity, the combined transcriptional repressions, can lead to robust synthetic oscillators with a previously unachievable simple design.
Lira: Rotational Invariant Shape and Electrostatic Descriptors for Small Molecules and Protein Pockets based on Real Spherical Harmonics
Authors: Caires Fernando R. , Silva Samuel R. , Veríssimo-Alves Marcos , Pinheiro Vitor B. , Montalvão Rinaldo W.
Published: January 2022

Abstract

Motivation

Modern AI-based tools are increasing the number of protein structures available, creating an opportunity and a challenge for automated high-throughput drug discovery pipelines. The amount of data is overwhelming for the current methods, thus demanding new high-performance approaches for Machine Learning-based rational drug design. As shape and electrostatics are the main components for understanding protein-ligand interaction; they are the primary targets for efficient AI-compatible descriptors and their associated comparison methods.

Results

The Lira toolbox is a set of components devised for describing, comparing and analysing shape and electrostatics for small ligands, peptides and protein pockets. It can generate databases with descriptors for tens of millions of shapes in a few hours, which can then be queried in seconds. The Lira design, focused on performance and reliability, makes its integration into AI-driven rational drug design pipelines simple.

Availability and implementation

Lira packages, available for download at https://pinheirolab.com/, are free to use for research and educational purposes.
A Population Response Model of Ensemble Perception
Authors: Utochkin Igor S. , Choi Jeunghwan , Chong Sang Chul
Published: January 2022

Ensemble representations have been considered as one of the strategies that the visual system adopts to cope with its limited capacity. Thus, they include various statistical summaries such as mean, variance, and distributional properties and are formed over many stages of visual processing. The current study proposes a population coding model of ensemble perception to provide a theoretical and computational framework for these various facets of ensemble perception. The proposed model consists of a simple feature layer and a pooling layer. We assumed ensemble representations as population responses in the pooling layer and decoded various statistical properties from population responses. Our model successfully predicted averaging performance in orientation, size, color, and motion direction across different tasks. Furthermore, it predicted variance discrimination performance and the priming effects of feature distributions. Finally, it explained the well-known variance and set size effects and has a potential for explaining the adaptation and clustering effects.
The effects of electroencephalogram feature-based transcranial alternating current stimulation on working memory and electrophysiology
Authors: Zeng Lanting , Guo Mingrou , Wu Ruoling , Luo Yu , Wei Pengfei
Published: January 2022

Transcranial alternating current stimulation (tACS) can influence cognitive functions by modulating brain oscillations. However, results regarding the effectiveness of tACS in regulating cognitive performance have been inconsistent. In the present study, we aimed to find EEG characteristics associated with the improvements in working memory performance, to select tACS stimulus targets and frequency based on this feature, and to explore effects of selected stimulus on verbal working memory. To achieve this goal, we first investigated the EEG characteristics associated with improvements in working memory performance with the aid of EEG analyses and machine learning techniques. These analyses suggested that 8 Hz activity in the prefrontal region was related to accuracy in the verbal working memory task. The tACS stimulus target and pattern were then selected based on the EEG feature. Finally, the selected tACS frequency (8 Hz tACS in the prefrontal region) was applied to modulate working memory. The performance of working memory was improved significantly using the selected stimulation than using 40 Hz and sham stimulation (Especially for participants with low verbal working memory). In conclusion, using EEG features related to positive behavioral changes to select brain regions and stimulation patterns for tACS is an effective intervention for improving working memory. Our results contribute to the groundwork for future tACS closed-loop interventions for cognitive deterioration.
Detecting Antibody Reactivities in Phage ImmunoPrecipitation Sequencing Data
Authors: Chen Athena , Kammers Kai , Larman H Benjamin , Scharpf Robert B. , Ruczinski Ingo
Published: January 2022

Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a recently developed technology to assess antibody reactivity, quantifying antibody binding towards hundreds of thousands of candidate epitopes. The output from PhIP-Seq experiments are read count matrices, similar to RNA-Seq data; however some important differences do exist. In this manuscript we investigated whether the publicly available method edgeR1 for normalization and analysis of RNA-Seq data is also suitable for PhIP-Seq data. We find that edgeR is remarkably effective, but improvements can be made and introduce a Bayesian framework specifically tailored for data from PhIP-Seq experiments (Bayesian Enrichment Estimation in R, BEER).
Understanding immune-driven brain aging by human brain organoid microphysiological analysis platform
Authors: Song Sunghwa , Ao Zheng , Cai Hongwei , Li Xiang , Miao Yifei , Wu Zhuhao , Krzesniak Jonathan , Gu Mingxia , Lee Luke P. , Guo Feng
Published: January 2022

The aging of the immune system drives systemic aging and the pathogenesis of age-related diseases. However, a significant knowledge gap remains in understanding immune-driven aging, especially in brain aging, due to the limited current in vitro models of neuro-immune interaction. Here we report the development of a human brain organoid microphysiological analysis platform (MAP) to discover the dynamic process of immune-driven brain aging. We create the organoid MAP by 3D printing that can confine organoid growth and perfuse oxygen and nutrients (and immune cells) to generate standardized human cortical organoids that promote viability, maturation, and commitment to human forebrain identity. Dynamic rocking flow is incorporated for the platform that allows us to perfuse primary monocytes from young (20 to 30-year-old) and aged (>60-year-old) donors and culture human cortical organoids for modeling and analyzing the aged immune cell interacting organoid tissues systematically. We discovered the aged monocytes had increased infiltration and promoted the expression of aging-related markers (e.g., p16 in astrocytes neighboring to monocytes) within human cortical organoids, indicating that aged monocytes may drive brain aging. We believe that our human brain organoid MAP provides promising solutions for basic research and translational applications in aging, neuroimmunological diseases, autoimmune disorders, and cancers.