bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Imaging Biomarkers in Crohn Disease
Authors: Bane Octavia , Gee Michael S. , Menys Alex , Dillman Jonathan R. , Taouli Bachir
Published: February 2021

In this review article, we present the latest developments in quantitative imaging biomarkers based on magnetic resonance imaging (MRI), applied to the diagnosis, assessment of response to therapy, and assessment of prognosis of Crohn disease. We also discuss the biomarkers’ limitations and future prospects. We performed a literature search of clinical and translational research in Crohn disease using diffusion-weighted MRI (DWI-MRI), dynamic contrast-enhanced MRI (DCE-MRI), motility MRI, and magnetization transfer MRI, as well as emerging topics such as T1 mapping, radiomics, and artificial intelligence. These techniques are integrated in and combined with qualitative image assessment of magnetic resonance enterography (MRE) examinations. Quantitative MRI biomarkers add value to MRE qualitative assessment, achieving substantial diagnostic performance (area under receiver-operating curve = 0.8–0.95). The studies reviewed show that the combination of multiple MRI sequences in a multiparametric quantitative fashion provides rich information that may help for better diagnosis, assessment of severity, prognostication, and assessment of response to biological treatment. However, the addition of quantitative sequences to MRE examinations has potential drawbacks, including increased scan time and the need for further validation before being used in therapeutic drug trials as well as the clinic.
MR Enterography of Complicated Crohn Disease
Authors: Grajo Joseph R. , Huang Chenchan , Dillman Jonathan R. , Gee Michael S. , Jaffe Tracy A. , Soto Jorge A. , Baker Mark E.
Published: February 2021

Stricturing and penetrating disease are complications of Crohn disease (CD) that significantly affect patient outcomes. Careful evaluation for such complications is critical to the interpretation of magnetic resonance enterography. This manuscript outlines the key findings related to stricturing and penetrating CD and discusses current understanding of the pathophysiology and prognosis of complicated CD based on the literature.
Is Nasal Packing Necessary After Endoscopic Dacryocystorhinostomy Without Stent and Mucosal Flaps Preservation?
Authors: Demir Deniz
Published: February 2021

Objective:

This study aimed to evaluate the effect of nasal packing on the surgical success and postoperative complications of endoscopic dacryocystorhinostomy (EnDCR) without using stents and mucosal flaps.

Methods:

The retrospective study comprised of 75 eyes of 65 consecutive patients undergoing EnDCR with the biting and removing technique. The patients were assigned to 2 groups depending on whether the biodegradable synthetic polyurethane foam was used or not (the packing group, 34 eyes; the nonpacking group, 41 eyes). At least 6 months after the EnDCR, the postoperative outcomes including anatomical and functional successes, and the postoperative complications such as synechia, granuloma, and bleeding were compared between the packing and nonpacking groups.

Results:

Synechia was lower in the packing group (23.5% versus 24.4%) but it was not statistically significant (P = 0.93). There were also no significant differences in the granuloma and bleeding complications between the 2 groups (respectively, P = 0.72, P = 0.08). The success rates of anatomical and functional reached 88% in the packing group compared with 82.9%, and 75.6% in the nonpacking group (respectively, P = 0.74, P = 0.76).

Conclusions:

The present study findings suggest that both groups have no superiorities over each other in the surgical outcomes after the EnDCR. However, further randomized studies are recommended before the generalization can be made.
Quality, Reliability, and Readability of Online Information on Rhinoplasty
Authors: Ahsanuddin Salma , Cadwell Joshua B. , Povolotskiy Roman , Paskhover Boris
Published: February 2021

Background:

With an ever-growing reliance on technology, patients are increasingly resorting to websites for their medical information. This study evaluates the readability, quality, and reliability of online information available on rhinoplasty provided by academic centers or impartial reference sources and private practice websites.

Methods:

A cross-sectional study from July to August 2019 was performed looking at the first 42 informational websites on a Google search for the term nose job. Websites were categorized as belonging to impartial sources and academic centers or private practices. Two independent reviewers evaluated websites on their quality, readability, reliability, and technical qualities using several validated measures. The Health on the Net code (HONcode) and DISCERN questionnaire were used to assess the quality and reliability of the information presented on the websites. Significance tests were performed using SPSS Version 25.

Results:

Of the 42 websites, 23 were impartial sources or academic centers (54.8%) and 19 were private practice websites (47.6%). The mean (±SD) for the HONcode and DISCERN scores were 5.7 (±2.8) and 2.6 (±0.7), respectively. The mean (SD) HONcode scores for impartial sources and private practice websites were 7.1 (±2.9) and 4.1 (±1.5), respectively (P < 0.001). The mean (±SD) DISCERN scores were 2.9 (±0.7) and 2.3 (±0.5), respectively (P = 0.009). There was no statistically significant difference in scores for readability and technical qualities.

