bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of laser acupuncture on adhesive small bowel obstruction
Authors: Shih Chun-Han , Hsieh Ting-Min , Wu Bei-Yu , Liu Chun-Ting
Published: March 2021

Background:

Adhesive small bowel obstruction (ASBO) is one of the most common complications and is a major cause of re-admission after intra-abdominal surgery. The initial management of patients with ASBO is nonoperative treatment such as nil per os and decompression using a nasogastric tube. However, the ideal management of ASBO remains controversial.

Methods:

This study will be a prospective, single-center, double-blind randomized controlled trial. Ninety two participants diagnosed with ASBO will be randomly assigned to either the verum or the sham laser acupuncture (SLA) group in a 1:1 ratio. All participants will undergo laser acupuncture (LA) or SLA once a day on 6 acupoints (LI4, PC6, ST25, ST36, CV4 and CV12) for 6 consecutive days after enrollment. The primary outcome measure will be the success rate of conservative treatment for ASBO. Secondary outcomes will be time to oral intake and length of hospital stay. The serum levels of lipase, amylase, cortisol, motilin, ghrelin, and intestinal fatty acid binding protein (I-FABP) will also be measured before intervention, on day 4, and on the day of discharge, respectively. Data will be analyzed by Chi-Squared test or t test between 2 groups.

Objectives:

The aim of this protocol is to investigate the clinical efficacy of LA on ASBO.

Trial registration:

ClinicalTrials.gov Identifier: NCT04318821. Registered on 24 March 2020.
The tongue features associated with chronic kidney disease
Authors: Chen Jia-Ming , Chiu Ping-Fang , Wu Feng-Mei , Hsu Po-Chi , Deng Li-Jyun , Chang Chia-Chu , Chiang John Y. , Lo Lun-Chien
Published: March 2021

Background:

Traditional Chinese medicine (TCM) tongue diagnosis plays an important role in differentiation of symptoms because the tongue reflects the physiological and pathological condition of the body. The automatic tongue diagnosis system (ATDS), which noninvasively captures tongue images, can provide objective and reliable diagnostic information. Chronic kidney disease (CKD) currently is an important global public health problem and contributor to morbidity and mortality from non-communicable diseases. Thus, it is interesting to analyze and probe the relationship between tongue examination and CKD.

Methods:

This protocol is a cross-sectional, case-controlled observational study investigating the usefulness of the ATDS in clinical practice by examining its efficacy as a diagnostic tool for CKD. Volunteers over 20 years old with and without CKD will be enrolled. Tongue images will be captured and the patients divided into 2 groups: CKD group and healthy group. Nine primary tongue features will be extracted and analyzed, including tongue shape, tongue color, tooth mark, tongue fissure, fur color, fur thickness, saliva, ecchymosis, and red dots.

Result:

The results of this study will systematically evaluate tongue manifestations of patients and examine its efficacy as an early detection and diagnosis of CKD.

Discussion:

The aim of this protocol is to investigate discriminating tongue features to distinguish between CKD and normal people, and establish differentiating index to facilitate the noninvasive detection of CKD.

Trial registries:

ClinicalTrials.gov; Identifier: NCT04708743.
Acupuncture and related therapies for poststroke insomnia
Authors: Zhan Chao , Hu Zhao-Duan , Zhao Yan , Fang Xiao-Ming , Cheng Wei , Lu Song , Chen Zhi-Wei
Published: March 2021

Objective:

To compare and evaluate the clinical effects on patients with poststroke insomnia of various acupuncture and acupuncture-related therapies.

Methods:

In order to analyze the direct and indirect evidence from related studies, we used network meta-analysis (NMA). In order to collect randomized controlled trials (RCTs) of acupuncture and related therapies in the treatment of poststroke insomnia, 3 English and 4 Chinese databases were searched. After 2 researchers independently screened the literature, extracted the information, and assessed the probability of bias in the included studies, the data was analyzed using Stata15.0 and WinBUGS1.4.3 software.

Results:

Based on the existing data, the pros and cons of different acupuncture-related therapies are compared extensively, the effectiveness of different acupuncture-related therapies is ranked compared to drugs with hypnotic effect in poststroke insomnia care, and the best methods or combinations of acupuncture intervention are summarized.

Conclusion:

This study will provide new evidence for the safety and effectiveness of acupuncture-related therapies in the treatment of poststroke insomnia, and may be helpful for clinicians, poststroke insomnia patients, and clinical guideline makers to choose the optimal combination of acupuncture for the treatment of poststroke insomnia.

Registration Number:

INPLASY202120028.
Novel treatments for alcoholic hepatitis
Authors: German Margarita N. , Musto Jessica , Lucey Michael R.
Published: March 2021

Purpose of review

The current article aims to review the latest literature on updates in therapeutics for alcohol-associated liver disease (ALD), integration of treatment of alcohol use disorder (AUD) into the management of ALD, and the role of liver transplantation for alcoholic hepatitis.

