bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying the Risk Factors and Estimating the Prognosis in Patients with Pelvis and Spine Ewing Sarcoma
Authors: Jiang Runyi , He Shaohui , Sun Haitao , Gong Haiyi , Yang Xinghai , Cai Xiaopan , Wei Haifeng , Xiao Jianru
Published: March 2021

Study Design.

Retrospective analysis.

Objective.

The study was designed to: (1) figure out risk factors of metastasis; (2) explore prognostic factors and develop a nomogram for pelvis and spine Ewing sarcoma (PSES).

Summary of Background Data.

Tools to predict survival of PSES are still insufficient. Nomogram has been widely developed in clinical oncology. Moreover, risk factors of PSES metastasis are still unclear.

Methods.

The data were collected and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. The optimal cutoff values of continuous variables were identified by X-tile software. The prognostic factors of survival were performed by Kaplan–Meier method and multivariate Cox proportional hazards modeling. Nomograms were further constructed for estimating 3- and 5-year cancer-specific survival (CSS) and overall survival (OS) by using R with rms package. Meanwhile, Pearson χ
2 test or Fisher exact test, and logistic regression analysis were used to analyze the risk factors for the metastasis of PSES.

Results.

A total of 371 patients were included in this study. The 3- and 5-year CSS and OS rate were 65.8 ± 2.6%, 55.2 ± 2.9% and 64.3 ± 2.6%, 54.1 ± 2.8%, respectively. The year of diagnosis, tumor size, and lymph node invasion were associated with metastasis of patients with PSES. A nomogram was developed based on identified factors including: age, tumor extent, tumor size, and primary site surgery. The concordance index (C-index) of CSS and OS were 0.680 and 0.679, respectively. The calibration plot showed the similar trend of 3-year, 5-year CSS, and OS of PSES patients between nomogram-based prediction and actual observation, respectively.

Conclusion.

PSES patients with earlier diagnostic year (before 2010), larger tumor size (>59 mm), and lymph node invasion, are more likely to have metastasis. We developed a nomogram based on age, tumor extent, tumor size, and surgical treatments for determining the prognosis for patients with PSES, while more external patient cohorts are warranted for validation.

Level of Evidence: 3
The Role of Vertebral Porosity and Implant Loading Mode on Bone-Tissue Stress in the Human Vertebral Body Following Lumbar Total Disc Arthroplasty
Authors: Bonnheim Noah B. , Adams Mark F. , Wu Tongge , Keaveny Tony M.
Published: March 2021

Study Design.

Micro-computed tomography- (micro-CT-) based finite element analysis of cadaveric human lumbar vertebrae virtually implanted with total disc arthroplasty (TDA) implants.

Objective.

(1) Assess the relationship between vertebral porosity and maximum levels of bone-tissue stress following TDA; (2) determine whether the implant's loading mode (axial compression vs. sagittal bending) alters the relationship between vertebral porosity and bone-tissue stress.

Summary of Background Data.

Implant subsidence may be related to the bone biomechanics in the underlying vertebral body, which are poorly understood. For example, it remains unclear how the stresses that develop in the supporting bone tissue depend on the implant's loading mode or on typical inter-individual variations in vertebral morphology.

Methods.

Data from micro-CT scans from 12 human lumbar vertebrae (8 males, 4 females; 51–89 years of age; bone volume fraction [BV/TV] = 0.060–0.145) were used to construct high-resolution finite element models (37 μm element edge length) comprising disc-vertebra-implant motion segments. Implants were loaded to 800 N of force in axial compression, flexion-, and extension-induced impingement. For comparison, the same net loads were applied via an intact disc without an implant. Linear regression was used to assess the relationship between BV/TV, loading mode, and the specimen-specific change in stress caused by implantation.

Results.

The increase in maximum bone-tissue stress caused by implantation depended on loading mode (P < 0.001), increasing more in bending-induced impingement than axial compression (for the same applied force). The change in maximum stress was significantly associated with BV/TV (P = 0.002): higher porosity vertebrae experienced a disproportionate increase in stress compared with lower porosity vertebrae. There was a significant interaction between loading mode and BV/TV (P = 0.002), indicating that loading mode altered the relationship between BV/TV and the change in maximum bone-tissue stress.

Conclusion.

Typically-sized TDA implants disproportionately increase the bone-tissue stress in more porous vertebrae; this affect is accentuated when the implant impinges in sagittal bending.

Level of Evidence: N/A
Adolescent Weight Management Intervention in a Nonclinical Setting: Changes in Eating-Related Cognitions and Depressive Symptoms
Authors: Darling Katherine E. , Rancourt Diana , Evans E. Whitney , Ranzenhofer Lisa M. , Jelalian Elissa
Published: March 2021

Objective:

The present study was a secondary data analysis of a randomized controlled trial (RCT) to examine changes in depressive symptoms and eating-related cognitions in teens who participated in a nonclinic-based adolescent behavioral weight control treatment delivered by YMCA coaches. Differences in intervention effects were also examined by sex.

Methods:

Adolescents (N = 66; 13–17 years; 60.6% girls) with overweight (10.6%) or obesity (53.0% with severe obesity) participated in an RCT comparing 2 versions of an evidence-based intervention. Adolescents completed measures of eating-related cognitions (Eating Disorder Examination Questionnaire) and depressive symptoms (Children's Depressive Inventory-2) at baseline and end of active treatment (16 weeks).