Conclusions:

While impartial sources and academic centers score higher on quality and reliability scores, their scores were also low. These findings are concerning as many consumers use the information provided by online websites to guide decisions regarding their health.
Clinical Evaluation of Unsintered Hydroxyapatite Particles/Poly L-Lactide Composite Device in Craniofacial Surgery
Authors: Osawa Sayuri , Hashikawa Kazunobu , Naruse Hidemi , Terashi Hiroto
Published: February 2021

A total of 47 patients who underwent the craniofacial implantation of unsintered hydroxyapatite particles and a poly-L-lactide device were evaluated for clinical local findings and computed tomography (CT) images after about 6 months. Long-term follow-up of 3 patients was done from 5 to 11 years. The patients underwent CT imaging pre- and postoperatively, while local clinical examination was done upon follow-up. For the 3 patients who were followed up for more than 5 years, implant changes were evaluated by using CT. Computed tomography revealed 3 patients of dislocation, 2 patients of insufficient bone union, and 3 patients of implant breakage. All patients healed well with no complications requiring a secondary operation. The CT findings of the long-term cases revealed the following: a plate and screw were still present 5 years postsurgery (patient 1), mesh implants were completely resorbed after 9 years and 6 months (patient 2), and plates were almost resorbed after 11 years but some of their shapes remained (patient 3).

The unsintered hydroxyapatite/poly-L-lactide device is useful in the maxillofacial region in terms of strength and radiographic contrast. However, since the absorption rate is slow, it is necessary to keep in mind its long-term radiographic detectability and the possibility of late-onset granuloma.
Myositis Ossificans Traumatica, an Unusual Cause of Mandibular Hypomobility
Authors: Karimi Abbas , Tavakoli Iman , Jalilimanesh Kimia , Tavakoli Ehsan , Tavakoli Ali
Published: February 2021

Myositis ossificans traumatica is a rare condition in which causes restriction of mandibular movement. In this entity, temporomandibular joint is depleted of any problems; although all the patients have the history of trauma to the mandible and the face. Myositis ossificans traumatica can involve other parts of the body like femoral region with higher incidence in compare to the maxillofacial area. Blunt trauma to the head and neck causes muscle contusion injury, hematoma formation in the injured muscles or nearby soft tissues. Calcification of hematoma and heterotopic bone formation in the muscle, soft tissue, or near bony structures causes progressive decrease in mouth opening. Surgical removal of calcified body has been the only and one method for treatment of this disorder but rate of recurrence is high in the literature. The authors want to introduce 2 new cases of myositis ossificans traumatica, and then discuss about etiology and different treatment modalities.
The Effects of Intraoperative Local Tranexamic Acid on Periorbital Edema and Ecchymosis in Septorhinoplasty
Authors: İpek Havva Duru , Bezgin Selin Üstün , Çakabay Taliye , Çelebi Şaban
Published: February 2021

Introduction:

The aim of the present study is to examine the effect of local administration of tranexamic acid (TXA) through lateral osteotomy line on postoperative periorbital edema and ecchymosis.

Material-Method:

Thirty patients underwent open technical septorhinoplasty were included. Before lateral osteotomies, the surgeon opened narrow subperiosteal tunnels on the both sides. After lateral osteotomies, the surgeon irrigated TXA into the right tunnel with the broken tip of the injection and the same amount of saline into the left tunnel. The patient's photographs were taken on the first, third, and seventh postoperative days. Periorbital edema and ecchymoses were evaluated by the blinded author. The statistical differences between the 2 sides were analyzed.

Results:

Lower Eyelid Edema values were significantly lower in the TXA(+) group than the TXA(–) group on the third day (P = 0.001). There was no statistically significant difference between the sides in terms of lower eyelid edema values on the first and seventh days (P = 0.065, P = 0.317). Upper and lower eyelid ecchymosis values were significantly lower in TXA(+) group than TXA(–) group on the first, third, and seventh days (P < 0.05). Upper eyelid edema values were found to be significantly lower in the TXA(+) group than the TXA(–) group on the first and third days (P = 0.002, P = 0.005). There was no statistically significant between the sides in terms of upper eyelid edema (P = 0.315) on the seventh day.

Conclusions:

It was observed in the present study that local administration of TXA in septorhinoplasty was effective in reducing postoperative periorbital edema and ecchymosis.

Level of evidence: 2c
Mandibular Reconstruction With the Iliac Flap Under the Guidance of A Series of Digital Surgical Guides
Authors: Qiu Shiyu , Kang Yifan , Ding Mengkun , Zhu Houwei , Zhang Yu , Zhang Lei , Shan Xiaofeng , Cai Zhigang
Published: February 2021

The authors aimed to evaluate the accuracy of mandibular reconstruction with the iliac flap under the guidance of a series of digital surgical guides. Seven patients were enrolled to evaluate the accuracy of reconstruction immediately after surgery. Patients underwent mandibular reconstruction with a vascularized iliac flap guided by a series of digital surgical guides at the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, from September 2017 to June 2018.