Recent findings

ALD has recently become the most common indication for liver transplantation due to the increasing prevalence of AUD and the paucity of therapeutic options. There is broad consensus on the importance of early identification of AUD and the incorporation of its treatment in the management of ALD. New targets for treatment of alcoholic hepatitis include the gut–liver axis, anti-inflammatory drugs, antioxidants, and drugs with hepatic regenerative potential. Fecal transplantation in particular has had favorable outcomes at 1 year. n-Acetylcysteine in addition to corticosteroids, granulocyte colony stimulating factor, and IL-22 have also shown improved short-term outcomes. A number of other therapies are being studied in clinical trials and their results are anxiously awaited.

In summary, there are several promising therapeutic options under clinical investigation for the treatment of alcoholic hepatitis and ALD; however, alcohol abstinence is key. In the absence of other effective therapies, liver transplantation for ALD remains a life-saving treatment with excellent patient and graft survival.
Intricacies of conditional genetics in vascular biology
Authors: Garcia-Gonzalez Irene , Benedito Rui
Published: March 2021

Purpose of review

Conditional or inducible recombinase-based genetics is still the gold standard to analyse gene function, given its high specificity, temporal control, limited toxicity and the many available genetic tools. However, it is based on methods that have inherent limitations and shortcomings. The purpose of this review is to summarize and contrast the different available methods used to perform conditional gene function analysis to better inform the community about their particularities and the need to use better methods.

Recent findings

As any other biomedical field, the vascular biology field has moved from using and analysing standard gene knockout (KO) mice, to use conditional genetics to delete a given gene only at a given time point, cell-type or organ of interest. This is the only way to accurately understand a gene function and avoid other confounding factors. Therefore, nowadays the majority of laboratories working with mice use CreERT2-tamoxifen-inducible genetics. However, this necessary transition from the relatively simple KO genetics to the more sophisticated conditional genetics brought a series of additional methodological issues that are often overlooked or unappreciated. Recent findings from several laboratories have shown how important is to know what to expect from and control for in conditional genetics. Without this a priori knowledge, the quality, robustness, time and costs of conditional genetic experiments can be significantly compromised.

We start this review by discussing the intricacies of the most simple and widely used methods to perform conditional genetics and then extend on the need of novel and more advanced methods to increase the ease, efficiency and reliability of conditional mutagenesis and gene function analysis.
Virtual Communication Embedded Bedside ICU Rounds: A Hybrid Rounds Practice Adapted to the Coronavirus Pandemic
Authors: Bavare Aarti C. , Goldman Jordana R. , Musick Matthew A. , Sembera Kerry A. , Sardual Alex A. , Lam Anne K. , Tume Sebastian C. , Thammasitboon Satid X. , Williams Eric A.
Published: March 2021

OBJECTIVES:

Coronavirus disease 2019 containment strategies created challenges with patient-centered ICU rounds. We examined how hybrid rounds with virtual communication added to in-person rounds could facilitate social distancing while maintaining patient-centered care.

DESIGN:

Continuous quality improvement.

SETTING:

Quaternary care referral pediatric hospital.

PATIENTS:

Daytime rounds conducted on PICU patients.

INTERVENTIONS:

Following a needs assessment survey and pilot trials, multiple technological solutions were implemented in a series of plan-do-study-act cycles. Hybrid rounds model was deployed where a videoconference platform was used to establish communication between the bedside personnel (nurse, patient/family, and partial ICU team) with remotely located remaining ICU team, ancillary, and consultant providers. Floor labels marking 6-feet distance were placed for rounders.

MEASUREMENTS AND MAIN RESULTS:

Outcome metrics included compliance with social distancing, mixed methods analysis of surveys, direct interviews of providers and families, and reports of safety concerns. The clinicians adopted hybrid rounds readily. Compliance with social distancing and use of floor labels needed reminders. One-hundred fourteen providers completed the feedback survey. Twenty-five providers and 11 families were interviewed. Feedback about hybrid rounds included inability to teach effectively, suboptimal audio-video quality, loss of situational awareness of patient/unit acuity, alarm interference, and inability to socially distance during other ICU interactions. Benefits noted were improved ancillary input, fewer interruptions, improved efficiency, opportunity to integrate with data platforms, and engage remote consultants and families. Nurses and families appreciated the efforts to ensure safety but wanted the ICU attending/fellow supervising the team to participate at bedside, during rounds. Clinicians appreciated the multidisciplinary input but felt that teaching was difficult.

CONCLUSIONS:

Hybrid rounds employed during pandemic facilitated social distancing while retaining patient-centered multidisciplinary ICU rounds but compromised teaching during rounds. A change to ingrained rounding habits needs team commitment and ongoing optimization. The hybrid rounds model has potential for generalizability to other settings.
Impact of Modified Cardiac Rehabilitation Within a Stroke Recovery Program on All-Cause Hospital Readmissions
Authors: Cuccurullo Sara J. , Fleming Talya K. , Kostis John B. , Greiss Christine , Eckert Anne , Ray Arlen Razon , Scarpati Rosann , Zinonos Stavros , Gizzi Martin , Cosgrove Nora M. , Cabrera Javier , Oh-Park Mooyeon , Kostis William J.
Published: March 2021

Objective

A Stroke Recovery Program (SRP) including cardiac rehabilitation demonstrated lower all-cause mortality rates, improved cardiovascular function, and overall functional ability among stroke survivors. Neither an effect of SRP on acute care hospital readmission rates nor cost savings have been reported.

