bluuebunny/crossref_metadata_2025 huggingface dataset:
River Fishes and Other Vertebrate Communities
Authors: Mallin Michael A.
Published: November 2023

Habitats along the river continuum are highly variable and are exploited by a diverse community of fishes. Species of minnows, carp, suckers, catfishes, perches, sunfish, bass, salmonids, and sturgeon are distributed among the upper and lower water columns, riffles and pools, rocky or sandy bottom, snags, cold and warm waters, swift and slow currents and feed on periphyton, macrophytes, zooplankton, invertebrates, and smaller fish. Some species such as salmonids are anadromous and migrate along the river according to life stage. Part-time users of lotic habitats include amphibians—salamanders, frogs, and toads—many species of which have suffered losses through fungal disease. Reptiles such as turtles, snakes, and crocodilians are highly visible part-time river users; the alligator is an ecological engineer that creates wetland habitats and large crocodiles are powerful apex predators whose prey includes humans. A number of fur-bearing mammals use streams and rivers; the beaver, once highly prized for its fur, is also a well-known ecological engineer that creates and destroys habitats by tree removal and dam building. Hippopotami are massive and highly dangerous river users that engineer habitats and whose dung production can change river water chemistry through massive nutrient oversupply that causes algal blooms and fish kills. Birds use the stream environment as both generalists and obligate users, feeding on plants, seeds, invertebrates, other birds, small mammals, and fish through floating and diving, swimming, wading, and aerial searching. Some, especially predators and carrion feeders, have suffered highly visibly from chemical pollution through the food chain.
Blackwater Streams and Rivers
Authors: Mallin Michael A.
Published: November 2023

Blackwater systems are called so because the water is darkly colored from leachate from organic acids from riparian swamp vegetation. Such systems can be found in many locations throughout the world but are especially prominent and well studied in the Mid-Atlantic to the Southeast Coastal Plain of the USA. Besides the coloration, pH can be quite low from organic acids, yet rich faunal communities are present. Along the river continuum, heterotrophy gets stronger rather than weaker as in uncolored waters because the colored DOM attenuates light in deeper rivers, so phytoplankton blooms are relegated to shallow streams or surface cyanobacterial blooms. The snag (large woody debris) community is vitally important since snags are solid substrata in a sandy environment, and a food web consists of benthos living on snags consuming food materials from the current, in turn being consumed by small fish, which in turn are consumed by piscivores. Another food web is sediment-based upon oligochaetes and chironomids.
The Ecology of Tidal Creeks
Authors: Mallin Michael A.
Published: November 2023

The study of tidal creeks has been heretofore ignored in classical river ecology, yet such creeks are highly abundant in Coastal Plain regions and present in coastal tectonic and mountain areas as well. Creek sediments can be rocky, muddy, or sandy, depending upon region. These creeks serve as vitally important means of materials transfer between dissolved and particulate forms, inorganic nutrients and phytoplankton, zooplankton and higher organisms, and freshwater and marine environments. Tidal creeks are well known as primary nursery areas that are important to fish production through supply of food and protection from larger predators. They are described by the Strahler stream order system, with lowest-order (headwaters; fresh to oligohaline) areas strongly impacted by human pollutants, with fecal microbe abundance, nitrate and ammonium, and metals and chemical pollution positively correlated with watershed impervious surface coverage. Riparian areas of continental-draining tidal creeks are heavily used as residential areas, agricultural areas, golf course locations, and sites of numerous marinas. Oyster reefs in these creeks serve as passive ecological engineers, providing structure, habitat for fish and invertebrates, food for humans, and a means of clearing water of suspended solids, bacteria, and phytoplankton through large-scale filtration.
Industrial Pollution of Streams and Rivers
Authors: Mallin Michael A.
Published: November 2023

Streams and rivers are used by industries of all types as source water and as repositories of wastewater; streams are also beset with pollutant spills. Power plants that produce steam discharge heated effluents into rivers and reservoirs; sometimes metals that are byproducts of coal burning (mercury and selenium, for instance) pollute waters enough to damage the fishery. Throughout the twentieth century and into the twenty-first century rivers continue to be polluted with Hg, Cd, As, Pb, and other metals. Pesticides enter streams in runoff or airborne deposition, and even long-banned pesticides and other chemicals are in stream sediments. Toxic polychlorinated biphenyls (PCBs) are one such group; other toxic compounds in streams include dioxins and polycyclic aromatic hydrocarbons (PAHs), which are urban stream pollutants. More recently, plastics pollution in rivers has achieved huge interest, and the negative impacts of waterborne per- and polyfluoroalkyl substances (PFASs) are of great concern and study.
Vascularized Brain Assembloids With Enhanced Cellular Complexity Provide Insights Into the Cellular Deficits of Tauopathy
Authors: Sun Xiaohuan , Kofman Simeon , Ogbolu Victor C , Karch Celeste M , Ibric Larisa , Qiang Liang
Published: November 2023