Results:

There were no significant effects of group, time, or group by time interaction for depressive symptoms, global eating-related cognitions, dietary restraint, or eating concerns (ps > 0.05). Shape concerns (p = 0.04) and weight concerns (p = 0.02) significantly decreased over the intervention. Significant interactions between sex and time on global eating-related cognitions (p < 0.001), eating (p = 0.002), shape (p = 0.02), and weight concerns (p = 0.004) were detected such that female participants' scores decreased over the course of the treatment, but male participants' scores did not.

Conclusion:

The results demonstrate some positive and no detrimental effects of a nonclinic-based behavioral weight control intervention on adolescents' eating-related cognitions and depressive symptoms. The findings may mitigate concerns that dissemination of structured, nonclinic-based weight management programs for adolescents will produce negative eating and mood outcomes; however, replication of results in larger trials is needed.
Navigating Medical Care for a Young Adult with Developmental Disability
Authors: Goss Megan , Afghani Behnoosh , Piazza Cathleen C. , Sabapathy Thusa , Key Tayler , Keating Sarah , Nyp Sarah S.
Published: March 2021

CASE:

Sam is a 20-year-old young man with intermittent gastritis, autism spectrum disorder, and intellectual disability who was admitted to the hospital because of nutritional concerns. His parents have legal guardianship and report that he has had increasing frequency of refusal to eat, resulting in a 15-pound weight loss over the past 3 months. On admission, a multidisciplinary team including specialists in gastroenterology, nutrition, feeding (behavioral and mechanical), psychiatry, palliative care, and social work was engaged to develop an evaluation and care plan. Sam's nutritional assessment was significant for severe malnutrition. An upper endoscopy was performed and was without abnormalities, including signs of significant gastritis.

An upper endoscopy was performed and was without abnormalities, including signs of significant gastritis.

A carefully obtained history found that Sam does not have a primary care physician. He was recently hospitalized at another facility because of his weight loss and nutritional concerns but was discharged against medical advice because of parental dissatisfaction with his care. His mother shared that she has tried many strategies to encourage Sam to eat including pushing spoons of food into his mouth, syringe feeding, and verbally pleading with Sam to take a bite, but all of these have been without success.

Because of concerns that persistent attempts to verbally and physically coerce Sam to eat may be contributing to his aversion to food/eating, the feeding team provided Sam's parents with education and coaching for utilization of behavioral cues to determine when Sam wanted to eat. Despite parents expressing their understanding of the importance of avoiding physical attempts to “make” Sam eat and the team palliative care physician meeting with Sam's parents to elicit their goals for Sam's care, his nurses reported observing several instances of Sam's mother tapping a loaded spoon on his lips. Because of minimal oral intake, a nasogastric tube was placed for provision of hydration and nutrition. Sam's parents consented to the use of soft restraints and the presence of a bedside patient care assistant because of Sam becoming agitated and pulling at the tube.

After 10 days of hospitalization, Sam was taking about 50% of his goal intake by mouth. Unfortunately, Sam removed his NG tube, and his parents refused to allow the tube to be replaced. Sam's parents then discharged him against medical advice, stating that they believed he would recover better at home. What are important considerations in caring for patients like Sam in the hospital setting and beyond?
Characterization of the 2019 Micrographic Surgery and Dermatologic Oncology Standardized Letter of Recommendation
Authors: Abidi Nadia Y. , Wanner Brian , Brown Mariah , Golda Nicholas , Hajar Tamar , Rohani Pooyan , Yu Siegrid S. , Carr David R.
Published: March 2021

BACKGROUND

Traditional letters of recommendation used for postgraduate medical training applications have multiple limitations, including a lack of clarity, inflated and overly flattering assessments, and low reliability between interpreting faculty. A micrographic surgery and dermatologic oncology (MSDO) standardized letter of recommendation (SLOR) was created to improve the efficiency, validity, and stratification of applicants to dermatology fellowship training programs.

OBJECTIVE

To analyze the MSDO SLOR for trends in grading based on letter-writer and applicant characteristics and to evaluate its ability to demonstrate differences between applicants.

METHODS

Standardized letter of recommendations received by 4 fellowship programs from the 2019 San Francisco Match application cycle were reviewed retrospectively.

RESULTS

Two hundred forty-nine SLORs were analyzed from 140 applicants. Grade inflation and limited variability in scores were evident. Higher scores correlated with the length of the relationships between letter-writers and applicants and with female letter-writer gender. There was no applicant gender or ethnicity bias detected.

CONCLUSION

Despite score inflation, the MSDO SLOR allows for differentiation between fellowship applicants. Future studies are needed to further evaluate the reliability of the SLOR and find ways to improve its content.
Changes in Metronidazole and Vancomycin Utilization for Nonsevere Clostridioides difficile Infection Among Institutions Caring for Children
Authors: Stultz Jeremy S. , Hopp Jaclyn , Orndahl Christine M. , Omecene Nicole E. , Pakyz Amy L.
Published: March 2021

Clostridioides difficile infection guidelines were published in final format on April 1, 2018. Among 4962 and 3545 C. difficile infection cases in children the year before and after publication, oral metronidazole use decreased from 63.0% to 44.3% (P < 0.001) and oral vancomycin use increased from 27.3% to 47.7% (P < 0.001). Quarterly metronidazole utilization decreased postguidelines among 117 institutions, incidence rate ratios 0.86 (95% confidence intervals: 0.78–0.96).
Arabic Cross-Cultural Adaptation and Validation of Health-Related Quality of Life Measures for Chronic Otitis Media (COMQ-12)
Authors: Elzayat Saad , Elfarargy Haitham H. , Mandour Mahmoud , Lotfy Rasha , Barbara Maurizio
Published: March 2021

Objective:

Our study aimed to translate the chronic otitis media questionnaire-12 (COMQ-12) into the Arabic language, evaluate the internal consistency of the test and test-retest reliability, and validate the adaptation for further use in Arabic studies.