All flaps survived. Chromatographic analysis showed that the area with a chromatographic difference of ≤1 mm between preoperative virtual surgical planning model and postoperative mandible accounted for 73.97% ± 3.89% of mandible surface, the area ≤2 mm accounted for 87.21% ± 2.65%, and the area ≤3 mm accounted for 94.09% ± 2.50%. In all of the 7 cases, the mean of maximum deviation was 6.25 ± 1.00 mm, and the mean of average deviation was 0.95 ± 0.13 mm. The authors conclude that mandibular reconstruction with the iliac flap under the guidance of a series of digital surgical guides is accurate and effective.
Cumulative 5-year Results of a Randomized Controlled Trial Comparing Biological Mesh With Primary Perineal Wound Closure After Extralevator Abdominoperineal Resection (BIOPEX-study)
Authors: Blok Robin D. , Sharabiany Sarah , Stoker Jaap , Laan Ellen T. M. , Bosker Robbert J. I. , Burger Jacobus W. A. , Chaudhri Sanjay , van Duijvendijk Peter , van Etten Boudewijn , van Geloven Anna A. W. , de Graaf Eelco J. R. , Hoff Christiaan , Hompes Roel , Leijtens Jeroen W. A. , Rothbarth Joost , Rutten Harm J. T. , Singh Baljit , Vuylsteke Ronald J. C. L. M. , de Wilt Johannes H. W. , Dijkgraaf Marcel G. W. , Bemelman Willem A. , Musters Gijsbert D. , Tanis Pieter J.
Published: February 2021

Objective:

To determine long-term outcomes of a randomized trial (BIOPEX) comparing biological mesh and primary perineal closure in rectal cancer patients after extralevator abdominoperineal resection and preoperative radiotherapy, with a primary focus on symptomatic perineal hernia.

Summary Background Data:

BIOPEX is the only randomized trial in this field, which was negative on its primary endpoint (30-day wound healing).

Methods:

This was a posthoc secondary analysis of patients randomized in the BIOPEX trial to either biological mesh closure (n = 50; 2 dropouts) or primary perineal closure (n = 54; 1 dropout). Patients were followed for 5 years. Actuarial 5-year probabilities were determined by the Kaplan-Meier statistic.

Results:

Actuarial 5-year symptomatic perineal hernia rates were 7% (95% CI, 0–30) after biological mesh closure versus 30% (95% CI, 10–49) after primary closure (P = 0.006). One patient (2%) in the biomesh group underwent elective perineal hernia repair, compared to 7 patients (13%) in the primary closure group (P = 0.062). Reoperations for small bowel obstruction were necessary in 1/48 patients (2%) and 5/53 patients (9%), respectively (P = 0.208). No significant differences were found for chronic perineal wound problems, locoregional recurrence, overall survival, and main domains of quality of life and functional outcome.

Conclusions:

Symptomatic perineal hernia rate at 5-year follow-up after abdominoperineal resection for rectal cancer was significantly lower after biological mesh closure. Biological mesh closure did not improve quality of life or functional outcomes.
Internal and External Validation of an Alcohol Biomarker for Screening in Trauma
Authors: Afshar Majid , Baker Kenneth , Corral Josefine , Ross Erin , Lowery Erin , Gonzalez Richard , Burnham Ellen L. , Callcut Rachael A. , Kornblith Lucy Z. , Hendrickson Carolyn , Kovacs Elizabeth J. , Joyce Cara
Published: February 2021

Objective:

We aimed to examine biomarkers for screening unhealthy alcohol use in the trauma setting.

Summary and Background Data:

Self-report tools are the practice standard for screening unhealthy alcohol use; however, their collection suffers from recall bias and incomplete collection by staff.

Methods:

We performed a multi-center prospective clinical study of 251 adult patients who arrived within 24 hours of injury with external validation in another 60 patients. The Alcohol Use Disorders Identification Test served as the reference standard. The following biomarkers were measured: (1) PEth; (2) ethyl glucuronide; (3) ethyl sulfate; (4) gamma-glutamyl-transpeptidase; (5) carbohydrate deficient transferrin; and (6) blood alcohol concentration (BAC). Candidate single biomarkers and multivariable models were compared by considering discrimination (AUROC). The optimal cutpoint for the final model was identified using a criterion for setting the minimum value for specificity at 80% and maximizing sensitivity. Decision curve analysis was applied to compare to existing screening with BAC.

Results:

PEth alone had an AUROC of 0.93 [95% confidence interval (CI): 0.92–0.93] in internal validation with an optimal cutpoint of 25 ng/mL. A 4– variable biomarker model and the addition of any single biomarker to PEth did not improve AUROC over PEth alone (P > 0.05). Decision curve analysis showed better performance of PEth over BAC across most predicted probability thresholds. In external validation, sensitivity and specificity were 76.0% (95% CI: 53.0%–92.0%) and 73.0% (95% CI: 56.0%–86.0%), respectively.

Conclusion and Relevance: PEth alone proved to be the single best biomarker for screening of unhealthy alcohol use and performed better than existing screening systems with BAC. PEth may overcome existing screening barriers.
Outcomes of a Multicenter Training Program in Robotic Pancreatoduodenectomy (LAELAPS-3)
Authors: Zwart Maurice J.W. , Nota Carolijn L.M. , de Rooij Thijs , van Hilst Jony , te Riele Wouter W. , van Santvoort Hjalmar C. , Hagendoorn Jeroen , Borei Rinkes Inne H.M. , van Dam Jacob L. , Latenstein Anouk E.J. , Takagi Kosei , Tran Khé T.C. , Schreinemakers Jennifer , van der Schelling George P. , Wijsman Jan H. , Festen Sebastiaan , Daams Freek , Luyer Misha D. , de Hingh Ignace H.J.T. , Mieog Jan S.D. , Bonsing Bert A. , Lips Daan J. , Hilal Mohammed Abu , Busch Olivier R. , Saint-Marc Olivier , Zehl Herbert J. , Zureikat Amer H. , Hogg Melissa E. , Molenaar I. Quintus , Besselink Marc G. , Koerkamp Bas Groot ,   for the Dutch Pancreatic Cancer Group
Published: February 2021

Objective:

To assess feasibility and safety of a multicenter training program in robotic pancreatoduodenectomy (RPD) adhering to the IDEAL framework for implementation of surgical innovation.