Advanced technologies have enabled the engineering of self-organized 3-dimensional (3D) cellular structures from human induced pluripotent stem cells (hiPSCs), namely organoids, which recapitulate some key features of tissue development and functions of the human central nervous system (CNS). While hiPSC-derived 3D CNS organoids hold promise in providing a human-specific platform for studying CNS development and diseases, most of them do not incorporate the full range of implicated cell types, including vascular cell components and microglia, limiting their ability to accurately recreate the CNS environment and their utility in the study of certain aspects of the disease. Here we have developed a novel approach, called vascularized brain assembloids, for constructing hiPSC-derived 3D CNS structures with a higher level of cellular complexity. This is achieved by integrating forebrain organoids with common myeloid progenitors and phenotypically stabilized human umbilical vein endothelial cells (VeraVecs), which can be cultured and expanded in serum-free conditions. Compared with organoids, these assembloids exhibited enhanced neuroepithelial proliferation, advanced astrocytic maturation, and increased synapse numbers. Strikingly, the assembloids derived from hiPSCs harboring the tauP301S mutation exhibited increased levels of total tau and phosphorylated tau, along with a higher proportion of rod-like microglia-like cells and enhanced astrocytic activation, when compared to the assembloids derived from isogenic hiPSCs. Additionally, the tauP301S assembloids showed an altered profile of neuroinflammatory cytokines. This innovative assembloid technology serves as a compelling proof-of-concept model, opening new avenues for unraveling the intricate complexities of the human brain and accelerating progress in the development of effective treatments for neurological disorders.
Dispensing Methadone at Hospital Discharge: One Hospital's Approach to Implementing the “72-hour Rule” Change
Authors: Skogrand Emily , Sharpe Jackie , Englander Honora
Published: November 2023

Objectives

Methadone for opioid use disorder treatment in ambulatory settings is restricted to federally licensed opioid treatment programs (OTPs) in the United States. However, these restrictions do not apply during hospitalization. A recent change to the rule governing methadone in non-OTP settings created an opportunity to dispense methadone at hospital discharge for up to 72 hours.

Methods

Here, we describe one hospital's approach to dispensing methadone at discharge in alignment with the “72-hour rule,” including implementation challenges and considerations for other hospitals planning on adopting this practice. Implementation included creating a workflow and detailed documents outlining dispensing procedure, educating interprofessional staff, and coordinating with local OTPs.

Results

Our experiences highlight the importance of pharmacy champions to support implementation and interdisciplinary staff education, the need to consider electronic health record capabilities, and the importance of having policies and practices that support appropriate interpretation of the “72-hour rule” renewal timeline.

Conclusions

Exceptions to federal regulations allow greater flexibility in discharge planning for patients with opioid use disorder; however, dispensation workflow falls outside standard hospital care and may be challenging to implement.
Evaluating the Interaction between Pain Intensity and Resilience on the Impact of Pain in the Lives of People with Fibromyalgia
Authors: Teixeira Livia Agostinho , de Oliveira Vidal Edison Iglesias , Blake Holly , de Barros Guilherme Antonio Moreira , Fukushima Fernanda Bono
Published: November 2023

Objective:

Recent theoretical models posit that resilience acts as a resource/mechanism opposing pain catastrophizing and other vulnerability sources against pain adaptation. The aim of this study was to investigate the relationship between resilience, pain and functionality in people living with fibromyalgia.

Methods:

We conducted a cross-sectional online survey of people participating in Brazilian fibromyalgia virtual support groups on Facebook in May 2018. Resilience was evaluated by the Connor-Davidson Resilience Scale. Average pain and the degree of interference of pain in the lives of participants (DIPLP) were assessed using the Brief Pain Inventory. The association between these three variables was evaluated through multivariable robust linear regression with adjustment for 21 potential confounders.

Results:

We included 2176 participants with fibromyalgia. Resilience was associated with a decreased DIPLP (β: -0.38, 95%CI: -0.54 to -0.22,P<0.001) but not with average pain scores (β: -0.01, 95%CI: -0.18 to 0.16,P=0.93). A significant interaction between resilience and average levels of pain on the DIPLP was observed so that resilience showed a much stronger protective association among participants with average null-to-mild pain than among those with moderate and severe pain levels.

Discussion:

Our results provide evidence against beliefs that the pain of people with fibromyalgia is related to low psychological resilience and shed light on the complex interrelationships between resilience, pain, and functionality. This research signals both the relevance and limits of resilience in the management of fibromyalgia. Future studies evaluating behavioral interventions for fibromyalgia should consider how those interventions interact with baseline pain levels and resilience.
Development of a radiomics model to discriminate ammonium urate stones from uric acid stones in vivo: A remedy for the diagnostic pitfall of dual-energy computed tomography
Authors: Zheng Junjiong , Zhang Jie , Cai Jinhua , Yao Yuhui , Lu Sihong , Wu Zhuo , Cai Zhaoxi , Tuerxun Aierken , Batur Jesur , Huang Jian , Kong Jianqiu , Lin Tianxin
Published: November 2023

Background:

Dual-energy computed tomography (DECT) is purported to accurately distinguish uric acid stones from non-uric acid stones. However, whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains unknown. Therefore, we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing them.

