bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of Infected Galactocele and Breast Implant with Uninterrupted Breastfeeding
Authors: Kornfeld Hannah , Johnson Arianne , Soares Marc , Mitchell Katrina
Published: November 2021

Infected breast implants during lactation present a rare but challenging clinical scenario that may result in early cessation of breastfeeding and unnecessary morbidity to mother and infant. We present the case of a 39-year-old African American primigravid woman with a history of bilateral retropectoral textured implants placed three years prior. Five days after delivering a healthy, full-term infant via cesarean section, she sought evaluation for nipple pain and trauma. She was instructed to use a nipple shield and pump every 2–3 hours in addition to breastfeeding, which resulted in iatrogenic hyperlactation. One week postpartum, the patient was started on antibiotics for presumed mastitis. Ultrasound demonstrated a complex fluid collection at the 12 o’clock periareolar position, as well as peri-implant fluid. She subsequently underwent aspirations of a periareolar complex galactocele and aspirations of peri-implant fluid. She continued on antibiotics without improvement. The patient proceeded to implant removal and definitive drainage of the galactocele at four months postpartum. Throughout her course, the patient provided her infant with exclusive breastmilk, including breastfeeding in the perioperative area of the operating room. This case demonstrates an example of safe surgical removal of infected breast implants and management of an infected galactocele without interruption of breastfeeding.
Application of hyperglycemia/diabetes-derived polygenic risk scores on the risk of poor outcomes after an ischemic stroke
Authors: Chen Yu-Lun , Chi Nai-Fang , Chiou Hung-Yi , Hu Chaur-Jong , Jeng Jiann-Shing , Tang Sung-Chun , Lin Huey-Juan , Hsieh Yi-Chen ,   on behalf of the Formosa Stroke Genetic Consortium
Published: November 2021

Background:

Unfavorable prognoses are often accompanied for hyperglycemic stroke patients. This study aimed to construct a hyperglycemia/diabetes-derived polygenic risk score (PRS) to improve the predictive performance for poor outcome risks after a stroke and to evaluate its potential clinical application.

Methods:

A hospital-based cohort study was conducted including 1320 first-ever acute ischemic stroke (AIS) patients and 1210 patients who completed the follow-up at 3 months. PRSs were calculated for hyperglycemia/diabetes mellitus using results from genome-wide association studies in Asians. An unfavorable functional outcome was defined as a modified Rankin Scale score of ≥3 at 3, 6, and 12 months of follow-up. The prediction of a poor prognosis was evaluated using measures of model discrimination, calibration, and net reclassification improvement (NRI).

Results:

The second to fourth PRS quartiles (≥Q2) were significantly associated with higher risks of unfavorable outcomes at 3 months compared with the first quartile as the reference group after adjusting for age, baseline stroke severity, hypertension, diabetes, dyslipidemia, smoking, heart disease, and ischemic stroke subtype (p for trend <0.0001). The addition of the PRS to traditional risk predictors of poor outcomes after an AIS significantly improved the model fit (likelihood ratio test p < 0.0001) and enhanced measures of reclassification (NRI, 0.245; 95% confidence interval [CI], 0.195-0.596). The corrected C-index for the PRS combining traditional risk factors at 3 months after a stroke was 0.899 (95% CI, 0.878-0.980). Among hyperglycemic AIS patients, those who did not take an antidiabetic drug and whose PRS was ≥Q2 had higher risks of an unfavorable outcome at 3 months compared with patients who took the medicine.

Conclusion:

The hyperglycemia/diabetes-derived PRS was associated with poor outcomes after an AIS, but further studies are needed to validate its use for clinical applications.
Predictability of the preoperative lateral fulcrum radiograph of success in one-level vertebroplasty to treat painful osteoporotic vertebral fracture
Authors: Chang Yu-Chuan , Yao Yu-Cheng , Lin Hsi-Hsien , Wang Shih-Tien , Chang Ming-Chau , Chou Po-Hsin
Published: November 2021

Background:

Restoration of height or angle has been reported following vertebroplasty (VP). The purpose of the study was to investigate the predictive value of the preoperative lateral fulcrum radiograph (LFR) of success in one-level VP for painful osteoporotic vertebral fracture.

Methods:

From January 2017 to January 2018, 71 patients (mean age, 76 years) receiving VP were retrospectively analyzed. Painful vertebra was defined as pseudarthrosis or edematous change in magnetic resonance imaging (MRI) scan. Fulcrum flexibility (FF) and fulcrum restoration index (FRI) of the vertebral wedge angle (VWA), regional kyphotic angle (RKA), and anterior vertebral body height (AVBH) were investigated. Back pain was evaluated using a visual analogue scale.

Results:

The 30 males and 41 females were followed for an average of 21 months. The sensitivity of LFR and MRI to detect pseudarthrosis was 92% and 97%, respectively. Preoperative FF of VWA, RKA, and AVBH was 52.4%, 58.3%, and 60%, respectively, indicating similar potential restoration ability. Postoperative average FRI for VWA, RKA, and AVBH was 1.29 ± 2.98, 0.46 ± 1.16, and 1.04 ± 1.68, respectively. Final average FRI was 0.94 ± 2.96, −0.03 ± 2.25, and 0.6 ± 2.04, respectively. VWA and AVBH had better immediate restoration, and VWA had better final maintenance. All parameters progressive lost significant levels of restoration to similar degrees but without increase in back pain.