Design

This prospective matched cohort study included 193 acute stroke survivors admitted to an inpatient rehabilitation facility between 2015 and 2017. The 105 SRP participants and 88 nonparticipants were matched exactly for stroke type, sex, and race and approximately for age, baseline functional scores, and medical complexity scores. Primary outcome measured acute care hospital readmission rate up to 1 yr post-stroke. Secondary outcomes measured costs.

Results

A 22% absolute reduction (P = 0.006) in hospital readmissions was observed between the SRP participant (n = 47, or 45%) and nonparticipant (n = 59, or 67%) groups. This resulted in significant cost savings. The conventional care cost to the Center for Medicare and Medicaid Services for stroke patients for both readmissions and outpatient therapy is estimated at $9.67 billion annually. The yearly cost for these services with utilization of the SRP is $8.55 billion.

Conclusion

Acute care hospital readmissions were reduced in stroke survivors who participated in SRP. Future study is warranted to examine whether widespread application of a similar program may improve quality of life and decrease cost.
Out of the Laboratory and Into the Field: Validation of Portable Cell Culture Protocols
Authors: McDade Thomas W. , Aronoff Jacob E. , Leigh Adam K. K. , Finegood Eric D. , Weissman-Tsukamoto Rachel M. , Brody Gene H. , Miller Gregory E.
Published: March 2021

Objective

Field-based research on inflammation and health is typically limited to baseline measures of circulating cytokines or acute-phase proteins, whereas laboratory-based studies can pursue a more dynamic approach with ex vivo cell culture methods. The laboratory infrastructure required for culturing leukocytes limits application in community-based settings, which in turn limits scientific understandings of how psychosocial, behavioral, and contextual factors influence the regulation of inflammation. We aim to address this gap by validating two “field-friendly” cell culture protocols, one using a small volume of venous whole blood and another using finger-stick capillary whole blood.

Methods

We evaluated the performance of both protocols against a standard laboratory-based protocol using matched venous and capillary blood samples collected from young adults (n = 24). Samples were incubated with lipopolysaccharide and hydrocortisone, and the production of proinflammatory cytokines interleukin 1β, interleukin 6, and tumor necrosis factor α was measured in response.

Results

Comparisons indicate a high level of agreement in responses across the protocols and culture conditions. The overall correlation in results was 0.88 between the standard and small-volume protocols and 0.86 between the standard and capillary blood protocols. Repeatability for the small-volume and capillary blood protocols was high, with mean coefficients of variation across five replicates of 6.2% and 5.4%, respectively.

Conclusions

These results demonstrate the feasibility of culturing cells and quantifying the inflammatory response to challenge outside the laboratory, with a wide range of potential applications in biobehavioral research in community-based and remote field settings.
Qualitative and Quantitative Analysis of a Spiral Gradient Echo Sequence for Contrast-Enhanced Fat-Suppressed T1-Weighted Spine Magnetic Resonance Imaging
Authors: Sartoretti Elisabeth , Sartoretti Thomas , van Smoorenburg Luuk , Sartoretti-Schefer Sabine , Wyss Michael , Binkert Christoph A.
Published: March 2021

Objectives

Pulse sequences with non-Cartesian k-space sampling enable improved imaging in anatomical areas with high degrees of motion artifacts. We analyzed a novel spiral 3-dimensional (3D) gradient echo (GRE) magnetic resonance imaging (MRI) sequence (“spiral,” 114.7 ± 11 seconds) and compared it with a radial 3D GRE (“vane,” 216.7 ± 2 seconds) and a conventional Cartesian 2D turbo spin echo (TSE) sequence (“TSE,” 266.7 ± 82 seconds) for contrast-enhanced fat-suppressed T1-weighted spine imaging.

Materials and Methods

Forty consecutive patients referred for contrast-enhanced MRI were prospectively scanned with all 3 sequences. A qualitative analysis was performed by 3 readers using 4- or 5-point Likert scales to independently grade images in terms of overall image quality, occurrence of artifacts, lesion conspicuity, and conspicuity of nerve roots. The numbers of visible nerve roots per sequence and patient were counted in consensus. Coefficient of variation measurements were performed for the paravertebral musculature (CVPM
) and the spinal cord (CVSC
).