Study Design:

A prospective observation monocenter cohort study.

Settings:

This study was done at Kafrelsheikh University Hospital, Egypt.

Patients:

One hundred twenty five ear pathology-free patients were asked to complete the questionnaire forming group A. One hundred twenty five patients with different forms of COM completed the questionnaire 2 weeks before the planned ear surgery and the same day of the operation, forming group B. Those patients who underwent the ear surgery, completed the questionnaire again 6 months after the operation forming group C.

Intervention:

We did an Arabic forward and backward translation of the original COMQ-12. The patients in group B underwent ear surgery (tympanoplasty with or without mastoidectomy). After fulfilling the questionnaire in different groups, we assessed the psychometric properties of the Arabic version of COMQ-12: internal consistency, reliability, reproducibility, validity, and responsiveness.

Main Outcome Measures:

Cronbach's α was 0.973. The Spearman's rank correlation coefficient was 0.981, while the Intraclass correlation coefficient was 0.973.

Results:

A statistically significant difference was present between group A (average total score 2.38 ± 1.543) and group B (average total score 35.86 ± 5.98). Also, there was a statistically significant difference between group B and group C (average total score 7.46 ± 8.294). The calculated cut-off point of the total score was more than or equal to eight.

Conclusion:

The cross-culturally Arabic adaptation of COMQ-12 was reliable, valid with strong internal consistency and responsiveness. It can detect the significant effect of COM on the quality of life of Arabic patients. This effect would be improved obviously after surgical management that markedly enhanced the preoperative hearing problem.
Risk Factors for Suboptimal Bowel Preparation for Colonoscopy in Pediatric Patients
Authors: Reddy Pooja , Mencin Ali , Lebwohl Benjamin
Published: March 2021

Background/Aims:

Suboptimal bowel cleansing is common in children and can impact diagnostic and therapeutic outcomes. We aimed to identify risk factors for suboptimal bowel preparation for colonoscopy in pediatric patients.

Methods:

This was a retrospective study of all patients ages 0 to 21 years who underwent colonoscopy at a children's hospital from 2015 to 2019 in the United States. Demographics and clinical information were obtained from the electronic health record. The primary outcome was suboptimal bowel preparation measured by the endoscopist on a dichotomized Aronchik Scale. Univariate and multivariate regression modeling were used to determine independent predictors of suboptimal preparation.

Results:

Nine hundred and eight patients (mean age 12.17 years [±5.14], boys 465 (51.2%), were included in the analysis. Suboptimal preparation was noted in 242 (26.7%). On univariate analysis, suboptimal preparation was more common in those of younger age (38.6%), Medicaid (32.1%), Spanish as primary language (35.7%), and failure to thrive (FTT) (45.9%). Suboptimal preparations were less common in patients with inflammatory bowel disease (IBD) (11.6%). After adjustment for other covariates, IBD and FTT maintained their statistical associations, IBD (odds ratio [OR] 0.27 95% confidence interval [CI] 0.095–0.75, P = 0.01), FTT (OR 1.98 95% CI 1.28–3.06, P = <0.01).

Conclusions:

To our knowledge, this is the first investigation of pediatric patients to identify independent risk factors for suboptimal bowel preparation. We confirm Medicaid status and English as a second language as risk factors as well as highlight distinct associations from those reported in the adult literature including FTT and younger age. IBD was associated with optimal cleansing. Future research to understand the mechanisms of inferred risk or potential protection is required.
High-Intensity Focused Ultrasound Combined With Gonadotropin-Releasing Hormone Agonist or Levonorgestrel-Releasing Intrauterine System in Treating Dysmenorrhea of Severe Adenomyosis
Authors: Xu Yaping , Zhou Zhan , Wang Haili , Shao Lin , Liu Guoyan
Published: March 2021

Objective

The objective of this study was to investigate the efficacy of high-intensity focused ultrasound (HIFU) combined with gonadotropin-releasing hormone agonist or levonorgestrel-releasing intrauterine system (LNG-IUS) in treating dysmenorrhea in patients with severe adenomyosis.

Methods

A retrospective analysis was performed on 243 patients diagnosed with severe adenomyosis. Patients were divided into H (received HIFU alone), H-G (received HIFU combined with gonadotropin-releasing hormone agonist), and H-L (received HIFU combined with LNG-IUS) groups. Their clinical results were compared at 3 months, 6 months, and 12 months after treatment.

Results

The effective rates of dysmenorrhea relief in the 3 groups after 3 months were 95.24% in the H group, 98.8% in the H-G group, and 94.74% in the H-L group; those after 6 months were 88.10% in the H group, 95.18% in the H-G group, and 84.21% in the H-L group; those after 12 months were 77.38% in the H group, 79.52% in the H-G group, and 96.05% in the H-L group. There was significant difference in effective rates of dysmenorrhea relief among 3 groups after 12 months of treatment, but not 3 or 6 months. In addition, at 12 months after treatment, there were significant differences in the efficacy of dysmenorrhea between patients of different ages or different ablation rates in group H. However, there was no significant difference in the H-G group and the H-L group.