Background:

Good results for RPD have been reported from single center studies. However, data on feasibility and safety of implementation through a multicenter training program in RPD are lacking.

Methods:

A multicenter training program in RPD was designed together with the University of Pittsburgh Medical Center, including an online video bank, robot simulation exercises, biotissue drills, and on-site proctoring. Benchmark patients were based on the criteria of Clavien. Outcomes were collected prospectively (March 2016-October 2019). Cumulative sum analysis of operative time was performed to distinguish the first and second phase of the learning curve. Outcomes were compared between both phases of the learning curve. Trends in nationwide use of robotic and laparoscopic PD were assessed in the Dutch Pancreatic Cancer Audit.

Results:

Overall, 275 RPD procedures were performed in seven centers by 15 trained surgeons. The recent benchmark criteria for low-risk PD were met by 125 (45.5%) patients. The conversion rate was 6.5% (n = 18) and median blood loss 250ml [interquartile range (IQR) 150–500]. The rate of Clavien-Dindo grade ≥III complications was 44.4% (n = 122), postoperative pancreatic fistula (grade B/C) rate 23.6% (n = 65), 90-day complication-related mortality 2.5% (n = 7) and 90-day cancer-related mortality 2.2.% (n = 6). Median postoperative hospital stay was 12 days (IQR 8–20). In the subgroup of patients with pancreatic cancer (n = 80), the major complication rate was 31.3% and POPF rate was 10%. Cumulative sum analysis for operative time found a learning curve inflection point at 22 RPDs (IQR 10–35) with similar rates of Clavien-Dindo grade ≥III complications in the first and second phase (43.4% vs 43.8%, P = 0.956, respectively). During the study period the nationwide use of laparoscopic PD reduced from 15% to 1%, whereas the use of RPD increased from 0% to 25%.

Conclusions:

This multicenter RPD training program in centers with sufficient surgical volume was found to be feasible without a negative impact of the learning curve on clinical outcomes.
A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis
Authors: O’Leary D. Peter , Walsh Siun M. , Bolger Jarlath , Baban Chwanrow , Humphreys Hilary , O’Grady Sorcha , Hegarty Aisling , Lee Aoife M. , Sheehan Mark , Alderson Jack , Dunne Ruth , Morrin Martina M. , Lee Michael J. , Power Colm , McNamara Deborah , McCawley Niamh , Robb Will , Burke John , Sorensen Jan , Hill Arnold D.
Published: February 2021

Objective:

Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis.

Summary background data:

Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However the reported failure rates are highly variable and there is a paucity of data in relation to quality of life.

Methods:

Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy.

Results:

One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0,
P
< 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001).

Conclusions:

Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.
The Tangible Benefits of Living Donation: Results of a Qualitative Study of Living Kidney Donors
Authors: Van Pilsum Rasmussen Sarah E. , Robin Miriam , Saha Amrita , Eno Anne , Lifshitz Romi , Waldram Madeleine M. , Getsin Samantha N. , Chu Nadia M. , Al Ammary Fawaz , Segev Dorry L. , Henderson Macey L.
Published: February 2021

Background.

The framework currently used for living kidney donor selection is based on estimation of acceptable donor risk, under the premise that benefits are only experienced by the recipient. However, some interdependent donors might experience tangible benefits from donation that cannot be considered in the current framework (ie, benefits experienced directly by the donor that improve their daily life, well-being, or livelihood).

Methods.

We conducted semistructured interviews with 56 living kidney donors regarding benefits experienced from donation. Using a qualitative descriptive and constant comparative approach, themes were derived inductively from interview transcripts by 2 independent coders; differences in coding were reconciled by consensus.

Results.

Of 56 participants, 30 were in interdependent relationships with their recipients (shared household and/or significant caregiving responsibilities). Tangible benefits identified by participants fell into 3 major categories: health and wellness benefits, time and financial benefits, and interpersonal benefits. Participants described motivations to donate a kidney based on a more nuanced understanding of the benefits of donation than accounted for by the current “acceptable risk” paradigm.

Discussion.

Tangible benefits for interdependent donors may shift the “acceptable risk” paradigm (where no benefit is assumed) of kidney donor evaluation to a risk/benefit paradigm more consistent with other surgical decision-making.
Managing COVID-19-positive Solid Organ Transplant Recipients in the Community: What a Community Healthcare Provider Needs to Know
Authors: Basu Arpita , Patzer Rachel , Hosein Darya , Wang Zhensheng , Sharma Nitika , Franch Harold , Rahbari Oskoui Frederic , Gupta Divya , Subramanian Ram , Sridharan Lakshmi , Allison Wanda , Pastan Stephen , Larsen Christian
Published: February 2021

Background.