Conclusion:

LFR can help with evaluation for pseudarthrosis and the restoration effect of VP. VP had better immediate restoration of VWA and AVBH and better final VWA maintenance.
HMGB1 Inhibitor Effectively Alleviates Psoriasis-Like Lesions and Inflammatory Cytokines in K14-VEGF Transgenic Mice
Authors: Fu Li-Xin , Yin Bin , Cao Na , Qin Sha , Lei Xiao-Yu , Chen Tao , Guo Zai-Pei
Published: November 2021

Objective:

Anti-high-mobility group box 1 (HMGB1) is involved in the pathogenesis of many inflammatory and autoimmune diseases, including psoriasis. The present study aimed to investigate the therapeutic effects of HMGB1 monoclonal antibody (mAb) in keratin 14 (K14)-vascular endothelial growth factor (VEGF) transgenic homozygous mice.

Methods:

Twelve VEGF transgenic mice were randomly divided into two groups of six mice each: the anti-HMGB1 mAb group and the immune complex (IC) mAb group. The mice underwent intraperitoneal injection of anti-HMGB1 mAb or IC mAb once every 2 days for a total of three treatments. Compare the lesions on the ears of the mice and evaluate the severity of the lesions using the baseline and clinical scores on the last day of treatment. The changes in psoriasis-like lesions, cellular infiltration of T cells, dendritic cells, and neutrophils were detected by hematoxylin–eosin staining and immunohistochemistry. The mRNA expression of the inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, interferon-γ, and IL-17 in the lesions were assessed by real-time quantitative polymerase chain reaction. The number of γ
δ T cells in the lesions of two groups were detected by flow cytometry. The t test was used to compare their differences.

Results:

The anti-HMGB1 mAb effectively ameliorated the clinical skin lesions. The clinical scores in the anti-HMGB1 mAb group were lower than those in the IC mAb group (6.00 ± 0.52 vs. 10.83 ± 0.48, P < 0.001). Histopathologic changes and improvements in the K14-VEGF transgenic homozygous mice were evident after three treatments. The scores of mice in the anti-HMGB1 mAb group were significantly lower than those in the IC mAb group (3.25 ± 0.71 vs. 6.95 ± 0.83, P = 0.0033). The average epidermal thickness in the anti-HMGB1 mAb group was reduced by about 45% when compared with that in the IC mAb group (32.15 ± 7.08 vs. 64.69 ± 7.93, P = 0.0054). Moreover, anti-HMGB1 mAb also decreased the number of infiltrating CD3+ T cells, myeloperoxidase-positive neutrophils, and CD11c+ dendritic cells. The ratio of ear skin γ
δ T cells was reduced in anti-HMGB1 mAb treated group. The mRNA expression of IL-6, tumor necrosis factor-α, interferon-γ, and IL-17 in the anti-HMGB1 mAb group were significantly reduced when compared with IC mAb group (0.36 ± 0.070 vs.1.98 ± 0.62, P = 0.0148; 6.43 ± 1.37 vs. 13.80 ± 1.33, P = 0.0006; 2.62 ± 0.83 vs. 7.77 ± 1.32, P = 0.0026; 4.69 ± 1.13 vs.11.41 ± 1.92, P = 0.0054).

Conclusion:

HMGB1 blockade (anti-HMGB1 mAb) reduced leukocyte infiltration and suppressed inflammatory cytokine expression in this K14-VEGF transgenic mouse model, markedly reducing the severity of the psoriasis-like lesions. HMGB1 blockade might serve as a potential target for the treatment of psoriasis.
Optimized scheme for paired transverse corrective forces in S-shaped scoliosis via ultrasound and application in Chêneau brace: a pilot study
Authors: Wang Li , Xia Nan , Wang Chun , Zheng Qian , Ma Christina Zonghao , Youssef Ahmed S. A. , Zhang Chao , Deng Youbin , Zhu Guoli , Huang Xiaolin
Published: November 2021

Background:

There is currently no consensus on the optimal positions of the transverse corrective forces (TCFs) for scoliosis braces.

Objectives:

This study aimed to explore an optimal scheme of placing paired TCF for S-shaped adolescent idiopathic scoliosis and its feasibility in Chêneau brace (CB) treatment.

Study design:

Cross-over feasibility pilot trial.

Methods:

Ten S-shaped adolescent idiopathic scoliosis participants were invited to receive four tests with different paired TCF positions under ultrasound. The positions of the paired TCF were test 1: thoracic apical vertebra (AV), lumbar AV; test 2: 2 cm inferior to thoracic AV, lumbar AV; test 3: thoracic AV, 2 cm superior to lumbar AV; and test 4: 2 cm inferior to thoracic AV, 2 cm superior to lumbar AV. The test scheme with the highest mean in-force correction rate (IFCR) for the thoracic spinous process angle (SPA) was further applied in the CB fabrication of 4 additional participants.

Results:

A significant higher mean IFCR of the thoracic SPA of 63.6% was found in test 2 (P < 0.001), which also contributed to its higher overall IFCR of the SPA of 64.6% (P = 0.001). Moreover, the mean in-brace correction rates for the thoracic and overall curves in CB were 46.4% and 51.8%, respectively. No adverse events were reported.