Conclusions

High-intensity focused ultrasound alone is effective in alleviating the symptoms of dysmenorrhea in short term. However, HIFU combined with LNG-IUS improves the therapeutic effect for a longer period.
Revisiting DCE-MRI
Authors: Breit Hanns C. , Block Tobias K. , Winkel David J. , Gehweiler Julian E. , Glessgen Carl G. , Seifert Helge , Wetterauer Christian , Boll Daniel T. , Heye Tobias J.
Published: March 2021

Purpose

The aim of this study was to investigate the diagnostic value of descriptive prostate perfusion parameters derived from signal enhancement curves acquired using golden-angle radial sparse parallel dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) with high spatiotemporal resolution in advanced, quantitative evaluation of prostate cancer compared with the usage of apparent diffusion coefficient (ADC) values.

Methods

A retrospective study (from January 2016 to July 2019) including 75 subjects (mean, 65 years; 46–80 years) with 2.5-second temporal resolution DCE-MRI and PIRADS 4 or 5 lesions was performed. Fifty-four subjects had biopsy-proven prostate cancer (Gleason 6, 15; Gleason 7, 20; Gleason 8, 13; Gleason 9, 6), whereas 21 subjects had negative MRI/ultrasound fusion-guided biopsies. Voxel-wise analysis of contrast signal enhancement was performed for all time points using custom-developed software, including automatic arterial input function detection. Seven descriptive parameter maps were calculated: normalized maximum signal intensity, time to start, time to maximum, time-to-maximum slope, and maximum slope with normalization on maximum signal and the arterial input function (SMN1, SMN2). The parameters were compared with ADC using multiparametric machine-learning models to determine classification accuracy. A Wilcoxon test was used for the hypothesis test and the Spearman coefficient for correlation.

Results

There were significant differences (P < 0.05) for all 7 DCE-derived parameters between the normal peripheral zone versus PIRADS 4 or 5 lesions and the biopsy-positive versus biopsy-negative lesions. Multiparametric analysis showed better performance when combining ADC + DCE as input (accuracy/sensitivity/specificity, 97%/93%/100%) relative to ADC alone (accuracy/sensitivity/specificity, 94%/95%/95%) and to DCE alone (accuracy/sensitivity/specificity, 78%/79%/77%) in differentiating the normal peripheral zone from PIRADS lesions, biopsy-positive versus biopsy-negative lesions (accuracy/sensitivity/specificity, 68%/33%/81%), and Gleason 6 versus ≥7 prostate cancer (accuracy/sensitivity/specificity, 69%/60%/72%).

Conclusions

Descriptive perfusion characteristics derived from high-resolution DCE-MRI using model-free computations show significant differences between normal and cancerous tissue but do not reach the accuracy achieved with solely ADC-based classification. Combining ADC with DCE-based input features improved classification accuracy for PIRADS lesions, discrimination of biopsy-positive versus biopsy-negative lesions, and differentiation between Gleason 6 versus Gleason ≥7 lesions.
Photon-Counting Multienergy Computed Tomography With Spectrally Optimized Contrast Media for Plaque Removal and Stenosis Assessment
Authors: Sartoretti Thomas , Eberhard Matthias , Nowak Tristan , Gutjahr Ralf , Jost Gregor , Pietsch Hubertus , Schmidt Bernhard , Flohr Thomas , Alkadhi Hatem , Euler André
Published: March 2021

Purpose

The aim of this study was to systematically evaluate the potential to combine investigational contrast media with spectrally optimized energy-thresholding of photon-counting detector computed tomography (PCCT) for subtraction of calcified plaques in a coronary artery stenosis phantom.

Methods

A small vessel phantom containing 3 fillable tubes (diameter, 3 mm each) with calcified plaques was placed into an anthropomorphic chest phantom. The plaques had incremental thicknesses ranging from 0.3 to 2.7 mm, simulating vessel stenoses ranging from 10% to 90% of the lumen diameter. The phantom was filled with 5 different investigational contrast media (iodine, bismuth, hafnium, holmium, and tungsten) at equal mass concentrations (15 mg/mL) and was imaged on a prototype PCCT at 140 kVp using optimized, contrast media–dependent energy thresholds. Contrast maps (CMs) were reconstructed for each contrast medium by applying a linear 2-material decomposition algorithm. Image noise magnitude and noise texture of CM were compared among the contrast media using the noise power spectrum. Two blinded readers independently rated the vessel lumen visualization on short-axis and the overall subjective image quality on long-axis CM relative to iodine as the reference standard. Four readers determined the highest degree of stenosis that could be assessed with high diagnostic confidence on long-axis CM.

Results

Average image noise on CM was lower for tungsten (49 HU) and hafnium (62 HU) and higher for bismuth (81 HU) and holmium (165 HU) compared with iodine (78 HU). Noise texture of CM was similar among the contrast media. Interreader agreement for vessel lumen visualization on short-axis CM ranged from moderate to excellent (k = 0.567–0.814). Compared with iodine, lumen visualization of each reader was improved using tungsten (P < 0.001 for both readers), similar to improved using hafnium (P = 0.008, P = 0.29), similar using bismuth (P = 0.38, P = 0.69), and decreased using holmium (both, P < 0.001). Overall subjective image quality was similar for holmium and superior for tungsten, hafnium, and bismuth as compared with iodine. Higher-degree stenoses were evaluable with high confidence using tungsten (mean, 70%; interquartile range, 70%–70%), bismuth (70%; 60%–70%), and hafnium (75%; 70%–80%) compared with iodine (50%; 50%–60%) and holmium (50%; 50%–60%).