Results

Spiral (median [interquartile range], 5 [4–5]) exhibited improved overall image quality in comparison to TSE (3 [3–4]) and vane (4 [4–5]; both P < 0.001). Vane surpassed TSE in terms of overall image quality (P < 0.001). Spiral (4 [3.75–4]) and vane (3.5 [3–4]) presented with less artifacts than TSE (3 [2.75–3.25]; both P < 0.001). Spiral (4 [4–5]) outperformed vane (4 [3–5]; P = 0.01) and TSE (4 [3–4]; P = 0.04) in terms of lesion conspicuity. Conspicuity of nerve roots was superior on spiral (3 [3–4]) and vane (4 [3–4]) when compared with TSE (1.5 [1–2]; both P < 0.001). Readers discerned significantly more nerve roots on spiral (4 [2.75–8]) and vane (4 [3.75–7.25]) images when compared with TSE (2 [0–4]; both P < 0.001). Interreader agreement ranged from moderate (α = 0.639) to almost perfect (α = 0.967). CVPM
and CVSC
were significantly lower on spiral as compared with vane and TSE (P < 0.001, P = 0.04). Vane exhibited lower CVPM
and CVSC
than TSE (P < 0.001, P = 0.01).

Conclusions

A novel spiral 3D GRE sequence improves contrast-enhanced fat-suppressed T1-weighted spinal imaging qualitatively and quantitatively in comparison with a conventional Cartesian 2D TSE sequence and to a lesser extent with a radial 3D GRE sequence at shorter scan times.
Keystone Flaps for Coverage of Defects in the Posterior Neck and Lower Occipital Scalp: A Retrospective Clinical Study
Authors: Kong Yu Taek , Kim Junekyu , Shin Hyun Woo , Kim Kyu Nam
Published: March 2021

The coverage of the posterior neck and lower occipital scalp defects should be approached carefully. Thick, stiff, and inelastic skin properties of these areas tend to make coverage of even small defects difficult. Herein, the authors present a retrospective review of our experience with posterior neck and lower occipital scalp reconstruction using the keystone flap (KF) and describe the expanding versatility of KF reconstruction. The medical records of 17 patients who underwent KF reconstruction to cover the posterior neck and lower occipital defect from April 2017 to May 2020 were reviewed. Clinical and operative data were collected. All defects were successfully covered with the KFs. The defect sizes ranged from 2.5 × 3.5 cm to 6 × 11 cm, and the flap sizes ranged from 3 × 5.5 cm to 9 × 18 cm. All flaps fully survived, although marginal maceration developed in one case; however, it healed with conservative management. The final results were favorable, and all patients were satisfied with their final outcomes. Consequently, the KF can be considered as a good reconstruction modality with few complications and provides an alternative to other reconstructive options for coverage of the posterior neck and lower occipital defects.
Heads Up Play: Acute Assessment and Management of Basketball-Related Craniofacial Injuries by On-Court Personnel
Authors: Slavin Benjamin R. , Pierrot Randall G. , Sprau Annelise C. , Wolfe Erin M. , Mathew Prakash J. , Chopra Karan , Thaller Seth R.
Published: March 2021

Introduction:

With a following of over 825 million people, basketball currently ranks amongst the world's most popular sports. Despite a number of concussion awareness and player safety protocols that have been implemented at the professional level of organized play, a standardized, layperson-friendly algorithm for the acute management of basketball-related craniofacial injuries does not appear to presently exist.

Methods:

This 10-year retrospective cohort study was conducted using the National Electronic Injury Surveillance System database to examine basketball-related craniofacial injuries from 2010 to 2019. Within the National Electronic Injury Surveillance System dataset, factors including patient age, gender, diagnosis, injury type, and injury location were included in our analysis.

Results:

Overall, 22,529 basketball-related craniofacial injuries occurred between 2010 and 2019 in players ages 5 to 49 years old. Adolescent (12–18-year-old) and young adult (19–34-year-old) age groups had the highest incidence of craniofacial injuries. The adolescent cohort experienced a significantly greater proportion of concussions and lower proportion of both facial lacerations and fractures compared with the within group null hypothesis of equal proportions (P < 0.05). The young adult cohort experienced a significantly greater proportion of facial lacerations and fractures and lower proportion of concussions, contusions/abrasions, hematomas, and internal injuries compared to this cohort's null hypothesis (P < 0.05). Males experienced a significantly greater proportion of fractures, lacerations, and dental injuries and lower proportion of concussions, contusions/abrasions, and internal injuries compared to the hypothesized equality of proportions (P < 0.05). Females experienced a significantly greater proportion of concussions, contusions/abrasions, and internal injuries and lower proportion of fractures, lacerations, and dental injuries compared to the hypothesized equality of proportions (P < 0.05).

Conclusions:

Although several steps have already been taken at the professional level to try to promote player safety, particularly with concussion protocols and prevention of lower extremity injuries, there remains a paucity of resources to guide management of other types of acute craniofacial injury. The role of layperson-friendly educational interventions remains intriguing as a potential means of improving outcomes regardless of socioeconomic status or health literacy. Additional studies still need to be completed to determine efficacy and best future direction.
Outcomes of Graves’ Disease Patients Following Antithyroid Drugs, Radioactive Iodine, or Thyroidectomy as the First-line Treatment
Authors: Liu Xiaodong , Wong Carlos K. H. , Chan Wendy W. L. , Tang Eric H. M. , Woo Yu Cho , Lam Cindy L. K. , Lang Brian H. H.
Published: March 2021

Background:

The long-term outcomes of first-line choice among ATD, RAI, and thyroidectomy for GD patients remain unclear.