Methods:

This research included two steps. For the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones, 178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were enrolled. For model construction, 93, 40, and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training, internal validation, and external validation sets, respectively. Radiomics features were extracted from non-contrast CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a radiomics signature. Then, a radiomics model incorporating the radiomics signature and clinical predictors was constructed. The performance of the model (discrimination, calibration, and clinical usefulness) was evaluated.

Results:

When patients with ammonium urate stones were included in the analysis, the accuracy of DECT in the diagnosis of uric acid stones was significantly decreased. Sixty-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT. A radiomics model incorporating the radiomics signature, urine pH value, and urine white blood cell count was constructed. The model achieved good calibration and discrimination {area under the receiver operating characteristic curve (AUC; 95% confidence interval [CI]), 0.944 (0.899–0.989)}, which was internally and externally validated with AUCs of 0.895 (95% CI, 0.796–0.995) and 0.870 (95% CI, 0.769–0.972), respectively. Decision curve analysis revealed the clinical usefulness of the model.

Conclusions:

DECT cannot accurately differentiate ammonium urate stones from uric acid stones. Our proposed radiomics model can serve as a complementary diagnostic tool for distinguishing them in vivo.
A Preliminary Validation of an Optimal Cutpoint in Total Number of Patient-Reported Symptoms in Head and Neck Cancer for Effective Alignment of Clinical Resources With Patients’ Symptom Burden
Authors: Van Cleave Janet H. , Concert Catherine , Kamberi Maria , Zahriah Elise , Most Allison , Mojica Jacqueline , Riccobene Ann , Russo Nora , Liang Eva , Hu Kenneth S. , Jacobson Adam S. , Li Zujun , Moses Lindsey E. , Persky Michael J. , Persky Mark S. , Tran Theresa , Brody Abraham A. , Kim Arum , Egleston Brian L.
Published: November 2023

Background:

Patients with head and neck cancer (HNC) often experience high symptom burden leading to lower quality of life (QoL).

Objective:

This study aims to conceptually model optimal cutpoint by examining where the total number of patient-reported symptoms exceeds patients’ coping capacity, leading to a decline in QoL in patients with HNC.

Methods:

Secondary data analysis of 105 individuals with HNC enrolled in a clinical usefulness study of the NYU Electronic Patient Visit Assessment (ePVA), a digital patient-reported symptom measure. Patients completed ePVA and European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 v3.0. The total number of patient-reported symptoms was the sum of symptoms as identified by the ePVA questionnaire. Analysis of variance was used to define the optimal cutpoint.

Results:

Study participants had a mean age of 61.5, were primarily male (67.6%), and had stage IV HNC (53.3%). The cutpoint of 10 symptoms was associated with a significant decline of QoL (F = 44.8, P < .0001), dividing the population into categories of low symptom burden (<10 symptoms) and high symptom burden (≥10 symptoms). Analyses of EORTC function subscales supported the validity of 10 symptoms as the optimal cutpoint (physical: F = 28.3, P < .0001; role: F = 21.6, P < .0001; emotional: F = 9.5, P = .003; social: F = 33.1, P < .0001).

Conclusions:

In HNC, defining optimal cutpoints in the total number of patient-reported symptoms is feasible.

Implications for Practice:

Cutpoints in the total number of patient-reported symptoms may identify patients experiencing a high symptom burden from HNC.

What is Foundational:

Using optimal cutpoints of the total number of patient-reported symptoms may help effectively align clinical resources with patients’ symptom burden.
A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis: A multicenter plasma biomarker analysis
Authors: Tornai David , Mitchell Mack , McClain Craig J. , Dasarathy Srinivasan , McCullough Arthur , Radaeva Svetlana , Kroll-Desrosiers Aimee , Lee JungAe , Barton Bruce , Szabo Gyongyi
Published: November 2023

Background:

Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The MELD assesses disease severity and mortality; however, it is not specific for AH. We screened plasma samples from patients with severe AH for biomarkers of multiple pathological processes and identified predictors of short-term mortality.

Methods:

Plasma was collected at baseline from 85 patients with severe AH (MELD≥20, Maddrey’s discriminant function≥32) enrolled in the Defeat Alcoholic Steatohepatitis clinical trial (investigating IL-1 receptor antagonist+pentoxifylline+zinc vs. methylprednisolone+placebo). Samples were analyzed for 43 biomarkers and the markers’ association with 28- and 90-day mortalities was assessed.

Results:

Thirty-one (36.5%) patients died during the 90-day follow-up with similar ratios in the treatment groups. Eight biomarkers showed an association with mortality. IL-6, IL-22, interferon-α2, soluble TNF receptor 1, lipocalin-2, and α-fetoprotein levels were associated with 28-day mortality, while IL-6, IL-13, and endotoxin levels with 90-day mortality. In multivariable Cox regression, encephalopathy, lipocalin-2, and α-fetoprotein levels were independent predictors of 28-day mortality, and IL-6, IL-13, international normalized ratio levels, and age were independent predictors of 90-day mortality. The combination of IL-13 and age had superior performance in predicting 90-day mortality compared with MELD in the total cohort and the individual treatment groups.