Conclusions:

Placing paired TCF at the lumbar AV and 2 cm inferior to the thoracic AV achieved better treatment efficacy than other schemes. The practical application of this scheme on the CB was feasible.
The Risk of Postoperative Complications After Major Elective Surgery in Active or Resolved COVID-19 in the United States
Authors: Deng John Z. , Chan Janine S. , Potter Alexandra L. , Chen Ya-Wen , Sandhu Harpal S. , Panda Nikhil , Chang David C. , Yang Chi-Fu Jeffrey
Published: November 2021

Objective:

To assess the association between the timing of surgery relative to the development of Covid-19 and the risks of postoperative complications.

Summary Background Data:

It is unknown whether patients who recovered from Covid-19 and then underwent a major elective operation have an increased risk of developing postoperative complications.

Methods:

The risk of postoperative complications for patients with Covid-19 undergoing 18 major types of elective operations in the Covid-19 Research Database was evaluated using multivariable logistic regression. Patients were grouped by time of surgery relative to SARS-CoV-2 infection; that is, surgery performed: (1) before January 1, 2020 (“pre-Covid-19”), (2) 0 to 4 weeks after SARS-CoV-2 infection (“peri-Covid-19”), (3) 4 to 8 weeks after infection (“early post-Covid-19”), and (4) ≥8 weeks after infection (“late post-Covid-19”).

Results:

Of the 5479 patients who met study criteria, patients with peri-Covid-19 had an elevated risk of developing postoperative pneumonia [adjusted odds ratio (aOR), 6.46; 95% confidence interval (CI): 4.06–10.27], respiratory failure (aOR, 3.36; 95% CI: 2.22–5.10), pulmonary embolism (aOR, 2.73; 95% CI: 1.35–5.53), and sepsis (aOR, 3.67; 95% CI: 2.18–6.16) when compared to pre-Covid-19 patients. Early post-Covid-19 patients had an increased risk of developing postoperative pneumonia when compared to pre-Covid-19 patients (aOR, 2.44; 95% CI: 1.20–4.96). Late post-Covid-19 patients did not have an increased risk of postoperative complications when compared to pre-Covid-19 patients.

Conclusions:

Major, elective surgery 0 to 4 weeks after SARS-CoV-2 infection is associated with an increased risk of postoperative complications. Surgery performed 4 to 8 weeks after SARS-CoV-2 infection is still associated with an increased risk of postoperative pneumonia, whereas surgery 8 weeks after Covid-19 diagnosis is not associated with increased complications.
Multi-institutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas
Authors: McIntyre Caitlin A. , Rodrigues Clifton , Santharaman Aadhithyaraman Vaithiya , Goldman Debra A. , Javed Ammar A. , Ciprani Debora , Pang Nan , Lokshin Anna , Gonen Mithat , Al Efishat Mohammad A. , He Jin , Burkhart Richard , Burns William , Weiss Matthew , D’Angelica Michael I. , Kingham T. Peter , Balachandran Vinod P. , Drebin Jeffrey A. , Jarnagin William R. , Lillemoe Keith D. , Brugge William , Casey Brenna , Lennon Anne Marie , Schattner Mark , Wolfgang Christopher L. , del Castillo Carlos Fernandez , Allen Peter J.
Published: November 2021

Objective:

Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas.

Summary of Background Data:

Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4).

Methods:

This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms.

Results:

Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5–38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5.

Conclusions:

This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.
Thromboelastometry fails to detect autoheparinization after major trauma and hemorrhagic shock
Authors: Zipperle Johannes , Oberladstätter Daniel , Weichselbaum Nadja , Schlimp Christoph J. , Hofmann Nikolaus , Iapichino Giacomo , Voelckel Wolfgang , Ziegler Bernhard , Grottke Oliver , Osuchowski Marcin , Schöchl Herbert
Published: November 2021

BACKGROUND

Heparan sulfate is an integral component of the glycocalyx that provides an anticoagulant layer close to the endothelium. Hypoperfusion, inflammation, and sympathoadrenal activation following major trauma result in glycocalyx shedding and subsequent release of heparan sulfate into the bloodstream. The possible anticoagulant effect of this “autoheparinization” has been suggested as a potential driver of trauma-induced coagulopathy. We investigated whether thromboelastometry can be used to detect trauma-induced autoheparinization.

METHODS

This study comprised three parts. First, in a retrospective clinical study of 264 major trauma patients, the clotting time (CT) in the intrinsic activation (INTEM) and intrinsic activation plus heparinase (HEPTEM) assays were evaluated upon emergency room admission. Second, in an in vivo experimental rat model of hemorrhagic-traumatic shock, the release of heparan sulfate was investigated with INTEM and HEPTEM analyses of whole blood. Third, in vitro spiking of whole blood from healthy volunteers was undertaken to assess the effects of clinically relevant quantities of heparan sulfate and heparin on CT in the INTEM and HEPTEM assays.

RESULTS

In the first part, severe injury and hemorrhagic shock was not associated with any increases in INTEM CT versus HEPTEM CT. Part 2 showed that an approximate threefold increase in heparan sulfate resulting from hemorrhagic traumatic shock in rats did not prolong INTEM CT, and no significant differences between INTEM CT and HEPTEM CT were observed. Third, spiking of whole blood with heparan sulfate had no impact on INTEM CT, whereas heparin elicited significant prolongation of INTEM CT.