Objective:

To compare the long-term morbidity, mortality, relapse, and costs of GD patients receiving first-line treatment.

Methods:

A population-based retrospective cohort of GD patients initiating first-line treatment with ATD, RAI, or thyroidectomy as a first-line primary treatment between 2006 and 2018 from Hong Kong Hospital Authority was analyzed. Risks of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension were estimated using Cox proportional hazards regression models. The 10-year healthcare costs, change of comorbidities, and risk of relapse were compared across treatments.

Results:

Over a median follow-up of 90 months with 47,470 person-years, 6385 patients (ATD, 74.93%; RAI, 19.95%; thyroidectomy, 5.12%) who received first-line treatment for GD were analyzed. Compared with ATD group, patients who had undergone surgery had significantly lower risks of all-cause mortality [hazard ratio (HR) = 0.363, 95% confidence interval (CI) = 0.332–0.396], CVD (HR = 0.216, 95% CI = 0.195–0.239), AF (HR = 0.103, 95% CI = 0.085–0.124), psychological disease (HR = 0.279, 95% CI = 0.258–0.301), diabetes (HR = 0.341, 95% CI = 0.305–0.381), and hypertension (HR = 0.673, 95% CI = 0.632–0.718). Meanwhile, RAI group was also associated with decreased risks of all-cause mortality (HR = 0.931, 95% CI = 0.882–0.982), CVD (HR = 0.784, 95% CI = 0.742–0.828), AF (HR = 0.622, 95% CI = 0.578–0.67), and psychological disease (HR = 0.895, 95% CI = 0.855–0.937). The relapse rate was 2.41% in surgery, 75.60% in ATD, and 19.53% in RAI group. The surgery group was observed with a significant lower Charlson Comorbidity Index score than the other 2 groups at the tenth-year follow-up. The mean 10-year cumulative healthcare costs in ATD, RAI, and surgery group was US$23915, US$24260, and US$20202, respectively.

Conclusions:

GD patients who received surgery as an initial treatment appeared to have lower chances of all-cause mortality, CVD, AF, psychological disease, diabetes, and hypertension in the long-term when compared to those treated with ATD or RAI. The surgery group had the lowest relapse and direct healthcare costs among the 3 treatment modalities. This long-term cohort study suggested surgery may have a larger role to play as an initial treatment for GD patients.
Antifungal Prophylaxis After Lung Transplantation: Where Are We Now?
Authors: De Mol Wim , Bos Saskia , Beeckmans Hanne , Lagrou Katrien , Spriet Isabel , Verleden Geert M. , Vos Robin
Published: March 2021

Background.

Lung transplantation is an important treatment option for various end-stage lung diseases. However, survival remains limited due to graft rejection and infections. Despite that fungal infections are frequent and carry a bad prognosis, there is currently no consensus on efficacy, optimal drug, route, or duration of antifungal prophylaxis. This narrative review summarizes current strategies for antifungal prophylaxis after lung transplantation.

Methods.

English language articles in Embase, Pubmed, UptoDate, and bibliographies were used to assess the efficacy and safety of available antifungal agents for prophylaxis in adult lung transplant recipients.

Results.

Overall, there are limited high-quality data. Universal prophylaxis is more widely used and may be preferable over targeted prophylaxis. Both formulations of inhaled amphotericin B and systemic azoles are effective at reducing fungal infection rates, yet with their own specific advantages and disadvantages. The benefit of combination regimens has yet to be proven. Considering the post-transplant timing of the onset of fungal infections, postoperative prophylaxis during the first postoperative months seems indicated for most patients.

Conclusions.

Based on existing literature, universal antifungal prophylaxis with inhaled amphotericin B and systemic voriconazole for at least 3–6 mo after lung transplantation may be advisable, with a slight preference for amphotericin B because of its better safety profile.
Survival Benefit of Donation After Circulatory Death Kidney Transplantation in Children Compared With Remaining on the Waiting List for a Kidney Donated After Brain Death
Authors: Kizilbash Sarah J. , Evans Michael D. , Chavers Blanche M.
Published: March 2021

Background.

Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking.

Methods.

We used Scientific Registry of Transplant Recipients to identify 285 pediatric (<18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival.

Results.

DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P < 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03).

Conclusions.

Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.
CXCL12 promotes spinal nerve regeneration and functional recovery after spinal cord injury
Authors: Li Jingyuan , Wu Yanqiong , Chen Ping , Huang Xiaoxia , Liu Yongli , Peng Minjing , Wu Rong-Qian
Published: March 2021