Conclusions

Spectral optimization in PCCT combined with investigational contrast media can improve calcium subtraction and stenosis assessment in small vessels. Contrast maps of tungsten and, to a lesser extent, hafnium as contrast media yielded superior image noise properties and improved vessel lumen visualization, along with a higher subjective image quality compared with the reference standard iodine.
Surgical Outcome of Pharyngocutaneous Fistula After Total Laryngectomy
Authors: Higashino Takuya , Oshima Azusa , Fukunaga Yutaka , Hayashi Ryuichi
Published: March 2021

Background

The management of pharyngocutaneous fistula is challenging. We typically treat postlaryngectomy pharyngocutaneous fistulas with a pedicled pectoralis major flap transfer. This study analyzed the outcomes of our surgical treatments for pharyngocutaneous fistula to propose considerations for surgical strategies.

Methods

This retrospective review included all patients who underwent surgical repair of a postlaryngectomy pharyngocutaneous fistula at the National Cancer Center Hospital East in Kashiwa, Japan, from January 2005 to December 2019.

Results

The final analysis included 33 cases (median age, 71 years). Twenty-two cases had a history of radiotherapy to the head and neck region. Wound closures were performed with a pedicled pectoralis major musculocutaneous flap (n = 26) or pedicled pectoralis major muscle flap (n = 7). In 1 case, a deltopectoral flap was combined with the pectoralis major musculocutaneous flap. The median total operation time was 236 minutes, the median blood loss during surgery was 144 mL, and the median hospital stay after the reconstructive surgery was 39 days. Minor leakage occurred in 19 cases, and major leakage occurred in 2 cases. The fistula was finally cured successfully in 31 cases. We compared the outcomes in patients with leakage after surgical repair to those in patients without leakage after surgical repair to determine the risk factors for leakage after surgical repair of a pharyngocutaneous fistula. Five patients in the nonleakage group and 17 in the leakage group had a history of preoperative radiation (P = 0.052). The median preoperative blood values in the nonleakage and leakage groups were as follows: albumin, 3.6 and 3.2 g/dL (P = 0.061), and C-reactive protein, 2.36 and 6.77 mg/dL (P = 0.031), respectively. The time between the occurrence of the fistula and reconstructive surgery was 32 and 9 days in the nonleakage and leakage groups, respectively (P = 0.009).

Conclusions

Our surgical treatment for postlaryngectomy pharyngocutaneous fistula succeeded in 31 of 33 cases (94%). This study demonstrated that pedicled pectoralis major flap transfer is useful for the treatment of postlaryngectomy pharyngocutaneous fistula.
Evaluating thunderclap headache
Authors: Chen Chun-Yu , Fuh Jong-Ling
Published: March 2021

Purpose of review

Thunderclap headache (TCH) is an abrupt-onset of severe headache that needs to be thoroughly investigated because the most common secondary cause is subarachnoid hemorrhage (SAH). There has been no consensus guideline regarding the diagnostic workup. This review aims to provide an update on the evaluation of TCH.

Recent findings

The most important update in the 2019 American College of Emergency Physicians guideline for evaluation of acute headache in the emergency department is that negative noncontrast brain computed tomography (CT) findings within 6 h from ictus essentially excludes SAH. Additionally, the updated guideline recommends that after a negative brain CT, CT angiogram is a reasonable alternative to lumbar puncture if clinical suspicion of an intracranial source of SAH is high. An important update of reversible vasoconstriction syndrome (RCVS), the second most common etiology of TCH, is the RCVS2 score development based on clinical and radiological features, providing high specificity and sensitivity for distinguishing RCVS from other intracranial arteriopathies.

Although the evaluation of TCH is exhaustive, the potentially catastrophic consequence of a missed diagnosis of sentinel headache justifies the efforts. Awareness of the clinical features and application of diagnostic tools specific for different pathological conditions can facilitate the diagnostic workup.
Early multiple sclerosis: diagnostic challenges in clinically and radiologically isolated syndrome patients
Authors: Calabrese Massimiliano , Marastoni Damiano , Crescenzo Francesco , Scalfari Antonio
Published: March 2021

Purpose of review

With the introduction of new diagnostic criteria, the sensibility for multiple sclerosis (MS) diagnosis increased and the number of cases with the clinically isolated syndrome (CIS) decreased. Nevertheless, a misdiagnosis might always be around the corner, and the exclusion of a ‘better explanation’ is mandatory.

There is a pressing need to provide an update on the main prognostic factors that increase the risk of conversion from CIS or from radiologically isolated syndrome (RIS) to MS, and on the potential ‘red flags’ to consider during the diagnostic workup.

Recent findings

We discuss diagnostic challenges when facing patients presenting with a first demyelinating attack or with a RIS, with a focus on recently revised diagnostic criteria, on other neuroinflammatory conditions to be considered in the differential diagnosis and on factors distinguishing patients at risk of developing MS.

A correct definition of a ‘typical’ demyelinating attack, as well as a correct interpretation of MRI findings, remains crucial in the diagnostic process. The cerebrospinal fluid examination is warmly recommended to confirm the dissemination in time of the demyelinating process and to increase the diagnostic accuracy.