Conclusions:

We identified predictors of short-term mortality in a cohort exclusively involving patients with severe AH. We created a composite score of IL-13 and age that predicts 90-day mortality regardless of the treatment type with a performance superior to MELD in severe AH.
Orbital Fibrotic Band as Cause of Monocular Elevation Deficiency
Authors: Atilla Huban , Çaliş Karanfil Feyza , Bingöl Kiziltunç Pinar
Published: November 2023

Monocular elevation deficiency is a congenital, unilateral inability of elevation. It is classified as innervational, restrictive, or combine types. Here, we report a rare case of monocular elevation deficiency who had 60 PD left hypotropia and left ptosis with limited elevation (−5) both on abduction and adduction. Orbital MRI revealed a hypointense fibrotic band between the superior oblique and superior rectus muscles extending obliquely in the superonasal direction between the sclera and orbital roof. She was successfully treated after severing the fibrotic band between the sclera and bony orbit.
Complications of foldable intraocular lenses requiring explantation or secondary intervention: 2022 survey with update of long-term trends
Authors: Renschler Andy , Kelkar Neil , Eid Kevin , Hawn Vivian , Bundogji Nour , Werner Liliana , Mamalis Nick
Published: November 2023

Purpose:

To assess the complications that resulted in the explantation or secondary intervention with foldable intraocular lenses (IOLs).

Setting:

University setting, Salt Lake City, Utah.

Design:

Survey study.

Methods:

For the 25th consecutive year, surgeons were surveyed regarding complications associated with foldable IOLs requiring explantation or secondary intervention over the 2022 calendar year. These forms were made available online using the ASCRS and ESCRS websites and a fax-on-demand service. Surgeons completed 1 survey for each foldable IOL requiring explantation or secondary intervention. Further analysis determined complication trends related to specific IOL styles, materials, and types over the past 16 years (2007 to 2022).

Results:

103 completed surveys were returned in 2022 contributing to a total of 1627 tabulated surveys since 2007. In the 2022 survey, dislocation/decentration continued to be the most common complication overall. Glare/optical aberrations was a common complication associated with multifocal IOLs continuing a 16-year trend. In addition, hydrophilic acrylic IOLs as well as some silicone lenses in eyes with asteroid hyalosis demonstrated calcification as the most common complication necessitating explantation.

Conclusions:

Dislocation/decentration remains the leading cause of explantation in most IOL types. Glare/optical aberrations continue to be an associated complication of multifocal IOLs suggesting this ongoing issue has yet to be resolved with this type of IOL. In addition, calcification of hydrophilic acrylic lenses and silicone lenses is a rare event but continues to occur.
The Standardization of Home Blood Pressure Monitoring in Primary Care
Authors: Knoll Lisa , Elwell Joy , Arcari-Couture Jill , Alexander Nanette
Published: November 2023

Current guidelines recommend the use of home blood pressure monitoring (HBPM) to screen for and manage hypertension. In this study, a quality improvement project was designed to standardize the use of HBPM in a primary care setting and demonstrate improved blood pressure outcomes. Initial systolic and diastolic values were compared to averages from patient logs. Patient and provider feedback was collected. Only 40% of patients enrolled presented to follow-up with actionable HBPM data. Patients encountered logistical challenges in obtaining and presenting HBPM data. Interprofessional collaboration and improved information technology systems would improve outcomes. This will require increased policy and insurer support to make this possible in small settings.
Management advice for patients with reflux-like symptoms: an evidence-based consensus
Authors: Hungin A. Pali , Yadlapati Rena , Anastasiou Foteini , Bredenoord Albert J. , El Serag Hashem , Fracasso Pierluigi , Mendive Juan M , Savarino Edoardo V. , Sifrim Daniel , Udrescu Mihaela , Kahrilas Peter J
Published: November 2023