The current surge of coronavirus 2019 (COVID-19) cases in certain parts of the country has burdened the healthcare system, limiting access to tertiary centers for many. As a result, COVID-19-positive Solid Organ Transplant (SOT) recipients are increasingly being managed by local healthcare providers. It is crucial for community providers to understand disease severity and know if COVID-19-impacted SOT recipients have a different clinical course compared with COVID-19-negative SOT recipients with a similar presentation.

Methods.

We conducted a retrospective analysis on SOT recipients suspected to have COVID-19 infection tested during March 14, 2020–April 30, 2020. Patients were followed from time of testing to May 31, 2020.

Results.

One hundred sixty SOT recipients underwent testing: 22 COVID-19 positive and 138 COVID-19 negative. COVID-19-positive patients were more likely to have rapid progression of symptoms (median 3 vs 6 d, P = 0.002), greater hospitalizations (78% vs 64%, P < 0.017), and need for intensive care unit care (45% vs 17%, P < 0.001) Severe COVID-19 infection was not observed in patients on Belatacept for immunosuppression (30% vs 87%,P = 0.001). COVID- 19 positive patients in the intensive care unit were more likely to have multifocal opacities on radiological imaging in comparison to those admitted to the medical floor (90% vs 11%). Survival probability was similar in both cohorts.

Conclusion.

COVID-19-infected SOT recipients have a propensity for rapid clinical decompensation. Local providers need to be work closely with transplant centers to appropriately triage and manage COVID-19 SOT recipients in the community.
Is Prosocial Behavior Associated With Increased Registration for Deceased Organ Donation? A Cross-sectional Study of Ontario, Canada
Authors: Wilk Piotr , Richard Lucie , Ouédraogo Alexandra M. , Garg Amit X. , Maltby Alana , Shariff Salimah Z.
Published: February 2021

Background.

A community that promotes prosocial behaviors such as organ donor registration or charitable giving could reinforce those behaviors among its residents. Understanding the nature of the relationship between prosocial behaviors at the community level and an individual’s decision to engage in prosocial behavior can help in the targeting of communities with lower rates of prosocial activities. The objective of this study was to assess if the likelihood that an individual is a registered deceased organ donor in Ontario, Canada, is associated with community-level charitable giving.

Methods.

This cross-sectional population-based study involved individual- and community-level data from multiple administrative data sources from ICES and Statistics Canada. To assess the unadjusted and adjusted effects of community-level charitable giving on organ donor registration, we ran 4 sequential multilevel random intercept logistic regression models and used a number of individual- and community-level confounding factors.

Results.

Statistically significant between-community variance (0.322, SE = 0.020) and interclass correlation coefficient (0.089) suggest that substantial variation in organ donor registration can be attributed to the between-community differences. Community-level charitable giving was correlated with organ donor registration (odds ratios, 1.351; 95% confidence intervals, 1.245-1.466) in the model containing only individual-level confounding factors. However, this relationship became statistically nonsignificant (odds ratios, 0.982; 95% confidence intervals, 907-1.063) when a series of community-level confounding factors were added to the model. Among these confounding factors, individuals’ immigration status and community-level ethnic/immigrant concentration had the most pronounced association with organ donor registration.

Conclusion.

The identification of the characteristics of populations and communities with low organ donor registration rates may inform future initiatives in the area of organ donation awareness and promotion to make them more effective among those particular groups.
Noninvasive direct current stimulation for schizophrenia: a review
Authors: Lindenmayer Jean-Pierre , Fitapelli Brianna
Published: February 2021

Purpose of review

To provide an update of recent studies describing the effects of transcranial direct current stimulation (tDCS) on patients with schizophrenia, with particular focus on auditory verbal hallucinations (AVH), cognitive deficits, and negative symptoms.

Recent findings

As a low-cost, easy-to-use neuromodulation technique, tDCS may have clinical implications for those suffering from treatment-persistent AVH, negative symptoms, and cognitive symptoms in schizophrenia. Over the past decade, tDCS has shown no effects for negative symptoms, except when used at a high frequency of sessions, and inconclusive results for AVH and cognitive symptoms. The treatment has little to no adverse effects.

The studies reviewed here support the need for further investigation and empirical data regarding the use of tDCS. The underlying mechanisms of tDCS as well as the most effective stimulation parameters must be better understood. Findings support the need for increased duration and frequency of tDCS sessions. One of the next steps is the investigation of effects of concomitant nonpharmacological treatments with tDCS.
Uncovering interpretable potential confounders in electronic medical records
Authors: Zeng Jiaming , Gensheimer Michael F. , Rubin Daniel L. , Athey Susan , Shachter Ross D.
Published: February 2021

Randomized clinical trials (RCT) are the gold standard for informing treatment decisions. Observational studies are often plagued by selection bias, and expert-selected covariates may insufficiently adjust for confounding. We explore how unstructured clinical text can be used to reduce selection bias and improve medical practice. We develop a framework based on natural language processing to uncover interpretable potential confounders from text. We validate our method by comparing the estimated hazard ratio (HR) with and without the confounders against established RCTs. We apply our method to four cohorts built from localized prostate and lung cancer datasets from the Stanford Cancer Institute and show that our method shifts the HR estimate towards the RCT results. The uncovered terms can also be interpreted by oncologists for clinical insights. We present this proof-of-concept study to enable more credible causal inference using observational data, uncover meaningful insights from clinical text, and inform high-stakes medical decisions.
Variations in housing affordability and health relationships by measurement and sub-population assessment
Authors: Raderman Will , Rogers Nina T. , Murray Emily T.
Published: February 2021