CONCLUSION

Despite structural similarity between heparan sulfate and heparin, the amounts of heparan sulfate shed in response to trauma did not exert an anticoagulant effect that was measurable by the intrinsically activated CT in thromboelastometry. The extent to which heparan sulfate contributes to trauma-induced coagulopathy has yet to be elucidated.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
In-hospital outcomes in autogenous vein versus synthetic graft interposition for traumatic arterial injury: A propensity-matched cohort from PROOVIT
Authors: Stonko David P. , Betzold Richard D. , Abdou Hossam , Edwards Joseph , Azar Faris K. , Elansary Noha N. , Treffalls Rebecca N. , Savidge Samuel G. , DuBose Joseph J. , Feliciano David V. , Morrison Jonathan J.
Published: November 2021

BACKGROUND

The ideal conduit for traumatic arterial repair is controversial. Autologous vein was compared with synthetic interposition grafts in the acute setting. The primary outcome was in-hospital reoperation or endovascular intervention.

METHODS

The American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry from November 2013 to January 2019 was queried for arterial injuries requiring interposition vein or graft repair. Patients with no recorded Injury Severity Score were excluded, and multiple imputation was used for other missing data. Patients treated with synthetic grafts (SGs) were propensity matched to patients with vein grafts (VGs) to account for preoperative differences.

RESULTS

Four hundred sixty from 19 institutions were identified, with 402 undergoing VG and 58 SG. In the SG group, 45 were PTFE grafts, 5 were Dacron, and 8 had other conduits. The SG group was more severely injured at admission with more gunshot wounds and higher mean Injury Severity Score, lactate, and first-24-hour transfusion requirement. In addition, the SG cohort had significantly lower admission systolic blood pressure, pH, and hemoglobin. After propensity matching, 51 patients with SG were matched with 87 patients with VG. There were no differences in demographics, clinical parameters, or diagnostic evaluation techniques postmatch. The need for reoperation or endovascular intervention between the matched groups was equivalent (18%; p = 0.8). There was no difference in any secondary outcome including thrombosis, stenosis, pseudoaneurysm, infection, or embolic event, and hospital and intensive care unit length of stay were the same.

CONCLUSION

American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry data demonstrate that SGs are used in more critically ill patients. After controlling for relevant clinical factors and propensity matching, there is no in-hospital difference in rate of reoperation or endovascular intervention, or any secondary outcome between VG and SG.

LEVEL OF EVIDENCE

Prognostic and Epidemiolgic, Level III.
Understanding the geography of trauma: Combining spatial analysis and funnel plots to create comprehensive spatial injury profiles
Authors: Abraham Peter J. , Crowley Brandon M. , Moore Dylana , Stephens Shannon W. , Minor Michael , Griffin Russell L. , Hashmi Zain , Holcomb John B. , Kerby Jeffrey D. , Jansen Jan O.
Published: November 2021

BACKGROUND

Understanding geographic patterns of injury is essential to operating an effective trauma system and targeting injury prevention. Choropleth maps are helpful in showing spatial relationships but are unable to provide estimates of spread or degrees of confidence. Funnel plots overcome this issue and are a recommended graphical aid for comparisons that allow quantification of precision. The purpose of this project was to demonstrate the complementary roles of choropleth maps and funnel plots in providing a thorough representation of geographic trauma data.

METHODS

This is a retrospective analysis of emergency medical service transport data of adult patients in Alabama from July 2015 to June 2020. Choropleth maps of case volume and observed-to-expected ratios of incidence were created using US Census Bureau data. Funnel plots were created to relate incidence rate to county population. Subgroup analyses included patients with critical physiology, penetrating, blunt, and burn injuries.

RESULTS

We identified 65,247 trauma incidents during the study period. The overall statewide incidence rate was 133 per 10,000 persons. The highest number of incidents occurred in the most populous counties (Jefferson, 10,768; Mobile, 5,642). Choropleth maps for overall incidence and subgroups highlighted that spatial distribution of overall case volume and observed-to-expected ratios are not always congruent. Funnel plots identified possible and probable outliers, and revealed skewed or otherwise unique patterns among injury subgroups.

CONCLUSION

This study demonstrates the complementarity of choropleth maps and funnel plots in describing trauma patterns. Comprehensive geospatial analyses may help guide a data-driven approach to trauma system optimization and injury prevention. Combining maps of case counts, incidence, and funnel plots helps to not only identify geographic trends in data but also quantify outliers and display how far results fall outside the expected range. The combination of these tools provides a more comprehensive geospatial analysis than either tool could provide on its own.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level IV.
Precision targeting of the vagal anti-inflammatory pathway attenuates the systemic inflammatory response to burn injury
Authors: Costantini Todd W. , Coimbra Raul , Weaver Jessica L. , Eliceiri Brian P.
Published: November 2021

BACKGROUND

The systemic inflammatory response (SIRS) drives late morbidity and mortality after injury. The α7 nicotinic acetylcholine receptor (α7nAchR) expressed on immune cells regulates the vagal anti-inflammatory pathway that prevents an overwhelming SIRS response to injury. Nonspecific pharmacologic stimulation of the vagus nerve has been evaluated as a potential therapeutic to limit SIRS. Unfortunately, the results of clinical trials have been underwhelming. We hypothesized that directly targeting the α7nAchR would more precisely stimulate the vagal anti-inflammatory pathway on immune cells and decrease gut and lung injury after severe burn.