Patients with reflux-like symptoms (heartburn and regurgitation) are often not well advised on implementing individualised strategies to help control their symptoms using dietary changes, lifestyle modifications, behavioural changes or fast-acting rescue therapies. One reason for this may be the lack of emphasis in management guidelines owing to ‘low-quality’ evidence and a paucity of interventional studies. Thus, a panel of 11 gastroenterologists and primary care doctors used the Delphi method to develop consolidated advice for patients based on expert consensus. A steering committee selected topics for literature searches using the PubMed database, and a modified Delphi process including two online meetings and two rounds of voting was conducted to generate consensus statements based on prespecified criteria (67% voting ‘strongly agree’ or ‘agree with minor reservation’). After expert discussion and two rounds of voting, 21 consensus statements were generated, and assigned strength of evidence and Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) rating. Eleven statements achieved the strongest (100%) agreement: five are related to diet and include identification and avoidance of dietary triggers, limiting alcohol, coffee and carbonated beverages, and advising patients troubled by postprandial symptoms not to overeat; the remaining six statements concern advice around smoking cessation, weight loss, raising the head-of-the-bed, avoiding recumbency after meals, stress reduction and alginate use. The aim of developing the consensus statements is that they may serve as a foundation for tools and advice that can routinely help patients with reflux-like symptoms better understand the causes of their symptoms and manage their individual risk factors and triggers.
Clinical Data Do Not Reliably Predict Duodenal Histology at Follow-up in Celiac Disease
Authors: Patel Natalie , Leffler Daniel A. , Al-Toma Abdulbaqi , Mulder Chris J. , Elli Luca , Gan Geliang , Patil Pallavi , Atsawarungruangkit Amporn , Kuijpers Karel C. , Del Gobbo Alessandro , Goldsmith Jeffrey , Hintze Zach , Pacheco M. Cristina , Vieth Michael , Melcher Balint , Salomao Marcela , Pai Rish , Hart John , Olivas Andrea , Naini Bita , Meyerson Cherise , Choi Won-Tak , Kakar Sanjay , Westerhoff Maria , Cheng Jerome , Gopal Purva , Hammer Suntrea , Moreno Prats Mariana , Bronner Mary P. , Robert Marie E.
Published: November 2023

Validated nonbiopsy methods to assure duodenal mucosal healing in celiac disease are lacking, yet ongoing mucosal injury is associated with anemia, osteoporosis, and lymphoma. Most providers utilize clinical data as surrogates of mucosal status to avoid additional esophagogastroduodenoscopy. The reliability of such surrogates to predict mucosal recovery has been incompletely evaluated. The aim of this study was to rigorously assess patterns of histologic mucosal recovery at follow-up in celiac disease and to correlate findings with clinical data. Gastrointestinal pathologists from 13 centers evaluated initial and follow-up duodenal biopsies from 181 celiac disease patients. Marsh scores and intraepithelial lymphocytes (IELs)/100 enterocytes were assessed blindly. Histology at follow-up was correlated with symptoms, immunoglobulin A anti–tissue transglutaminase titers and gluten-free diet adherence. Fifty-six/181 (31%) patients had persistent villous blunting and 46/181 (25%) patients had just persistently elevated IELs at follow-up, with only 79/181 (44%) patients having complete histologic remission. IEL normalization (82/181; 45%) lagged villous recovery (125/181;69%). In a minority of patients, villous blunting was limited to proximal duodenal biopsies. No correlation was found between Marsh scores and symptoms, normalization of immunoglobulin A anti–tissue transglutaminase serology, or diet adherence. Children showed greater recovery of Marsh score (P<0.001) and IELs (P<0.01) than adults. Persistent mucosal injury is common in celiac disease, with discordant villous/IEL normalization. Pathologist awareness of expected findings in celiac disease follow-up biopsies, including their frequent lack of correlation with clinical data, is important for patient management, and has implications for eligibility criteria for therapeutics currently in development.
Preoperative indicators of the effectiveness of surgical release in de Quervain patients: a prospective cohort study
Authors: Bosman Romy , Hundepool C. A. , van der Oest Mark JW , Duraku Liron S. , Souer J. S. , Selles Ruud W. ,   Hand-Wrist Study Group, Zuidam J Michiel
Published: November 2023

Background:

A significant proportion of patients still report pain following a surgical release for de Quervain disease (DQ). This study aimed to investigate the effectiveness of a surgical release for DQ and to identify the preoperative factors associated with pain after a surgical release for DQ.

Methods:

This prospective cohort study includes 707 patients who underwent a surgical release and completed the Visual Analog Scale Questionnaire (VAS, range 0-100). We used a paired t-test to analyse the effectiveness of the surgical release on pain at three months post-operatively compared to the pre-operatively measured outcome. A hierarchical multivariable linear regression model was created to investigate the contribution of the patient- and disease characteristics to post-operative pain.

Results:

All VAS domains showed improvement after surgical release. On average, the mean VAS pain decreased by 44 points (95% CI 42; 46). Smoking (B=6.37; p<0.01), younger age (B=-0.35; p<0.01), longer duration of complaints (B=0.13; p<0.01), concomitant surgery (B=14.40; p<0.01) and higher VAS pain scores at intake (B=0.15; p<0.01) were associated with worse VAS pain scores post-operatively. Together, the variables explained 11% of the variance in mean VAS pain score at three months of follow-up.

Conclusion:

This study confirms that surgical treatment for patients with DQ significantly reduces patient-reported pain. Smoking, younger age, concomitant surgery, duration of complaints, and higher VAS pain scores at intake are associated with worse patient-reported pain three months after surgical release. However, the small effects suggest that these factors should not be considered the only important factors.

Level of Evidence:

Therapeutic, II.
Death by the minute: Inequities in trauma care for victims of firearm violence
Authors: Poulson Michael , Jay Jonathan , Kenzik Kelly , Torres Crisanto , Sanchez Sabrina E. , Saillant Noelle , Holena Daniel , Galea Sandro , Scantling Dane
Published: November 2023

BACKGROUND

Gunshot wounds (GSWs) remain a significant source of mortality in the United States. Timely delivery of trauma care is known to be critical for survival. We sought to understand the relationship of predicted transport time and death after GSW. Given large racial disparities in firearm violence, we also sought to understand disparities in transport times and death by victim race, an unstudied phenomenon.