Past studies have shown that the more unaffordable housing is to people, the worse their health, particularly mental health. However, the commonly used housing affordability indicator, the 30% measure, has limitations. There is evidence that other indicators, including the ‘30/40’ measure, might be more precise in characterizing housing unaffordability by taking into account absolute values of household incomes. In this paper, we use cross-sectional data from the UK Household Longitudinal Study, to evaluate relationships between two affordability measures (30%, 30/40) with 3 health measures: general, physical and mental health. We use logistic regression and effect modification to test whether relationships varied by age, ethnicity, housing tenure, urbanicity and sex. Out of 35,114 participants with complete data, housing was classified as unaffordable for 24.2% using the 30% measure and 10.2% for the 30/40 measure. In age-adjusted analyses, higher unaffordability was associated with worse health for all three health measures, with associations stronger for the 30/40 vs the 30% unaffordability measure. In models adjusted for age, sex and urbanicity, both ethnicity and tenure independently modified associations; with modification showing small differences by unaffordability and health measure. Further studies are needed to disentangle complex relationships between household income, housing costs, ethnicity and tenure.
To what extent do we need to rely on non-pharmaceutical interventions while COVID-19 vaccines roll out in 2021?
Authors: Yang Juan , Marziano Valentina , Deng Xiaowei , Guzzetta Giorgio , Zhang Juanjuan , Trentini Filippo , Cai Jun , Poletti Piero , Zheng Wen , Wang Wei , Wu Qianhui , Zhao Zeyao , Dong Kaige , Zhong Guangjie , Viboud Cécile , Merler Stefano , Ajelli Marco , Yu Hongjie
Published: February 2021

Abstract

COVID-19 vaccination is being conducted in over 190 countries/regions to control SARS-CoV-2 transmission and return to a pre-pandemic lifestyle. However, understanding when non-pharmaceutical interventions (NPIs) can be lifted as immunity builds up remain a key question for policy makers. To address it, we built a data-driven model of SARS-CoV-2 transmission for China. We estimated that to prevent the escalation of local outbreaks to widespread epidemics, stringent NPIs need to remain in place at least one year after the start of vaccination. Should NPIs alone be capable to keep the reproduction number (Rt) around 1.3, the synergetic effect of NPIs and vaccination could reduce up to 99% of COVID-19 burden and bring Rtbelow the epidemic threshold in about 9 months. Maintaining strict NPIs throughout 2021 is of paramount importance to reduce COVID-19 burden while vaccines are distributed to the population, especially in large populations with little natural immunity.
Psilocybin-induced changes in brain network integrity and segregation correlate with plasma psilocin level and psychedelic experience
Authors: Madsen Martin K. , Stenbæk Dea S. , Arvidsson Albin , Armand Sophia , Marstrand-Joergensen Maja R. , Johansen Sys S. , Linnet Kristian , Ozenne Brice , Knudsen Gitte M. , Fisher Patrick M.
Published: February 2021

The emerging novel therapeutic psilocybin produces psychedelic effects via engagement of cerebral serotonergic targets by psilocin (active metabolite). The serotonin 2A receptor critically mediates these effects by altering distributed neural processes that manifest as increased entropy, reduced functional connectivity (FC) within discrete brain networks (i.e., reduced integrity) and increased FC between networks (i.e., reduced segregation). Reduced integrity of the default mode network (DMN) is proposed to play a particularly prominent role in psychedelic phenomenology, including perceived ego-dissolution. Here, we investigate the effects of a psychoactive oral dose of psilocybin (0.2-0.3 mg/kg) on plasma psilocin level (PPL), subjective drug intensity (SDI) and their association in fifteen healthy individuals. We further evaluate associations between these measures and resting-state FC, measured with functional magnetic resonance imaging, acquired over the course of five hours after psilocybin administration. We show that PPL and SDI correlate negatively with measures of network integrity (including DMN) and segregation, both spatially constrained and unconstrained. We also find that the executive control network and dorsal attention network desegregate, increasing connectivity with other networks and throughout the brain as a function of PPL and SDI. These findings provide direct evidence that psilocin critically shapes the time course and magnitude of changes in the cerebral functional architecture and subjective experience following psilocybin administration. Our findings provide novel insight into the neurobiological mechanisms underlying profound perceptual experiences evoked by this emerging transnosological therapeutic and implicate the expression of network integrity and segregation in the psychedelic experience and consciousness.
Extreme Phenotypic Diversity in Operant Responding for an Intravenous Cocaine or Saline Infusion in the Hybrid Mouse Diversity Panel
Authors: Bagley Jared R. , Khan Arshad H. , Smith Desmond J. , Jentsch James D.
Published: February 2021