METHODS

C57BL/6 mice underwent 30% total body surface area steam burn. Mice were treated with an intraperitoneal injection of a selective agonist of the α7nAchR (AR-R17779) at 30 minutes postburn. Intestinal permeability to 4 kDa FITC-dextran was measured at multiple time points postinjury. Lung vascular permeability was measured 6 hours after burn injury. Serial behavioral assessments were performed to quantify activity levels.

RESULTS

Intestinal permeability peaked at 6 hours postburn. AR-R17779 decreased burn-induced intestinal permeability in a dose-dependent fashion (p < 0.001). There was no difference in gut permeability to 4 kDa FITC-dextran between sham and burn-injured animals treated with 5 mg/kg of AR-R17779. While burn injury increased lung permeability 10-fold, AR-R17779 prevented burn-induced lung permeability with no difference compared with sham (p < 0.01). Postinjury activity levels were significantly improved in burned animals treated with AR-R17779.

CONCLUSION

Directly stimulating the α7nAchR prevents burn-induced gut and lung injury. Directly targeting the α7nAChR that mediates the cholinergic anti-inflammatory response may be an improved strategy compared with nonspecific vagal agonists.
The feasibility and reliability of frailty assessment tools applicable in acute in-hospital trauma patients: A systematic review
Authors: Cords Charlotte I. , Spronk Inge , Mattace-Raso Francesco U.S. , Verhofstad Michiel H.J. , van der Vlies Cornelis. H. , van Baar Margriet E.
Published: November 2021

BACKGROUND

Assessing frailty in patients with an acute trauma can be challenging. To provide trustworthy results, tools should be feasible and reliable. This systematic review evaluated existing evidence on the feasibility and reliability of frailty assessment tools applied in acute in-hospital trauma patients.

METHODS

A systematic search was conducted in relevant databases until February 2020. Studies evaluating the feasibility and/or reliability of a multidimensional frailty assessment tool used to identify frail trauma patients were identified. The feasibility and reliability results and the risk of bias of included studies were assessed. This study was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and registered in Prospective Register of Systematic Reviews (ID: CRD42020175003).

RESULTS

Nineteen studies evaluating 12 frailty assessment tools were included. The risk of bias of the included studies was fair to good. The most frequently evaluated tool was the Clinical Frailty Scale (CFS) (n = 5). All studies evaluated feasibility in terms of the percentage of patients for whom frailty could be assessed; feasibility was high (median, 97%; range, 49–100%). Other feasibility aspects, including time needed for completion, tool availability and costs, availability of instructions, and necessity of training for users, were hardly reported. Reliability was only assessed in three studies, all evaluating the CFS. The interrater reliability varied between 42% and >90% agreement, with a Krippendorff α of 0.27 to 0.41.

CONCLUSION

Feasibility of most instruments was generally high. Other aspects were hardly reported. Reliability was only evaluated for the CFS with results varying from poor to good. The reliability of frailty assessment tools for acute trauma patients needs further critical evaluation to conclude whether assessment leads to trustworthy results that are useful in clinical practice.

LEVEL OF EVIDENCE

Systematic review, Level II.
Tunneling nanotubes provide a novel route for SARS-CoV-2 spreading between permissive cells and to non-permissive neuronal cells
Authors: Pepe Anna , Pietropaoli Stefano , Vos Matthijn , Barba-Spaeth Giovanna , Zurzolo Chiara
Published: November 2021

SARS-CoV-2 entry into host cells is mediated by the binding of its spike glycoprotein to the angiotensin-converting enzyme 2 (ACE2) receptor, highly expressed in several organs, but very low in the brain. The mechanism through which SARS-CoV-2 infects neurons is not understood. Tunneling nanotubes (TNTs), actin-based intercellular conduits that connect distant cells, allow the transfer of cargos, including viruses. Here, we explored the neuroinvasive potential of SARS-CoV-2 and whether TNTs are involved in its spreading between cellsin vitro. We report that neuronal cells, not permissive to SARS-CoV-2 through an exocytosis/endocytosis dependent pathway, can be infected when co-cultured with permissive infected epithelial cells. SARS-CoV-2 induces TNTs formation between permissive cells and exploits this route to spread to uninfected permissive cells in co-culture. Correlative Cryo-electron tomography reveals that SARS-CoV-2 is associated with the plasma membrane of TNTs formed between permissive cells and virus-like vesicular structures are inside TNTs established both between permissive cells and between permissive and non-permissive cells. Our data highlight a potential novel mechanism of SARS-CoV-2 spreading which could serve as route to invade non-permissive cells and potentiate infection in permissive cells.
Rhinovirus-induced epithelial RIG-I inflammasome activation suppresses antiviral immunity and promotes inflammatory responses in virus-induced asthma exacerbations and COVID-19
Authors: Radzikowska U , Eljaszewicz A , Tan G , Stocker N , Heider A , Westermann P , Steiner S , Dreher A , Wawrzyniak P , Rückert B , Rodriguez-Coira J , Zhakparov D , Huang M , Jakiela B , Sanak M , Moniuszko M , O’Mahony L , Kebadze T , Jackson DJ , Edwards MR , Thiel V , Johnston SL , Akdis CA , Sokolowska M
Published: November 2021