Spinal cord injury (SCI) leads to permanent loss of motor and sensory function due to the complex mechanisms of the external microenvironment and internal neurobiochemistry that restrict neuronal plasticity and axonal regeneration. Chemokine CXCL12 was verified in regulating the development of central nervous system (CNS) and repairing of CNS disease. In the present study, CXCL12 was downregulated in the spinal cord after SCI. SCI also induced gliosis and loss of synapse. Intrathecal treatment of CXCL12 promoted the functional recovery of SCI by inducing the formation of neuronal connections and suppressing glia scar. To confirm whether CXCL12 promoted synapse formation and functional neuronal connections, the primary cortical neurons were treated with CXCL12 peptide, the synapse was examined using Immunofluorescence staining and the function of synapse was tested using a whole-cell patch clamp. The results indicated that CXCL12 peptide promoted axonal elongation, branche formation, dendrite generation and synaptogenesis. The electrophysiological results showed that CXCL12 peptide increased functional connections among neurons. Taken together, the present study illustrated an underlying mechanism of the development of SCI and indicated a potential approach to facilitate functional recovery of spinal cord after SCI.
Passive skeletal muscle can function as an osmotic engine
Authors: Wold Ethan S. , Sleboda David A. , Roberts Thomas J.
Published: March 2021

Muscles are composite structures. The protein filaments responsible for force production are bundled within fluid-filled cells, and these cells are wrapped in ordered sleeves of fibrous collagen. Recent models suggest that the mechanical interaction between the intracellular fluid and extracellular collagen is essential to force production in passive skeletal muscle, allowing the material stiffness of extracellular collagen to contribute to passive muscle force at physiologically relevant muscle lengths. Such models lead to the prediction, tested here, that expansion of the fluid compartment within muscles should drive forceful muscle shortening, resulting in the production of mechanical work unassociated with contractile activity. We tested this prediction by experimentally increasing the fluid volumes of isolated bullfrog semimembranosus muscles via osmotically hypotonic bathing solutions. Over time, passive muscles bathed in hypotonic solution widened by 16.44 ± 3.66% (mean ± s.d.) as they took on fluid. Concurrently, muscles shortened by 2.13 ± 0.75% along their line of action, displacing a force-regulated servomotor and doing measurable mechanical work. This behaviour contradicts the expectation for an isotropic biological tissue that would lengthen when internally pressurized, suggesting a functional mechanism analogous to that of engineered pneumatic actuators and highlighting the significance of three-dimensional force transmission in skeletal muscle.
Hide-and-seek strategies and post-contact immobility
Authors: Franks Nigel R. , Worley Alan , Sendova-Franks Ana B.
Published: March 2021

To understand why an animal might gain by playing dead, or more precisely, exhibit post-contact immobility (PCI), we consider the context in which this behaviour occurs. Is it, for example, a method by which a potential victim encourages a predator to direct its attention elsewhere? We investigate this possibility by using the marginal value theorem to analyse predator behaviour in the context of this defence strategy by potential prey. We consider two models. In the first, (random revisiting) the predator may return to sites it has already depleted within the patch. In the second, (systematic search) the predator goes only to new sites within the patch. The results of the two models are qualitatively extremely similar. We show that when prey occur in patches, PCI favours prey survival. Indeed, certain antlion larvae have PCI durations characterized by very long half-lives. These appear to be of such long durations that further increases would convey no substantial benefits in redirecting potential predators to other antlions within the patch and subsequently to other patches.
Causes of delayed outbreak responses and their impacts on epidemic spread
Authors: Tao Yun , Probert William J. M. , Shea Katriona , Runge Michael C. , Lafferty Kevin , Tildesley Michael , Ferrari Matthew
Published: March 2021

Livestock diseases have devastating consequences economically, socially and politically across the globe. In certain systems, pathogens remain viable after host death, which enables residual transmissions from infected carcasses. Rapid culling and carcass disposal are well-established strategies for stamping out an outbreak and limiting its impact; however, wait-times for these procedures, i.e. response delays, are typically farm-specific and time-varying due to logistical constraints. Failing to incorporate variable response delays in epidemiological models may understate outbreak projections and mislead management decisions. We revisited the 2001 foot-and-mouth epidemic in the United Kingdom and sought to understand how misrepresented response delays can influence model predictions. Survival analysis identified farm size and control demand as key factors that impeded timely culling and disposal activities on individual farms. Using these factors in the context of an existing policy to predict local variation in response times significantly affected predictions at the national scale. Models that assumed fixed, timely responses grossly underestimated epidemic severity and its long-term consequences. As a result, this study demonstrates how general inclusion of response dynamics and recognition of partial controllability of interventions can help inform management priorities during epidemics of livestock diseases.
Cornish science, mine experiments and Robert Were Fox's Penjerrick letters
Authors: Gillin Edward J.
Published: March 2021

In 2019 a collection of letters from the nineteenth-century natural philosopher Robert Were Fox was discovered in his home at Penjerrick in Cornwall. Fox came to the attention of scientific audiences for experimentally establishing that temperature increases with depth beneath the Earth's surface, and later secured fame for his magnetic dipping needle, developed to measure terrestrial magnetic phenomena. The newly uncovered Penjerrick letters constitute a valuable archival discovery with important historical ramifications for our understanding of Fox's work and its place within nineteenth-century science. As well as highlighting the central role of networking in promoting provincial science, the letters reveal the prominence of the Cornish mine as a site of experiment within British scientific culture. These venues presented Fox with unique spaces in which to scrutinize nature, but such philosophical investigations were unverifiable within a laboratory and appeared susceptible to inaccuracies arising from the working conditions of this uncontrollable environment. Nevertheless, the Cornish mine was crucial to the development of Fox's dipping needle, which became the premier device for making magnetic observations at sea in the 1840s. In this article, I demonstrate the epistemologically problematic nature of the mine as an experimental space that was to take on a central role in the worldwide magnetic survey that historians have described as the ‘Magnetic Crusade’.
Quantifying the risk of vector-borne disease transmission attributable to genetically modified vectors
Authors: Hosack Geoffrey R. , Ickowicz Adrien , Hayes Keith R.
Published: March 2021