METHODS

Firearm mortality data were obtained from the Boston Police Department 2005 to 2023. Firearm incidents were mapped using ArcGIS. Predicted transport times for each incident to the closest trauma center were calculated in ArcGIS. Spatial autoregressive models were used to understand the relationship between victim race, transport time to a trauma center, and mortality associated with the shooting incidents.

RESULTS

There were 4,545 shooting victims with 758 deaths. Among those who lived, the median transport time was 9.4 minutes (interquartile range, 5.8–13.8) and 10.5 minutes (interquartile range, 6.4–14.6; p = 0.003) for those who died. In the multivariable logistic regression, increased transport time to the nearest trauma center (odds ratio, 1.024; 95% confidence interval, 1.01–1.04) and age (odds ratio, 1.016; 95% confidence interval, 1.01–1.02) were associated with mortality. There was a modest difference in median transport time to the nearest trauma center by race with non-Hispanic Black at 10.1 minutes, Black Hispanic 9.2 minutes, White Hispanic 8.5 minutes, and non-Hispanic White 8.3 minutes (p < 0.001).

CONCLUSION

Our results highlight the relationship of transport time to a trauma center and death after a GSW. Non-White individuals had significantly longer transport times to a trauma center and predicted mortality would have been lower with White victim transport times. These data underscore the importance of timely trauma care for GSW victims and can be used to direct more equitable trauma systems.

LEVEL OF EVIDENCE

Prognostic/Epidemiological; Level III.
Structural Basis for Mis18 Complex Assembly: Implications for Centromere Maintenance
Authors: Thamkachy Reshma , Medina-Pritchard Bethan , Park Sang Ho , Chiodi Carla G. , Zou Juan , de la Torre-Barranco Maria , Shimanaka Kazuma , Abad Maria Alba , Páramo Cristina Gallego , Feederle Regina , Ruksenaite Emilija , Heun Patrick , Davies Owen R. , Rappsilber Juri , Schneidman-Duhovny Dina , Cho Uhn-Soo , Arockia Jeyaprakash A.
Published: November 2023

The centromere, defined by the enrichment of CENP-A (a Histone H3 variant) containing nucleosomes, is a specialised chromosomal locus that acts as a microtubule attachment site. To preserve centromere identity, CENP-A levels must be maintained through active CENP-A loading during the cell cycle. A central player mediating this process is the Mis18 complex (Mis18α, Mis18ý and Mis18BP1), which recruits the CENP-A specific chaperone HJURP to centromeres for CENP-A deposition. Here, using a multi-pronged approach, we characterise the structure of the Mis18 complex and show that multiple hetero- and homo-oligomeric interfaces facilitate the hetero-octameric Mis18 complex assembly composed of 4 Mis18α, 2 Mis18ý and 2 Mis18BP1. Evaluation of structure-guided/separation-of-function mutants reveals structural determinants essential for Mis18 complex assembly and centromere maintenance. Our results provide new mechanistic insights on centromere maintenance, highlighting that while Mis18α can associate with centromeres and deposit CENP-A independently of Mis18ý, the latter is indispensable for the optimal level of CENP-A loading required for preserving the centromere identity.
MPRAbase: A Massively Parallel Reporter Assay Database
Authors: Zhao Jingjing , Baltoumas Fotis A. , Konnaris Maxwell A. , Mouratidis Ioannis , Liu Zhe , Sims Jasmine , Agarwal Vikram , Pavlopoulos Georgios A. , Georgakopoulos-Soares Ilias , Ahituv Nadav
Published: November 2023

Massively parallel reporter assays (MPRAs) represent a set of high-throughput technologies that measure the functional effects of thousands of sequences/variants on gene regulatory activity. There are several different variations of MPRA technology and they are used for numerous applications, including regulatory element discovery, variant effect measurement, saturation mutagenesis, synthetic regulatory element generation or characterization of evolutionary gene regulatory differences. Despite their many designs and uses, there is no comprehensive database that incorporates the results of these experiments. To address this, we developed MPRAbase, a manually curated database that currently harbors 129 experiments, encompassing 17,718,677 elements tested across 35 cell types and 4 organisms. The MPRAbase web interface (http://www.mprabase.com) serves as a centralized user-friendly repository to download existing MPRA data for independent analysis and is designed with the ability to allow researchers to share their published data for rapid dissemination to the community.
Crosstalk between salicylic acid signaling and the circadian clock promotes an effective immune response
Authors: Fraser Olivia , Cargill Samantha J , Spoel Steven H , van Ooijen Gerben
Published: November 2023