Rhinoviruses (RV) and inhaled allergens, such as house dust mite (HDM) are the major agents responsible for asthma onset, exacerbations and progression to the severe disease, but the mechanisms of these pathogenic reciprocal virus-allergen interactions are not well understood. To address this, we analyzed mechanisms of airway epithelial sensing and response to RV infection using controlled experimental in vivo RV infection in healthy controls and patients with asthma and in vitro models of HDM exposure and RV infection in primary airway epithelial cells. We found that intranasal RV infection in patients with asthma led to the highly augmented inflammasome-mediated lower airway inflammation detected in bronchial brushes, biopsies and bronchoalveolar lavage fluid. Mechanistically, RV infection in bronchial airway epithelium led to retinoic acid-inducible gene I (RIG-I), but not via NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, which was highly augmented in patients with asthma, especially upon pre-exposure to HDM. This excessive activation of RIG-I inflammasomes was responsible for the impairment of antiviral type I/III interferons (IFN), prolonged viral clearance and unresolved inflammation in asthma in vivo and in vitro. Pre-exposure to HDM amplifies RV-induced epithelial injury in patients with asthma via enhancement of pro-IL1β expression and release, additional inhibition of type I/III IFNs and activation of auxiliary proinflammatory and pro-remodeling proteins. Finally, in order to determine whether RV-induced activation of RIG-I inflammasome may play a role in the susceptibility to severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection in asthma, we analyzed the effects of HDM exposure and RV/SARS-CoV-2 coinfection. We found that prior infection with RV restricted SARS-CoV-2 replication, but co-infection augmented RIG-I inflammasome activation and epithelial inflammation in patients with asthma, especially in the presence of HDM. Timely inhibition of epithelial RIG-I inflammasome activation may lead to more efficient viral clearance and lower the burden of RV and SARS-CoV-2 infections.
Northern Cerrado Native Vegetation is a Refuge for Birds Under Current Climate Change
Authors: Hidasi-Neto José , Alves Gomes Nicole Mércia , Pinto Nelson Silva
Published: November 2021

Climate Change is already seen as one of the biggest threats to biodiversity in the 21st century. Not much studies direct attention to its effects on whole communities of threatened hotspots. In the present work, we combine ecological niche modelling (ENM) with a future climate scenario of greenhouse gases emissions to study the future changes in alpha and beta diversity of birds of the Brazilian Cerrado biome, a hotspot of biodiversity with high velocity of climate change and agricultural expansion. In general, we found heterogeneous results for changes in species richness, spatial and temporal taxonomic and functional beta diversity, and mean ecological distinctiveness. Contrary to a previous study on Cerrado mammals, species richness is expected to increase in Northern Cerrado, where homogenization of communities (decreasing spatial turnover) is also expected to occur especially through local invasions. We show that biotic homogenization (which is composed of local extinction of natives and local invasion of exotic species) will occur in two biological groups but through different subprocesses: local extinctions for mammals and local invasions for birds. Distinct conservation management actions should be directed depending on the outcomes of analyzes of alpha and spatial and temporal beta diversity, for example controlling species invasions in Northern Cerrado. Conservation studies should continue evaluating Cerrado in Brazil even under covid pandemic, as environmental situation in the country is not good and incentives for scientific studies are almost nonexistent.
Angiogenesis is critical for the regenerative effects of exercise
Authors: Wariyar Supriya S. , Brown Alden D. , Tian Tina , Pottorf Tana S , Ward Patricia J.
Published: November 2021

Summary Abstract

Enhancing axon regeneration is a major focus of nerve injury research, and the quality of the surgical nerve repair plays a large role in the aggregate success of nerve regeneration. Additionally, exercise is known to promote successful axon regeneration after surgical nerve repair. In this study, we asked how exercise-induced nerve regeneration is affected when a transected nerve is repaired with or without fibrin glue. Fibrin glue repaired nerves exhibited greater vasculature within the tissue bridge compared to nerves that were intrinsically repaired. Fibrin glue repaired nerves also exhibited more robust axon regeneration after exercise compared to nerves that were not repaired with fibrin glue. When angiogenesis of the tissue bridge was prevented, exercise was unable to enhance regeneration despite the presence of fibrin glue. These findings suggest that the biological properties of fibrin glue enhance angiogenesis within the repair site, and a vascularized bridge is required for enhanced axon elongation with exercise. The combination of fibrin glue repair and exercise resulted in notable differences in vascular growth, axon elongation, neuromuscular junction reinnervation, and functional recovery. Fibrin glue should be considered as an adjuvant for nerve repair to enhance the subsequent efficacy of activity- and physical therapy-based treatment interventions.
A Random Sequencing Approach for the Analysis of the Trypanosoma cruzi Genome: General Structure, Large Gene and Repetitive DNA Families, and Gene Discovery
Authors: Agüero Fernán , Verdún Ramiro E. , Frasch Alberto Carlos C. , Sánchez Daniel O.
Published: November 2021