The relative risk of disease transmission caused by the potential release of transgenic vectors, such as through sterile insect technique or gene drive systems, is assessed with comparison with wild-type vectors. The probabilistic risk framework is demonstrated with an assessment of the relative risk of lymphatic filariasis, malaria and o'nyong'nyong arbovirus transmission by mosquito vectors to human hosts given a released transgenic strain of
Anopheles coluzzii
carrying a dominant sterile male gene construct. Harm is quantified by a logarithmic loss function that depends on the causal risk ratio, which is a quotient of basic reproduction numbers derived from mathematical models of disease transmission. The basic reproduction numbers are predicted to depend on the number of generations in an insectary colony and the number of backcrosses between the transgenic and wild-type lineages. Analogous causal risk ratios for short-term exposure to a single cohort release are also derived. These causal risk ratios were parametrized by probabilistic elicitations, and updated with experimental data for adult vector mortality. For the wild-type, high numbers of insectary generations were predicted to reduce the number of infectious human cases compared with uncolonized wild-type. Transgenic strains were predicted to produce fewer infectious cases compared with the uncolonized wild-type.
Perspective on musculoskeletal modelling and predictive simulations of human movement to assess the neuromechanics of gait
Authors: De Groote Friedl , Falisse Antoine
Published: March 2021

Locomotion results from complex interactions between the central nervous system and the musculoskeletal system with its many degrees of freedom and muscles. Gaining insight into how the properties of each subsystem shape human gait is challenging as experimental methods to manipulate and assess isolated subsystems are limited. Simulations that predict movement patterns based on a mathematical model of the neuro-musculoskeletal system without relying on experimental data can reveal principles of locomotion by elucidating cause–effect relationships. New computational approaches have enabled the use of such predictive simulations with complex neuro-musculoskeletal models. Here, we review recent advances in predictive simulations of human movement and how those simulations have been used to deepen our knowledge about the neuromechanics of gait. In addition, we give a perspective on challenges towards using predictive simulations to gain new fundamental insight into motor control of gait, and to help design personalized treatments in patients with neurological disorders and assistive devices that improve gait performance. Such applications will require more detailed neuro-musculoskeletal models and simulation approaches that take uncertainty into account, tools to efficiently personalize those models, and validation studies to demonstrate the ability of simulations to predict gait in novel circumstances.
The effects of climate change on floral anthocyanin polymorphisms
Authors: Sullivan Cierra N. , Koski Matthew H.
Published: March 2021

Pigmentation affords resistance to abiotic stressors, and thus can respond adaptively or plastically to drought and extreme temperatures associated with global change. Plants frequently display variability in flower coloration that is underlain by anthocyanin pigmentation. While anthocyanin polymorphisms impact plant–animal interactions, they also impact reproductive performance under abiotic stress. We used descriptions of flower colour from over 1900 herbarium records representing 12 North American species spanning 124 years to test whether anthocyanin-based flower colour has responded to global change. Based on demonstrated abiotic associations with performance of anthocyanin colour morphs, we predicted pigmentation would increase in species experiencing increased aridity, but decline in those experiencing larger increases in temperature. We found that the frequency of reports of pigmented morphs increased temporally in some taxa but displayed subtle declines in others. Pigmentation was negatively associated with temperature and positively associated with vapour pressure deficit (a metric of aridity) across taxa. Species experiencing larger temperature increases over time displayed reductions in pigmentation, while those experiencing increases in aridity displayed increases in pigmentation. Change in anthocyanin-based floral colour was thus linked with climatic change. Altered flower coloration has the strong potential to impact plant–animal interactions and overall plant reproductive performance.
Motivating data contributions via a distinct career currency
Authors: Westoby Mark , Falster Daniel S. , Schrader Julian
Published: March 2021

If collecting research data is perceived as poorly rewarded compared to data synthesis and analysis, this can slow overall research progress via two effects. People who have already collected data may be slow to make it openly accessible. Also, researchers may reallocate effort from collecting fresh data to synthesizing and analysing data already accessible. Here, we advocate for a second career currency in the form of data contributions statements embedded within applications for jobs, promotions and research grants. This workable step forward would provide for peer opinion to operate across thousands of selection and promotion committees and granting panels. In this way, fair valuation of data contributions relative to publications could emerge.
Nutrient conditions are primary drivers of bacterial capsule maintenance in
Klebsiella
Authors: Buffet Amandine , Rocha Eduardo P. C. , Rendueles Olaya
Published: March 2021