The rotation of Earth creates a cycle of day and night, leading to predictable changes in environmental conditions. The circadian clock synchronizes an organism with these environmental changes and alters their physiology in anticipation. Prediction of the probable timing of pathogen infection enables plants to prime their immune system without wasting resources or sacrificing growth. Here, we explore the relationship between the immune hormone salicylic acid (SA), and the circadian clock in Arabidopsis. We found that SA altered circadian rhythmicity through the SA receptor and master transcriptional coactivator, NPR1. Reciprocally, the circadian clock gates SA-induced expression of NPR1-dependent immune genes. Furthermore, the clock gene CCA1 is essential for SA-induced immunity to the major bacterial plant pathogenPseudomonas syringae. These results reveal new interactions between the circadian clock and SA signaling which produce an effective immune response. Understanding how and why the immune response in plants is linked to the circadian clock is crucial in working towards improved crop productivity.
Genetic adaptation to ammonium sustains wheat grain quality and alleviates acclimation to CO2enrichment
Authors: Kasemsap Pornpipat , Bloom Arnold J.
Published: November 2023

Plants synthesize protein through assimilating inorganic nitrogen. Yet, the extent to which soil nitrogen sources alter crop responses to atmospheric CO2remains uncertain. We assessed wheat (Triticum aestivumL.) biomass under CO2enrichment in genotypes that demonstrated a preference for ammonium (NH4+) or nitrate (NO3−), and contrasting degrees of NH4+tolerance. Nitrogen-form preference, but not NH4+tolerance, correlated with CO responses. Notably, NH4+-preferring genotypes maintained higher biomass and sustained grain nitrogen concentrations, thus avoiding CO2acclimation, the decline in biomass stimulation after prolonged exposure to CO2enrichment. Furthermore, NH4+nutrition accelerated flowering and increased spike biomass. Breeding for NH4+-adapted genotypes may not only improve climate resilience, but also potentially accelerate development and increase yield without any penalty on grain quality. Because wheat provides 20% of the protein and carbohydrate in the human diet, our study provided strategies to sustain food security under the atmospheric conditions anticipated in the future.

Highlight

Breeding for NH4+-adapted genotypes may not only improve climate resilience, but also potentially accelerate development and increase yield without any penalty on grain quality under elevated CO2atmospheres.
Profiling functional networks identify activation of corticostriatal connectivity in ET patient after MRgFUS thalamotomy
Authors: Lin Jiaji , Kang Xiaopeng , Zhou Jiayou , Zhang Dekang , Hu Jianxing , Lu Haoxuan , Pan Longsheng , Lou Xin
Published: November 2023

Objective

MR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. The current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy.

Methods

We retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used to functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms.

Results

MRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week postoperatively. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P= 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P< 0.05), as well as hemisphere lateralization (P< 0.001). The PLS main component significantly accounted for 33.68% and 34.16% of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P= 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day postoperatively (β = 2.94,P= 0.03).

Conclusions

MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.
VTA projections to M1 are essential for reorganization of layer 2-3 network dynamics underlying motor learning
Authors: Ghanayim Amir , Benisty Hadas , Cohen-Rimon Avigail , Schwartz Sivan , Talmon Ronen , Schiller Jackie
Published: November 2023

The primary motor cortex (M1) is crucial for motor skill learning. Previous studies demonstrated that skill acquisition requires dopaminergic VTA (ventral-tegmental area) signaling in M1, however little is known regarding the effect of these inputs at the neuronal and network levels. Using dexterity task, calcium imaging, chemogenetic silencing, and geometric data analysis, we demonstrate VTA-dependent reorganization of M1 layer 2-3 during motor learning. While average activity and average functional connectivity of layer 2-3 network remain stable during learning, the activity kinetics, the correlational configuration of functional connectivity, and average connectivity strength of layer 2-3 neurons gradually transform towards an expert configuration. In addition, task success-failure outcome signaling gradually emerges. Silencing VTA dopaminergic inputs to M1 during learning, prevents all these changes. Our findings demonstrate dopaminergic VTA-dependent formation of outcome signaling and new connectivity configuration of the layer 2-3 network, supporting reorganization of the M1 network for storing new motor skills.
Spatial transcriptomics defines injury-specific microenvironments in the adult mouse kidney and novel cellular interactions in regeneration and disease
Authors: Polonsky Michal , Gerhardt Louisa M. S. , Yun Jina , Koppitch Kari , Colón Katsuya Lex , Amrhein Henry , Zheng Shiwei , Yuan Guo-Cheng , Thomson Matt , Cai Long , McMahon Andrew P.
Published: November 2023

Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, and injury-invoked inflammation and fibrosis. Deciphering molecular pathways and cellular interactions driving these processes is challenging due to the complex renal architecture. Here, we applied single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics revealed injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predictedClcf1-Crfl1in a molecular interplay between persistently injured proximal tubule cells and neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis revealed cellular microenvironments resembling early tertiary lymphoid structures and identified associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.