An early and accurate diagnosis of MS requires careful consideration of all clinical, paraclinical and radiological data, as well the reliable exclusion of other mimicking pathological conditions. This is advocated to promptly initiate an appropriate disease-modifying therapy, which can impact positively on the long-term outcome of the disease.
Facial pain beyond trigeminal neuralgia
Authors: May Arne , Hoffmann Jan
Published: March 2021

Purpose of review

Trigeminal neuralgia is a well-known facial pain syndrome with several treatment options. In contrast, non-neuralgiform idiopathic facial pain syndromes are relatively rare, reflected by the fact that, until 2020, no internationally accepted diagnostic classification existed. Like trigeminal neuralgia, these non-dental facial pain syndromes need to be managed by neurologists and pain specialists, but the lack of pathophysiological understanding has resulted in an underrepresented and undertreated patient group.

Recent findings

This work provides a brief overview of the most common primary facial pain syndromes, namely, the facial attack-like facial pain, which corresponds to attack-like headache, the persistent idiopathic facial pain (formerly ‘atypical facial pain’), and trigeminal neuropathy. What these disorders have in common is that they should all be treated conservatively.

On the basis of pragmatic classifications, permanent and attack-like primary facial pain can be relatively easily differentiated from one another. The introduction of the new International Classification of Orofacial Pain offers the opportunity to better coordinate and concentrate scientific efforts, so that in the future the therapy strategies that are still inadequate, can be optimized.
Electroconvulsive Therapy Use in Psychiatric Hospitalizations in Portugal
Authors: Mota Pedro , Gonçalves-Pinho Manuel , Ribeiro João Pedro , Macedo Silvério , Freitas Alberto , Mota Jorge
Published: March 2021

Objectives

The primary aim of this study was to describe a Portuguese nationwide epidemiological perspective on the use of electroconvulsive therapy (ECT) in hospitalized psychiatric patients. The secondary aims of the study were to characterize clinical and sociodemographic trends of hospitalized patients treated with ECT.

Methods

A retrospective-observational study was conducted using an administrative database gathering every registered Portuguese public hospital hospitalizations from 2008 to 2015. We selected all hospitalizations with a procedure code 94.27 (Other electroshock therapy) defined by the International Classification of Diseases version 9, Clinical Modification. Variables included birth date, sex, address, primary and secondary diagnoses, admission/discharge date, length of stay, and discharge status from each single hospitalization episode. We also calculated Portugal's inpatient ECT prevalence rate (iP%).

Results

There were a total of 879 registered hospitalizations with ECT within the 8-year period of this study. Most occurred in female patients (53.4%), belonging to the age group of 51 to 70 years old, with a mean age of 50.5 years. The median length of stay was 43.0 days with an interquartile range of 27.0 to 68.0. The most frequent primary diagnosis was major depressive disorder, recurrent episode, representing 19.6% of all hospitalizations. The iP% for the study period was 0.71%.

Conclusions

In Portugal, most of the patients who received ECT were women above middle age, and depressive disorders were the most common indication. Portugal's iP% represents a low rate when compared with other European countries, which might indicate an underutilization of ECT in Portuguese psychiatric hospitals.
Rhizobium changzhiense sp. nov., isolated from effective nodules of Vicia sativa L. in North China
Authors: Zhang Junjie , Peng Shanshan , Andrews Mitchell , Liu Chunzeng , Shang Yimin , Li Shuo , Wang Entao , Zhang Xiaoxia
Published: March 2021

Three fast-growing rhizobial strains isolated from effective nodules of common vetch (Vicia sativa L.) were characterized using a polyphasic approach. All three strains were assigned to the genus

Rhizobium

on the basis of the results of 16S rRNA gene sequence analysis. Phylogenetic analysis based on concatenated atpD-recA genes separated the strains into a distinct lineage represented by WYCCWR 11279T, which showed average nucleotide identity values of 95.40 and 93.61 % with the most similar phylogenetic type strains of

Rhizobium sophorae

CCBAU 03386T and

Rhizobium laguerreae

FB TT, respectively. The digital DNA–DNA hybridization relatedness values between WYCCWR 11279T and the closest related type strains were less than 70 %. Therefore, a novel rhizobial species is proposed, Rhizobium changzhiense sp. nov., and strain WYCCWR 11279T (=HAMBI 3709T=LMG 31534T) is designated as the type strain for the novel species.
De novoassembly of 64 haplotype-resolved human genomes of diverse ancestry and integrated analysis of structural variation
Authors: Ebert Peter , Audano Peter A. , Zhu Qihui , Rodriguez-Martin Bernardo , Porubsky David , Bonder Marc Jan , Sulovari Arvis , Ebler Jana , Zhou Weichen , Mari Rebecca Serra , Yilmaz Feyza , Zhao Xuefang , Hsieh PingHsun , Lee Joyce , Kumar Sushant , Lin Jiadong , Rausch Tobias , Chen Yu , Ren Jingwen , Santamarina Martin , Höps Wolfram , Ashraf Hufsah , Chuang Nelson T. , Yang Xiaofei , Munson Katherine M. , Lewis Alexandra P. , Fairley Susan , Tallon Luke J. , Clarke Wayne E. , Basile Anna O. , Byrska-Bishop Marta , Corvelo André , Chaisson Mark J.P. , Chen Junjie , Li Chong , Brand Harrison , Wenger Aaron M. , Ghareghani Maryam , Harvey William T. , Raeder Benjamin , Hasenfeld Patrick , Regier Allison , Abel Haley , Hall Ira , Flicek Paul , Stegle Oliver , Gerstein Mark B. , Tubio Jose M.C. , Mu Zepeng , Li Yang I. , Shi Xinghua , Hastie Alex R. , Ye Kai , Chong Zechen , Sanders Ashley D. , Zody Michael C. , Talkowski Michael E. , Mills Ryan E. , Devine Scott E. , Lee Charles , Korbel Jan O. , Marschall Tobias , Eichler Evan E.
Published: March 2021