The fitness cost associated with the production of bacterial capsules is considered to be offset by the protection provided by these extracellular structures against biotic aggressions or abiotic stress. However, it is unknown if the capsule contributes to fitness in the absence of these. Here, we explored conditions favouring the maintenance of the capsule in
Klebsiella pneumoniae,
where the capsule is known to be a major virulence factor. Using short-term experimental evolution on different
Klebsiella
strains, we showed that small environmental variations have a strong impact on the maintenance of the capsule. Capsule inactivation is frequent in nutrient-rich, but scarce in nutrient-poor media. Competitions between wild-type and capsule mutants in nine different strains confirmed that the capsule is costly in nutrient-rich media. Surprisingly, these results also showed that the presence of a capsule provides a clear fitness advantage in nutrient-poor conditions by increasing both growth rates and population yields. The comparative analyses of the wild-type and capsule mutants reveal complex interactions between the environment, genetic background and serotype even in relation to traits known to be relevant during pathogenesis. In conclusion, our data suggest there are novel roles for bacterial capsules yet to be discovered and further supports the notion that the capsule's role in virulence may be a by-product of its contribution to bacterial adaptation outside the host.
Covariation in population trends and demography reveals targets for conservation action
Authors: Morrison Catriona A. , Butler Simon J. , Robinson Robert A. , Clark Jacquie A. , Arizaga Juan , Aunins Ainars , Baltà Oriol , Cepák Jaroslav , Chodkiewicz Tomasz , Escandell Virginia , Foppen Ruud P. B. , Gregory Richard D. , Husby Magne , Jiguet Frédéric , Kålås John Atle , Lehikoinen Aleksi , Lindström Åke , Moshøj Charlotte M. , Nagy Károly , Nebot Arantza Leal , Piha Markus , Reif Jiří , Sattler Thomas , Škorpilová Jana , Szép Tibor , Teufelbauer Norbert , Thorup Kasper , van Turnhout Chris , Wenninger Thomas , Gill Jennifer A.
Published: March 2021

Wildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified. Targeted actions to improve conditions on poor-quality sites could be an effective approach, but only if local conditions consistently influence local demography and hence population trends. Using long-term measures of abundance and demography of breeding birds at survey sites across Europe, we show that co-occurring species with differing migration behaviours have similar directions of local population trends and magnitudes of productivity, but not survival rates. Targeted actions to boost local productivity within Europe, alongside large-scale (non-targeted) environmental protection across non-breeding ranges, could therefore help address the urgent need to halt migrant landbird declines. Such demographic routes to recovery are likely to be increasingly needed to address global wildlife declines.
Influence of water content on mechanical behaviour of gastropod taenioglossan radulae
Authors: Krings Wencke , Kovalev Alexander , Gorb Stanislav N.
Published: March 2021

One molluscan autapomorphy is the radula, the organ used for feeding. Here, for the first time, the performance and failure of taenioglossan radular teeth were tested in a biomechanical experiment which in turn allowed building hypotheses about tooth functionalities. Shear load was applied to tooth cusps with a force transducer until structural failure occurred, the broken area was measured, and finally breaking stress was calculated. These experiments were carried out under dry and wet conditions. Our results show that certain tooth types can resist higher stresses and are rather specialised to loosen food items from a surface, whereas other teeth can only gather food particles. The experiments additionally illustrate the high influence of the water content on the resulting breaking stress. When wet teeth were tested, their ductility and ability to avoid being fractured by an obstacle increased. Their flexibility also allowed them support from teeth of adjacent tooth rows, which made the whole system less prone to failure. Our results were compared with the previous data on the mechanical properties and feeding simulations. This study provides a keystone for further comparative studies aiming at connecting diversity of radulae with their possible adaptations to the ingesta.
Identification and phylogenetic analysis of RNA binding domain abundant in apicomplexans or RAP proteins
Authors: Hollin Thomas , Jaroszewski Lukasz , Stajich Jason E. , Godzik Adam , Le Roch Karine G.
Published: March 2021

The RNA binding domain abundant in apicomplexans (RAP) is a protein domain identified in a diverse group of proteins, called RAP proteins, many of which have been shown to be involved in RNA binding. To understand the expansion and potential function of the RAP proteins, we conducted a hidden Markov model based screen among the proteomes of 54 eukaryotes, 17 bacteria and 12 archaea. We demonstrated that the domain is present in closely and distantly related organisms with particular expansions in Alveolata and Chlorophyta, and are not unique to Apicomplexa as previously believed. All RAP proteins identified can be decomposed into two parts. In the N-terminal region, the presence of variable helical repeats seems to participate in the specific targeting of diverse RNAs, while the RAP domain is mostly identified in the C-terminal region and is highly conserved across the different phylogenetic groups studied. Several conserved residues defining the signature motif could be crucial to ensure the function(s) of the RAP proteins. Modelling of RAP domains in apicomplexan parasites confirmed an ⍺/β structure of a restriction endonuclease-like fold. The phylogenetic trees generated from multiple alignment of RAP domains and full-length proteins from various distantly related eukaryotes indicated a complex evolutionary history of this family. We further discuss these results to assess the potential function of this protein family in apicomplexan parasites.