One-Sentence Summary:Spatial transcriptomics predicted a molecular interplay amongst neighboring cell-types in the injured mammalian kidney

Main Text:
A successional shift enhances stability in ant symbiont communities
Authors: Parmentier Thomas , Bonte Dries , De Laender Frederik
Published: November 2023

Throughout succession, communities undergo structural shifts, which can alter the relative abundances of species and how they interact. It is frequently asserted that these alterations beget stability, i.e. that succession selects for communities better able to resist perturbations. Yet, whether and how alterations of network structure affects stability during succession in complex communities is rarely studied in natural ecosystems. Here, we explore how network attributes influence stability of different successional stages of a natural network: symbiotic arthropod communities forming food webs inside red wood ant nests. We conducted extensive field sampling to compare the composition of the symbiont community across 51 host nests of varying age, representing different succession stages. We recorded abundance of 16 functional groups of symbionts spanning different specialization and trophic levels. Joint species distribution modelling indicated nest age as the driver of the compositional shifts: symbiont communities in old nests contained a greater proportion of specialists and more even species abundance distributions. We then reconstructed community matrices and showed that this enhanced evenness lead to an augmented food web stability of the symbiont communities in older nests. Overall, this study demonstrates that succession begets stability in a natural ecological network by making the community more even.
Testing of various protocols for human skin cryopreservation by vitrification method
Authors: Riabinin Andrei , Pankratova Maria , Rogovaya Olga , Vorotelyak Ekaterina , Vasiliev Andrey
Published: November 2023

Optimization of skin cryopreservation technology is an important task for translational medicine, pharmacology, and a list of other fields. One of the promising approaches is vitrification. This rapid freezing technique allows one to ensure minimal damage to the sample by equating the formation of ice crystals and dehydration both in the cytoplasm of cells and in the extracellular space. This study is aimed at finding the optimal combination of cryoprotective agents (DMSO, glycerol, sucrose and polyethylene glycol) to achieve the highest viability of skin samples after vitrification.
Development of attenuated coxsackievirus B3 vectored intranasal pre-emptive pan-coronavirus vaccine
Authors: Deng Huixiong , He Xuanting , Li Yanlei , Wang Haoyang , Wang Shenmiao , Gu Liming , Zhang Hengyao , Zhu Jiacheng , Li Rui , Wang Gefei
Published: November 2023

SARS-CoV-2 has the ability to evade immunity, resulting in breakthrough infections even after vaccination. Similarly, zoonotic coronaviruses pose a risk of spillover to humans. There is an urgent need to develop a pre-emptive pan-coronavirus vaccine that can induce systemic and mucosal immunity. Here, we employed a combination of immune-informatics approaches to identify shared immunodominant linear B- and T-cell epitopes from SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs), as well as zoonotic coronaviruses. Epitope-guided vaccine were designed and the attenuated coxsackievirus B3 vectored intranasal vaccines rCVB3-EPI and rCVB3-RBD-trimer were constructed. The immunogenicity of these candidate vaccines was evaluated using Balb/c mice. The results demonstrated effective immune responses, including the production of SARS-CoV-2-specific IgG and sIgA antibodies, as well as T cell-mediated responses. However, further verification is required to assess cross-reactivity with various variants. Our intranasal pre-emptive pan-coronavirus vaccine design framework offers an appealing candidate for future vaccine development.
Mechanisms of transcriptional regulation inAnopheles gambiaerevealed by allele specific expression
Authors: Dyer Naomi A. , Lucas Eric R. , Nagi Sanjay C. , McDermott Daniel P. , Brenas Jon H. , Miles Alistair , Clarkson Chris S. , Mawejje Henry D. , Wilding Craig S. , Halfon Marc S. , Asma Hasiba , Heinz Eva , Donnelly Martin J.
Published: November 2023

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both incis, by regulatory sequences on the same chromosome, and bytransacting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations incis-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb resistant and susceptibleAnopheles gambiaestrains to identifycis-regulated genes that might be responsible for the resistant phenotype using RNAseq, andcis-regulatory module sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele specific expression in hybrids of insecticide susceptible and resistant strains, suggestingcisregulation is an important mechanism of gene expression regulation inAnopheles gambiae. The genes showing allele specific expression included a higher proportion ofAnophelesspecific genes on average younger than genes those with balanced allelic expression.

Author Summary

The evolution of insecticide resistance, including resistance that is due to changes in the expression levels of certain resistance associated genes is threatening progress in malaria control. We investigated how the expression of genes in the malaria vectorAnopheles gambiaeis controlled, by implementing a method for the first time in this species. Each mosquito inherits a set of chromosomes from both parents, so has a maternal and paternal copy of most genes. When a gene is expressed, the DNA encoding that gene is transcribed into messenger RNA. This process is controlled by the cellular environment and by other DNA sequences on the same chromosome as each gene. We crossed mosquitoes from insecticide resistant and susceptible strains to equalize the cellular environment and then measured the levels of messenger RNA from both gene copies. 115 genes showed consistently different messenger RNA levels between gene copies in most crosses, suggesting these genes are regulated by factors on the same chromosome. There were relatively more Anopheles specific genes with imbalanced expression. Using machine learning we identified DNA sequences that may be responsible for controlling gene expression in mosquito tissues; several of these sequences were close to genes with imbalanced expression.