A random sequence survey of the genome of Trypanosoma cruzi, the agent of Chagas disease, was performed and 11,459 genomic sequences were obtained, resulting in ∼4.3 Mb of readable sequences or ∼10% of the parasite haploid genome. The estimated total GC content was 50.9%, with a high representation of A and T di- and trinucleotide repeats. Out of the estimated 5000 parasite genes, 947 putative new genes were identified. Another 1723 sequences corresponded to genes detected previously in T. cruzi through expression sequence tag analysis. 7735 sequences had no matches in the database, but the presence of open reading frames that passed Fickett's test suggests that some might contain coding DNA. The survey was highly redundant, with ∼35% of the sequences included in a few large sequence families. Some of them code for protein families present in dozens of copies, including proteins essential for parasite survival and retrotransposons. Other sequence families include repetitive DNA present in thousands of copies per haploid genome. Some families in the latter group are new, parasite-specific, repetitive DNAs. These results suggest that T. cruzi could constitute an interesting model to analyze gene and genome evolution due to its plasticity in terms of sequence amplification and divergence. Additional information can be found at http://www.iib.unsam.edu.ar/tcruzi.gss.html.

[The sequence data described in this paper have been submitted to the dbGSS database under the following GenBank accession nos.:AQ443439–AQ443513, AQ443743–AQ445667, AQ902981–AQ911366,AZ049857–AZ051184, and AZ302116–AZ302563.]
Tropheryma whipplei Twist: A Human Pathogenic Actinobacteria With a Reduced Genome
Authors: Raoult Didier , Ogata Hiroyuki , Audic Stéphane , Robert Catherine , Suhre Karsten , Drancourt Michel , Claverie Jean-Michel
Published: November 2021

The human pathogen Tropheryma whipplei is the only known reduced genome species (<1 Mb) within the Actinobacteria [high G+C Gram-positive bacteria]. We present the sequence of the 927,303-bp circular genome of T. whipplei Twist strain, encoding 808 predicted protein-coding genes. Specific genome features include deficiencies in amino acid metabolisms, the lack of clear thioredoxin and thioredoxin reductase homologs, and a mutation in DNA gyrase predicting a resistance to quinolone antibiotics. Moreover, the alignment of the two available T. whipplei genome sequences (Twist vs. TW08/27) revealed a large chromosomal inversion the extremities of which are located within two paralogous genes. These genes belong to a large cell-surface protein family defined by the presence of a common repeat highly conserved at the nucleotide level. The repeats appear to trigger frequent genome rearrangements in T. whipplei, potentially resulting in the expression of different subsets of cell surface proteins. This might represent a new mechanism for evading host defenses. The T. whipplei genome sequence was also compared to other reduced bacterial genomes to examine the generality of previously detected features. The analysis of the genome sequence of this previously largely unknown human pathogen is now guiding the development of molecular diagnostic tools and more convenient culture conditions.
Evolutionary Role of Restriction/Modification Systems as Revealed by Comparative Genome Analysis
Authors: Rocha Eduardo P.C. , Danchin Antoine , Viari Alain
Published: November 2021

Type II restriction modification systems (RMSs) have been regarded either as defense tools or as molecular parasites of bacteria. We extensively analyzed their evolutionary role from the study of their impact in the complete genomes of 26 bacteria and 35 phages in terms of palindrome avoidance. This analysis reveals that palindrome avoidance is not universally spread among bacterial species and that it does not correlate with taxonomic proximity. Palindrome avoidance is also not universal among bacteriophage, even when their hosts code for RMSs, and depends strongly on the genetic material of the phage. Interestingly, palindrome avoidance is intimately correlated with the infective behavior of the phage. We observe that the degree of palindrome and restriction site avoidance is significantly and consistently less important in phages than in their bacterial hosts. This result brings to the fore a larger selective load for palindrome and restriction site avoidance on the bacterial hosts than on their infecting phages. It is then consistent with a view where type II RMSs are considered as parasites possibly at the verge of mutualism. As a consequence, RMSs constitute a nontrivial third player in the host–parasite relationship between bacteria and phages.
Genome Evolution at the Genus Level: Comparison of Three Complete Genomes of Hyperthermophilic Archaea
Authors: Lecompte Odile , Ripp Raymond , Puzos-Barbe Valérie , Duprat Simone , Heilig Roland , Dietrich Jacques , Thierry Jean-Claude , Poch Olivier
Published: November 2021