Cocaine self-administration is complexly determined trait, and a substantial proportion of individual differences in cocaine use is determined by genetic variation. Cocaine intravenous self-administration (IVSA) procedures in laboratory animals provide opportunities to prospectively investigate neurogenetic influences on the acquisition of voluntary cocaine use. Large and genetically diverse mouse populations, including the Hybrid Mouse Diversity Panel (HMDP), have been developed for forward genetic approaches that can reveal genetic variants that influence traits like cocaine IVSA. This population enables high resolution and well-powered genome wide association studies, as well as the discovery of genetic correlations. Here, we provide information on cocaine (or saline - as a control) IVSA in 65 strains of the HMDP. We found cocaine IVSA to be substantially heritable in this population, with strain-level intake ranging for near zero to >25 mg/kg/session. Though saline IVSA was also found to be heritable, a very modest genetic correlation between cocaine and saline IVSA indicates that operant responding for the cocaine reinforcer was influenced by a substantial proportion of unique genetic variants. These data indicate that the HMDP is suitable for forward genetic approaches for the analysis of cocaine IVSA, and this project has also led to the discovery of reference strains with extreme cocaine IVSA phenotypes, revealing them as polygenic models of risk and resilience to cocaine reinforcement. This is part of an ongoing effort to characterize genetic and genomic variation that moderates cocaine IVSA, which may, in turn, provide a more comprehensive understanding of cocaine risk genetics and neurobiology.
Heartbeat-evoked potentials during interoceptive-exteroceptive integration are not consistent with precision-weighting
Authors: Banellis Leah , Cruse Damian
Published: February 2021

Interoceptive-exteroceptive integration is fundamental for a unified interactive experience of the world with the body. Predictive coding accounts propose that these integrated signals operate predictively, with regulation by precision-weighting. Heartbeat-evoked potentials (HEPs) are one means to investigate integrated processing. In a previous study, consistent with predictive coding characterisations of precision-weighting, we observed modulation of HEPs by attention. However, we found no evidence of HEP modulation by participants’ interoceptive ability, despite the characterisation by predictive coding theories of trait abilities as a similar reflection of differential precision-weighting. In this study, we sought to more sensitively test the hypothesised trait-precision influences on HEPs by using an individually-adjusted measure of interoceptive performance. However, contrary to a precision-weighted predictive coding framework, we failed to find evidence in support of the HEP modulations by attentional-precision or trait-precision. Nonetheless, we observed robust HEP effects indicative of an expectation of a sound on the basis of a heartbeat -i.e. interoceptive-exteroceptive integration. It is possible that under our more individually-tailored task, participants relied less on attentional-precision to ‘boost’ predictions due to an enhanced perception of cardio-audio synchrony. Furthermore, assessing interoceptive ability is challenging, thus variations in performance may not accurately reflect trait-precision variations. Nevertheless, in sum, our findings are inconsistent with a precision-weighted prediction error view of the HEP, and highlight the need for clearer definitions of the manipulation and measurement of precision in predictive coding. Finally, our robust interoceptive-exteroceptive integration HEP effects may provide a valuable tool for investigating such integration in both clinical conditions and cognition.

Impact statement

We investigate heart-evoked potentials during interoceptive-exteroceptive integration to determine whether cross-modal integrated processes operate under a precision-weighted predictive coding framework. Using a more sensitive individually-tailored task, we found no evidence of the modulation of cardio-audio expectation by attention or individual differences in interoceptive perception (i.e. by state or trait measures of precision). Nonetheless, we replicate evidence of cardiac-driven predictions of auditory stimuli, providing a potential tool for investigating their relationship with emotion and embodied selfhood.
PML-Dependent Memory of Type I Interferon Treatment Results in a Restricted Form of HSV Latency
Authors: Suzich Jon B. , Cuddy Sean R. , Baidas Hiam , Dochnal Sara , Ke Eugene , Schinlever Austin R. , Babnis Aleksandra , Boutell Chris , Cliffe Anna R.
Published: February 2021

Herpes simplex virus (HSV) establishes latent infection in long-lived neurons. During initial infection, neurons are exposed to multiple inflammatory cytokines but the effects of immune signaling on the nature of HSV latency is unknown. We show that initial infection of primary murine neurons in the presence of type I interferon (IFN) results in a form of latency that is restricted for reactivation. We also found that the subnuclear condensates, promyelocytic leukemia-nuclear bodies (PML-NBs), are absent from primary sympathetic and sensory neurons but form with type I IFN treatment and persist even when IFN signaling resolves. HSV-1 genomes colocalized with PML-NBs throughout a latent infection of neurons only when type I IFN was present during initial infection. Depletion of PML prior to or following infection did not impact the establishment latency; however, it did rescue the ability of HSV to reactivate from IFN-treated neurons. This study demonstrates that viral genomes possess a memory of the IFN response duringde novoinfection, which results in differential subnuclear positioning and ultimately restricts the ability of genomes to reactivate.
Dynamic blinking in the head of hardyhead silverside fish
Authors: Iwasaka Masakazu
Published: February 2021