Long-read and strand-specific sequencing technologies together facilitate thede novoassembly of high-quality haplotype-resolved human genomes without parent–child trio data. We present 64 assembled haplotypes from 32 diverse human genomes. These highly contiguous haplotype assemblies (average contig N50: 26 Mbp) integrate all forms of genetic variation across even complex loci such as the major histocompatibility complex. We focus on 107,590 structural variants (SVs), of which 68% are inaccessible by short-read sequencing. We identify new SV hotspots (spanning megabases of gene-rich sequence), characterize 130 of the most active mobile element source elements, and find that 63% of all SVs arise by homology-mediated mechanisms—a twofold increase from previous studies. Our resource now enables reliable graph-based genotyping from short reads of up to 50,340 SVs, resulting in the identification of 1,525 expression quantitative trait loci (SV-eQTLs) as well as SV candidates for adaptive selection within the human population.
Resilience through diversity: Loss of neuronal heterogeneity in epileptogenic human tissue impairs network resilience to sudden changes in synchrony
Authors: Rich Scott , Chameh Homeira Moradi , Lefebvre Jeremie , Valiante Taufik A
Published: March 2021

A myriad of pathological changes associated with epilepsy can be recast as decreases in cell and circuit heterogeneity. We thus propose recontextualizing epileptogenesis as a process where reduction in cellular heterogeneity in part, renders neural circuits less resilient to seizure. By comparing patch clamp recordings from human layer 5 (L5) cortical pyramidal neurons from epileptogenic and non-epileptogenic tissue, we demonstrate significantly decreased biophysical heterogeneity in seizure generating areas. Implemented computationally, this renders model neural circuits prone to sudden transitions into synchronous states with increased firing activity, paralleling ictogenesis. This computational work also explains the surprising finding of significantly decreased excitability in the population activation functions of neurons from epileptogenic tissue. Finally, mathematical analyses reveal a unique bifurcation structure arising only with low heterogeneity and associated with seizure-like dynamics. Taken together, this work provides experimental, computational, and mathematical support for the theory that ictogenic dynamics accompany a reduction in biophysical heterogeneity.
Exploring bacterial diversity via a curated and searchable snapshot of archived DNA sequences
Authors: Blackwell Grace A. , Hunt Martin , Malone Kerri M. , Lima Leandro , Horesh Gal , Alako Blaise T.F. , Thomson Nicholas R , Iqbal Zamin
Published: March 2021

The open sharing of genomic data provides an incredibly rich resource for the study of bacterial evolution and function, and even anthropogenic activities such as the widespread use of antimicrobials. Whilst these archives are rich in data, considerable processing is required before biological questions can be addressed. Here, we assembled and characterised 661,405 bacterial genomes using a uniform standardised approach, retrieved from the European Nucleotide Archive (ENA) in November of 2018. A searchable COBS index has been produced, facilitating the easy interrogation of the entire dataset for a specific gene or mutation. Additional MinHash and pp-sketch indices support genome-wide comparisons and estimations of genomic distance. An analysis on this scale revealed the uneven species composition in the ENA/public databases, with just 20 of the total 2,336 species making up 90% of the genomes. The over-represented species tend to be acute/common human pathogens. This aligns with research priorities at different levels from individuals with targeted but focused research questions, areas of focus for the funding bodies or national public health agencies, to those identified globally as priority pathogens by the WHO for their resistance to front and last line antimicrobials. Understanding the actual and potential biases in bacterial diversity depicted in this snapshot, and hence within the data being submitted to the public sequencing archives, is essential if we are to target and fill gaps in our understanding of the bacterial kingdom.
Independent and distinct patterns of abnormal lateral orbitofrontal cortex activity during compulsive grooming and reversal learning normalize after fluoxetine
Authors: Manning Elizabeth E , Geramita Matthew A , Piantadosi Sean C , Pierson Jamie L , Ahmari Susanne E
Published: March 2021

Background

Patients with obsessive-compulsive disorder (OCD) display disrupted performance and abnormal lateral orbitofrontal cortex (LOFC) activity during reversal learning tasks, yet it is unknown whether compulsions and reversal learning deficits share a common neural substrate. To answer this question, we measured neural activity within vivocalcium imaging in LOFC during compulsive grooming and reversal learning before and after fluoxetine treatment.

Methods

Sapap3-knockout (KO) mice were used as a model for OCD-relevant behaviors.Sapap3-KOs and control littermates were injected with virus encoding GCaMP6f and implanted with gradient-index lenses to visualize LOFC activity using miniature microscopes. Grooming, reversal learning, and neural activity were measured pre- and post-fluoxetine treatment (18mg/kg, 4 weeks).

Results

Baseline compulsive grooming and reversal learning impairments in KOs improved after fluoxetine treatment. Additionally, KOs display distinct patterns of abnormal LOFC activity during grooming and reversal learning, both of which normalize after fluoxetine. Finally, modulation in response to reversal learning and compulsive behavior are independent, as reversal learning-associated neurons are distributed randomly amongst grooming-associated neurons (i.e. overlap is what would be expected by chance).