We have compared three complete genomes of closely related hyperthermophilic species of Archaea belonging to thePyrococcus genus: Pyrococcus abyssi, Pyrococcus horikoshii, and Pyrococcus furiosus. At the genomic level, the comparison reveals a differential conservation among four regions of the Pyrococcus chromosomes correlated with the location of genetic elements mediating DNA reorganization. This discloses the relative contribution of the major mechanisms that promote genomic plasticity in these Archaea, namely rearrangements linked to the replication terminus, insertion sequence-mediated recombinations, and DNA integration within tRNA genes. The combination of these mechanisms leads to a high level of genomic plasticity in these hyperthermophilic Archaea, at least comparable to the plasticity observed between closely related bacteria. At the proteomic level, the comparison of the threePyrococcus species sheds light on specific selection pressures acting both on their coding capacities and evolutionary rates. Indeed, thanks to two independent methods, the “reciprocal best hits“ approach and a new distance ratio analysis, we detect the false orthology relationships within the Pyrococcus lineage. This reveals a high amount of differential gains and losses of genes since the divergence of the three closely related species. The resulting polymorphism is probably linked to an adaptation of these free-living organisms to differential environmental constraints. As a corollary, we delineate the set of orthologous genes shared by the three species, that is, the genes that may characterize the Pyrococcus genus. In this conserved core, the amino acid substitution rate is equal between P. abyssi and P. horikoshii for most of their shared proteins, even for fast-evolving ones. In contrast, strong discrepancies exist among the substitution rates observed in P. furiosus relative to the two other species, which is in disagreement with the molecular clock hypothesis.
Single Nucleotide Polymorphism Markers for Genetic Mapping in Drosophila melanogaster
Authors: Hoskins Roger A. , Phan Alexander C. , Naeemuddin Mohammed , Mapa Felipa A. , Ruddy David A. , Ryan Jessica J. , Young Lynn M. , Wells Trent , Kopczynski Casey , Ellis Michael C.
Published: November 2021

For nearly a century, genetic analysis in Drosophila melanogaster has been a powerful tool for analyzing gene function, yet Drosophila lacks the molecular genetic mapping tools that recently have revolutionized human, mouse, and plant genetics. Here, we describe the systematic characterization of a dense set of molecular markers in Drosophila by using a sequence tagged site-based physical map of the genome. We identify 474 biallelic markers in standard laboratory strains of Drosophila that span the genome. Most of these markers are single nucleotide polymorphisms and sequences for these variants are provided in an accessible format. The average density of the new markers is one per 225 kb on the autosomes and one per megabase on the X chromosome. We include in this survey a set of P-element strains that provide additional use for high-resolution mapping. We show one application of the new markers in a simple set of crosses to map a mutation in the hedgehog gene to an interval of <1 Mb. This new map resource significantly increases the efficiency and resolution of recombination mapping and will be of immediate value to the Drosophila research community.
Annotation Transfer for Genomics: Measuring Functional Divergence in Multi-Domain Proteins
Authors: Hegyi Hedi , Gerstein Mark
Published: November 2021

Annotation transfer is a principal process in genome annotation. It involves “transferring” structural and functional annotation to uncharacterized open reading frames (ORFs) in a newly completed genome from experimentally characterized proteins similar in sequence. To prevent errors in genome annotation, it is important that this process be robust and statistically well-characterized, especially with regard to how it depends on the degree of sequence similarity. Previously, we and others have analyzed annotation transfer in single-domain proteins. Multi-domain proteins, which make up the bulk of the ORFs in eukaryotic genomes, present more complex issues in functional conservation. Here we present a large-scale survey of annotation transfer in these proteins, using scop superfamilies to define domain folds and a thesaurus based on SWISS-PROT keywords to define functional categories. Our survey reveals that multi-domain proteins have significantly less functional conservation than single-domain ones, except when they share the exact same combination of domain folds. In particular, we find that for multi-domain proteins, approximate function can be accurately transferred with only 35% certainty for pairs of proteins sharing one structural superfamily. In contrast, this value is 67% for pairs of single-domain proteins sharing the same structural superfamily. On the other hand, if two multi-domain proteins contain the same combination of two structural superfamilies the probability of their sharing the same function increases to 80% in the case of complete coverage along the full length of both proteins, this value increases further to > 90%. Moreover, we found that only 70 of the current total of 455 structural superfamilies are found in both single and multi-domain proteins and only 14 of these were associated with the same function in both categories of proteins. We also investigated the degree to which function could be transferred between pairs of multi-domain proteins with respect to the degree of sequence similarity between them, finding that functional divergence at a given amount of sequence similarity is always about two-fold greater for pairs of multi-domain proteins (sharing similarity over a single domain) in comparison to pairs of single-domain ones, though the overall shape of the relationship is quite similar. Further information is available athttp://partslist.org/funcorhttp://bioinfo.mbb.yale.edu/partslist/func.
Genomics and Hearing Impairment
Authors: Keats Bronya J. B. , Berlin Charles I.
Published: November 2021

Hearing impairment is clinically and genetically heterogeneous. There are >400 disorders in which hearing impairment is a characteristic of the syndrome, and family studies demonstrate that there are at least 30 autosomal loci for nonsyndromic hearing impairment. The genes that have been identified encode diaphanous (HDIA1), α-tectorin (TECTA), the transcription factorPOU4F3, connexin 26 (GJB2), and two unconventional myosins (MYO7A and MYO15), and four novel proteins (PDS,COCH, DFNA5, DFNB9). The same clinical phenotype in hearing-impaired individuals, even those within the same family, can result from mutations in different genes. Conversely, mutations in the same gene can result in a variety of clinical phenotypes with different modes of inheritance. For example, mutations in the gene encoding MYO7A cause Usher syndrome type IB, autosomal-recessive nonsyndromic hearing impairment (DFNB2), and autosomal-dominant nonsyndromic hearing impairment (DFNA11). Additionally, the mouse ortholog of theMYO7A gene is the shaker-1 gene. Mouse models such asshaker-1 have facilitated the identification of genes that cause hearing impairment in humans. The availability of high-resolution maps of the human and mouse genomes and new technologies for gene identification are advancing molecular understanding of hearing impairment and the complex mechanisms of the auditory system.