Dynamic light reflection can serve a similar purpose to tools such as digital line processing devices. It is interesting, therefore, that evidence of dynamic light reflection can also be found in the animal kingdom and that there may be alternative ways of actuating light control. This study discovered that several features contained in the heads of hardyhead silverside fish, particularly around the edges of the iris, caused blinking using environmentally scattered light. Analyzing the blinking using recorded video of the fish iris revealed that circular cells existing in the iris changed their light intensity at 2 Hz. These 5–10-μm-diameter cells are normally blue. However, it is found that a distinct light intensity changed in 0.04 seconds, and additional green and yellow colors overlapped with the blue. It is hoped that utilizing the mechanism that controls the rapid changes in light intensity using only environmental lighting can reduce electrical power usage in display devices.
Somatosensory innervation of healthy human oral tissues
Authors: Moayedi Yalda , Michlig Stephanie , Park Mark , Koch Alia , Lumpkin Ellen A
Published: February 2021

The oral somatosensory system relays essential information about mechanical stimuli to enable oral functions such as feeding and speech. The neurochemical and anatomical diversity of sensory neurons across oral cavity sites have not been systematically compared. To address this gap, we analyzed healthy human tongue and hard palate innervation. Biopsies were collected from 12 volunteers and underwent multiplex fluorescent immunohistochemistry (≥2 specimens per marker/structure). Afferents were analyzed for markers of neurons (βIII tubulin), myelinated afferents (neurofilament heavy, NFH), and Merkel cells and taste cells (keratin 20, K20). Hard-palate innervation included Meissner’s corpuscles, glomerular endings, Merkel cell-neurite complexes, and free nerve endings. The organization of these somatosensory endings is reminiscent of fingertips, suggesting that the hard palate is equipped with a rich repertoire of sensory neurons for pressure sensing and spatial localization of mechanical inputs, which are essential for speech production and feeding. Likewise, the tongue is innervated by afferents that impart it with exquisite acuity and detection of moving stimuli that support flavor construction and speech. Filiform papillae contain end bulbs of Krause, as well as endings that have not been previously reported, including subepithelial neuronal densities, and NFH+ neurons innervating basal epithelium. Fungiform papillae had Meissner’s corpuscles and densities of NFH+ intraepithelial neurons surrounding taste buds. The differing compositions of sensory endings within filiform and fungiform papillae suggest that these structures have distinct roles in mechanosensation. Collectively, this study has identified previously undescribed afferent endings in human oral tissues and provides an anatomical framework for understanding oral mechanosensory functions.
The genomic signature of wild-to-crop introgression during the domestication of scarlet runner bean (Phaseolus coccineusL.)
Authors: Guerra-García Azalea , Rojas-Barrera Idalia C. , Ross-Ibarra Jeffrey , Papa Roberto , Piñero Daniel
Published: February 2021

The scarlet runner bean is an open-pollinated legume from the highlands of Mesoamerica that is cultivated in small-scale agriculture for its dry seeds and immature pods. Demographic bottlenecks associated with domestication might reduce genetic diversity and facilitate the accumulation of deleterious mutations. Conversely, introgression from wild relatives could be a source of variation.

Using Genotyping by Sequencing data (79,286 SNVs) from 237 cultivated and wild samples, we evaluated the demographic history of traditional varieties from different regions of Mexico and looked for evidence of introgression between sympatric wild and cultivated populations.

Traditional varieties have high levels of diversity, even though there is evidence of a severe initial genetic bottleneck, followed by a population expansion. Introgression from wild to domesticated populations was detected, but not in the opposite direction. This asymmetric introgression might contribute to the recovery of genetic variation and it has occurred at different times: constantly in the center of Mexico; recently in the North West; and anciently in the South.

Several factors are acting together to increase and maintain genetic diversity inP. coccineuscultivars, such as demographic expansion and introgression. Wild relatives represent a valuable genetic resource and have played a key role in scarlet runner bean evolution via introgression into traditional varieties.
Akaike model selections of the vegetation structures and aerosphere factors in supporting lesser short nosed fruit bat (Cynopterus brachyotisMuller, 1838) populations in Asia mountainous paddy fields
Authors: Basukriadi Adi , Nurdin Erwin , Wibowo Andri , Gunawan Jimi
Published: February 2021

As an aerial and arboreal fauna, the abundances and populations of fruit batCynopterus brachyotiswere influenced by the vegetation structures and aerosphere condition variables of fruit bat ecosystems. While mountaineous paddy field is an unique habitat since the trees are scarce and has exposure to the aerosphere variables including air temperature and humidity. Here this paper aims to select the best vegetation structures and aerosphere factors that support the abundance ofC. brachyotisin mountainous paddy field landscape in West Java. The model selection was using AIC methodology by testing 15 models including 5 single models and 10 combination models of explanatory variables. Based on the model, tree height and combinations of tree height and elevation produced the best prediction for the bat abundances, as described by low values of AIC and the highest values of R2and adjusted R2. For the best models, the AIC values ranged from 16.674 to 17.603, from 0.3404 to 0.4144 (R2), and 0.2461 to 0.2192 for adjusted R2. Regarding conservation ofC. brachyotisand learning from the model, the conservation approaches mainly in mountainous paddy fields are encouraged to protect and conserve high altitude landscapes and trees with height > 10 m. Whereas the AIC results show lack of aerosphere variable effects onC. brachyotis(AIC: 19.346-20.406, R2: 0.1124-0.001353, and adjusted R2: −0.01444 − −0.1413).