Conclusions

In OCD, the LOFC is disrupted during both compulsive behaviors and reversal learning, yet whether these behaviors share common neural underpinnings is unknown. We find that the LOFC plays distinct and independent roles in compulsive grooming and impaired reversal learning and their improvement with fluoxetine. These findings suggest that LOFC plays separate roles in pathophysiology and treatment of different perseverative behaviors in OCD.
Pneumococcal genetic variability influences age-dependent bacterial carriage
Authors: Kremer PHC , Ferwerda B , Bootsma HJ , Rots NY , Wijmega-Monsuur AJ , Sanders EAM , Trzciński K , Wyllie AL , Turner P , van der Ende A , Brouwer MC , Bentley SD , van de Beek D , Lees JA
Published: March 2021

The pneumococcal conjugate vaccine (PCV) primarily reduces disease burden in adults through a reduction in carriage prevalence of invasive serotypes in children. Current vaccine formulations are the same for both adults and children, but tailoring these formulations to age category could optimize vaccine efficacy. Identification of specific pneumococcal genetic factors associated with carriage in younger or older age groups may suggest alternative formulations and contribute to a better mechanistic understanding of immunity. Here, we used whole genome sequencing to dissect pneumococcal variation associated with age. We performed genome sequencing in a large carriage cohort, and conducted a meta-analysis with an existing carriage study. We compiled a dictionary of pathogen genetic variation including serotype, sequence cluster, sequence elements, SNPs, burden combined rare variants, and clusters of orthologous genes (COGs) for each cohort – all of which used in a genome-wide association with host age. Age-dependent colonization had some heritability, though this varied between cohorts (h2= 0.10, 0.00 – 0.69 95% CI in the first; h2= 0.46, 0.33 – 0.60 95% CI in the second cohort). We found that serotypes and genetic background (strain) explained most of the heritability in each cohort (h2serotype= 0.06 and h2GPSC= 0.04 in the first; h2serotype= 0.20 and h2GPSC= 0.23 in the second cohort). We found one candidate association (p = 1.2×10−9) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, association with age was highly cohort and strain dependent, supporting proposals for a future vaccination strategy which is primarily targeted using serotypes rather than proteins, and is tailored towards specific pathogen populations.
Identification of gene products involved in plant colonization byPantoeasp. YR343 using a diguanylate cyclase expressed in the presence of plants
Authors: Bible Amber N. , Chang Mang , Morrell-Falvey Jennifer L.
Published: March 2021

Microbial colonization of plant roots is a highly complex process that requires the coordination and regulation of many gene networks, yet the functions of many of these gene products remain poorly understood.Pantoeasp. YR343, a gamma-proteobacterium isolated from the rhizosphere ofPopulus deltoides, forms robust biofilms along the root surfaces ofPopulusand possesses plant growth-promoting characteristics. The mechanisms governing biofilm formation along plant roots by bacteria, includingPantoeasp. YR343, are not fully understood and many genes involved in this process have yet to be discovered. In this work, we identified three diguanylate cyclases in the plant-associated microbePantoeasp. YR343 that are expressed in the presence of plant roots, One of these diguanylate cyclases, DGC2884 localizes to discrete sites in the cells and its overexpression results in reduced motility and increased EPS production and biofilm formation. We then performed a genetic screen by expressing this diguanylate cyclase from an inducible promoter in order to identify candidate downstream effectors of c-di-GMP signaling which may be involved in root colonization byPantoeasp. YR343. Further, we demonstrate the importance of other domains in DGC2884 to its activity, which in combination with the genes identified by transposon mutagenesis, may yield insights into activity and regulation of homologous enzymes in medically and agriculturally relevant microbes.
Site-specific phosphorylation of PSD-95 dynamically regulates the post-synaptic density as observed by phase separation
Authors: Vistrup-Parry Maria , Chen Xudong , Johansen Thea L. , Bach Sofie , Buch-Larsen Sara C. , Bartling Christian R. O. , Ma Chenxue , Clemmensen Louise S. , Nielsen Michael L. , Zhang Mingjie , Strømgaard Kristian
Published: March 2021

Postsynaptic density protein 95 is a key scaffolding protein in the postsynaptic density of excitatory glutamatergic neurons, organizing signaling complexes primarily via its three PSD-95/Discs-large/Zona occludens domains. PSD-95 is regulated by phosphorylation, but technical challenges have limited studies of the molecular details. Here, we genetically introduced site-specific phosphorylations in single, tandem and full-length PSD-95 and generated a total of 11 phosphorylated protein variants. We examined how these phosphorylations affected binding to known interaction partners and the impact on phase separation of PSD-95 complexes, and identified two new phosphorylation sites with opposing effects. Phosphorylation of Ser78 inhibited phase separation with the glutamate receptor subunit GluN2B and the auxiliary protein stargazin, whereas phosphorylation of Ser116 induced phase separation with stargazin only. Thus, by genetically introducing phosphoserine site-specifically and exploring the impact on phase separation, we have provided new insights into the regulation of PSD-95 by phosphorylation and the dynamics of the PSD.

Graphical Abstract: Phosphorylation of PSD-95.

Illustration of the interaction between the PDZ domains of PSD-95 and the NMDA receptor (NMDAR) (PDB: 4PE5) at the plasma membrane. PSD-95 interacts with the AMPA receptor (AMPAR) (PDB: 3KG2) through Stargazin (PDB: 5KBU). Using the software Ranch, a model of FL PSD-95 was generated using known structural domains of PSD-95 connected via a fully-flexible linker (PDZ1-2, PDB: 3GSL; PDZ3, PDB: 5JXB; SH3-GK, PDB: 1KJW).

Illustration of the effect of phosphorylation of PSD-95 on the formation of condensates at the PSD. PSD-95 can phase separate with receptors and intracellular proteins, and phosphorylation is can affect this interaction and lead to alterations, both negative and positive, in the formation of condensates.